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Preface 
 
 These three lectures were delivered before 
 the students of the Medico-Chirurgical College. 
 Owing to the many requests for several parts 
 of our various publications of the work done 
 in the laboratory I have thought it best to 
 incorporate the results in a general review of 
 the internal secretions. While many state- 
 ments are contradictory, yet I have included 
 them, as the whole subject is in a stage of flux 
 and reflux. "Dire n'est rien; faire est tout" — 
 Renan. Isaac Ott. 
 
 Sept. 28, igio. 
 
in the laboratory of our college. It was the 
 genial Franco-American physiologist, Brown- 
 Sequard, who in 1856 first stated that the adrenals 
 when removed caused the death of the animal. 
 This was the commencement of the discoveries 
 about glands with an internal secretion. 
 
 I was the first to state, in the Medical Bulletin, 
 1897, that "the adrenals enlarged the lumen 
 of the intestine at the moment of the injection 
 of the filtrate. When the arterial tension is 
 mounting the intestine is relaxing." 
 
 This property of the adrenal is of value in 
 intestinal hemorrhage of typhoid fever in 
 slowing the peristalsis. In the same paper I 
 showed that the spleen had a most marked 
 effect in exciting peristaltic movements. I have 
 also shown in the laboratory that iodothyrin 
 excites peristalsis and explains the diarrhea 
 in exophthalmic goitre, where we usually have 
 a hyperthyroidism. We also found that the 
 mammary, prostate and spermin were power- 
 ful excitants of uterine contraction. 
 
 The parathyroids were first discovered by 
 Sandstroem, a Swedish anatomist, in 1880. 
 They are often called by the Germans, epithelial 
 bodies (Epithelkoerper). 
 
 Parathyroids, Position of. — In the cat the 
 parathyroids are very regularly four in number, 
 two on each lobe; an external one more or less 
 free ui!)on the external surface of the thyroid, 
 and an internal one embedded in the substance 
 of the lobe nearer to the internal than the ex- 
 
ternal surface of the thyroid, and always smaller 
 than the external. From their anatomical posi- 
 tion the cat is the most suitable animal for 
 parathyroidectomy. In color and size they, 
 resemble in the cat miliary tubercles. 
 
 The rabbit has two thyroid lobes connected 
 by an isthmus. In each lobe is embedded a 
 parathyroid. Two additional parathyroids, one 
 on each side, lie distinct from the thyroid, 
 usually at some distance from it. He has four 
 parathyroids. 
 
 In the dog there are four parathyroids, but 
 the external pair are usually embedded in the 
 thyroid. The internal parathyroids are rarely 
 seen exposed upon the internal surface of the 
 thyroid. 
 
 Guinea Pig. — The thyroids usually consist of 
 two separate and distinct lobes, with occasion- 
 ally an isthmus uniting the lower ends of the 
 lobes. The number and position of the para- 
 thyroids is variable, more so than in any other 
 animal. Each lobe of the thyroid contains a 
 parathyroid embedded more or less in its tissue; 
 besides these, two additional parathyroids on 
 each side separated from the thyroid and varia- 
 ble in position in the levels of the thyroids. 
 He has four parathyroids. 
 
 Rats. — The thyroid consists of two lobes 
 united by an isthmus, one parathyroid to each 
 lobe, lying on the external surface. It is easily 
 accessible and can be readily cauterized. 
 
8 
 
 In the monkey there are four parathyroids, 
 always embedded in the substance of the thyroid, 
 two in each lobe. 
 
 In man, the parathyroids are three or four 
 in number, two on each side in front of the 
 vertebral column just behind the rear margins 
 of the lateral lobes of the thyroid gland. The 
 inferior thyroid artery is in close relation with 
 them. A small grain of Indian corn repre- 
 sents their size and shape. Their color is red- 
 dish yellow or reddish brown (Fig. i). 
 
 Fig. 1. — The Four Parathyroids in Man — Posterior View 
 (Zuckerkandl). 
 
 Gilbride, in man, found that the most common 
 site of the parathyroids is in the region of the 
 inferior poles of the thyroid gland; the superior 
 
or external glands are behind and close to the 
 inferior border of the lateral lobes and in close 
 proximity to the inferior thyroid artery, the 
 inferior or internal glands lying posterior and 
 below the superior glands, nearer the median 
 line or below the thyroid and resting on the 
 anterior and lateral surface of the trachea. 
 
 W. Berkeley, in 125 autopsies, occasionally 
 found as many as five or six, often only two or 
 three, but always one, parathyroid. 
 
 Proportion of Parathyroid to That of the Thy- 
 roid. — Thyroid tablets of commerce are chiefly 
 from the glands of the lamb. The fresh thyroids 
 of six mature lambs weighed 24.7 grams (dried 
 8.4 grams), while twelve external parathyroids, 
 fresh, weighed 0.23 gram (dried 0.09 gram). 
 In feeding with thyroid tablets the parathyroids 
 play an exceedingly small part in the medica- 
 tion. 
 
 Histology. — These glands are rich in cellular 
 elements and enclosed by a delicate capsule 
 of connective tissue. In the parathyroid, trabec- 
 ulae run from the deep surface of the enveloping 
 capsule, branch and unite to divide the interior 
 of the gland into polygonal compartments. 
 The cells are small, with a large round nucleus. 
 The amount of protoplasm in the cell is small. 
 The cells of the parathyroid are in structure 
 very different from those of the thyroid. The 
 cells are of two types, the chief and oxyphile, 
 which are considered by Forsythe to repre- 
 sent two stages in the activity of one kind of 
 
lO 
 
 cell. In repose, the clear protoplasm of the 
 chief cells are filled with oxyphile granules 
 which are subsequently extruded, and run to- 
 gether to form drops of colloid material which 
 enters the blood via the lymphatics. 
 
 In the parathyroids the masses of polyhedral 
 cells are in varying stages of active secretion; 
 often, however, a drop of the colloid secretion 
 forces the cells apart. The formation of vesicles 
 in the isolated parathyroid is quite common 
 in the glands of man. 
 
 Morphology. — Three diverticula form the thy- 
 roid, a median one growing from the second 
 visceral arch and which moves to a pretracheal 
 position, where it is connected with the lateral 
 thyroid buds which develop from the dorsal 
 wall of the fourth inner pharyngeal cleft. 
 
 Parathyroids are thickenings of the epithelium 
 on the dorsal aspect of the third and fourth 
 visceral clefts. The thymus arises as a pair 
 of outgrowths from the epithelium of the third 
 cleft. 
 
 Chemistry of the Parathyroids. — The colloid 
 material secreted by the parathyroid is now 
 conceded not to contain iodine. Glycogen is 
 found in abundance. 
 
 Blood Supply. — The parathyroids receive their 
 blood supply usually from the inferior thyroid 
 artery. Nate Ginsburg has shown that one of 
 the superior parathyroids derives its blood 
 supply from the superior parathyroid artery 
 instead of from the inferior thyroid artery. 
 
II 
 
 Ginsburg also found that there is an anastomosis 
 between the parathyroid arteries on one side 
 with those of the other, so if one of the inferior 
 or superior thyroid arteries is intact the blood 
 supply not only of the parathyroid bodies of 
 one side, but those on the other, are preserved. 
 
 Parathyroids in Thymus. — Erdheim found small 
 accessory parathyroid glandules in the thymus. 
 This has also been seen by Pepere in rabbits 
 and in man. Harvier and MoreP found in half 
 of the cases a group of parathyroids in the cat, 
 chiefly in the cervical lobes. They found that 
 tetany did not ensue unless these thymic para- 
 thyroids were also removed. Dr. Scott and I 
 have frequently noted and removed the thymic 
 parathyroids. 
 
 Changes in Parathyroids after Removal of 
 Thyroids. — When the thyroids were removed 
 it was found, by Vincent and Jolly, that the 
 parathyroid tissue approximates in appearance 
 to ordinary thyroid tissue. There is, however, 
 no hypertrophy of the tissues of the parathyroids. 
 
 Walter Edmunds^ has shown by experiments 
 upon dogs that the parathyroids even when left 
 in animals with great thyroid insuflEiciency do 
 not change into thyroid proper. 
 
 What is Tetany? — This name "tetanie" was 
 first used by Lucien Vavirsort in 1852. It is 
 not a distinct disease, but a symptom-complex. 
 It consists of spontaneous intermittent muscular 
 contractions, attended with decreasing strength 
 
 1 Comptes Rendus de la Biologic, May, 1909, p. 837. 
 
 2 Journal of Pathology and Bacteriology, 1910, p. 288. 
 
12 
 
 until death ensues. There is also a spastic, 
 tottering gait, tachycardia, dyspnea, rapid 
 emaciation and psychical depression. It is as- 
 sociated with hypoparathyroidism. 
 
 When all the parathyroids are removed there 
 is partial paralysis, especially of the extensors; 
 trembling in all the muscles, followed by a series 
 of convulsive attacks, with loss of appetite; 
 there is often vomiting and dyspnea, which 
 is replaced by polypnea during the convul- 
 sive attack. The temperature rises during the 
 convulsions, which fact we have often observed. 
 This tetany begins in twenty-four to forty - 
 eight hours after the operation in the dog and 
 cat. The dog generally dies from the second 
 to the fifth day in convulsions. Robert Quest, 
 in 1905, analyzed the brains of three infants 
 dead by tetany and found the amount of cal- 
 cium to be small. There was also a change 
 in the proportion between the amount of sodium 
 to that of calcium. 
 
 Oddo and Sarles found the urine in the tetany 
 of infants to have an exaggerated amount of 
 calcium phosphates. They explained the cause 
 of tetany to be due to loss of calcium salts. 
 Silvestri (1906) held that tetany and eclampsia 
 could be explained by a diminution of the cal- 
 cium in the organism. 
 
 Netter cured three cases of tetany in infants 
 with calcium chloride by the mouth. Mac- 
 Callum and Voegtlin confirmed the results of 
 
13 
 
 Quest as to the lessened amount of calcium in 
 the brain. They also confirmed the results 
 of Oddo and Sarles that there was an increased 
 excretion of calcium in the urine. MacCallum 
 and Voegtlin also found the calcium content 
 in the muscles and blood to be one-half the usual 
 amount. Halstead has cured tetany in man, 
 due to the removal of the parathyroids in opera- 
 tions on the thyroid, by calcium. 
 
 MacCallum and Voegtlin arrested tetany for 
 twenty-fours hours in dogs when seven grains 
 of calcium lactate were given by the vein. Beebe 
 has shown that injection of parathyroid ex- 
 tract causes the symptoms of tetany to vanish 
 for a time, but death finally ensued, just as it 
 did in animals after the use of calcium lactate. 
 
 Quantity of Calcium. — Parhon, Dumitresco 
 and Nissipesco^ found that in proportion to 
 weight, animals, cats chiefly and dogs, the 
 proportion of calcium in the nerve centers was 
 greater after thyroparathyroidectomy than in 
 normal animals. They do not confirm Silvestri 
 and MacCallum's results. 
 
 Leopold and V. Reuss^ in rats after removal 
 of the parathyroids found rather an increase 
 of calcium in the body when compared with 
 noirmal animals. These experiments would 
 rather support the theory of Stoelzner, that 
 there is a hypercalcification which causes tetany. 
 
 Quest made some experiments upon dogs 
 
 1 Compies Rendus de la Societe de Biologie, 1909. May, p. 792. 
 - Wiener Klin. Wochenschrift, No. 35, 1908, p. 1243. 
 
14 
 
 by subcutaneous injection of calcium chloride 
 solution to produce an excess of calcium in 
 the body. He never observed an elevation of 
 the electric excitability of the nerves. The 
 faradic current showed a prompt depression 
 of irritability.^ These experiments tend to prove 
 that Stoltzner's idea that an excess of calcium 
 causes tetany is not correct. 
 
 Musser and Goodman^ studied the metab- 
 olism of a case of surgical or post-operative 
 tetany. They found no "diabetes calcareus," 
 but a marked diminution of the calcium in 
 the urine. They found no relation between 
 the amount of calcium and the severity of the 
 symptoms. They pertinently ask: If tetany 
 is due to a withdrawal of calcium, why should 
 the symptoms persist when the organism is 
 in the perpetual condition of calcium store? 
 Leopold and Von Reuss suggest that the poison 
 which normally is paralyzed by the parathyroids 
 is able to precipitate calcium and leads to the 
 deprivation of the organism of active calcium 
 in a physiological sense. This might explain 
 that with normal or increased total calcium 
 there could be a poverty in ' active calcium. 
 
 Musser and Goodman found a high percentage 
 of ammonia in the urine, it never falling below 
 5 per cent. This coefficient of ammonia bore 
 a distinct relation to tetany. They practically 
 found that . when rigidity or some distress ref- 
 
 ' Berliner Klinische W ochenschrifi, 1910, p. 1074. 
 
 - University of Penna. Medical Bulletin, p. 90, May, 1909. 
 
15 
 
 erable to the tetany was complained of, the 
 ammonia percentage was raised. They are 
 of the opinion that an acidosis may be the under- 
 lying feature of surgical tetany. 
 
 MacCallum and Voegtlin have discovered 
 in parathyroidectomized animals: (i) a marked 
 reduction in the calcium content of the tissues, 
 especially of the blood and brain; (2) an in- 
 creased output of calcium in the urine and feces 
 on the development of tetany; (3) an increased 
 output of nitrogen in the urine; (4) an increased 
 output of ammonia in the urine, with an in- 
 creased ammonia ratio in the urine; and (5) 
 an increased amount of ammonia in the blood. 
 
 Jean V. Cooke^ found in dogs dying from 
 parathyroid tetany a slightly greater amount 
 of calcium in the brain than in the brain of 
 normal dogs, which indicates that a decreased 
 calcium content of the brain is not constant 
 in tetany. After removal of the parathyroids, 
 with the animal fasting, the elimination in urine 
 of magnesium is greatly increased, while that 
 of calcium remains unchanged. The augmenta- 
 tion of magnesium begins before tetany is ob- 
 served. It is suggested that tetany represents 
 a condition of altered salt equilibrium in the 
 nerve cells brought about by a disturbance in 
 the catalytic processes of the body which in- 
 creases the acid factors. 
 
 Walter Edmunds^ found in animals, if a large 
 
 ' Proceedings of Society for Experimental Biology and Medicine, 
 1909. p. 13. 
 
 ^ Journal of Pathology and Bacteriology, 1910, p. 290. 
 
.16 
 
 amount of calcium was given or mainly fed on 
 milk previous to the operation, that after a total 
 thyroidectomy which includes the parathyroids 
 the symptoms ensuing are removed or tem- 
 porarily mitigated. The calcium and milk was 
 continued after the operation. 
 
 Poison in the Blood of Animals in Tetany. — 
 Pfeififer and Mayer found in the sera of six out 
 of seventeen dogs, which had tetany after re- 
 moval of the parathyroids, a toxic principle. 
 This was shown by experiments upon mice. 
 
 Berkeley and Beebe regard tetany to be due 
 to a metabolic poison: (i) the symptoms have 
 a central origin; (2) the symptoms are shown 
 best in young animals and are more severe if 
 the animal is kept on a meat diet; (3) the symp- 
 toms have a close relation to certain chemical 
 conditions which are accompanied by severe 
 nutritional disturbances; (4) gastric tetany is 
 accompanied by severe metabolic disturbances, 
 it has similar symptoms and is promptly re- 
 lieved by intravenous injection of calcium and 
 by parathyroid and nucleoproteid ; (5) bleed- 
 ing followed by intravenous infusion relieves 
 the animal, a procedure well suited to free the 
 body from a circulating poison; (6) symptoms 
 are promptly relieved by the injection of fresh 
 parathyroid nucleoproteid; (7) injections of 
 known simple poisons, such as ammonia and 
 xanthin, produce symptoms which can be 
 promptly relieved by injections of calcium or 
 strontium salts similar to the relief obtained 
 
17 
 
 by the same means in tetany; (8) parathyroid 
 tetany has a deranged metabolism accompanied 
 by a large increase in the excretion of ammonia. 
 
 Meljnikow/ in tetany of rabbits after re- 
 moval of parathyroids, found that injections 
 of calcium acetate quickly improved the ani- 
 mals, but it was quite temporary. He states 
 that the parathyroids have a specific histo- 
 logical structure which is not converted into 
 thyroid tissue. Goitre degeneration of the thy- 
 roid has but little effect upon the parathyroids. 
 There is some regressive change, probably due 
 to mechanical pressure from the enlarged thy- 
 roid, and not to any physiological connection 
 with the thyroid. 
 
 Beebe found that strontium acted equally 
 well as calcium in relieving tetany. Barium 
 also relieves tetany. These facts indicate that 
 calcium loss is only a part of the factors in the 
 course of tetany. 
 
 Bleeding cures tetany, but it can not do it 
 by loss of calcium, as this operation diminishes 
 this element more. It is not likely in forty- 
 eight hours after the operation that in the onset 
 of tetany the hypocalcification is so great as 
 to cause the disease, for plenty of calcium can 
 come from the store-house in the bones. 
 
 Magnesium also relieves tetany, according 
 to MacCallum and Beebe. Neither barium 
 nor magnesium should be used, as they are 
 toxic to the heart. Beebe found parathyroid 
 
 1 Wiener Klinische Wochensckrifi, 1910, p. 410. 
 
nucleoproteid to relieve tetany. The globulin 
 in parathyroids has no effect on tetany. The 
 nucleoproteid will relieve tetany if given by 
 the mouth, but is much more quickly and cer- 
 tainly effective when given subcutaneously or 
 intraperitoneally. 
 
 Berkeley and Beebe are inclined to believe 
 that the parathyroids are chiefly concerned in 
 furnishing enzymes, which are of prime im- 
 portance in the intermediary metabolism of 
 nitrogen. They do not believe that the ab- 
 normal secretion of calcium is the cause of 
 tetany, but a deranged metabolism giving rise 
 to an active poison. 
 
 Clara Jacobson finds in the blood of para- 
 thyroidectomized animals an increase of am- 
 monia and she believes it is directly responsible 
 for the tetany, as the concentration of ammonia 
 in the blood of the parathyroidectomized cats 
 and dogs is sufficient to cause tetany, tremors, 
 and depression in the normal animal. Nor- 
 mally in cats it is 1.57 milligrams per 100 cc, 
 but in parathyroidectomized animals it is 
 on an average of 6 animals 2.53.^ 
 
 Our experiments were made upon sixty cats 
 and two dogs. One hundred and thirty- three 
 observations were made on these sixty-two 
 animals. The cats were first etherized, then 
 the parathyroids removed under antiseptic pre- 
 cautions. The thymus was always examined 
 
 1 Proceedings of Society for Experimental Biology and Medi- 
 cim. Vol. VIII, No. 4. p. 124. 
 
19 
 
 for parathyroids. The cat has usually four 
 parathyroids, but more may exist. In young 
 cats the parathyroids have a looser anatomical 
 relation to the thyroid than later in life. In 
 many cases some of the thyroid was removed 
 in the desire to obtain all the parathyroids, 
 but enough thyroid was left to maintain its 
 functions. When removal in part of the para- 
 thyroids was ineffectual to produce a tetany, 
 then the thyroid was also removed, and we 
 always found it contained a parathyroid larger 
 than the normal. In cats, when all the para- 
 thyroids were removed symptoms of tetany 
 came on in about forty-eight hours as a rule. 
 The first symptoms were a slowness in move- 
 •ment and a state of apathy. The animals 
 were disposed to remain in one place. First, 
 as a rule, was developed a lifting of the pos- 
 terior extremities and sometimes of the an- 
 terior, as though the animal had been stepping 
 in water. The posterior extremities were stiff- 
 like in movement and spread apart in their 
 gait. Then trembling ensued in the extrem- 
 ities, followed by convulsions of the whole 
 body. In the convulsive state the animal 
 usually made loud cries before and after the 
 convulsion. Conjunctivitis was frequently noted 
 in the tetania parathyreopriva. The sense of 
 hearing, sight, smell, and taste remained. They 
 did not respond to petting. They also had the 
 projecting abdomen noted by Hagenbach. 
 
 In some old cats some time after removal 
 
20 
 
 of parathyroids and thyroids and careful ex- 
 amination of the thymus, no tetany ensued 
 for two weeks. Now, Bell and Martin have, 
 shown that pituitary increases the calcium 
 content of the blood. Hence, it is probable 
 that the well-developed pituitary of old animals 
 was sufficient to delay the appearance of tetany, 
 although the animals were kept on a meat diet, 
 which favors tetany. We injected subcutane- 
 ously in animals with tetany about ten to twenty 
 grains of pituitary extract, rubbed up with dis- 
 tilled water. Then in about three hours the 
 vacillating, spastic gait disappeared, the tremor 
 was replaced by steadiness, and the lifting of 
 the feet as though wet with water disappeared. 
 The head, which usually hung down, was ele- 
 vated, and the whole bearing of the animal 
 was changed. This continued for about twenty- 
 four hours, when tetany reappeared. In no 
 case were we able to prevent death by repeated 
 injection of the pituitary. We also injected 
 pituitary by the vein, but the best results were ob- 
 tained by subcutaneous injections. That neither 
 calcium nor its combination with other salts 
 was concerned in the action of the pituitary 
 was proved by. the fact that incineration of 
 the pituitary extract and the injection of the 
 ash was not followed by any curative effect. 
 The extract was subjected to intense heat in 
 a capsule for a couple of hours, then the re- 
 maining salts were dissolved in distilled water 
 and injected subcutaneously and by the vein. 
 
21 
 
 All our observations show that it is an organic 
 body in the pituitary which abates the tetany. 
 We also tried pituitrin, an acidulated extract 
 of the infundibular part of the pituitary. It 
 was used subcutaneously in doses of 4 cc. up 
 to 28 cc. It acts rapidly in the relief of tetany, 
 but the action is much more fugitive than the 
 pituitary extract. Pituitary extract by the 
 jugular is not as effective as subcutaneously. 
 
 Adrenalin was given by the jugular, in the 
 cat, and some improvement was noted. Lowen- 
 thal and Wiebrecht saw a good effect in human 
 tetany by adrenal extract. 
 
 lodothyrin was also given by the jugular, and 
 it had a quieting" action upon the tremor. 
 
 Mammary gland, thymus, testicle, prostate, 
 spleen, spinal cord (all rubbed up with distilled 
 water), and Poehl's spermin had no effect upon 
 tetany; they were all given subcutaneously. 
 Pancreas had a quieting effect in seven cases 
 out of ten. 
 
 As to the comparative value of pituitary 
 extract and calcium lactate, our experiments 
 did not show any particular difference. The 
 intravenous injection of calcium lactate passed 
 off quickly, while the subcutaneous effect of 
 pituitary came on slower and continued longer. 
 
 Pituitrin did not have the permanent effect 
 that the gland substance did. Evidently in 
 tetany the gland itself should be used, as there 
 is something wanting in the pituitrin. The 
 "Vaporole" Extract of Infundibulum (i cc.) 
 
22 
 
 2o% (Burroughs Wellcome & Co.) may be 
 the best to use. It is inferable that the in- 
 fundibular lobe is the active part of the gland 
 in antagonizing the tetany after the removal 
 of the parathyroids. 
 
 As to the cause of tetany, we have two theories, 
 one of hypocalcification, held by Silvestri, 
 Netter, Quest and MacCallum; the other, that 
 the removal of the parathyroids leaves a poison 
 in the blood (Pfeiffer and Mayer), or, according 
 to Berkeley and Beebe, it is a poison generated 
 in proteid metabolism. 
 
 Beebe's experiments showing that strontium 
 will relieve tetany quite as well as calcium 
 indicate that hypo-calcification is not the whole 
 cause of tetany, but only an epiphenomenon. 
 
 Our experiments show that: 
 
 (i) Removal of the parathyroids alone causes 
 tetany. 
 
 (2) Pituitary extract will temporarily cure 
 tetany. 
 
 (3) Between the parathyroids and the pitui- 
 tary there is a co-operative action. 
 
 (4) The infundibular lobe contains the active 
 principle. 
 
 (5) Tetany is not due to want of calcium, 
 but to a poison in the blood. 
 
 The nucleoproteid^ (S. P. Beebe's method)^ 
 was used in part of the experiments upon the 
 intestine, uterus and kidney. The gland itself 
 
 1 Thanks to kindness of Dr. W. N. Berkeley, of New York. 
 ^ The Old Dominion Jo%irn<ll of Medicine and Surgery, April, 
 1909. p. 231. 
 
■\rf' 
 
lines represent drops of urini 
 
■/■/v■^A"■/.'^f^'''■,/-V 
 
 ' II 1 V fi 11 " n H- If 'fi' V 1,1 ,1 M ',' 1,1 ',0 V ' 
 
 v\^/\^^v\'v^l^/V\^^A;Vvv^^,v^/'v^^V■ 
 
 —Effect of nucleoproteid (3 gtts) on the t 
 
 t does not alter the pulse rate. The vertical lines represent drops of urine noted witli an elect 
 
23 
 
 was also used. It was rubbed up with distilled 
 water, heated and filtered. The intestine and 
 uterine tissue were excised and placed in Ringer's 
 solution and attached to a Porter heart-lever. 
 The oxygen was bubbling through the solu- 
 tion at about the rate of 200 per minute. The 
 temperature of the Ringer solution was 37° C. 
 It is the method of Magnus. The nucleoproteid 
 increased the tonus and extent of the contrac- 
 tions of the intestine (Fig. 2). It also increased 
 the force of the contractions of the uterine 
 tissue (Fig. 3). 
 
 Studies were also made upon the circulation. 
 The arterial pressure after injection per jugular 
 of three drops of nucleoproteid rose slightly 
 and then fell. Doses of ten to fifteen drops 
 caused an immediate fall of pressure. The 
 pulse rate was not changed much (Fig. 4). 
 
 In the cat Vg grain of the powdered 
 parathyroid per jugular in a watery solution 
 momentarily depressed the pulse rate and later 
 increased it above normal. The blood pressure 
 at the time of the injection fell greatly, but 
 afterwards rose again but seldom to normal. 
 
 Respiration.- — One-eighth grain of the para- 
 thyroid per jugular decreased the rate of 
 respiration. The nucleoproteid by the jugular 
 increased it. 
 
 Temperature. — -Large doses of the nucleo- 
 proteid reduced the temperature in rabbits 
 which were permitted to run about the labora- 
 tory. 
 
24 
 
 Diuresis. — Our experiments were made mainly 
 upon cats; a few rabbits were also used. The 
 animal was bound down, given 5 cc. of paralde- 
 hyde by the mouth, then chloroform was given. 
 The abdomen was opened in the median line 
 over the bladder, the bladder drawn out and 
 an incision made into it. A funnel-shaped 
 glass tube with a flange was inserted into the 
 bladder and walls of this viscus tied about the 
 flange. Then the bladder was filled with the 
 urine previously obtained from the bladder. 
 If this was not sufficient to fill the bladder, 
 then Ringer's solution was added. By means 
 of a piece of rubber tubing attached to the 
 funnel-shaped tube the urine was . permitted 
 to drop into the capsule. This was done for 
 about fifteen minutes, when each drop of urine 
 was noted on the smoked drum with an elec- 
 tric marker. Then the extract or powdered 
 gland was rubbed up with distilled water, fil- 
 tered and injected into the jugular. The drops 
 of urine were again noted. The bladder was 
 kept moist with absorbent cotton wet with 
 Ringer's solution. The blood pressure was fre- 
 quently noted at the time the urine was drop- 
 ping. 
 
 We found that the parathyroid nucleoproteid 
 in some cases increased diuresis in a half- hour 
 tenfold (Fig. 5). The pancreas, thymus and 
 extract of the renal cortex were also found by 
 us to be excitants of diuresis. 
 
 This diuretic action by the parathyroids 
 
Pjq 5 »f urine. Normally it was 4 drops in 
 
Fig. 5. — One drop of nucleoproteid increased urinary secretion tenlold between ] 
 
 ical lines indicate drops of urine. Normally it was 4 dre 
 
25 
 
 is greater than that of any of the glandular 
 extracts, not excepting pituitrin. It is a di- 
 rect action upon the glandular epithelium, 
 as it occurs in experiments where the blood- 
 pressure is falling from the beginning. 
 
 The small size of the four parathyroids 
 in the cat must secrete a very minute quantity 
 of material to act upon the kidneys. Accord- 
 ing to the size of the dose, it is probably one 
 of the strongest of all' diuretics. Hence the 
 parathyroids, in addition to the maintenance 
 of the reflex activity of the nerve cells, also 
 have another great and important function, 
 the stimulation of the renal epithelium. 
 
 Action on Pupil. — Meltzer^ was first in show- 
 ing that adrenalin dilated the pupil wlien locally 
 applied to the eye of a rabbit in which extirpa- 
 tion of the superior cervical ganglion had been 
 done twenty-four hours previously. It had 
 no effect on the normal eye, but Schultz has 
 since shown that large doses frequently applied 
 dilate it also. Our experiments were made 
 • upon rabbits. The superior cervical ganglion 
 was excised under ether and next day the nucleo- 
 proteid of the parathyroids dropped into both 
 eyes. The intensity of the light was regulated 
 so as to be about the same. The rabbit was 
 placed upon a table and permitted to run over 
 it. The diameter of the pupil was measured 
 with a pair of compasses. On the normal 
 eye it dilated the pupil; on the eye on the side 
 
 1 Am. Journal of Physiology, Vol. XI, 1904. p. 28. 
 
26 
 
 where the superior cervical ganglion was ex- 
 cised it at first contracted and then dilated the 
 pupil. 
 
 PATHOLOGY. 
 
 Paralysis Agitans. — Dr. W. N. Berkeley, of 
 New" York, has put forth a theory, also inde- 
 pendently propounded by Lundborg, that this 
 disease can be greatly benefited by the use 
 of the parathyroids. The trembling, rigidity, 
 salivation and the propulsive movements of 
 animals resemble somewhat the symptoms of 
 paralysis agitans. Besides, cases of myxedema 
 and exophthalmic goitre are sometimes asso- 
 ciated with paralysis agitans. Here the para- 
 thyroids may be involved. On post mortem 
 Berkeley has found a sclerosis of the parathy- 
 roids. Dr. Camp reported two cases of paralysis 
 agitans in which the parathyroids were dis- 
 eased. In one there was some colloid material, 
 and in both there was a peculiar infiltration 
 with fat, especially in relation to the blood 
 vessels. Dr. Berkeley, from an experience cover- 
 ing several years, has arrived at the conclusion 
 that nearl}^ all the patients with paralysis agitans 
 slowly respond to the treatment by parathy- 
 roids. In 25 per cent, of the cases the response 
 is temporary and imperfect. Seventy-five per 
 cent, showed progressive benefit during the 
 entire period: the rigidity diminished, the pain 
 lessened, salivation was cured, the shaking dimin- 
 ished or was cured, voluntary control of the 
 muscles greatly increased, and restlessness and 
 
27 
 
 insomnia were nearly or quite abolished. Berkeley 
 states that these glands are antispasmodic in 
 their action, and may be of service in a number 
 of different diseases. 
 
 Krdheim, in 1883, found in a case of paralysis 
 agitans a hyperplasia; the oxyphile cells of 
 the parathyroids were unusually enlarged. 
 
 Roussy and Jean Clunet^ in four cases of 
 paralysis agitans found histological evidence 
 of a hyper-function in the parathyroid glands. 
 
 MEDICAL TETANY. 
 
 Tetany of Gastric Origin. — In two cases of 
 tetany due to dilation of the stomach, and one 
 by an enteritis, there were no corresponding 
 changes in the parathyroid sufficient to account 
 for the tetany. There was a possible insuffi- 
 ciency of secretion by the glandules. 
 
 MacCallum (1905) . examined the parathy- 
 roids in an old man dead from gastric tetany, 
 caused by pyloric stenosis and gastric ulcer. 
 He found five rather large parathyroids, which 
 showed large groups of eosinophile cells under- 
 going mitosis to a large degree. He inferred 
 a hyperplasia of the glandules. He thinks 
 the dilated stomach generated a poison which 
 the parathyroid secretion neutralized. But as 
 it was an insufficient neutralizer, tetany ensued 
 on account of the excess of the poison. 
 
 Berkeley reports a case occurring in the prac- 
 tice of Dr. W. B. James of gastric tetany in a 
 
 1 Comptes Rend2is de la Societe de Biologie, Vol. LXVIII, 
 p. 320, 1910. 
 
28 
 
 man 35 years old who had extreme dilatation 
 of the stomach. He had violent symptoms, 
 and his life was despaired of. Capsules of 
 parathyroid improved and cured him. Dr. 
 Kinnicutt had a patient with gastric tetany 
 in which the capsules cured the tetany, but the 
 patient died. He had extreme dilatation of 
 the stomach. Calcium lactate given by Dr. 
 Beebe also reduced this patient's tetany. 
 
 Tetany of Pregnancy. — Idiopathic tetany was 
 first described in 1830, by Stringheim. N. 
 Weiss, in 1880, connected tetany with thyroidec- 
 tomy. It has been found that in animals which 
 have two of the parathyroids removed, not all 
 of them, that at the end of pregnancy tetany 
 ensues. After the delivery the tetany disap- 
 pears. At the end of a second pregnancy tetany 
 again ensues. Here we have a hypoparathy- 
 roidism. These facts led to the theory that 
 puerperal eclampsia is due to deficiency of 
 secretion by the parathyroid. 
 
 Pepere (1905) had four cases of eclampsia, 
 in three he found two parathyroids missing, 
 and in one he discovered a severe injury of one 
 parathyroid because of a cystic degeneration, 
 while the other three were intact. 
 
 Zanfrognini (1905) found in a case of eclampsia 
 only two parathyroids present, and no trace of 
 hypertrophy in them. He also (1905) treated 
 five cases of eclampsia with the parathyroidine 
 of Vassale, when the convulsions ceased, albumen 
 
29 
 
 disappeared from the urine and the pulse was 
 better. 
 
 The tetany can ensue in the first pregnancy, 
 and also take place in the second pregnancy, 
 or it can first occur in later pregnancies. It 
 may take place in the first month, or about the 
 sixth month, or shortly ante partum. Its course 
 is inconstant. Weiss saw in the fourth month 
 of pregnancy after a total thyroidectomy a 
 tetany which towards the end of pregnancy 
 stopped, but post partum again returned. Meinert 
 (1889) had a case in the fourth month of preg- 
 nancy with a one-sided thyroidectomy, and 
 tetany ensued. The second pregnancy was 
 free from tetany. In the eleventh pregnancy 
 strong tetany ensued about the eighth month. 
 Several cases are recorded similar to the above 
 by Von Kiselsberg, Westphal, Peham, and 
 Dienst. 
 
 Tetany of Infants. — In two cases of tetany 
 of infants, Erdheim found in both cases a hemor- 
 rhage in the parathyroids. 
 
 Haberfeld has found that the parathyroids 
 can be a seat of hemorrhage causing a hypo- 
 plasia. It is in the parenchyma of the gland 
 that the lesion is seated. He found in many 
 cases of tetany in children that the parathy- 
 roids were the seat of hemorrhage.^ 
 
 SURGICAL TETANY. 
 Tetany Due to Surgical Procedures in Man. — 
 In 1886 Billroth did a total thyroidectomy 
 
 ^Wiener Klin. Wochenschrift, XXIII, 27, p. 1017. 
 
30 
 
 for an adenocarcinoma of the thyroid, and a 
 temporary tetany ensued. In 1892 a second 
 operation was made on this patient, a resection 
 of the manubrium sterni. On the ninth day 
 after the operation tetany ensued and recurred 
 often in the following years. It is supposed 
 that the first operation removed only part of 
 the parathyroids, while the second operation 
 injured the glandules in the th3'mus, as there 
 was metastasis in the neck at the time of the 
 second operation. Kocher observed a tetany 
 resulting in death, after ligature of four of the 
 arteries suppljdng the thyroid, and Kopp also 
 observed tetany after ligature of two and three 
 arteries of the thyroid. Dr. J. J. Putnam, of 
 Boston, in a case of post-operative tetany, 
 greatly relieved the tetany by the use of the 
 parathyroid capsules of Berkeley. 
 
 Halstead (1907), of Baltimore, Pool (1907), 
 of New York, and Branham (1908), of Texas 
 have reported cases of tetany after thyroidec- 
 tomy. Halstead's case was greatly relieved 
 by parathyroids. 
 
 In case of carcinoma of the thyroid the whole 
 gland must be removed, notwithstanding the 
 tetany, as it can be alleviated by the means 
 already specified. The great number of opera- 
 tions now for exophthalmic goitre and goitre 
 proper make surgical tetany an important 
 subject. Patients with Graves' disease bear 
 badly the loss of parathyroids. 
 
 In disease of the thyroid not malignant the 
 
31 
 
 surgeon must not only leave a part of the thyroid 
 to prevent myxedema, but also the para- 
 thyroids to prevent tetany. Two of these 
 bodies in man are extra-capsular and can be 
 avoided in the operation. If all the para- 
 thyroids are removed, then transplantation of 
 these bodies must be attempted. 
 
 Transplantation of Parathyroids for the Cure 
 of Tetany. — Transplantation does not succeed 
 unless some of the parathyroids have been pre- 
 viously removed. 
 
 Von Eiselsberg, in 1892, transplanted the 
 parathyroids successfully, and they were func- 
 tionally active. 
 
 Many others have done the same. W. S. 
 Halstead,^ of Baltimore, has found that auto- 
 transplantation of parathyroid glandules into 
 the thyroid and behind the rectus abdominis 
 muscle has been successful in 61 per cent, of 
 cases in which a deficiency greater than one- 
 half of the parathyroids had been created. 
 Isotransplantation has been uniformly success- 
 ful. One parathyroid graft may suffice to 
 maintain the animal in good health and spirits 
 for many months. 
 
 Danielsen^ relates a case of tetany occurring 
 on the sixth day after a thyroidectomy. The 
 transplants from two other parathyroids which 
 had been removed and placed between the 
 fascia and the peritoneum cured the tetany. 
 
 ' Journal of Experimental Med., Vol, XI, No. 1, p. 198. 
 - Muiichener Medizinische Wochenschrifi, 1910, p. 973. 
 
32 
 
 In mild cases of tetany he recommends 3 
 grains chloral a day, and protracted warm baths. 
 
 Messrs. Herman and Harvey^ have made a 
 series of experiments upon dogs, and have found 
 that auto-transplantations are more successful 
 than iso-transplantations. They think the vis- 
 ceral peritoneum is superior to the spleen as 
 a site for the transplantation of parathyroid. 
 They also show that isotransplantation is possi- 
 ble. 
 
 Schneider^ reports a case of sarcoma of the 
 thyroid and parathyroids whose removal was 
 followed by severe tetany. Fresh parathyroid 
 substance from the horse, dried and powdered, 
 was given and he says that a specific favorable 
 effect on the tetany was unmistakable. The 
 patient was a woman of 40. She succumbed, 
 before the year was out, to the progress of the 
 malignant disease. 
 
 Tumors of Parathyroids. — Berard and Alamar- 
 tine^ found from an examination of the para- 
 thyroids a case of tumor of one parathyroid. 
 From the records they have assembled twenty- 
 nine cases of tumor of the parathyroid. Of 
 these cases three were malignant, and metastasis 
 proved fatal after removal of the primary tumor. 
 In twent5^-four cases the tumor was formed 
 solely of parathyroid tissue, while in five there 
 were islands of thyroid tissue. Rapid growth 
 
 ' University of Penna. Medical Bulletin, June, 1909, p. 136. 
 - Jaurnal of Am. Med. Association, 1910, p. 1912. 
 3 Journal Am. Med. Association, 1909, p. 241. 
 
33 • 
 
 of a tumor in a parathyroid indicates malig- 
 nancy. 
 
 Changes in Teeth. — Erdheim noted not only 
 tetany in the rat, but changes in the teeth with 
 which the rat gnaws. The enamel on the anterior 
 surface of the teeth becomes opaque, and white 
 spots appear in it. The teeth often break off 
 in the alveolus. This happens first in the upper 
 jaw, then in the lower. The microscopic changes 
 in the teeth show changes first in the dentine, 
 then in the enamel and its epithelium. There 
 is a hypocalcification in the dentine. After 
 the fracture of the teeth, the teeth in the antago- 
 nizing jaw attain great length. Erdheim has 
 also noted changes in the lens, resulting in 
 cataract. In four cases of puerperal eclampsia, 
 there was hyperemia of the parathyroids and 
 in two one of the parathyroids had a small 
 circumscribed spot, an injury of the parenchyma, 
 and in one "of these two cases a small hemor- 
 rhage into the glands. 
 
 Erdheim believes that there is a connection 
 between osteomalacia and parathyroid insufii- 
 ciency, the direct result of the involvement of 
 calcium metaboUsm. 
 
 Osteomalacia puerperalis, according to Erd- 
 heim, is associated with disease of the epithelial 
 bodies. Here he found often hypertrophy of 
 the parathyroids and consequently a hyperpara- 
 thyroidism. 
 
 In congenital cretins, where the thyroid is 
 absent, the symptoms of cretinism continue 
 
34 
 
 although all the parathyroids are present. 
 The growth of the bones in these cases is re- 
 tarded; the presence of the epithelial bodies 
 does not prevent it. They are not converted 
 into thyroid tissue, as held by some English 
 physiologists. 
 
 Roussy and Clunet^ ha\e studied the thyro- 
 parathyroid apparatus in two congenital cases 
 of myxedema aged 28 years. They found the 
 thyroid reduced to the volume of a grain of 
 wheat and it had an embryonic histological 
 structure comparable to that met with in the 
 first months of fetal life. The parathyroids 
 were well developed, the volume of each one 
 exceeded by 30 to 40 times that of the thyroid; 
 their structure was normal without any sign 
 of hyper- or hypo-function. These adults con- 
 firm the generally admitted fact of the em- 
 bryological, anatomical and functional inde- 
 pendence of the parathyroids and the thyroid; 
 
 Hair. — Pfeiflfer and Mayer noted a great 
 shedding of hair in rats during tetan3^ 
 
 Paraesthesia. — Vassale noted, in a bitch after 
 he had removed the three parathyroids during 
 the period of lactation, a pruritus of the nose. 
 Erdheim pointed out that after tetany in rats, 
 due to removal of the parathyroids, they spent 
 a great part of the day in making a toilet for 
 their nose. They even used, in addition to 
 their anterior extremities, their posterior ex- 
 tremities to scratch their nose, and did it con- 
 
 1 Compt. rend. Sociele de Biologie, 1910, p. 818. 
 
tinuously and in a cramp-like manner until 
 they were tired. Then after a rest they con- 
 tinued the scratching. Erdheim has also noted 
 in tetany of pregnant women a paraesthesia. 
 
 Vincent and Jolly and Berkeley have alluded 
 to the curious "paw shaking" on the second 
 day after removal of the parathyroids. We 
 have also noted this action in the cat, as though 
 the cat had wet his foot by stepping in water. 
 It is a paraesthesia, and probably due to changes 
 in the center of touch. 
 
 Uterine Inertia. — In pregnant women who 
 have tetania parathyreopriva, abortion has en- 
 sued; there was atony of the uterus and tam- 
 poning had to be resorted to. I have shown 
 that the parathyroid extract strongly excites 
 uterine contraction, and its absence may ac- 
 count for the uterine atony. The parathyroids 
 have close relations with the sexual organs. 
 
 Urinary Secretion in Nephritis. — In a case of 
 chronic interstitial nephritis, one grain of the 
 gland three times a day by the mouth increased 
 the quantity of urine a half pint daily in forty- 
 eight hours. In this case, a man of 65 years 
 of age, it seemed to produce an extremely fre- 
 quent desire to micturate. 
 
 Glucose. — After the injection of nucleoproteid 
 of the parathyroid by the vein, glucose appeared 
 in the urine to the extent of 1^/2 per cent., as 
 shown by the fermentation test and Fehling's 
 test. 
 
36 
 
 IT MAY BE CONCLUDKD: 
 
 (i) That the parathyroids are embryologically, 
 histologically and physiologically distinct from 
 the thyroids. The only thing they have in 
 common is their position in the neck. 
 
 (2) The parathyroids, unlike the thyroids, 
 contain no iodine. 
 
 (3) Deficiency of the secretion by the para- 
 thyroids is the cause of tetany. 
 
 (4) The tetany from removal of the para- 
 thyroids can be greatly benefited by pituitary 
 extract, calcium, strontium and parathyroid 
 extract. They can carry the patient along until 
 the small piece of parathyroid can hypertrophy 
 and supply the secretion. 
 
 (5) The grafting of a parathyroid is a cure for 
 tetany. 
 
 (6) When the parathyroids cause tetany, 
 they do it by absence of their secretion, and not 
 by calcium changes. 
 
 (7) In tetany there is a poison in the blood 
 which has been found to kill mice when the 
 serum is injected. 
 
 (8) That hypocalcification is affirmed and 
 denied by experimental tests to exist in tetany. 
 The calcium changes are only an epiphenome- 
 non. 
 
 (9) Of all the glandular extracts the para- 
 thyroids are the most powerful diuretics. They 
 act directly on the renal epithelium, as the- 
 urinary secretion is increased when the arterial 
 
37 
 
 tension is lowered from the beginning of the 
 injection of nucleoproteid by the jugular. 
 
 (id) The parathyroids increase uterine con- 
 tractions and intestinal peristalsis. 
 
 (ii) When locally applied, the nucleoproteid 
 of the parathyroid dilated the pupil. 
 
 (12) The nucleoproteid of the parathyroid 
 in small doses momentarily increases and then 
 decreases the arterial tension. Large doses 
 decrease it at once. The pulse is decreased 
 by powdered parathyroid and then increased. 
 
 (13) Nucleoproteid increases the rate of res- 
 piration. Powdered parathyroid decreased it. 
 
 (14) Large doses of the nucleoproteid lowers 
 the temperature. 
 
 I cannot close with better words than those 
 uttered to the students of this college in 1896, 
 in an introductory lecture by me. They are 
 as true now as they were thirteen years ago. 
 
 Glandular physiology, in its wide-spread rami- 
 fications, applied to other ductless glands of 
 the body, has revolutionized many parts of 
 physiology and pathology. It is only in its 
 infancy. Its maze of metabolic changes hold 
 many facts to be discovered. The secretion 
 of the ductless gland opens up new avenues 
 of investigation, which wiU enrich the science 
 of physiology and the practical application of 
 these facts in therapeutics. We have a silent 
 and hitherto unsuspected secretion going on 
 which plays a most important and unknown 
 part in our economy. 
 
38 
 
 Very potent- remedies are the ductless glands, 
 where but a few millionths of a grain of a gland, 
 like the adrenal, greatly elevated arterial tension. 
 Several of these animal extracts, as I have 
 shown, are thermogenic agents; others are 
 not. Some, like the thyroid, greatly depress 
 the rate of the heart. 
 
 When we see the cures produced by the 
 thyroid powder, in myxedema, cretinism, and 
 obesity, when we see the changes of acromegaly 
 arrested by the pituitary, Addison's disease 
 improved by the adrenals, we can not help 
 noting their power. We see in the action of 
 these extracts the simple external manifesta- 
 tions of the great forces at play in the nutrition 
 of the economy. 
 
 REFERENCES : 
 
 Quest: Wiener Klinische Wochenschrift, 1906. 
 
 NETTER: Comptes Rendus de la Societe de Biologic, 
 1907, page 376. 
 
 HagEnbach: Mitteilungen aus den Greanzgebieten der 
 Medizin iind Chinirgie, 1907, p. 330. 
 
 Erdheim: Mitteilungen aus den Grenzgebieten der 
 Medizin and Chirurgie, Band 16, Heft 4 X 5, p. 632. 
 
 Pfeiffer und Mayer: Mitteilungen aus den Grenz- 
 gebieten der Medizin und Chirurgie, 1907, p. 379. 
 
 MacCallum: The Physiology and Pathology of the 
 Parath3n-oid Glands. Proceedings of the Pathological 
 Society of Philadelphia, 1908, April and May. 
 
 BEEBE: The Inhibition of Tetany by Extract of the 
 Parath5T-oid. Am. Journal of Physiology, Vol. XIX. 
 
 W. G. MacCallum and Voegtlin: Journal of Ex- 
 pcri'ynental Medicine, Jan., 1906. 
 
 Berkeley and Beebe: Journal of Medical Research, 
 Feb., 1909. 
 
39 
 
 Bell and Hick: British Medical Journal, 1909, p. 
 
 517- 
 
 PEPERE: Le Ghiandole Paratiroidee, 1906. 
 
 Vincent and Jolly: Journal of Physiology, Vol; 
 XXXII, p. 65. 
 
 W. S. Carter: Texas State Journal of Medicine, Jan., 
 1908. 
 
 Moussu: Recherches sur les Fonctions Thyroidienne 
 et Parathyroidienne, 1897. 
 
 Minkiewitsch: Tetania parathyreopriva und Hyper- 
 parathyreosis, 1908. 
 
 Forsyth, David: The Quarterly Journal of Medicine, 
 1908, Vol. I, Nos. 2 and 3. 
 
 Geiss: Ueber tetanie tuich partial strumectomie-ln- 
 augural Dissertation Gottingen, 1902. 
 
 A. BiEdl: Innere Secretion, 1904. 
 
 A. Frouin: La Presse Medicate, 1909, No. 62, p. 609. 
 
 L. CoTONi: Revue de Medicine, 1909, No. 8, p. 615. 
 
 Karl Petren: Upsala Lakareforenings Forhandlingar, 
 i909-'io, Haft 102, p. I. 
 
SECOND LECTURE— THE PITUITARY/ 
 
 Gentlemen: — Last year the parathyroids served 
 as a subject for the introductory lecture. As 
 the ductless glands have been the object of 
 much experimentation in conjunction with Dr. 
 J. C. Scott in our laboratory, I have selected 
 this year the pituitary gland, which is fast 
 coming into great prominence both in surgical 
 and in therapeutical relations. In the lecture 
 I shall use the words hypophysis and pituitary 
 as interchangeable in meaning. For excess of 
 secretion, hyperhypophysy ; for deficit of secre- 
 tion, hypohypophysy. I prefer these words 
 to hyperpituitarism and hypopituitarism. 
 
 I shall not consider the surgical procedures 
 for the removal of the gland. In this lecture 
 only the main points will be taken up, but they 
 will bear on the practical side of medicine. 
 
 The hypophysis is situated at the base of the 
 brain in the sella turcica of the sphenoid bone (Fig. 
 6). In man the pituitary weighs about }4 gram. 
 
 Diameters of Pituitary Fossa. — Porier makes 
 the diameters of the pituitary fossa as follows •? 
 
 Male (anterior-posterior.) Female. 
 
 0.75 to 1.45 centimeters 0.75 to 1.30 centimeters 
 
 Transverse 
 
 0.70 to 1.50 centimeters 0.80 to 1.50 centimeters 
 
 Depth 
 0.60 to 1.20 centimeters 0.60 to 1.39 centimeters 
 
 1 Lecture delivered Sept. 28, 1910, before the Sophomore 
 class of the Medico-Chirurgical College of Philadelphia. 
 
 2 Jaugeas, Les Rayons de Rontgen dans le diagnostic et iraii- 
 ment des Tumeurs Hypophys aires. 1909. __ 
 
41 
 
 Chemical Nature. — Simpson and Hunter found 
 in eleven fresh pituitaries of the slaughter-house 
 from the sheep a minimal amount of iodine — 
 
 Fig. 6. — Mesial section through the pituitary region in the child. 
 
 A. Foramen of Monro. 
 
 B. Anterior Commissure. 
 
 C. Ventricle III. 
 
 D. Corpus mammillare. 
 
 E. Subarachnoid tissue in cisterna basalis. 
 
 F. Infundibulum. 
 
 G. Pituitary body. 
 H. Cisterna pontis. 
 I. Basi-occipital. 
 
 J. Sphenoidal sinus. 
 
 not more than 0.005 milligram. In sheep 
 they removed the thyroid, leaving behind the 
 
two external parathyroids, and after forty- 
 seven to fifty-six days the sheep were killed, 
 but no iodine was found in their pituitaries.^ 
 Halliburton, Candler and Sikes^ found no iodine 
 in the human pituitary by Baumann's method. 
 
 Dr. H. Gideon Wells^ analyzed twenty-two 
 pituitaries from patients who had not received 
 iodine while in the hospital. He did not find 
 a trace of iodine by Baumann's method. In 
 three glands from patients who had received 
 iodine he found a trace of iodine, probably about 
 0.02 milligram. The inference is that the 
 pituitary contains no iodine. 
 
 W. Neubert found glycogen constantly in 
 the epithelium of the colloid- cysts lying in the 
 boundary between the anterior and posterior 
 lobes. It is also found in the nervous portion 
 of the hypophysis. This glycogen is markedly 
 increased in diabetic cases. ^ 
 
 Histology — The pituitary is composed of three 
 parts: (i) the large anterior epithelial lobe, 
 pars anterior; (2) a much smaller posterior, 
 nervous or infundibular lobe, . pars posterior; 
 and (3) the pars intermedia. The ectoderm 
 of the mouth (Rathke's pouch) originates the 
 anterior lobe, which soon becomes a glandular 
 structure. An outgrowth from the floor of 
 
 ' Quarterly Journal of Experimental Physiology, Vol. Ill, No. 
 2. p. 121. 
 
 - Quarterly Journal of Experimental Physiology, 1909, p. 
 229. 
 
 ^ Journal of Biological Chemistry. Vol. VII, No. 4, p. 250. 
 
 "^ Beitrdge zur Path. Anat. und zur Allg. Path.. 1909, XIV, 38; 
 Journal of Am. Medical Association. No. 24, p. 2023, 1909. 
 
43 
 
 the third ventricle from the infundibular pouch 
 of the thalmencephalon, the mid-brain, de- 
 velops the posterior lobe. The posterior lobe 
 consists of two parts : ( i ) the neuroglia cells 
 and fibers with ependymal cells, and (2) the 
 pars intermedia, composed of epithelial cells 
 from a diverticulum of buccal epithelium, the 
 posterior pharynx, and is ectodermic in origin. 
 Herring finds in the cat the posterior lobe 
 of the pituitary is hollow and its cavity is in 
 free communication with the third ventricle 
 of the brain, while the epithelium of the anterior 
 lobe affords a nearly complete investment of 
 the posterior lobe. In the dog the posterior 
 lobe is solid, but the neck is hollow and in com- 
 munication with the third ventricle. The 
 epithelial part of the pituitary is composed 
 of two distinct parts, an anterior lobe consist- 
 ing of solid columns of cells, and a pars inter- 
 media which lies between the anterior lobe 
 and the nervous tissue, forming a close-fitting 
 investment of the latter. The anterior lobe 
 contains cells which are clear or hold in their 
 protoplasm varying amounts of granules which 
 stain deeply. The pars intermedia consists 
 of finely granular cells, in layers of various 
 thicknesses and closely applied to the posterior 
 lobe. Colloid material is found between the 
 cells of the pars intermedia, which appears 
 to pass into the nervous substance of the gland 
 and then into the third ventricle. The infundib- 
 ular or nervous part is made up of neuroglia 
 
44 
 
 cells and fibers. It has no true nerve cells, 
 and the nerves supplying the pituitary probably 
 reach it through the sympathetic fibers supply- 
 ing the blood vessels. The nervous part con- 
 tains columns of epithelial cells from the pars 
 intermedia, and islets of these cells are found 
 in the substance of the infundibular lobe. The 
 nervous part contains large amounts of colloid 
 like that of the thyroid.^ 
 
 The anterior lobe is a gland which must dis- 
 charge its secretion directly into the vascular 
 sinuses. The secretion of the pars intermedia 
 seems to be secreted into the substance of the 
 brain. 
 
 The function of the pars intermedia is to 
 generate a colloid material which acts upon 
 the circulation and the kidneys. 
 
 Haberfeld has examined the pharynx in man 
 for remains of the embryonal diverticulum 
 which finally forms the pituitary. He in- 
 vestigated fifty-one subjects whose ages ranged 
 from fetal life to old age. In all cases he found 
 a definite structure which he calls the -phsLryn- 
 geal pituitary gland. It is made up of a string 
 of cells, is 5 millimeters in length, and runs 
 immediately behind the vomer upwards and 
 backwards. It is composed of cells similar to 
 those in the pituitary, but the chief cells are 
 the "Hauptzellen. "- 
 
 1 Herring, Quarterly Journal of Experimental Physiology, 
 1908. Vol. 1, No. 2, p. 156. 
 
 ^ Beilrdge zur Path. Anat. u. zur Allgemein Path., 1909, 
 
 p. 133. 
 
45 
 
 The pars anterior contains three kinds of 
 cells: (i) the " Hauptzellen ; " (2) Eosinophiles ; 
 (3) Basophiles. Erdheim and Stumme call the 
 eosinophiles or acidophiles and basophiles or 
 amphophiles or cyanophiles because their proto- 
 plasm intensely takes up stains, the chromo- 
 philes, while the "Hauptzellen" they call 
 chromophobes, because their protoplasm is very 
 difficult to stain. The most numerous cells 
 are the eosinophiles, the next in number the 
 basophiles. The "Hauptzellen" are less in 
 number than the eosinophiles and the baso- 
 philes, and usually are found in the center of 
 the alveolus. 
 
 The importance of these cells in the secretion 
 of the hypophysis has been the subject of several 
 theories. Thom holds that the strongly stain- 
 ing chromophile cells produce a secretion in 
 the form of fine granules. Their cell walls are 
 indistinct, the nucleus moves towards the periph- 
 ery, the granules escape and mix with an 
 incolorable secretory material furnished by 
 the chromophobes. Scaffidis, like Thom, makes 
 two kinds of secretory cells, so that the gland- 
 ular secretion is a mixture of two processes 
 of secretion. In the secretion of the two types 
 of cells, one reacts to an acid, the other reacts 
 to an alkali; these both concur to form the 
 colloid secretion of the hypophysis. Taunois 
 holds a view similar to that of Scaffidis.^ 
 
 The majority of authors believe the colloid 
 
 1 Launois, These, Paris, 1904. 
 
46 
 
 is the normal secretion of the hypophysis. 
 Cagnetto in a case of acromegaly found the 
 chromophile cells and colloid increased, while 
 in a case of tumor of the hypophysis without 
 acromegaly both chromophile cells and colloid 
 were diminished. A few authors believe they 
 have seen the passage of the colloid into the 
 blood. 
 
 Comte' in 1898 noted an increase in the size 
 of the pituitary in pregnancy. Hrdheim and 
 Stumme- have examined twenty-five normal 
 pituitaries. They make three types of cells. 
 
 During pregnancy the hypophysis increases 
 in weight and size and this increase is in the 
 pars anterior, the pars posterior remaining 
 unaltered. At the end of pregnancy the "Haupt- 
 zellen" are increased so much in number that 
 the eosinophiles, unchanged in number, take 
 the second place. A few weeks after delivery 
 the pregnancy cells decrease and at the end of 
 the second year post-partum the eosinophiles 
 are again predominant. The number of baso- 
 philes remains the same in pregnancy. The 
 "Hauptzellen" are the cells in which the pe- 
 culiar changes caused by pregnancy take place, 
 as they are enormously increased and con- 
 siderably hypertrophied. These pregnancy cells 
 in time atrophy and become the "Hauptzellen." 
 The number of "pregnancy cells" by multi- 
 
 ' Comte. Contribution a V Etude de I'hypophyse, 1898. 
 * Beiirdge zur Path. Anat. und zur Allgevieinun Path., p. 1, 
 1909. 
 
47 
 
 para is undoubtedly much greater than in the 
 primipara. 
 
 They claim that a skilled histologist can diag- 
 nose a former pregnancy from the pituitary 
 gland. The swelling of the gland is quite defi- 
 nite and in two cases there was a hernia of 
 the gland through a hole in the dura which 
 accommodates the infundibulum. 
 
 The bloated face, the swollen lips and the 
 enlargement of the hands have been referred 
 by Tandler and Gross to the enlargement of 
 the hypophysis by pregnancy — a hypersecretion. 
 
 These facts have been used as an argument 
 to support the theory of hypersecretion in acro- 
 megaly., . Von Reuss observed a bitemporal 
 hemianopsia in the course of a 14", 15" and 
 16" pregnancy, which gradually disappeared 
 after delivery. He thought there was a large 
 pituitary pressing upon the optic chiasm which 
 caused the hemianopsia. 
 
 Coagulation of Blood. — Weil and Boye and 
 Levan have shown in rabbits, dogs and man 
 that intravenously the posterior lobe causes 
 coagulation with great rapidity, notwithstand- 
 ing the alkaline solution in the manometer 
 tube. After an injection by the A'ein of the 
 anterior part of the pituitary, coagulation is 
 the exception. If the whole pituitary is in- 
 jected then coagulation^ is also exceptional. 
 
 Herry^ found that the extract of fresh organs 
 
 1 Compt. rendus de la Soc. de Biologie, p. 618, 1909. 
 
 2 Compt. rendus de la Soc. de Biologie, p. 603, 1910. 
 
48 
 
 (as spleen, kidney, lung, liver, thymus and 
 hypophysis) more completely corrected the diffi- 
 culty of coagulation of the blood in hemophilia 
 than fresh serum. Extracts from the dried 
 organs did not coagulate blood as well as the 
 fresh organs. 
 
 Action of Pituitary on the Circulation. — 
 Oliver and Shaefer (1895) stated that aqueous 
 or saline extracts may be boiled without losing 
 their activity and when injected produced a 
 rise of blood pressure. They also showed that 
 it was due to an action on the arterioles. Howell 
 (1898) found that it was the infundibular lobe 
 which elevated blood pressure. He also noted 
 a slowing of the heart. Shaefer and Swale 
 Vincent (1899) found the cardiac slowing ob- 
 served was not constant and that slowing en- 
 sues after section of vagi or previous atropiniza- 
 tion. Hence, the seat of the slowing is periph- 
 eral. Adrenalin acts on the vagus center. 
 Shaefer found that the second or third dose 
 did not produce a rise but invariably a fall 
 which lasts but a short time. 
 
 Shaefer and Swale Vincent believe this to 
 be due to a depressor substance, and that this 
 substance is soluble in alcohol, in which the 
 pressor substance is insoluble. This depressor 
 substance is not identical with choline as the 
 previous use of atropin does not prevent the 
 fall as is the case with choline. 
 
 Circulation, Effect of Anterior Lobe. — Dr. W. 
 J. Hamburger found, as previous observers 
 
49 
 
 did, that the intravenous injection of a saline 
 extract of the anterior lobe caused a distinct 
 fall of blood-pressure. This was usually ac- 
 companied by an acceleration and weakening 
 of the heart. That a second injection im- 
 mediately following the first does not produce 
 any change in blood pressure. After a consid- 
 erable interval the second injection produces 
 a fall. In a number of dogs the fall of arterial 
 tension was succeeded by an apparent toxic 
 action resulting in death. The depressor sub- 
 stance is soluble in alcohol, glycerin and salt 
 solutions, but insoluble in ether. 
 
 A secondary rise above normal follows the 
 depressor effect produced by an alcoholic ex- 
 tract of the anterior lobe.^ 
 
 Fodera and Pittau^ studied the hypophysis. 
 They did not confirm Von Cyon's statement 
 that the greatest activity was in boiled ex- 
 tracts, being superior to those obtained in the 
 cold or at a temperature below that of ebulli- 
 tion, or that the extracts of dried glands were 
 better than those obtained from fresh glands. 
 They could not find the slightest difference 
 in their activity. They experimented upon 
 frogs and rabbits. Between the extracts of 
 the posterior lobe as a whole and those of the 
 posterior lobe deprived of the small epithelial 
 layer there was no qualitative difference but 
 
 1 American Journal of Physiology, Vol. XXVI, p. 178. 
 ^ Archives Italienne de Biologie, Tome LII, Fasc. III. p. 
 370, 1909. 
 
50 
 
 onlv a slight quantitative diflference in favor 
 of the true posterior lobe. 
 
 In regard to the question of Salvioli and Car- 
 raro, about the importance of the epithelial 
 layer in the production of the phenornena of 
 posterior lobe, they answer in the affirrnative. 
 They believe that the epithelial layer secretes 
 a substance which penetrates into the infundib- 
 ular lobe and may be still further elaborated. 
 The anterior lobe is completely inactive, as the 
 activity of the whole lobe is no more active 
 than the posterior lobe alone. They obtained 
 no effect upon the heart and blood vessels of 
 'the frog by pituitary extracts. In dogs they 
 confirm Salvioli and Carraro that the extracts 
 of the hypophysis cause a short characteristic 
 diarrhea followed by tenesmus. Intravenous 
 injections are active. Hypodermic injections 
 and use by the mouth, even intracerebral 
 injections are inefficacious. Extracts of the 
 hypophysis of the cow, when given in large doses 
 to dogs and repeated many times a day, cause 
 emaciation. They did not find any prophylactic 
 or anaphylactic properties by intravenous in- 
 jections in dogs. 
 
 The Active Principle. — Is there more than 
 one active principle in pituitary;* Malcolm 
 obtained different results in metabolisni be- 
 tween the fresh and dried gland. Shaefer has 
 obtained diuretic results without blood pressure 
 action. Dale has thrown considerable doubt 
 upon the theory of more than one active prin- 
 
51 
 
 ciple. We have found pituitary extracts that 
 did not elevate blood-pressure but did have 
 diuretic effects. 
 
 Does the hypophysis contain adrenalin? Both 
 raise blood pressure, both dilate the pupil of 
 the enucleated frog's eye, both subcutaneously 
 produce glycosuria in rabbits. Adrenalin fre- 
 quently injected produces sclerosis of the aorta. 
 Meyers^ has shown that pituitary extract can 
 also injure the blood vessel. W. W. Harvey 
 has produced sclerotic effects in the coronary 
 arteries by repeated injections of the hypophy- 
 sis. - 
 
 Borchardt^ noted the absence of adrenalin 
 in the hypophysis, since Vulpian's test, the 
 addition of iron chloride, produced no green 
 color, as adrenalin does. There are two reac- 
 tions for adrenalin, which are very sensitive 
 and characteristic. The first is that of Comes- 
 sati. It is a red color by the oxidation of 
 adrenalin. Comessati used a 2% sublimate 
 solution as an oxygen bearer; but Frankel 
 and Allers* have shown that the reaction ensues 
 with other oxidizing substances, as copper 
 sulphate, potassium chlorate, and platinum 
 chloride. Frankel and Allers,^ have proposed 
 a new test for adrenalin. Adrenalin gives, 
 with a slight blue shade, a red color in the pres- 
 ence of some phosphoric acid, heated with a 
 
 1 Zeitschrijt iiir physiological Chem., 1903. 
 
 - Bio-Chemical Journal, p. 431, Vol. IV, No. 9. 
 
 3 Zeitschrift fiir Klin. Med., Bd. 66. 
 
 ^ Miinchener Med. Woch-enschrift, p. 1478. 1909. 
 
52 
 
 A''/iooo biniodate of sodium solution. A dilu- 
 tion 1 : 300,000 shows a perceptible reaction. 
 This test and that of Comessati with pituitrin 
 of Parke, Davis & Co. showed a negative reac- 
 tion. 
 
 Hence ' adrenalin and the active principle 
 of the pituitary are not the same substance. 
 
 Action on Kidneys. — Schafer and Herring^ 
 have shown that the infundibular part of the 
 pituitary body yields a substance soluble in 
 water and not destroyed by boiling, which has 
 a specific action on the kidney, dilating the 
 renal vessels and increasing the secretion from 
 the tubules. If the urinary flow is suppressed 
 from operative procedures or the anesthetic, 
 it causes a flow. They think it is as actively 
 diuretic as caffeine citrate. They found when 
 there was a general fall of blood pressure with 
 no increase, but even a shrinkage of the vol- 
 ume of the kidney, a diuretic action, indicating 
 a stimulation of the renal epithelium. This 
 shrinkage of the kidney precedes the dilata- 
 tion in some cases. Pituitary was found to 
 diminish the flow of pancreatic juice. 
 
 Hypodermically, the pituitary also slightly 
 raises blood pressure, dilates the kidney ves- 
 sels and increases the rate of flow of urine. 
 They also point out that the adrenals and pitui- 
 tary each consist of two parts, one epithelium, 
 the other part of neuroectodermic origin. The 
 
 ' Philosophical Transactions of the Royal Society of London, 
 pp. 1-29. 
 
53 
 
 epithelial parts of these two glands do not yield 
 any physiological effect, while those of neuroecto- 
 dermic origin furnish substances affecting the 
 heart and arteries. Here the similarity ends, 
 for adrenalin excites the sympathetic terminals 
 in general, while the pituitary does not. 
 
 Houghton and MerriP have studied the action 
 of adrenalin and the active principle of the 
 pituitary gland upon the urinary secretion. 
 Pituitary slowed the pulse rate after the use 
 of atropin and after section of vagi. Aldrich 
 obtained a crystalline picrate and a sulphate 
 from the infundibular part of the pituitary. 
 They found adrenalin to increase the blood 
 pressure and the flow of urine. They experi- 
 mented on normal man for several days where 
 the food, drink, habits, exercise and work were 
 the same. Then pituitary extract was given 
 internally. They found only a slight increase 
 of the urine in man. 
 
 Then they made experiments upon dogs, 
 anesthetized by morphine and chloretone with 
 cannulae in the ureters. The drops of urine, 
 were recorded with the blood pressure and the 
 respiratory movements. Adrenalin increased the 
 blood pressure from 56 to 88 mim. of mercury 
 which within six minutes had returned to normal. 
 The urine increased from 8 minims per minute 
 to 30 per minute, the maximum following 
 closely the maximum blood pressure. The in- 
 crease of urinary flow continued after the fall 
 
 ^Journal Am. Medical Association, 1908, p. 1849. 
 
54 
 
 of blood pressure to normal, and at the end 
 of fifteen minutes it was the same as at the be- 
 ginning of the experiment. They also per- 
 fused excised kidneys, noting the flow from 
 the renal vein and ureter, and found that pitui- 
 tary extract added to saline solution made the 
 venous flow and ureteral flow less than when 
 saline alone was used. They do not believe 
 in a specific action on the kidney cell, and if 
 so it is less marked than in the case of a i per 
 cent, saline solution. It is due to a rise in blood 
 pressure. 
 
 Pal noted in cats that the diuretic effect of 
 pituitary extract was marked, when given in- 
 travenously. He emptied the bladder of a 
 cat to which morphia and curare had been given, 
 and found that the intravenous injection of 
 two cubic centimeters of pituitary extract 
 filled the bladder in a very short time. As is 
 well known, the bladder is generally empty 
 after curare narcosis. Pal's experiments as to 
 the size of the kidney after the use of pituitary 
 were not uniform like those of Schafer. Pal 
 found that pituitary dilated the renal artery 
 and contracted the coronary arteries. 
 
 Pal,' hke Langendorff, found adrenalin di- 
 lated the coronary artery, while contracting 
 the renal and other arteries. He found pituitary 
 extract to dilate the renal arteries, but to con- 
 tract the coronary and other arteries. 
 
 We made 20 experiments. The volume of 
 
 Wiener Medizinische Wochenschrijt. 1909, p. 138. 
 
55 
 
 the kidney was registered by means of an air 
 oncometer and Albrecht's piston recorder. 
 
 Our experiments were mainly made upon 
 cats; a few were made with rabbits. The ani- 
 mal was bound down, given 5 cc. of paralde- 
 hyde by the mouth. Then chloroform was 
 given. The abdomen was opened in the median 
 line over the bladder, the bladder drawn out 
 and an incision made into it. A funnel-shaped 
 glass tube with a flange was inserted into the 
 bladder and the bladder tied tightly about the 
 flange. Then the bladder was filled with the 
 urine previously obtained from the bladder. 
 If this was not sufficient to fill the bladder, 
 Ringer's solution was added. By means of 
 a piece of rubber tubing attached to the funnel- 
 shaped glass tube the urine was allowed to 
 drop into the capsule. This was permitted 
 for about fifteen or twenty minutes when each 
 drop was noted on the smoked drum with an 
 electric marker. Then the extract of the gland, 
 rubbed up with distilled water and filtered, 
 was injected into the jugular and the drops of 
 urine again noted on the drum. The bladder 
 was kept moist with absorbent cotton wet 
 with Ringer's solution. The blood pressure 
 was frequently noted at the time the drops of 
 urine were registered. 
 
 The infundibular part of the pituitary is a 
 diuretic. As it does not markedly increase 
 the general arterial tension except for a moment 
 and then lowers it, it is inferable that the very 
 
56 
 
 short rise of blood pressure does not produce 
 diuresis which continues a considerable time 
 after the rise of blood pressure. 
 
 As the variations of arterial tension do not 
 play any part in the diuresis, it must be referred 
 to an action of the renal epithelium itself (Fig. 7). 
 
 Schaefer states that the anterior part of the 
 pituitary has no diuretic effect. The pars 
 intermedia also increases the secretion of urine. 
 
 Glycosuria. — It is one of the most frequent 
 symptoms of acromegaly. Hansemann found 
 it 19 times in 97 cases, while Marie observed 
 it in one- third to one-half of his cases. In all 
 these cases of acromegaly with glycosuria they 
 found hypertrophy, glioma, sarcoma, adenoma 
 and epithelioma of the pituitar}. Thaon in 
 a case of beginning neoplasm of the hypophysis 
 found a notable hypertrophy of the islets of 
 Langerhans, but there was no diabetes. Lorand 
 considered that lesions of the thyroid and pan- 
 creas played a great part in the production of 
 glycosuria in acromegalic patients. 
 
 Caselli destroyed the posterior lobe in a dog 
 without touching the anterior lobe, and gly- 
 cosuria appeared.^ 
 
 Polyuria and sometimes glycosuria occurs 
 in animals with a partial removal of the anterior 
 and a total removal of the posterior lobe accord- 
 ing to Gushing. 
 
 Borchardt- has proved that the hypodermic 
 
 ' Presbeunu, These. 1909. p. 70. 
 
 - Zeilschrift fiir Klinische Medizin. 1908, Band 66, p. 332. 
 
.i(v;V/^^''^'^^ 
 
 /VlVWVW\ 
 
 'm^'^'^''"^' 
 
 1-~~t-1 
 
 :ond line from top) 
 
57 
 
 use of the pituitary produced a small amount 
 of sugar in the urine. He used the boiled 
 filtered infusion of the gland, which was in- 
 jected hypodermically in rabbits and dogs. 
 The quantity of sugar obtained by him varied 
 from a trace to 4.2 per cent. The absolute 
 quantity of sugar was very small, not more 
 than a centigram. The sugar usually began 
 to appear in the urine three hours after the 
 injection. The amount of sugar excreted was 
 extraordinarily variable and to a great degree 
 independent of the amount of the gland in- 
 jected. He found that pituitary produced 
 glycosuria more easily in rabbits than in dogs. 
 
 Infundibulin. — -We have also studied the efi'ect 
 of injections of infundibulin in rabbits and cats. 
 The number of our experiments was fifteen. The 
 tests for glucose were Fehling's, fermentation and 
 the phenylhydrazine tests. The injection of 
 these extracts of the glands proceeds on the 
 theory that they act like a hypersecretion of 
 the gland. The first extract used was infundib- 
 ulin 20 per cent, extract of the pituitary (Bur- 
 roughs Wellcome, & Co.). Borchardt used the 
 whole gland to produce sugar. Falta was 
 unable to obtain in rabbits any glycosuria with 
 pituitrin, which is obtained from the infundib- 
 ular part of the pituitary. 
 
 We have made several experiments with 
 infundibulin, of which we injected i cc. into 
 the muscles of the rabbit, as Meltzer has shown 
 that adrenalin is more rapidly absorbed here 
 
58 
 
 than under the skin. In all cases at the end 
 of two and a half hours we found glucose in 
 the urine, the amount being about one-eighth 
 per cent. 
 
 In cats intramuscular and intraperitoneal 
 injection of the infundibulin produced similar 
 results. In acromegaly Hinsdale found in an 
 analysis of 130 cases that 10.8 per cent, had 
 sugar. Borchardt from an analysis of 176 
 cases of acromegaly holds that glycosuria is 
 more regularly associated with this disease 
 than with any other. However, there are 
 cases of tumor of the hypophysis without 
 acromegaly and which are not complicated with 
 diabetes. KoUaritz has collected 51 cases of 
 this nature. From our experiments we must 
 infer that the glycosuria is due to a hyper- 
 secretion of the infundibular part of the hypophy- 
 sis, perhaps of the pars intermedia. 
 
 Seat of the Glycosuria: (i) Removal of Thy- 
 roid.— In etherized cats we extirpated the 
 thyroid, leaving two or more parathyroids. 
 On the following day we found sugar in the urine 
 in a few cases. A similar result after removal 
 of the thyroid has been found in dogs by Fal- 
 kenberg and Rahel Hirsch.^ Falta, however, 
 did not obtain it in dogs. We found, however, 
 that the injections per jugular of the same dose of 
 infundibulin in the cat after the absence of 
 the thyroid was followed by a decrease in the 
 amount of sugar as compared with those animals 
 
 ' Zeitschrift fiir Klinische Medicin, 1908. p. 6. 
 
59 
 
 whose thyroid was intact. Before the removal 
 of the thyroid, infundibuHn caused 3 to 4 per 
 cent, of sugar in the urine; after the removal, 
 I to 2 per cent. We took care that the binding 
 down and the etherization did not produce 
 glycosuria. 
 
 (2) Removal of Adrenals. — In the etherized 
 cat we removed the adrenals with the most 
 careful antiseptic precautions. As they usually 
 die on the following day, we injected immediately 
 on the same day the infundibulin. It was 
 given by the jugular. In all cases sugar ap- 
 peared in the urine. However, Nishi has shown 
 that removal of adrenals is followed by hyper- 
 glycemia. 
 
 (3) Splanchnicotomy. — In cutting both splanch- 
 nics in the cat we followed the procedure 
 of Schultze.^ The animals were etherized 
 and the strictest antiseptic precautions fol- 
 lowed. The abdomen was closed by suture 
 and the animals placed in the cage until the 
 next day. Then they were again etherized, 
 jugular prepared and infundibulin injected. 
 But at no time afterward did we observe any 
 sugar in the urine. Pollak^ in a classification 
 of the glycosurias found that adrenalin pro- 
 duces sugar in the urine after splanchnicotomy, 
 being an agent which stimulates the terminals 
 of a sympathetic nerve. The glycosuria of 
 cafifein does not ensue after splanchnicotomy. 
 
 1 Archiv. fiir Experimentelle Pathologie und Pharmakologie, 
 Band 43, p. 189. 
 
 2 Archiv. f. ex. Path. u. Pharmakol, 1909, Band 61, p. 376. 
 
6o 
 
 According to Macleod, curare does not cause 
 any sugar in the urine after section of the splanch- 
 nics. 
 
 As section of the splanchnics arrests glycosuria 
 we must consider it due to an action of infundib- 
 ulin on the diabetic center in the medulla 
 acting through the splanchnics on the glycogen 
 of the liver. If the sympathetics influence 
 the adrenals, who then actuate the glycogen 
 in the liver, is a c^uestion not decided by these 
 experiments. 
 
 Stimulant of Ufistriped Fibers. — Dale^ used a 
 5 per cent, acid decoction of the fresh posterior 
 lobes of ox pituitaries. He found vaso-con- 
 striction of the pulmonary arteries on per- 
 fusion of lungs, which does not happen with 
 adrenahn. It also constricted the coronary 
 arteries; adrenalin dilates them. In perfused 
 mammalian heart (rabbit) the ventricle beat 
 becomes slightly slower and considerably more 
 vigorous; later, with persistent retardation, 
 it becomes weaker than before the injection. 
 All these changes ensue after an atropinization, 
 which excludes any action on the vagus. Hence 
 the action on the heart beat is probably due 
 to a direct effect on the heart muscle. It con- 
 stricts the muscular capsule of the spleen. It 
 also produced powerful uterine contractions. 
 On the intestines, in dogs, he has seen the move- 
 ments inhibited even when the splanchnics 
 were cut. Isolated pieces of intestine contract, 
 
 ' Biocliemical Jmirnal, Vol. IV, No. 9, p. 427, 1909. 
 
6i 
 
 though but feebly, when pituitary extract is 
 added. It is probable the inhibition just men- 
 tioned is due to intense anemia of the intestine 
 which the drug produces by vaso-constriction. 
 Hence the plain muscle of bladder and intes- 
 tine contract in response to pituitary extract, 
 but their sensitiveness is small in comparison 
 to that of some organs. Ergotoxine annuls 
 the motor "effects of the sympathetic nerves 
 and the action of adrenalin, so that the latter 
 produces in' the cat a fall of blood pressure 
 and relaxation of the pregnant uterus instead 
 of the customary rise and uterine contraction. 
 But pituitary extract acts after ergotoxine on 
 the arteries, contracting them and the uterine 
 muscle. 
 
 He infers that the characteristic action of 
 the infundibular part of the pituitary is to stimu- 
 late plain muscle fiber. There are no two active 
 principles, the pressor and diuretic according 
 to Dale. 
 
 Action on Intestinal Peristalsis. — Bell has 
 shown that infundibular extracts have an ac- 
 tion upon intestinal peristalsis in pithed rab- 
 bits, and he has advised its use in intestinal 
 paresis after abdominal operation. Our ex- 
 periments were made upon etherized rabbits. 
 A brass cannula with a rubber balloon over 
 its end was inserted into the small intestine, 
 near the stomach end. It was attached to 
 Albrecht's piston recorder and the normal 
 movements were registered. Then the infun- 
 
62 
 
 dibulin was injected per jugular and the subse- 
 quent movements of the intestine noted. It 
 had a marked action as is shown in Fig. 8. 
 
 Action upon the Uterus. — H. H. Dale, Bell 
 and Hick have shown that infundibulin is a 
 uterine stimulant. Our experiments were made 
 upon etherized cats and rabbits. The abdominal 
 cavity opened, the head in the Malassez holder 
 elevated and the opened walls of the abdomen 
 attached by hooks to a transverse bar. The 
 pelvic cavity was filled with normal saline, 
 heated to about the temperature of the body and 
 kept so by frequent additions. This solution 
 kept the uterus bathed. Then, as Cushny 
 has advised, we attached two threads to the 
 uterus and the other ends of the thread to a 
 myocardiographic lever which registered the 
 contractions of the uterus. It was a strong 
 stimulant of uterine contraction, as Fig. 9 
 shows. 
 
 Prof. Von Frankl-Hochwart and Frohlich 
 in the rabbit found that pituitrin by the vein 
 made the hypogastric nerve much more irritable, 
 and also the uterus itself much more active, 
 when the faradic current was applied to the hypo- 
 gastric nerve. This uterine action is independ- 
 ent of blood pressure. Only the first injection 
 is active as is the case in the action of pituitrin 
 upon heart and blood vessels. 
 
 Bladder. — Von. Frankl-Hochwart and Frohlich' 
 used pituitrin. In cats and dogs pituitrin ex- 
 
 1 Wiener Ktinische Wochensciirifl. 1909. p. 982. 
 
63 
 
 cited the muscle of the bladder to a great de- 
 gree and also considerably increased the ex- 
 citability of the motor nerves of the nervus 
 pelvicus as measured by the distance between 
 
 : coils of a DuBois inductorium. They used 
 It intravenously. Before the injection, the blad- 
 der contracted when the nervus pelvicus was 
 irritated with the secondary coil at 19 cm. 
 But after the injection of 0.5 pituitrin the blad- 
 der contracted at 26. The action was marked 
 and constant. We have repeated this ex- 
 periment in cats. The nervus pelvicus was 
 placed on Ludwig's shielded electrodes, and 
 a hollow glass tube with a short arm bent at 
 right angles was bound in the neck of the blad- 
 der. Then we used the weakest faradic cur- 
 rent that would make the warm Ringer solu- 
 tion mount up the tube. It was 20 cm. After 
 injecting one cc. of 20 per cent, extract of in- 
 fundibular part of the gland irritation of the 
 nerve causes an ascent of the fluid when the 
 DuBois coils were separated 28 cm. We also 
 attached the bladder to a water manometer, 
 opening the abdomen and severing the ureters, 
 then closing the abdomen except where the tube 
 attached to the manometer was connected. 
 In this way we had a registration of the move- 
 ments of the bladder. 
 
 When the infundibulin was injected we ob- 
 tained a marked vesical contraction (Fig. 10.) 
 If, however, the nervi pelvici were cut then 
 infundibulin had • hardly any effect, a slight 
 
64 
 
 increase at times of the contraction of the blad- 
 der. These experiments prove that infundib- 
 ulin mainly excites the bladder by an action 
 on the central nervous system. 
 
 In acromegaly there are bladder troubles, 
 perhaps due to hyperhypophysy, or pressure 
 on a vesical reflex center of 2" order in locus 
 niger. 
 
 Actioyi on the Pupil. — W. Cramer^ noted that 
 extracts of the posterior lobe of the pituitary 
 body of the ox produced a distinct dilatation 
 of the pupil of the enucleated eye of the frog. 
 The principle is distinct from that body in the 
 pituitary which produces diuresis. Ott and 
 Scott- found that the pituitary in the rabbit 
 dilates the pupil after removal twenty-four 
 hours previously of the superior cervical ganglion. 
 It was used locally, by the jugular, and sub- 
 cutaneously. In the normal eye no effect en- 
 sued. Pituitrin has the same effect, showng 
 it is the infundibular part that dilates the pupil. 
 
 Von Frankl-Hochwart and Frohlich found 
 by intravenous injection of pituitrin a narrow- 
 ing of the pupil. ^ 
 
 Temperature. — Mairet and Bosc have shown 
 that pituitary extracts when injected elevate 
 the temperature. Narbut found after removal 
 of the hypophysis a lowering of the tempera- 
 ture on the day of the operation and a marked 
 
 1 Quarterly Journal of Experimental Physiology, Vol. I, p. 
 187, April, 1908. 
 
 2 Tlie New York Medical Journai. Dec, 1908. 
 
 8 Wietier Klinische Wochenschrift, p. 982. 1908, July 8. 
 
65 
 
 sinking of it before death. Vassale and Sacchi 
 also noted a lowering of temperature after 
 removal of pituitary. Injections of the 
 hypophysis in these cases elevated the tempera- 
 ture. 
 
 Cushing found in animals suffering from hypo- 
 pituitarism a rise of 2° to 4° C. by the injection 
 of the boiled pars anterior. 
 
 After a partial removal of the pars anterior 
 and an entire removal of the posterior lobe 
 the temperature of the body just before the 
 death fell to 63.5° (Cushing). We have seen the 
 temperature fall to 94°, in monkeys after destruc- 
 tion of the pars anterior by the operation of 
 Paulesco. 
 
 Removal of Pituitary. — In 1886, Horsely first 
 made experiments for the removal of the 
 hypophysis on two dogs. They soon died without 
 any special disturbance. During the hfe of the 
 animals he noted an increase of the excitability 
 of the motor centers. A weak electric irrita- 
 tion of them caused unusually strong clonic cramps 
 of the whole body. Dastre removed the pitui- 
 tary, but the animals did not survive the opera- 
 tion. Gley also removed the hypophj^sis. 
 
 Marinesco operated on cats, which lived from 
 one to eighteen days. The result was a great 
 amount of wasting of the body, although arti- 
 ficially fed. 
 
 Vassale and Sacchi^ operated on dogs and 
 cats, and the longest time they lived was four- 
 
 1 Rivisia sperim di Freniatria, XVIII, 1892. Ibid.. XX, 1894. 
 
66 
 
 teen days. The symptoms mere apathy, motor 
 troubles, rigidity of the back, somnolence, 
 vacillating gait, dyspnea, anorexia, and polyuria. 
 The dogs also rapidly lost flesh, and had tonic 
 and clonic cramps with fibrillary contractions. 
 Injection of pituitary extract temporarily made 
 the symptoms better. The constant low tem- 
 perature was marked, but after the injection 
 of pituitary extract it returned to normal. 
 After the effect of the injection had passed off, 
 the temperature sank and at the same time 
 the general state was worse. Caselli operated 
 on 56 dogs and cats, producing extirpation, 
 and came to the conclusion that the pituitary 
 was a helping organ to the thyroid. The opera- 
 tions were made through the mouth, boring 
 through the base of the skull. The hypophysis 
 was destroyed by a sharp spoon, thermocautery 
 or through chemicals. 
 
 Caselli found that complete removal of the 
 functions of the pituitary caused at first slow- 
 ing of respiration, acceleration of pulse, then 
 depression of the psychical faculties, motor 
 troubles with curving of the spine, spastic gait 
 without tonic or clonic contractions, convul- 
 sive attacks, progressive cachexia, coma and 
 death. In partial lesion of the hypophysis, 
 in adults, you have the same symptoms as after 
 total ablation, but these symptoms, correspond- 
 ing to the functional insufficiency, gradually 
 disappear and the animal passes into a sub- 
 normal state compatible with life. Psychical 
 
67 
 
 depression persists. In animals which are grow- 
 ing, the functional arrest of the hypophysis 
 prevents their normal growth. The extirpa- 
 tion of the hypophysis modifies the course of 
 tetania parathyreopriva, the tetany ceases 
 after a short time and paralysis ensues, followed 
 by coma and death in forty-eight hours. ^ 
 
 Friedman and Maas arrived at the conclusion 
 that total extirpation of the pituitary was 
 not incompatible with life. Monaco and Van 
 Rynberk arrived at the same conclusion. Pir- 
 one operated on dogs, making partial and total 
 hypophysectomies, and considered that the 
 motor troubles, the apathy, psychic depression, 
 rapid wasting, cachexia and death were due 
 to pituitary insufficiency. He made some urinary 
 analyses on the operated animals, and found 
 an augmentation of urea and extractives. Gatta 
 made some experiments and arrived at the con- 
 clusion that the hypophysis is indispensable 
 to life. 
 
 Paulesco^ arrived at the gland by means 
 more adequate to remove the entire gland than 
 previous observers who probably did not re- 
 move the whole gland as they operated either 
 by way of the base of the skull or by the vertex. 
 Paulesco freely removed the temporal bone 
 on both sides, incised the dura mater, then 
 he elevated the brain on one side by a retractor 
 until the reddish yellow pituitary was seen 
 
 > Casein, Studi anatomici esperimentale sulla Fisiopathologia 
 Delia Glandola piluitaria, 1900. 
 
 2 L'Hypophyse du cerveau, 1908. 
 
68 
 
 lying in the sella turcica. Then it can by a 
 small curette be easily shelled out, and the 
 brain restored to its normal position and the 
 wound closed. On the first day after the opera- 
 tion the animal had no bad symptoms, but on 
 the second day they showed lassitude and died 
 without any clear reason. 
 
 Paulesco states that the mere separation of 
 the pars nervosa from the infundibulum has 
 sometimes proved as quickly fatal as the actual 
 removal of the gland. 
 
 Fichera (1906) and Gemelli^ state that re- 
 moval of the hypophysis is not followed by a 
 fatal result. It is probable that they did not 
 remove the whole gland, or the few cells in the 
 pharyngeal pituitary of Haberfeld compensated. 
 
 Masay- has tried to produce pituitary insuffi- 
 ciency, that is, a lessening of the functions of 
 the gland by preparing an anti-serum by intra- 
 peritoneal injection of a guinea pig with an 
 emulsion of a dog's pituitary at intervals of 
 two days. After five injections he collected 
 the blood of the guinea pig, centrifugalized it 
 and injected the serum (about 10 cc.) subcu- 
 taneously in the dog. After two or three of 
 such injections the dogs lost flesh, had muscular 
 weakness, especially of the posterior extremities, 
 also changes in the skeleton and histological 
 changes in the pituitary from a true cachexia 
 hypophysipriva. 
 
 ' Folio Neuro-Biologica. Nov., 1908. p. 167. 
 '^ L'Hypophyse, 1908. 
 
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69 
 
 Cyon^ holds that the pituitary gland contains 
 several substances, one of which acts on the 
 vagus, increasing its force and slowing its rate, 
 acting like muscarine. He also saw the rise 
 of blood pressure. His results have been con- 
 tradicted by several observers. An antitoxic 
 function of the hypophysis has been ascribed 
 to it by Guerrini, Gemelli and Thaon. 
 
 Narbut (1909) in Bechterew's laboratory found 
 on extirpation of the hypophysis a fall of tem- 
 perature on the day of operation, which he thinks 
 was probably due to injury of the tuber cinereum. 
 Dr. Sakovic has shown that lesion of the tuber 
 reduces the temperature. Narbut noted a marked 
 sinking of the temperature before death (Fig. 
 11). He also noted after removal of the pituitary 
 an arrest of growth in the anterior and posterior 
 extremities and a partial want of growth in 
 the skull. 
 
 The excretion of phosphorus and nitrogen 
 was increased both absolutely and relatively, 
 the excretion of the phosphates being increased 
 threefold. The oxygen consumption and the 
 CO2 exhalation was decreased. The water ex- 
 haled was decreased (Figs. 11 and 12).^ 
 
 Gushing, Crowe and Homans found that Ge- 
 melli's results were due to an incomplete re- 
 moval of the gland. Gushing found that young 
 animals, puppies, after hypophysectomy, do 
 not have cachexia hypophyseopriva until thirty- 
 
 1 Die Gefdssdrusen, 1910. 
 
 ' Bechterew, Die Funktionen der Nervencentra, Zweites Heft, 
 1909, p. 1219. 
 
70 
 
 six hours to two weeks or so after the operation; 
 with a transient glycosuria, with or without 
 polyuria, the animal is norrnal in appearance. 
 Then inactivity with a little stiffness and un- 
 steadiness of gait is seen, lower temperature, 
 awkward arching of back with incurvation of 
 tail. There is a slow pulse and respiration, 
 irregular muscular contraction, often snapping 
 of the jaws, coarse shivering movements like 
 in tetany. The animal is lethargic, indiiferefit 
 to his surroundings, becomes comatose, slow 
 pulse and occasional diaphragmatic respiratory 
 movement. The temperature falls to 20° C, 
 or lower. 
 
 In the hypophysectomized animals there were 
 striking changes in thyroid and testis. 
 
 In the removal of the pars posterior, although 
 some fragments of pars intermedia are left, 
 there is no post-operative alteration in blood 
 pressure, or in urinary secretion. In partial 
 removal of the anterior lobe, the animals re- 
 main undersized, acquire no secondary sexual 
 characteristics, have a tendency to hypotrichosis, 
 and have subnormal temperature. In several 
 adult males after a partial hypophysectomy of the 
 anterior part there is a loss of spermatozoa, 
 absence of mitosis and other peculiar changes 
 in the spermatogenetic epithelium and cer- 
 tain alterations in the interstitial cells of Leydig. 
 Histological changes are seen in the islets of 
 L-angerhans. ^ 
 
 1 Am. Journal of Medical Sciences, April, 1910, p. 473. 
 
71 
 
 Crowe, Gushing and Homans^ confirni Paules- 
 co's work, that the pars anterior of the hypophy- 
 sis is necessary to life. They show that 
 Von Cyon's views (previously contradicted) 
 are incorrect about the effect of mechanical 
 irritation of the pituitary affecting the circula- 
 tion or respiration. They observed no effect. 
 Removal of posterior lobe produces no cachexia 
 hypophyseopriva. Separation of the hypophy- 
 seal stalk, owing to circulatory disturbances, 
 is comparable either to a partial hypophysec- 
 tomy or to a total removal with immediate 
 reimplantation of the excised tissue elsewhere 
 in the body. The gland becomes reattached 
 and the pathways for posterior lobe secretion 
 supposed to traverse the pars nervosa on its 
 way to the infundibular cavity may become 
 obstructed by the scar leading to an accumula- 
 tion of hyaline material within the channels 
 of the pars nervosa. We have seen destruction 
 of the pars anterior in the monkey produce death 
 in 4 days. 
 
 Injections of Pituitary. — Intraperitoneal in- 
 jection of extracts of the hypophysis according 
 to Delille acts as follows: In small doses the 
 repetition of injections for 3 to 4 days causes 
 congestion and hyperactivity of the pituitary, 
 the eosinophile cells are very much greater, 
 the extra-cellular colloid was abundant. After 
 10 to 15 injections the eosinophile cells are 
 less, the basophiles relatively abundant, little 
 
 I Johns Hopkitu Bulletin, p. 127. May, 1910, 
 
72 
 
 extracellular colloid and a considerable quantity 
 of chromophobes, there is no congestion. These 
 facts have been confirmed in the main by Hal- 
 lion, Alquier and Guerrini. Under the influence 
 of injections of the whole hypophysis the adrenals 
 double in weight, there is a diffuse cortical 
 hyperplasia. The intraperitoneal injections seem 
 to stimulate the adrenal secretion. The pituitary 
 injections cause remarkable changes in the 
 thyroid which is poor in large vesicles; there 
 is little colloid, which finally disappears. At 
 the periphery of the thyroid the large vesicles 
 are nearly empty. The injections produced no 
 effect upon the ovary or testis of a rabbit treated 
 for more than a year. She was able to fecundate. 
 In small doses it produces slight congestion 
 of the liver and a granular fatty degeneration 
 at the peripher}^ of the lobule. The spleen 
 did not show any changes. The kidneys were 
 slightly congested; the glomerulus was always 
 increased in size. 
 
 Extracts of the posterior lobes cause the 
 same results as the whole gland. Extracts 
 of the anterior lobe cause a slight hyperactivity 
 of the hypophysis and do not change the adrenals. 
 The thyroid by injection of the pars anterior 
 shows a state of hyperfunction, the colloid is 
 very abundant, and the large vesicles are very 
 numerous. The anterior part causes the same 
 lesions as the whole gland, but the lesions are 
 less marked. The spleen is a little congested. 
 The islets of Langerhan's are also congested. 
 
73 
 
 Parhon and Golstein found the following changes 
 by the injection of the hypophysis: thyroid 
 nornial, atrophied seminiferous tubules; no 
 change in ovary, adrenals enlarged and in 
 a state of hyperplasia, fatty liver, spleen norraal, 
 and parenchymatous lesions of the kidneys. 
 
 G. Franchini^ arrived at the conclusion from 
 numerous experiments. 
 
 (i) The extract in rabbits only exception- 
 ally causes glycosuria. 
 
 (2) The extract of the hypophysis causes, 
 besides a toxic action, on rabbits and guinea 
 pigs, an especial action upon the intestinal 
 canal producing ulceration and hemorrhages. 
 
 (3) The greatest toxic activity is by the 
 vein, but it can also ensue by subcutaneous 
 or gastric exhibition. The act of digestion in 
 vitro partly weakens the toxic action. 
 
 (4) The glandular part isolated from the 
 pars intermedia produces only slight disturb- 
 ances. If the pars intermedia is combined with 
 it then it is toxic. The infundibular part iso- 
 lated from the pars intermedia has an especial ac- 
 tion upon metabolism and an action upon the 
 blood vessels and the organs of abdomen and 
 the pelvis. 
 
 (5) The infundibular part isolated from pars 
 intermedia contains a substance which dilates 
 the frog's pupil. This dilation is not produced 
 by the anterior lobes, but by the pars inter- 
 media and in a much less degree than by the 
 
 1 Berliner Klinisch-e Wochenschrift, 1910, p. 723. 
 
74 
 
 infundibular part. The serum from animals 
 who have received injections from the extract 
 of the posterior lobe produces dilated pupil. 
 The serum from animals injected with extract 
 of the isolated anterior glandular part isolated 
 from the pars intermedia very seldom causes 
 dilation of pupil, but if the pars intermedia 
 is combined with the glandular anterior part 
 the dilation of pupil is more frequent. 
 
 Gushing, Crowe and Homans^ found after 
 repeated injections of the posterior or infundib- 
 ular lobe that there was loss of weight, ex- 
 treme degree of hepatic degeneration and 
 necrosis, subsequently found under other ex- 
 perimental conditions. This same lesion with 
 no accompanying histologic changes in the 
 kidneys has been found in a number of hypophy- 
 sectomized animals ■without injections. 
 
 The subcutaneous administration of the pars 
 anterior caused no such disturbances even when 
 given daily over three months. Hence Gush- 
 ing used the pars anterior as a means of tiding 
 over periods of threatened cachexia hypophyseo- 
 priva in cases of almost total hypophysectomy. 
 He also used the pars anterior to produce hyper- 
 pituitarism. 
 
 Action of Pituitary on Metabolism. — Malcolm^ 
 studied the action of the pituitary on the ex- 
 cretion of inorganic substances. 
 
 Nitrogen. — The dried glandular portion of 
 
 ' Bulletin Johns Hopkins, May, 1910. 
 
 2 Jotirnal of Physiology. Vol. XXX. 1904, p. 270. 
 
75 
 
 the pituitary orally caused a slight retention 
 of nitrogen; the dried nervous portion had a 
 similar effect. The fresh entire gland increased 
 the output of nitrogen. 
 
 Phosphorus. — The glandular portion caused 
 a retention of phosphorus, while the nervous 
 part caused a loss followed by a retention. 
 
 Calcium and Magnesium. — Both dried gland- 
 ular and dried nervous part increased the 
 output of calcium (on a calcium-rich diet) ; 
 while the excretion of calcium in the glandular 
 case was accompanied by an increased output 
 of magnesium (in the feces at any rate), the 
 nervous was not, or not to the same extent, so 
 accompanied. This points to the nervous por- 
 tion having a katabolic action on the bony 
 tissues. 
 
 Thompson and Johnston^ found the injec- 
 tion of the entire pituitary to lead to loss of 
 weight by stimulating metabolism, increasing 
 the nitrogen, urea and phosphorus in the urine. 
 
 Sandri observed no effect upon the growth 
 of young mice from a two months' feeding of 
 the pars anterior of beef pituitary, while those 
 fed with posterior lobe showed a notable arrest 
 of development. 
 
 Gushing states that repeated daily injections 
 over long periods of the pars posterior leads 
 to progressive emaciation, often with marked 
 degenerative changes in the spleen and central 
 necroses in the liver. Similar results of auto- 
 
 ^ Journal of Physiology. 1905, p. 889. 
 
76 
 
 intoxication were not uncommonly seen after 
 operative removal of the gland. 
 
 Repeated daily hypodermic injections of the 
 anterior lobe caused loss of weight, which has 
 been seen by Casselli and others. 
 
 H. Salomon by feeding healthy men. with 
 large quantities of pituitary tablets found no 
 increase of the respiratory gases. 
 
 Franchini^ noted great changes by pituitary 
 in metabolism, especially in the inorganic part. 
 There is a great deficiency of calcium and mag- 
 nesium and, to a small degree, also of phos- 
 phorus in the body. In the circulating blood, 
 however, there is an increase of calcium and 
 magnesium. 
 
 Metabolism in Acromegaly. — A. Schiflf, of 
 Vienna, found that the giving of hypophysis to 
 an acromegalic caused a slight increase of nitrogen 
 excretion; the quantity of phosphorus, especially 
 by the intestine, was increased. 
 
 We may conclude that pituitary decreases the 
 phosphates in the urine and increases them in 
 the fecal matter. Infundibulin increases the 
 excretion of calcium by the intestine and of 
 magnesium by the urine. The nitrogen excreted 
 is increased. 
 
 Magnus Levy in a case of acromegaly found 
 that pituitary did not increase metabolism at 
 all, or not to any important extent. 
 
 Parhon^ has observed in acromegaly that 
 tablets of pituitary caused an augmentation of 
 
 1 Berlin Klin. Woch., 1910, p. 723. 
 
 2 Presbeanu, These, 1909. 
 
77 
 
 the phosphates and a retention of calcium salts. 
 
 Tauzk and Vas examined the excreta and 
 injecta for 8 days of an acromegalic and showed 
 that the weight of the body augmented. Nitrogen 
 and phosphorus were less in the excreta, while 
 the salts of calcium were eliminated in more con- 
 siderable quantity compared with those injected. 
 
 Moraczewski found in a case of acromegaly a 
 retention of chlorine, nitrogen, phosphorus and 
 salts of calcium. Audenino in studying two 
 cases of acromegaly found in the first period a 
 loss of nitrogen, which disappeared later. There 
 was also an increase in the earthy phosphates. 
 In the one case calcium was retained, in the 
 other eliminated in a great degree. 
 
 Parhon from an analysis of urine in acromegaly 
 found a constant retention of phosphorus, the 
 urea often diminished. 
 
 The eHmination of phosphoric acid was 
 diminished. 
 
 Franchini studied three cases of acromegaly. 
 He found in one a retention of N and CaO and 
 MgO and a loss of PjOj, and a less marked re- 
 tention of CI. In the second case he noted a 
 retention of N and CI and a loss of the three other 
 bodies. He noted an augmentation of elimina- 
 tion of calcium by the urine and a decrease of 
 its eUmination by the intestine. 
 
 Miller and Kds^U found in acromegaly a 
 marked retention of N, phosphorus and calcium. 
 
 1 Medical News, 1903. 
 
78 
 
 Parhon cites Silva who observed in acromegaly 
 a marked retention of nitrogen, increased elimina- 
 tion of sulphates and chlorides, while the phos- 
 phates were nearly normal. 
 
 It can be inferred from a study of the urinar}^ 
 excretions of acromegalics and when pituitary 
 is given to them, that the excretion of nitrogen 
 is less, that the phosphates are sometirhes in- 
 creased, at other times decreased, that calcium 
 in the majority of cases is less, although in some 
 experiments there was an increase of calcium in 
 the urine, and a decrease of it by the intestines. 
 
 Growth. — Shafer has made some experiments 
 with white rats, feeding them with powdered 
 anterior lobe of the pituitary, then weighing 
 them and comparing their weight with that of 
 control rats of the same litter. There seemed 
 to be an increase of weight in those fed with the 
 anterior part of the pituitary. 
 
 We have observed a great loss of weight in 
 rabbits by subcutaneous injection of the hy- 
 pophysis when continued for a few weeks. 
 Gushing has also observed a loss of weight by 
 the injection of the whole pituitary or of the 
 infundibular lobe alone. 
 
 Schafer^ thinks the pars anterior is probably 
 related to the growth of the cartilages, 
 bones, and connective tissue in general, due to 
 hormones. The function of the pars intermedia 
 is to produce a colloid material which contains 
 
 • Croonian Lecture, Proceedings of the Royal Society, B. Vol. 
 81. 1909. "Functions of the Pituitary Body." 
 
79 
 
 the active principle acting upon heart, blood 
 vessels and kidney. 
 
 Aschner has removed the hypophysis in a 
 young dog and compared it with a dog of the 
 same brood. The dog without the hypophysis 
 was stunted in growth. He holds that the hy- 
 pophysis is not necessary to life and that its 
 absence produces dwarfs. This is supported 
 by post-mortems in the case of dwarfs.^ 
 
 Relation between the Glatids. — Fichera found 
 after castration in roosters that the weight of 
 the anterior part of the pituitary doubled with 
 an increase of eosinophile cells. This also held 
 good for rabbits and oxen. Marenghi found after 
 extirpation of the adrenals in cats and rabbits 
 an increase of the pituitary. Rogowitsch found 
 a hypertrophy of the pituitary after removal 
 of the thyroids. This has been confirmed by 
 numerous observers, as Hofmeister, Comte, 
 Herring and others.^ 
 
 In castrates, the hypophysis is enlarged, as 
 has been shown by Fichera, Cimoroni, Tandler 
 and Gross. This hypertrophy is due to an 
 enormous increase of the chromophile cells 
 which are a Uttle'^ larger than the normal ones. 
 
 Comte, Mulon, Von Erdheim and Stumme 
 have shown the changes in pituitary during 
 pregnancy while in acromegaly there are changes 
 in the genitaUa. The thyroid when ablated 
 produces an arrest in the growth of the bones. 
 
 1 Wiener Klinische Wochenschrift, p. 572, 1910. 
 
 2 Oppenheim's Handbuch der Bio-Chemie, Band 3, erste Halfte. 
 p. 342. 
 
8o 
 
 Hinsdale examined the records of 57 cases of 
 autopsies of acromegalics; 15 times the thyroid 
 was enlarged, 11 times it was atrophied, and 12 
 times it was normal. 
 
 The persistence of the thymus has been noted 
 many times in the autopsies of acromegalics. 
 The thymus and the chromaffine tissue also 
 have a relation to the genital glands. 
 
 In myxedema and cretinism the hypophysis 
 is enlarged, as has been shown by Ponfick, 
 Dolega and others. 
 
 Parhon and Golstein and Pepere found that 
 extirpation of the parathyroids had an influence 
 upon the hypophysis which enlarges and the 
 chromophiles are very numerous (Fig 13). 
 
 Is Acromegaly a Hyperhypophysy'? — Pierre 
 Marie first pointed out that in acromegaly you 
 have a disease of the pituitary and held it was 
 due to a hypohypophysy. Tamburni and Benda 
 beUeved it was hyperhypophysy, an excess of 
 chromophile cells being present. Hochnegg, 
 in a case of acromegaly which was the first case 
 successfully operated on (1908), showed that a 
 year after the operation the length of the fingers 
 and the feet diminished. Here we have in man 
 (as Alfred Exner has stated) a decrease 
 where an operation produced hypohypophysy, 
 which reduced the acromegalic hands and feet. 
 
 Since Hochnegg's first successful case of 
 hypophysectomy for acromegaly, he has operated 
 on two other acromegalics, and one of these 
 showed a great similarity to the first case. 
 
Fig. 13. — A case of acromegaly (Bouchard). 
 
8i 
 
 The menses which had stopped for seven 
 years returned. An adenomatous tumor was 
 removed, the great increase of pain present 
 diminished, and the fat decreased. The hands 
 and feet diminished in size. The third case 
 was a woman thirty-four years old; her menses 
 had stopped for three and one-half years, and 
 she had marked symptoms of acromegaly. 
 She died shortly after the operation. All three 
 cases were adenomatous tumors.^ 
 
 The enlargement- of the pituitary during 
 pregnancy means an hyperhypophysy, and a 
 diminished function of the internal secretion of 
 the ovaries. In both cases of recovery after Hoch- 
 negg's operation there was marked enlargement 
 of the thyroid. Gushing observed a simular 
 effect after a hypophysectomy in man. 
 
 The operation of Hochnegg's was the first 
 experimental evidence in man to prove that 
 acromegaly was due to a hyperhypophysy and 
 not to hypohypophysy as held by Marie. 
 
 Gushing removed a part of the anterior lobe 
 in man, and a post-operative reduction in the 
 hands ensued. There are, however, cases of 
 acromegaly without enlargement of the hy- 
 pophysis, but minute changes in the h3TDophysis 
 might be overlooked, or even small tumors, as 
 in a case of Erdheim's, where with a normal 
 hypophysis a small tumor was found beneath 
 the sella completely separated from the pituitary. 
 
 1 Miiieilungen aus den Grenzgebieten der Med. und Chirurg., 
 1909, p. 620. 
 
82 
 
 Brissaud and Henry Meige were the first to 
 conclude that giantism and acromegaly are the 
 same disease. The appearance in youth is 
 giantism and in the adult it is acromegaly. 
 The age is the only difference. Halmagrand 
 (1907) holds that hyperhypophysy causes 
 giantism. 
 
 Launois and Roy (1904) hold that giantism 
 corresponds to a hyperacti\dty of the pituitary 
 before the union of the epiphyses and acromegaly 
 to the same hyperactivity after the union of the 
 epiphyses. Gushing states that hyperpituitarism 
 in youth gives giantism; in adult life it is 
 acromegaly. ^ 
 
 Sternberg arrived at the conclusion that in 
 acromegaly it was chiefly the anterior part of 
 the pituitary which was the constant seat of 
 the lesions. A histological study of a series 
 of tumors of the hypophysis has a common 
 mark, an increase of the chromophile cells, 
 cells which are supposed to be secretory cells. 
 Hence, Borchardt arrived at the conclusion that 
 there is a hyperfunction of the secretory elements 
 of the anterior part of the hypophysis, as the 
 cause of acromegaly, as Hanseman first stated, 
 and later Tamburini, Woods Hutchinson, Gubler 
 and Benda. Cagnetto found an increase of 
 chromophile cells, as did Achard, Loeper and 
 Lewis. Cagnetto in a case of tumor of the 
 hypophysis without acromegaly found there 
 was an absence of the chromophile cells in the 
 
 ' Journal Am. Med. Association, July, 1909, p. 255. 
 
83 
 
 anterior part of hypophysis. The same was 
 true in a case of Carbone. Hence we may infer 
 that giantism and acromegaly are due to hyper- 
 hypophysy of the anterior lobe of the hypophysis 
 and to a hypersecretion by the chromophile 
 cells of the pars anterior. 
 
 If the posterior lobe is also diseased you have 
 polyuria. We might add that glycosuria is 
 due to the invasion of the posterior lobe by 
 disease which is usually cancer or sarcoma. 
 
 Infantilism. — Meige's definition of infantilism 
 is an anomaly of development characterized by 
 the persistence in a subject having attained or 
 passed the stage of puberty, of morphological 
 characters belonging to an infant. 
 
 Marie believed that changes in the functions 
 of the sexual glands were initial symptoms in 
 acromegaly. A. Exner believes hyperhypophysy 
 secondarily leads to loss of function of the sexual 
 organs and amenorrhea. When the pituitary 
 was removed in cases of tumor then the menses 
 became regular. 
 
 The observations of skeletons of eunuchs by 
 Lortet, by Ecker and by Pirsche show that human 
 castrates have a retard of complete ossification 
 of the long bones. 
 
 Sellheim, Bonnet, Becker, Poncet, Pirsche 
 and Mobius, in the lower animals after castra- 
 tion, have shown the presence of active cartilages 
 in the long bones of the extremities and par- 
 ticularly at the epiphyses, which normally are 
 joined to the diaphyses. This fact explains the 
 
84 
 
 unequal development of the extremities in 
 relation to the trunk, and also the unequal 
 development of difTerent parts of the extremities 
 when compared among themselves. 
 
 Delille^ ascribes hypohypophysy as the cause of 
 pituitary obesity, associated with infantilism. 
 He also makes an obesity due to a hyperhy- 
 pophysy, which conduces to emaciation by the 
 hyperhypophysy, and causes hypothyroidism 
 and suppression of the activity of the sexual 
 organs and thus indirectly produces obesity. 
 Here we have a pluri glandular action con- 
 cerned in the production of obesity. The 
 bone changes, the obesity, hypertension in 
 arteries, and polyuria are due to hyperhypophysy. 
 
 Alfred Exner and V. Gschmeidler have grafted 
 several hypophyses into animals and found 
 afterwards a very marked increase of fat in 
 them compared with the ungrafted controls. 
 
 Tandler and Gross in cases of acromegaly 
 found changes in the epithelium of the semenif- 
 erous tubules and in the interstitial cells of the 
 testis and ovary. A. Exner remarks that it 
 is difficult to state if the increased amount 
 of hair and obesity is directly due to hyper- 
 hypophysy or is indirectly due to the hyper- 
 hypophysy action upon the interstitial cells 
 of the testis and ovary, and in this way causing 
 obesity and increased amount of hair. At the 
 menopause when the ovarian interstitial tissue 
 is lowered in function we have a beard develop, 
 
 1 These pour le Doctorat, May 13, 1909. 
 
85 
 
 and there is a more abundant growth of hair 
 about the Hnea alba. 
 
 During pregnancy we have more hair in the same 
 places and also in the majority of cases of obesity. 
 We know that in pregnancy we have hyper- 
 hypophysy. In the acromegalic after the re- 
 moval of the swollen hypophysis, the absent 
 menses return and impotency is lost. Here the 
 interstitial cells of the sexual glands have an 
 inhibition removed and recover their wonted 
 activity. Hence A. Kxner holds that the function 
 of the ovary and testis is partly to regulate 
 the sexual activity, the growth of hair and 
 obesity and that this function is inhibited by 
 increased activity of the pituitary. 
 
 The anterior part of the pituitary seems to 
 be associated with growth of the body with fat 
 metabolism, and sexual activity. Removal of the 
 posterior lobe causes no apparent disturbance 
 of the physiological balance of the body. 
 
 Boyce and Beadles, in a woman with a great 
 amount of subcutaneous and peritoneal fat, 
 weighing 84 kilograms, had a hypophysis nearly 
 double in size and the augmentation of volume 
 was only in the anterior lobe. 
 
 FrohUch first spoke of a dystrophia adiposo- 
 genitalis, where we have infantilism of the sexual 
 apparatus accompanied with obesity. These 
 patients are small in height, have a smaller 
 amount of hair, and excessive obesity, with symp- 
 toms of pressure in the vicinity of the hypophysis. 
 
 Von Eiselsberg has operated on these cases 
 
86 
 
 described by Frohlich where they had pituitary 
 disease without acromegaly, removing a part 
 of the hypophysis. After the operation the 
 fat diminished, the sexual apparatus was aroused 
 to awakened activity. 
 
 Gushing reports a case of a man aged 40 who 
 became very fat with polyuria and transient 
 glycosuria, with sub-normal temperature, slow 
 pulse, who had on post-mortem a primary tubercle 
 of the hypophysis. 
 
 Leman and Van Wart^ reported a case of 
 infantilism with an absence of the thyroid and 
 a tumor of the hypophysis. The woman was 
 white, her skeleton long. No axillary or 
 pubic hair, no mammary development, uterus 
 infantile, lack of ossification in the epiphyses, 
 and X-rays showed an enlargement of the 
 sella turcica. She was fed with thyroid but 
 without benefit. Pituitary extract improved 
 her, and she gained 15 pounds in weight, a pound 
 per week. 
 
 Crowe, Cushing and Romans^ have found 
 that in dogs partial removal of the anterior 
 lobe of the pituitary leads to a state of 
 adiposity accompanied by a secondary hypo- 
 plasia of the organs of generation in adults 
 or by a persistence of sexual infantilism in case 
 the primary hypophyseal deficiency antedates 
 adolescence. Polyuria, glycosuria, alterations in 
 the skin and its appendages (such as edemas 
 
 1 Archives of Internal Medicine. 1910. p. 519. 
 ^ J ohMs Hopkins Bulletin, p. 127, May, 1910. 
 
87 
 
 and hypotrichosis), the tendency to a subnormal 
 body temperature and psychic disturbances are 
 more or less frequent accompaniments, all of 
 them symptoms which occasionally occur with 
 states of adiposity and of sexual infantilism 
 in man in company with certain pituitary 
 body-tumors, states therefore which presumably 
 are due to deficiency of the pars anterior. 
 
 Gushing and his co-workers have undoubtedly 
 cleared up the question that the cases of infant- 
 ilism with excess of fat and atrophy of genitalia, 
 are due to hypopituitarism of the pars anterior. 
 How much the interstitial cells of Leydig .or 
 the interstitial cells of the ovary according to 
 the theory of Tandler and Gross play a part 
 in infantilism is still to be worked out. Gushing 
 has found changes in the Leydig cells of the 
 testes of the dog. 
 
 It must also be inferred according to Aschner 
 that hypohypophysy produces dwarfs. 
 
 Hence cases of infantilism may be divided 
 into two classes: (i) due to direct action of 
 hypohypophysy, (2) the other indirect due to the 
 hyperhypophysy, action on the thyroid producing 
 hypothyroidism and suppression of the activity 
 of the interstitial cells of the testis or ovary. 
 These are the cases of "pluriglandular insuffi- 
 ciency" of the French, authorities. 
 
 Transplants. — Growe, Gushing and Homans 
 had four cases in dogs of total hypophysectomy 
 with hypertrophic changes in the thyroid, but 
 where rectus implantation of the pituitary pro- 
 
88 
 
 longed the life of the animals. In another dog 
 they implanted in a cavity prepared, by inserting 
 a silver ball in bone marrow for ten days,^ and 
 then implanting the hypophysis from another 
 dog. Four days after the transplantation the 
 dog's hypophysis was removed; no symtoms 
 ensued from the operation. The animal's life 
 was prolonged over the usual period of three 
 to four days by the transplantation of hypophy- 
 seal tissue. In an auto-transplantation into 
 the cortex cerebri after a total h3'pophysectomy, 
 the duration of life was prolonged for eighteen 
 days, when he was killed. 
 
 Glandular transplants or injections of anterior 
 lobe emulsions definitely prolong the life of ani- 
 mals after total hypophysectomy and likewise 
 tide over periods of threatened cachexia hy- 
 pophyseopriva in animals retaining anterior 
 lobe fragments which temporarily may be 
 physiologically insufficient. They noted in some 
 of the hypoph^'sectomies a marked polyuria 
 with transplants even of the anterior lobe alone 
 in the transplant. This pol3mria disappears 
 after extirpation of the transplant.^ 
 
 A. Exner- has implanted hypophyses in young 
 rats. Their weight was increased, due to an 
 augmented length in part and to increased fat. 
 
 Therapeutical Application. 
 Shock. Intestinal Paresis, Uterine Contraction. 
 — Burroughs Wellcome & Co's infundibular 
 
 ' Quarterly Journal Experiment^ Physiology, 389, Vol. II, 
 No. 4, 1909. 
 
 ^ Zentralblatt jiir Physiologie, Band XXIV, p. 387. 
 
extract kept the blood, pressure in man elevated 
 for twelve hours. Bell recommends it for shock, 
 like Mummer}-, Lockhart and Symes.^ This 
 Wellcome extract of the infundibular lobe causes 
 powerful contractions of pregnant, puerperal 
 and menstruating uteri. Bell also found it 
 had a marked effect upon intestinal muscle, 
 and found it useful subcutaneously into the 
 muscles of the forearm for paresis and distension 
 of the bowel after abdominal operations. The 
 vaporole extract can be boiled and thus steril- 
 ized, but must be injected into the muscles to 
 avoid superficial sloughing from the local vaso- 
 constriction. The dose may be repeated with 
 an hour's interval. It acts better on paretic 
 intestine than on the normal one.- 
 
 G. G. Wray^ has treated post-operative shock 
 with considerable success. He injected i cc. 
 of Burroughs Wellcome & Go's. 20 per cent, infun- 
 dibular extract into the deltoid muscle. The 
 effect of the pituitary extract upon the small, 
 feeble pulse was to make it large, regular and 
 forceful. Its effect lasted about twelve to 
 fifteen hours. 
 
 Dr. J. A. Henton White, in a puerperal case 
 with pneumonia and a weak heart, used 12 
 minims of pituitary extract by injection into 
 the buttocks to stop post-partum hemorrhage. 
 The depression which ergot would cause was 
 unsuitable in this case. The pituitary caused, 
 
 1 British Med. Journal. Vol. H. p. 736, 1908. 
 
 2 BeU, British Medical Journal, p. 1609 Dec, 4, 1909. 
 
 3 British Medical Journal, 1909, p. 1745. 
 
90 
 
 after the grasping of the placenta, a violent 
 contraction of the uterus. The pulse instead 
 of being thready and uncountable soon acquired 
 a full volume and good tension. The general 
 condition was very good.^ 
 
 Thumin recommends in excessive menstruation, 
 due to ovarian disturbance or excessive desires 
 dependent upon an increased activity of the ovary 
 as in nymphomania and other psychoses, tablets 
 of the hypophysis. It is known that the ex- 
 cessive secretion in acromegaly causes a cessation 
 of menstruation and loss of sexual desire.^ 
 
 Tachycardia and Hypotension in Arteries. — ■ 
 When as a result of hypohypophysy by the toxines 
 of diphtheria, or those of endogenous origin, 
 then the use of pituitary is of great value. Hy- 
 pertension is an absolute contra-indication to 
 the use of pituitary extract. In the use of 
 pituitary you watch the pulse and pressure and 
 also examine the urine and blood. 
 
 Delille states that the extracts of the anterior 
 lobe do not produce an appreciable therapeutic 
 effect. Delille gives each day o.io gram to 
 0.40 gram of the whole dried gland. 
 
 Hallion and Carrion have seen a venous in- 
 jection of pituitary extract in the dog produce 
 an intense vaso-constriction of the thy- 
 roid as shown by the plethysmograph. This 
 explains the good effects of pituitary medication 
 in Basedow's disease.^ 
 
 ^British Med. Journal, 1910, p. 1282. 
 
 - Berlin Klinische Wochenschrift, 1909, p. 631. 
 
 3 Halmagrand, Etat. Actuel de V Infantilism, 1907, p. 58. 
 
91 
 
 H. Nageli and P. Vernier, of Geneva, have used 
 20-40 grams of powdered hypophysis extract 
 with good results in low arterial tension. 
 
 Which Preparation of the Pituitary is the Best 
 to Use in Tetany? — We have shown^ in feline 
 tetany that the pituitary gland given in distilled 
 water subcutaneously had an effect at least 
 equal to the calcium salts in alleviating the 
 tetany after complete parathyroidectomy. As 
 calcium has failed in several instances to cure 
 tetany in man it is necessary to seek other 
 agents to combat the disease. 
 
 Professor Pal, of Vienna, reports^ a case of 
 severe tetany in a boy. He gave pituitrin and 
 the tetany disappeared in twenty-four hours, 
 while the other symptoms retrograded. We 
 have made experiments with pituitrin in feline 
 tetany and find it has some effect which is, how- 
 ever, quite fu.gitive. We then tried the in- 
 fundibular extract of Burroughs Wellcome & 
 Co. (20 per cent.). It had a much more 
 prolonged action than pituitrin, even when we 
 gave the latter in ounce doses subcutaneously. 
 But neither pituitrin nor infundibular extract 
 had the continued power that the whole gland 
 exerts. We used all these preparations sub- 
 cutaneously. As the boiled filtered infusion 
 of the whole gland can not be readily used we 
 would recommend as the next best preparation 
 the 20 per cent, infundibular extract of Burroughs 
 
 1 Ott and Scott, New York Medical Journal, Dec. 10. 1908. 
 
 2 Wiener Klinische Wochenschrift, July 8, 1909, No. 27, p. 
 983. 
 
92 
 
 Wellcome & Co. by intramuscular injection, 
 in doses of i cc. three times a day. It should 
 not be used subcutaneously, as it might cause 
 some necrosis of the skin by the vaso-constriction. 
 As infundibular extract is not very poisonous, it 
 can be used oftener than three times a day if 
 the conditions necessitate it. 
 
THIRD LECTURE— THE CORRELATION OF 
 
 THE ACTION OF GLANDS WITH AN 
 
 INTERNAL SECRETION/ 
 
 Gentlemen: The functional relations between 
 the different internal secretions may be syner- 
 gistic, supplemental and antagonistic. The ac- 
 tive substances of the glands are necessary to 
 the normal action of the nervous system, the 
 circulation, metabolism and the growth of the 
 tissues. Glands with an internal secretion are 
 connected with the circulatory and lymphatic 
 system, for the reception of materials from the 
 blood and lymph and the ejection of their secre- 
 tions into them. The removal of one of these 
 secretions injures the whole organism and espe- 
 cially the bones and nervous system, when the 
 full growth of the body has not been accomplished. 
 It is not easy to definitely state the effect of 
 the removal of a certain gland with an internal 
 secretion, because it stands in a many-sided 
 relation to the other glands with a similar secre- 
 tion; you have a pluriglandular action. The 
 absence of the thyroid causes idiocy ; of parathy- 
 roid, tetany; of thymus, apathy; of ovary and 
 ' testis, a ^change in the whole psychical condition. 
 In anencephaly and hemicephaly the adrenals 
 are small or absent. In the human fetus 
 or the new-bom they are normally of enormous 
 size. In this defective development of the 
 
 1 Lecture delivered in the Course on Physiology, Medico - 
 Chirurgical College, 1909-1910. 
 
94 
 
 brain it is not the medulla but the cortex of the 
 adrenal which is wanting. There is a remarkable 
 relation between the growth of the brain and the 
 adrenals. I might state that it will be necessary 
 to repeat many facts noted in the preceding 
 lectures. I \vill first speak of the action of 
 glandular extracts upon the nervous system 
 and will explain to you what chromaffine sub- 
 stance is. 
 
 Chromaffine tissue is a tissue which stains 
 readily with chromic acid or its salts. This 
 tissue is found mainly in the medulla of the 
 adrenal, in some cells of the sympathetic ganglia, 
 in the cells of the carotid gland, and in the lower 
 animals a collection of cells at the point of 
 division of the abdominal aorta. Such collections 
 of cells containing chromaffine tissue have been 
 called, by Kohn, paraganglien. 
 
 Swale Vincent^ found that an extract of the 
 abdominal chromophile body of the dog had 
 precisely the same powerful effect upon blood 
 pressure as an extract from the medulla of the 
 adrenal. He stated that there seemed no reason 
 why the hypothesis that all the chromophile 
 cells had an internal secretion might not be 
 admitted though .this process was more com- 
 pletely elaborated in the larger chromophile 
 bodies and in the adrenal medulla. 
 
 Langley divided the sympathetic nervous 
 system. The true sympathetic arises from the 
 dorso-lumbar cord and is distributed to all 
 
 ^British Medical Jovrnal, 1910, p. 1151. 
 
95 
 
 parts of the body. The parasympathetic arises 
 from the mid-brain, bulb and sacral part of 
 the cord, and its chief nerves are the oculomotor, 
 chorda tympani, vagus and nervus erigens. 
 
 Adrenalin only stimulates the terminals of 
 the sympathetic nerv'ous system; it does not 
 affect the parasympathetic. Adrenalin acts upon 
 a "receptive substance" interposed between the 
 terminals and muscle tissue, according to Langley. 
 Infundibulin acts upon the sympathetic and 
 also upon the parasympathetic, as, for example, 
 in the increase of the excitability of the nerves 
 going to the uterus and bladder. Thyreoidin, 
 active principle of thyroid, also acts upon the 
 sympathetic nervous system and upon the 
 vagus. 
 
 About one millionth of a gram of adrenalin 
 elevates blood pressure. 
 
 In the case of the adrenalin we have a chemical 
 messenger, a hormone, for the sympathetic. 
 The adrenal cortex contains choline. Klose and 
 Vogt from experiments upon 54 dogs where the 
 thymus had been extirpated noted a slight 
 alteration in the psychical condition, apathy, 
 and after 4 to 14 months the animal had a 
 "cachexia thymopriva," "idiotia thymica," or 
 idiocy. 
 
 Removal of parathyroids decreases the gal- 
 vanic excitability of the nerves. Falta remarks 
 about the attempt to explain tetany after 
 parathyroidectomy by a deficiency of calcium 
 that it would be very wonderful when so com- 
 
96 
 
 plicated an affair could have an explanation so 
 simple. Removal of thyroid increases the galvanic 
 excitability of nerx'es. 
 
 Action on the Blood. — The blood is the receptacle 
 of all the internal secretions, a vehicle for all the 
 hormones. The thyroid stimulates the for- 
 mation of erythrocytes and mono-nuclear leuco- 
 cytes. Thyreoidin causes a disappearance of 
 the eosinophile cells (Falta). 
 
 The ovary increases the number of red cor- 
 puscles, but not their content of hemoglobin. 
 
 The liver and spleen regulate the richness of 
 hemoglobin. The insufficiency of the thyroid 
 secretion diminishes the number of the red 
 corpuscles, the amount of hemoglobin and 
 often produces an excess of leucocytes. 
 
 Adrenals on the Blood. — The majority of cases 
 of Addison's disease have a deficiency of cor- 
 puscles. Adrenalin or adrenal extract excites 
 the formation of all varieties of leucocytes and 
 diminishes the red corpuscles. Adrenalin pro- 
 duces a leucocytosis, especially of the poly- 
 nuclear neutrophiles and greatly diminishes 
 the eosinophiles (Falta). 
 
 Of all the internal secretions the adrenal is the 
 only one which is able in certain conditions to 
 decrease the red corpuscles in a constant and 
 progressive manner. As a rule it may be stated 
 that nearly all the internal secretions favor the 
 formation of blood. The hormones of the 
 internal secretions are a primary agent in the 
 
97 
 regulating mecliamsm of the manufacture of 
 blood. 1 
 
 Parathyroids. 
 
 Viscosity. — ^The researches of Fano and Rossi 
 have shown that removal of the parathyroid 
 in the dog does not have any influence upon 
 the viscosity of the blood. Removal of the 
 parathyroid causes a disappearance of the 
 eosinophile cells. 
 
 Blood Coagulation. — Salvioli believes orchitic 
 extract retards the coagulation of the blood. 
 
 Prostatic extract according to Zapelli and 
 Matozzi-Scafa in the dog retards coagulation. 
 Prostatic extract is very toxic. They state that 
 it has a paralyzing action upon the cardiac 
 apparatus and the center of respiration, which 
 I can confirm. 
 
 Infundibulin has no effect upon the blood. 
 However, W, Zyembicki,- in tumors of the hy- 
 pophysis, nearly always found eosinophilia. 
 
 Removal of pancreas causes a disappearance 
 of eosinophile cells. 
 
 Action on the Circulation and Diuresis. — In 
 considering the effect of some of the animal 
 extracts on the circulation, it must be remembered 
 that T. Klinoshita in Von Fiirth's laboratory 
 has found o.oi to 0.03 per cent, of cholin in the 
 pancreas, spleen, Hver, kidney, duodenum, muscle 
 and the lung of the cow.^ 
 
 Roger has found a h3rpotensive substance in 
 
 1 Secretions Internes, par Maurice Perrin, Paris, 1910. 
 
 2 Wiener Klinische Wochenschrift, 1910, p. 719. 
 ^Pfluger's Archiv, Band 132, p. 631, 1910. 
 
98 
 
 the adrenals like that in thyroid and hypophysis.' 
 
 Adrenalin and infundibulin both increase 
 blood pressure; the adrenalin does it rapidly 
 and it lasts only a short time; infundibulin does 
 it slowly, but it lasts for some time. Adrenalin 
 slows the heart to a marked degree, while 
 infundibulin retards it only a little. After 
 section of the vagi the heart is accelerated by 
 adrenalin. Adrenalin stimulates the cardio- 
 inhibitor}^ centre in the medulla oblongata, 
 infundibulin slows the heart even after section 
 of vagi or previous atropinization which paralyzes 
 the vagus, hence the cause of the slowing is 
 seated in the heart itself. Adrenalin dilates 
 the coronary arteries, infundibulin narrows them. 
 Adrenalin contracts the. renal arteries, infundib- 
 ulin dilates them. Adrenalin increases the 
 force of the heart muscle. 
 
 Thyreoidin, the active principle of the thyroid, 
 accelerates the heart beat and the blood pressure 
 is not elevated. 
 
 Jeandelize and Parisot found in a rabbit who 
 was thyroidectomized in his youth that after a 
 certain time there was arterial hypotension. 
 The serum of the animal also lowered arterial 
 tension. In thyroid insufficiency of man there 
 was a lower blood pressure. - 
 
 lodothy rin ( i grain) increased the flow of urine 
 to a small extent. It also increased the volume 
 of the kidney, although at the time the general 
 
 1 Compi. rend. Soc. de Biol.. 1910. Tome 69, p. 160. 
 
 2 Journal de Physiologie et de la Paihologie generate, 1910, 
 p. 339. 
 
99 
 
 blood pressure was decreasing the heart-beat 
 remained the same. The first injection of 
 iodothyrin in the cat elevated for the moment 
 arterial tension, but it soon fell. The heart- 
 beat was increased. 
 
 Coronedi^ confirms my results. He found the 
 thyro-parathyroid secretion kept the secretory- 
 activity of the kidneys, adequate to the needs 
 of the organism in dogs thyroidectomized. 
 After thyroidectomy the kidney of the dog has 
 a functional insufficiency. 
 
 Spinal cord (i/8 grain) had no effect on flow 
 of urine; did not alter rate of pulse; increased 
 blood pressure. 
 
 Prostate had no effect on urinary flow; did not 
 alter pulse rate; increased blood pressure. 
 
 Ovary reduced flow of urine; did not alter 
 pulse rate, but reduced arterial tension. 
 
 Spleen (3^ grain) reduced urinary flow; did 
 not alter pulse rate; lowered arterial tension. 
 
 Testicular extract (i/8) grain) did not affect 
 flow of urine or pulse; increased arterial tension. 
 
 Bielow^ found that the secretion of the corpus 
 luteum lowered blood pressure and slowed the 
 heart. He also calls the corpus luteum the 
 "glandula lutea ovarii." 
 
 Mammary gland (1/50 grain) produces a 
 slight increase of diuresis. The volume of the 
 kidney increased at the time the blood pressure 
 was falling, while the heart-beat was somewhat 
 
 1 Journal de Physiologie et de Pathologic. 1910, p. 599. 
 ^ Muenchener Medizinische Wochenschrift, 1910, p. 1707. 
 
lOO 
 
 increased. In the cat the mammary gland 
 extract increases the heart-beat and temporarily 
 increases the general arterial tension, after which 
 it falls considerably. 
 
 The parathyroid powdered extract (i/io to 
 1/5 grain) at first decreases the volume of the 
 kidney and then gradually increases it. The 
 increase of the kidney volume is often so great 
 that the registering pen cannot record it. The 
 primar}'^ decrease of kidney volume is due to a 
 temporary slowing of the heart. The subsequent 
 increase of volume in the kidney is not due to 
 any change in the rate of heart-beat, and the 
 general blood pressure at the time fell slightly. 
 As a diuretic, the parathyroids were the most 
 powerful of all the gland extracts. With the 
 nucleoproteid prepared according to Beebe's 
 method by Dr. W. N. Berkeley the increase in 
 the amount of urine was ten times that of normal. 
 We found the parathyroids in a case of inter- 
 stitial nephritis increased the quantity of urine 
 a half pint a day. 
 
 Thymus slightly increased the flow of urine. 
 It also augmented the volume of the kidney, 
 although the pulse rate remained unaltered and 
 the arterial tension was falling. 
 
 Lucien and Parisot found the thymus extracts 
 lowered blood pressure. They think this is due 
 to the lymphatic tissue in the gland and not the 
 gland itself or the corpuscles of Hassal.^ 
 
 The- pancreas increased the flow of urine. 
 
 > Zentralblaii f. Physiologi-e, Band 24, p. 2401. 
 
lOI 
 
 The volume of the kidney was slightly increased, 
 while the general blood pressure was decreasing, 
 and the rate of heart-beat considerably increased. 
 
 After injection by jugular of pancreas the urine 
 contained 1/4 per cent, of sugar, as shown by 
 the fermentation and Fehling's test. 
 
 Schaefer, Houghton and Merril have shown 
 that the pituitary extract (infundibular part) 
 increased the flow of urine. The volume of 
 the kidney was greatly augmented, so much so 
 that the- lever could not register at times. In- 
 fundibulin per jugular causes glucose to appear 
 in the urine. 
 
 The renal cortex increased the flow of urine. 
 The volume of the kidneys in doses of 1/50 
 to 1/25 of a grain did not change. 
 
 Adrenalin decreased momentarily the volume 
 of the kidney, while the blood pressure rose and 
 the heart was slowed. Afterwards the kidney 
 volume was greatly increased. 
 
 All these agents, the renal cortex, pituitary 
 extract, pancreas, parathyroid, mammary gland, 
 thymus, iodothyrin and adrenalin, are diuretics. 
 Gouin and Andouard found thymus in large 
 doses produced diuresis in the calf. The above 
 agents, except adrenalin, do not markedly in- 
 crease general arterial tension, except for a 
 moment, and then lower it. It is inferred that 
 the very short rise of blood pressure does not 
 produce the diuresis, which continues for a 
 considerable time afterwards. 
 
 As the changes of arterial tension do not play 
 
I02 
 
 any large part in the diuresis, it must be referred 
 to an action on the renal epithelium itself. 
 
 Action upon Intestinal Peristalsis. — Adrenalin 
 arrests it temporarily (Fig. 14), infundibulin 
 accelerates it. lodothyrin increases the fre- 
 quency and extent of contraction. Parathyroid, 
 mammary gland, spleen (Fig. 15), pancreas, 
 prostate, thymus, parotid, brain and spermine 
 (Poehl) increased the contractions.^ 
 
 Action upon Movements of Bladder. — Adrenalin 
 stops them temporarily, infundibulin increases 
 them. If the nervi pelvici in the cat, which 
 contain motor and (according to Langley) also 
 inhibitory fibers, are cut then infundibulin has 
 a very weak action. This shows it mainly 
 causes contractions of bladder by stimulating 
 the vesico-spinal center. As Von Frankl-Hoch- 
 wart and Frohlich have pointed out it increases 
 the irritability of the nervi pelvici. I can 
 confirm this. 
 
 Thyroid extract produced strong vesical con- 
 tractions. 
 
 Parathyroid increased the contractions of the 
 bladder. 
 
 Pancreas increased the vesical contractions 
 normally and after section of the nervd pelvici. 
 
 Normally thymus increased the extent of 
 the contractions of the bladder. 
 
 Ovary normally increased the extent of con- 
 tractions of the bladder. 
 
 ' Ott and Scott, Unpublished experiments, 1910. 
 

■;mmmmmmmmmwmm!>mwmmitimtmm^i 
 
 T.mmmmmtttttmm' 
 
spleen extract upon 
 
ncreas extract upo 
 
I03 
 
 Parotid considerably increased the frequency 
 of the contractions of the bladder. 
 
 Brain extract increased the frequency of the 
 vesical contractions.^ 
 
 Action upon the Uterus. — Adrenalin in unim- 
 pregnated uterus of the cat relaxes the uterus; 
 in a pregnant uterus it causes contraction. Here 
 the hypogastric nerv^e contains both augmentor 
 and inhibitory fibers going to the uterus. In- 
 fundibulin stimulates the cat's uterus to a marked 
 contraction^ so does iodothyrin, parathyroid, 
 mammary gland, spleen (Fig. i6), pancreas and 
 prostate (Fig. 17). Thymus and spermine 
 had some effect. Ovary had a very slight 
 action on unimpregnated uterus. 
 
 Action upon Pupil. — Adrenalin dilates the 
 pupil in rabbit with superior cervical ganglion 
 excised and in large doses the normal pupil. 
 Pituitary extract and pituitrin dilates- the ex- 
 cised pupil of the frog, and the pupil in the 
 rabbit on the side where the superior cervical 
 ganglion is excised. 
 
 Iodothyrin dilates the pupil on the side where 
 the superior cervical ganglion was excised; no 
 effect upon normal pupil. The dilation was 
 preceded by a slight contraction. 
 
 Parathyroid nucleoproteid on the normal eye 
 dilated the pupil, on the side with excised superior 
 cervical ganglion; it at first contracted and then 
 dilated it. The mammary gland had no effect. 
 
 Thymus had no effect upon the pupil. 
 
 1 Ott and Scott, Unpublished experiments, 1910. 
 
 2 ott and Scott, American Journal of Obstetrics, 1910, p. 766. 
 
I04 
 
 t:; Parotid and testicular extract contracted the 
 pupil upon both sides, the normal one and the 
 one with excised superior cervical ganglion. 
 
 The ovary had no effect. 
 
 Action on Temperature. — Narbut, like Vassale 
 and Sacchi, in Von Bechterew's laboratory, found 
 after removal of the hypophysis a lowering of 
 the temperature on the day of operation and a 
 marked sinking of it before death. 
 
 Gushing has shown that the removal of the 
 anterior part of the pituitary lowers temperature 
 to a great degree and injection of the pars an- 
 terior again elevates this low temperature. 
 
 Adrenalin increases temperature. 
 
 Infundibulin has a similar effect. 
 
 Glandular Glycosurias. — In 1889, Me ring and 
 Minkowski made a total extirpation of the 
 pancreas and observed sugar in the urine. 
 
 Forsbach^ has made some experiments, in 
 which two dogs of the same kind and same 
 brood had the skin, muscle and peritoneum of 
 each united together by ligatures. Here an 
 exchange of blood takes place by the newly 
 formed blood vessels and an exchange of lymph 
 through the communication of peritoneal cav- 
 ities. He showed that many things, as iodine, 
 sugar, strychnine, and so on, went from one 
 animal to the other. If now in the living. dogs 
 the pancreas is extirpated in one, then the usual 
 glycosuria did not ensue to the usual extent, 
 and in many cases was very little. If, however, 
 
 ' Deutsches Medizinische Wochenschrift. 1908. 
 
I05 
 
 the depancreated dog was separated from the 
 normal dog, then glycosuria took place to the 
 usual extent in the animal without the pancreas. 
 
 Minkowski and Hedon found in dogs that if 
 a transplant of a piece of the pancreas, the 
 "processus uncinatus," is made under the skin 
 of the abdomen and simultaneously or later the 
 remainder of the pancreas and its duct be ex- 
 tirpated, the appearance of sugar in the urine 
 was usually prevented, but ensued after removal 
 of the piece of pancreas in the subcutaneous 
 tissue. Pfiiiger ascribes the appearance of gly- 
 cosuria after removal of the pancreas to injury 
 of nerves in the duodenum. His view has been 
 contradicted by many observers. 
 
 It has been inferred that in the cells of islets 
 of Langerhans we have the internal secretion of 
 the pancreas. Severe diabetes can occur without 
 changes in the pancreas. 
 
 Opie studied very carefully the pancreas of 
 five diabetics. In three he observed marked 
 total hyaline degeneration of the islets. In 
 two others the degeneration was less marked. 
 Similar degenerations were not found by him 
 in the pancreas of non-diabetics. In the di- 
 abetic cases the parenchyma of the acinus was 
 more or less altered. Ugo Lombroso,^ from a 
 review of the literature of pathological and 
 anatomical facts, states that the internal function 
 of the pancreas can not be provided by only one 
 of the tissues of the gland, be it acini or islets. 
 
 ^ Ergebenisse der Physiologie, 1910, p. 47. 
 
io6 
 
 Lombroso,' from an analysis of experimental 
 work upon animals, concludes that both epi- 
 thelial tissue of pancreas, the acini as well as 
 the islets, take part in the internal secretion. 
 
 Cohnheim has shown that if the pancreas, 
 which contains a body not a ferment, and called 
 by him the activator, is mixed with muscle 
 extract in certain proportions, that the mixture 
 is a marked glycolytic agent. His theory has 
 been contradicted. 
 
 Adrenalin and infundibulin produce glycosuria, 
 the former after section of the splanchnics; 
 infundibulin has no effect after splanchnicotomy. 
 After extirpation of adrenals, diabetic puncture 
 fails to cause sugar in urine. 
 
 Parathyroid and pancreas in large doses 
 subcutaneously in rabbits produce a slight 
 glycosuria, i/8 per cent. Extirpation of 
 thyroid reduces the glycosuric action of in- 
 fundibulin, pancreas and parathyroid. In some 
 cases of dogs and cats sugar appears after ex- 
 tirpation of the thyroid alone. 
 
 It seems that the absence as well as the excess 
 of the internal secretion of the pancreas conduces 
 to glycosuria. 
 
 In thyroidectomized dogs Falta states that 
 adrenalin produces no glycosuria. Underhill, 
 however, finds that if the dose is large enough 
 sugar appears in the urine. 
 
 The present theory of diabetes is that a gly- 
 co-secretory center exists in the medulla oblongata, 
 
 1 Ergebenisse der Physiologic, 1910, p. 89. 
 
loy 
 
 from which fibers run down the cervdco-dorsal 
 cord to the solar plexus and then in the trunk 
 of the splanchnics to the liver cell. Falta 
 states that high section of the spinal cord, or 
 the withdrawal of the adrenals by section of 
 its nervous connection with the diabetic center, 
 leads to a very marked reduction of the amount 
 of sugar in the blood, like when you extirpate 
 the adrenals themselves. Fom the analogous 
 effects of diabetic puncture compared with 
 adrenalin injections, it is inferred that the 
 sympathetic fibers actuate the formation of 
 sugar in the liver lia the adrenals (Schur and 
 Wiesel). Normally diabetic puncture increases 
 the amount of adrenalin in the blood. 
 
 Falta states that after bilateral section of 
 the vagi the content of sugar in the blood is 
 elevated. There was also a well marked increase 
 and hypertrophy of the cells of Langerhans in 
 3 dogs who had their thyroid removed six months 
 previously. These facts lead Falta to think 
 that by the vagus and pancreas we have an 
 inhibitor}^ action, on the production of sugar 
 and an increase of sugar by the sympathetic 
 via the adrenals on the liver cell. By this 
 checking action the level of the content of sugar 
 in the blood is kept constant. 
 
 As Boruttau puts it, the adrenals produce 
 a hormone which sets in motion glycogeny in 
 the liver while the pancreas furnishes another 
 hormone by its internal secretion which an- 
 tagonizes the sugar driving function of the 
 
io8 
 
 adrenals. Hence the diabetes after pancreatic 
 extirpation is a negative pancreatic diabetes 
 and a positive adrenal diabetes. 
 
 Irritation of the sympathetic in the neighbor- 
 hood of the adrenals increases the amount of 
 adrenaUn secreted Adrenalin solution i : 1000,000 
 flowing into a vein (4.1 cubic centimeters per 
 minute) produces adrenalin glycosuria according 
 to Straub. 
 
 Phmglandidar Action. — Just as glands with 
 an external secretion concur in taking up the 
 work not accomplished by the others, and unite 
 in the perfection of the products to be brought 
 forth, in a similar way the glands with an internal 
 secretion concur in the metabolites to be pro- 
 duced, a sort of physiological balance is main- 
 tained between the activities of the different 
 glands in the wilderness of metabolism. 
 
 Klose and Vogt, from experiments upon 54 
 dogs in whom they extirpated the thymus, 
 had the following results: in the first 2 to 3 
 months, their weight increased like in the control 
 animals. There was slight alteration in their 
 psychical condition, apathy, increased appetite, 
 they were fat, the stage of adiposity. Then 
 the weight sank more or less rapidly and this 
 phase lasted 4 to 14 months. The animals 
 were idiotic, "cachexia thymipriva" (iodiotia 
 thymica) ; they had spontaneous fractures. Fin- 
 ally the animals died in a state of thymic coma 
 lasting 5 to 8 days. Rachitis, osteomalacia and 
 osteoporosis were present in the same animal. 
 
I09 
 
 The common cause was a great want of calcium 
 in the thymected organism. The cause of the 
 deficiency of calcium and the idiocy is an acidosis. 
 Klose holds that the thymus is the chief organ 
 for the synthesis of nuclein. 
 
 The removal of the thymus permits the lower 
 building stones of the organism, perhaps a great 
 excess of the incombustible phosphoric acid to 
 circulate in the blood. The acid dissolves the 
 calcium salts, or holds them in solution. Arti- 
 ficially produced fractures do not unite with 
 callus but only with connective tissue. The 
 chief organ which substitutes for the thymus 
 is the spleen. It acts after the phase of in- 
 volution of the thymus.^ 
 
 Worms and Pigache^ found in thyroidectomized 
 dogs and rabbits a disappearance of the thymus 
 which was replaced by connective tissue. 
 
 Renon and Delille* have found that injections 
 of the extract of the hypophysis cause a hyper- 
 function and very often hypertrophy of the 
 adrenals. Inversely the hypophysis of animals 
 treated by the adrenals have been found con- 
 gested and in hyperactivity. Parhon, Hallion 
 and Alquier, Renon and Delille are in concord 
 about this result. 
 
 New researches by Renon and Delille tend to 
 demon irate that it is only the extract of the 
 posterior lobe of the hypophysis which causes 
 a hypertrophy of the adrenals. The extract 
 
 1 Muenchener Medizinische Wochenschrift, 1910, p. 874. 
 
 2 Compi. rend. Soc. de Biol., LXVIII, 32, p. 500. 
 
 3 C. R. Soc. de Biol., June 13, 1908, 
 
no 
 
 of the anterior lobe is without eflfect, but pro- 
 vokes a hyperfunction of the thyroid, while 
 the extract of the posterior lobe has an opposite 
 action upon the thyroid. 
 
 Tandler^ holds that in the sexual glands we 
 have (i) a generative part, and (2) a part devoted 
 to an internal secretion. If you apply the X-rays 
 to the testes, then the generative part is destroyed, 
 but the internal secretion remains. The same 
 result can be obtained to a certain extent by 
 ligature of the vas deferens. I shall give you 
 an abstract of Tandler's lecture upon this subject 
 before the Royal Medical Society of Vienna. 
 
 Tandler, from an examination of the testes 
 in about 20 cases of cryptorchids, found in all 
 an absence of spermatogenesis, but regularly 
 normal developed Leydig cells. The bilateral 
 cryptorchid has the normal primary and second- 
 ary sexual characters, except he has azoospermia, 
 otherwise he is a normal individual. 
 
 Nielsen examined the testes in 20 cryptorchids 
 in the horse, and at no time saw spermatogenesis. 
 These facts show the worth of the interstitial 
 cells. 
 
 By these facts he has arrived at the conclusion 
 that the interstitial cells are the parts of the 
 testes concerned in the changes in the external 
 form of the body. The interstitial cells in the 
 ovary" are those in the stroma of this body. 
 The corpus luteum inhibits the internal 
 secretion of the ovary. In the castrated female 
 
 ' Wiener, Klinische Wochenschrift, 1910, p. 459. 
 
Ill 
 
 and in the pregnant one the hypophysis is 
 enlarged, hence there is a relation between the 
 ovary and the hypophysis. In the cow there 
 is not seldom a hypertrophy and persistence 
 of the corpus luteum reaching the size of a nut. 
 In this condition the state of "heat" does not 
 come on every 2 1 days. If, however, the corpus 
 luteum is extirpated, then typical heat comes 
 on in a few days. In woman, there is a per- 
 sistence of the corpus luteum of pregnancy. 
 At the same time, as a rule, ovulation is absent 
 in the cyclical activity of the ovary. The same 
 state of affairs persists after delivery, that is, 
 the corpus luteum may be the cause of delayed 
 menstruation during lactation. The interstitial 
 cells of the ovary are concerned with the internal 
 secretion of the ovary. The action of the inter- 
 stitial cells of these sexual glands upon the 
 form of the body starts in embryonic life. The 
 dimensions of the body and the changes in the 
 skeleton are conditioned upon the internal 
 secretion of the sexual glands. We know that 
 castration and hypoplasia of the sexual glands 
 leaves the epiphyses unjoined. During preg- 
 nancy the persistence of the corpus luteum is 
 inhibitory of an internal secretion of the ovary. 
 Loeb^ holds that at a certain period of "heat" 
 a few ovarian follicles rupture and become 
 transformed into corpora lutea. In the early 
 stages of their life the corpora lutea constitute 
 one of the factors, initiating growth processes in the 
 
 1 Journal Am. Med. Association, 1910, July 9, p. 166. 
 
112 
 
 uterine mucosa by means of an internal secretion. 
 If pregnancy takes place the ovum adds a me- 
 chanical stimulus to the sensitizing action of 
 the corpus luteum and a maternal placenta is 
 produced. A foreign body placed in the uterus 
 can do the same as the ovum. In this period 
 the corpus luteum exerts a new function, it 
 prevents the rupture of new follicles and 
 prolongs artificially the period of the sexual 
 cycle. Starling has shown that the dried embryo 
 contains a hormone which by the blood stimulates 
 the growth of the mammary gland. 
 
 The placenta according to Von Basch causes 
 the growth of the mammary gland even when 
 the nerves of the mamma are cut or even when 
 the gland is transplanted. The mammary gland 
 of the fetus often secretes milk, from the same 
 cause in the blood of the mother. 
 
 Rapid development of puberty goes with 
 early juncture of the epiphysis to the diaphysis 
 and necessarily short bones. 
 
 Hypoplasia of the sexual glands, or late puberty 
 of the individual, produces long bones. In 
 mankind the earlier puberty of the femal com- 
 pared with the male makes her bones shorter. 
 Hence, early puberty in hot climates produces 
 individuals short in stature, while late puberty 
 of cold climates produces tall individuals. 
 
 The influence of the sexual glands is seen in 
 the subcutaneous fat in castrates, at the meno- 
 pause and in old age. The hypophysis is a 
 regulator of the growth of the bones, especially 
 
113 
 
 in the promotion of their growth. The castrate 
 becomes tall from the greater action of the 
 anterior part of the hypophysis. 
 
 Nussbaum^ found in frogs castration caused the 
 secondary sexual characteristics to disappear 
 if the operation was done in their youth. The 
 pads on the thumbs disappear in the male. 
 If you inject testicular material from the same 
 species then they appear. Feeble nutrition 
 plays no part here. 
 
 Hypofunction of the ovary produces changes 
 in the hypophysis, which changes the growth 
 of the skeleton. 
 
 As to the growth of fat connected with the 
 sexual glands, we can speak of a hypophyseal fat. 
 
 As to the relation of the thyroid to the sexual 
 glands, we must remember the sterility of the 
 cretins, the genital disturbances in Basedow's 
 disease, and the changes in the thyroid at the 
 time of menstruation, during pregnancy and 
 at the menopause. 
 
 Walter Edmunds has found that lo grains 
 of thyroid extract administered three times 
 a day to rats will cause death in about twenty 
 days from congestion and hemorrhage into the 
 adrenals.^ 
 
 Thyroid and Growth of Bones. — H. Bircher^ 
 studied the effect of thyroid tablets upon the 
 growth of bones. He found the thyroid tablets 
 
 1 Pfluger's Archiv., 1909, Band 129. p. 110. 
 
 2 Personal communication. 
 
 3 Archiv. Klin. Ckir., Band 91. Heft 3, s. 554. 
 
114 
 
 lead to a more rapid calcification of the epiphyses 
 of the bone. They did not (as expected) lead 
 to an increase in the length of the bones. 
 
 Adrenals.— In the disease of the chromafhne 
 tissue of the adrenals, or Addison's disease, we 
 often have impotency and menstrual disturbances. 
 In a case of Addison's disease, post-mortem 
 sections of the testis by Kyrle showed especially 
 a want of spermatogenesis, and changes in the 
 interstitial cells. In a case of h3^poplasia of 
 the adrenals with an absence of the right adrenal 
 while the left adrenal was small and flat and the 
 cortex could hardly be seen, Schlangenhaufer 
 found similar but much more developed changes 
 in the testis. In the pseudo-hermaphrodites 
 there is enlargement of the adrenals. 
 
 Hypertrophy of adrenals is seen during men- 
 struation and pregnancy. Here the changes 
 in the adrenals are probably the primary cause 
 of changes in the ovary. 
 
 Hallion and Alquier have seen the prolonged 
 ingestion of adrenals cause histological changes 
 in the thyroid and adrenals. They found no 
 lesions in the kidney, testis, liver or hypophysis.^ 
 
 Ovaries and Adrenals. — F. Schenk- holds that 
 adrenals, ovaries and testicles have a definite 
 relation to each other. Castrated male or 
 female rabbits have a hypertrophy of the adrenals 
 and the hypertrophy is chiefly localized in their 
 cortex. 
 
 1 Compt. rend. Soc. de Biol., 1910, Tome 68, p. 966. 
 
 2 V. Brunnsche Beitrdge zur Klin. Chirurg. Bd., 67. 
 
115 
 
 Ovaries and Hypophysis. — E. Mayer^ concludes 
 that the hypophysis enlarges after castration 
 and after diseases in which there is a partial or 
 complete rest of the ovaries or testicles. 
 
 Alquier^ finds after ovariotomy less marked 
 histological changes in the hypophysis and thy- 
 roids than in animals which have been castrated. 
 The changes in the hypophysis and thyroid 
 are due to hyperf unction of these glands. As 
 to the effect of removal of ovaries upon the 
 adrenals the effects are yet doubtful. 
 
 Thymus. — The thymus and sexual glands are 
 complementary glands, thus the persistence of 
 the thymus in castrates and eunochoids. Persist- 
 ence of the thymus is a sign of general want 
 of maturity in the organism. In guinea pigs 
 and bulls, removal of thymus causes the testes to 
 greatly increase in size, hence it is probable 
 that the thymus has an internal secretion which 
 controls the growth of the testes. 
 
 Soli found in cocks that ablation of the thymus 
 retards the growth of the testicles. If the 
 cock lives until his period of copulation, then 
 the testis attains its normal development. He 
 holds that the thymus is in relation not only 
 with the development of the skeleton, but with 
 the regular and physiological development of 
 the testis.^ 
 
 Enlarged hypophysis inhibits the ovary and 
 
 1 Archiv. f. Gynekol., 1910, Band 90. 
 
 2 Gaz. d. hopiial, No. 59. 
 
 3 Journal de Physiologie et de Pathologie generate, 1910, p. 
 599. 
 
ii6 
 
 testis. Between the testis and ovary on one 
 side and the adrenal and thymus on the other 
 there is an atagonism. 
 
 Landau/ after removal of tht adrenals, found 
 no changes in the hypophysis, thyroid and 
 ovary. Feodossjeff^ after removal of the ovary 
 found a marked hyperplasia of the cell elements 
 of the adrenals. 
 
 Falta has made the most lucid explanation 
 of pluriglandular action. His theories rest 
 upon solid experimental work. 
 Th 
 
 C.S. 
 
 INHIBITION 
 
 Fig. 18. 
 
 Th = thyroid. P = pancreas. C. S. Chromaffine sub- 
 stance. Between Th and P, as well as between P and C. S., 
 there is a reciprocal inhibition; between Th and C. S., a 
 reciprocal promotion of each other's functions. The in- 
 hibition is stronger than the promotion (Falta). 
 
 1 Experimentelle Nebennieren Siudien, 1908. 
 - From Landau's work. 
 
117 
 
 The following is an abstract of Falta's paper.^ 
 As Falta has stated, the removal of a gland 
 with an internal secretion produces two results: 
 (i) the direct action of absence of the internal 
 secretion of the gland, and (2) an indirect action, 
 by the disturbance of the metabolism iii relation 
 to the other glands, as, for instance, between 
 the thyroid and pancreas there is inhibition 
 against each other, between the pancreas and 
 chromaffine tissue a reciprocal inhibition, while 
 between the thyroid and chromaffine tissue there 
 is a reciprocal promotion of activity. Thus, 
 extirpation of thyroid leads by removal of the 
 inhibition to hyper-function of the pancreas; 
 the extirpation of thyroid by the removal of 
 its power of promotion, to diminished adrenal 
 action. On the other hand, increased hyperthy- 
 roidism by increased inhibition leads to relative 
 insufficiency of the pancreas. Hyperthyroidism, 
 through increase of the promoting influences, 
 leads to increased adrenal action. Extirpation 
 of the pancreas by the retnoval of its internal 
 secretion directly prevents destruction of the 
 sugar, indirectly to absence of an intense inhibi- 
 tion of the thyroid, a hyperf unction of the 
 thyroid, which results in an increase of the 
 metabolism of the proteids, fats and inorganic 
 materials. If the pancreas's intense inhibition 
 upon the chromaffine tissue is removed, there 
 is a hyperfunction of the chromafhne tissue, with 
 
 1 Eppinger, Falta und Rudinger, Zeitschrift fiir Klinische 
 Medizin, 1908, pp. 1-52. 
 
ii8 
 
 consecutive, excessive, rapid mobilization of 
 the carbohydrates. The promotion of the ac- 
 tivity of the chromafiine tissues directly is by 
 the removal of the intense inhibition of the 
 pancreas on the chromafiine tissue, and indirectly 
 by the removal of the inhibition of the pancreas 
 on the thyroid, and thereby to increase of the 
 thyroid promoting action on the chromalKine 
 tissue, that is, the activity of the chromafhne 
 tissue is greatly increased. In this way the 
 well known intensity of pancreatic diabetes is 
 explained, and the two theories of diabetes, one 
 a disturbance in the destruction of sugar, the 
 other, a disturbance in formation of glycogen; 
 both may be right — due, according to the first 
 theory, to removal of pancreas; the second 
 theory, to a hyperf unction of the chromaffine 
 tissue. 
 
 Porges has shown in dogs that extirpation 
 of both adrenals causes a lowering of the amount 
 of sugar in the blood and only a small amount of 
 glycogen is to be found in the liver and muscle, 
 although they were tested a few hours after the 
 operation.^ 
 
 We can produce hyperaction of the adrenals 
 by injection of adrenalin. Then, as expected, 
 we directly have rapid, excessive mobilization 
 of the carbohydrates, and indirectly an inhibi- 
 tion of the pancreas function. By both ways 
 we have glycosuria. As a further indirect result 
 by the promotion of the thyroid, an increase 
 
 ^Berlin. Klin. Wochenschrift. No. 25, p. 1187. 
 
119 
 
 in the metabolism of the proteids and fats. 
 
 In extirpation of the thyroid we have as a 
 direct action the removal of the thyroid secretion, 
 and hence a depression of the metabolism of 
 the albumens, fats and inorganic salts, as an 
 indirect action by the removal of the promotion 
 of the thyroid on the chromaffine substance, 
 a slower mobilization of the carbohydrates, 
 and probably of the fats. Also by the want 
 of the thyroid we find an absence of the intense 
 inhibition of the thyroid on the pancreas; we 
 have hyperfunction of pancreas, which explains 
 why thyroidless dogs do not have glycosuria by 
 injections of adrenalin. 
 
 In depancreatized dogs, by adrenalin injection, 
 we have a secondary hyperfunction of the 
 chromaffine tissue, hence an increased destruction 
 of the proteids and fats, and the quotient of 
 dextrose to nitrogen is raised. Here we have 
 the mobilization of carbohydrates by adrenalin. 
 
 After removal of the thyroid and pancreas 
 we have complicated relations. 
 
 The removal of the inhibition of the pancreas 
 upon the chromaffine tissue is stronger than the 
 removal of the promotion of thyroid on the 
 chromaffine tissue, then hyperfunction of the 
 chromaffine tissue is not so completely intense 
 as after extirpation of the pancreas alone; hence, 
 there is a probable heightened mobiHzation of 
 fat. Hence, Falta gives the following explana- 
 tion: the mobilization of fat is increased, the 
 destruction of fat decreased, by the removal of 
 
I20 
 
 thyroid, and a very slow decrease of body weight 
 ensues, and in these circumstances we have sugar 
 from fats and a heightened quotient of dextrose 
 to nitrogen. 
 
 Relation of Internal Secretion to the Sym- 
 pathetic and Parasympathetic System. — Loewi 
 has shown by removal of the "pancreas in 
 dogs that dropping adrenalin into the eye causes 
 mydriasis. It would seem that adrenalin in 
 small doses does not act upon the normal eye, 
 for the pancreas has an inhibitory effect upon the 
 sympathetic nervous system. When the pan- 
 creas was removed the sympathetic became 
 more excitable and adrenalin now acts, when 
 normally it did not. In human diabetes the 
 adrenalin action on the pupil is inconstant. 
 
 In hyperthyroidism by continued use of thyroid 
 extract there seems to be an excitation of the 
 sympathetic, as exophthalmos, tachycardia, 
 tremor, sweat, and vaso-motor disturbances. 
 
 If a normal dog has thyroid extract fed to 
 him, then adrenalin acts upon the pupil. It 
 has been shown that in the normal thyroidless dogs 
 continued use of thyroid made them susceptible 
 to the action of adrenalin upon the pupil. Here 
 the thyroid increased the activity of the sym- 
 pathetic nervous system. 
 
 lodothyrin also heightens the excitability 
 of the sympathetic and adrenalin then acts 
 upon the normal pupil. In about 20 cases of 
 Basedow's disease the action of adrenalin only 
 dilated the pupil in 4 cases. 
 
121 
 
 Hyperthyroidism also acts upon the para- 
 sympathetic as an excitant, as is shown in the 
 well known antagonism between thyroid extract 
 and atropin. 
 
 Athyreoidism conduces to lessened excitability 
 of the sympathetic, for removal of the thyroid 
 prevents the pressor action of small doses of 
 adrenalin. 
 
 In thyroidless dogs Asber found that atropin 
 acted more intensely than in normal, the sphincter 
 is more easily paralyzed, since the excitation 
 state of the parasympathetic fibers of the oculo 
 motor is reduced. In thyroidless dogs pilocarpin 
 has a diminished activity. 
 
 In myxedema, or hypothyroidism, we have 
 a slow circulation, trophic disturbances and, 
 perhaps, the slowness of the intestinal move- 
 ments. 
 
 While adrenalin governs the sympathetic, 
 Falta thinks the pancreas secretion may govern 
 the vagus of the parasympathetic. 
 
 If the internal secretion of the pancreas 
 governs the vagus, then irritation of the vagus 
 must produce an increased production of the 
 internal secretion of the pancreas, a hyper- 
 function of the pancreas, while a paralysis of 
 the vagus is attended with a decrease of the 
 pancreatic secretion. Suitable doses of pilo- 
 carpin prevents adrenalin glycosuria. 
 
 In thyroidless dogs where we have a hyper- 
 function of the pancreas, atropin diminishes this, 
 and adrenalin again produces glycosuria. 
 
122 
 
 Action in Metabolism. — In these statements 
 I shall rely mainly upon Falta^ who has made 
 experiments upon this subject. In the state 
 of hunger, thyreoidin, adrenalin and infundib- 
 ulin increase proteid metabolism. Pancreas 
 and parathyroid inhibit proteid metabolism, as 
 their removal increases it. As to carbohydrates, 
 adrenalin and infundibulin increase their met- 
 abolism; pancreas and parathyroid inhibit it. 
 
 Thyreoidin accelerates fat metabolism ; pancreas 
 inhibits it. 
 
 Ingestion of thyroid tablets is followed by 
 increased excretion by the intestine of phos- 
 phates ; with the ingestion of . the hypophysis 
 a decrease of phosphates in urine and an increase 
 of them in the fecal matter ensues. 
 
 Thyreoidin and infundibulin increase the ex- 
 cretion of calcium by the intestine and of 
 magnesium by the urine. Osiris has shown 
 that the excretion of phosphorus by the kidneys 
 and intestines is exclusively dependent upon 
 the calcium metabolism, hence thyreoidin in- 
 creases the excretion of phosphorus. After 
 the use of adrenalin the quotient N : PvOg falls. 
 
 The parathyroids inhibit calcium excretion? 
 
 The chromaflfine system has an especial affinity 
 for metabolic changes in the tissues which are 
 rich in phosphorus and alkalies, while the pan- 
 creas protects them. 
 
 Feeding adrenalin to animals causes the ratio 
 of nitrogen to phosphorus pentoxid to decrease 
 
 1 Wiener Klinische Wochenschrift, 1909, pp. 1059-1062. 
 
123 
 
 while the calcium and sodium excreted is in- 
 creased. Removal of pancreas and parathyroids 
 markedly increases the excretion of chlorine 
 in the urine during the state of hunger. 
 
 Infundibulin increases the excretion of uric 
 acid. Here the increase of uric acid is due to 
 oxidation of allantoin. Adrenalin increases the 
 excretion of both uric acid and allantoin. 
 
 The continuous use of thyreoidin produces 
 no atheroma of the arterial walls, while adrenalin 
 and infundibulin cause it. In thyroidectomized 
 dogs, infundibulin has less action on proteid 
 metabolism. According to Diesing the pituitary 
 contains a peculiar organic combination of 
 phosphorus, the thyroid iodine, the spleen iron, 
 the thymus arsenic, and the adrenals sulphur. 
 These glands regulate the supply of these con- 
 stituents in the blood for the acts of metabolism. 
 
 Secretion and Excretion. — In conjunction with 
 Dr. Saml. B. Harris I have shown that adrenaUn 
 is excreted in small amounts by the kidney. 
 The urine of cats who had received adrenalin 
 a few hours previously was injected into jugular 
 and a rise of arterial tension ensued. Normally 
 the urine of the cat depresses the blood pressure. 
 Dale has shown that pituitary is also excreted 
 by the urine, as the urine of the cat after injection 
 of the pituitary had a pressor action when 
 tested on another cat. 
 
 Pemberton and Sweet have shown that the 
 adrenals and pituitary inhibit the activity of 
 the pancreatic secretion. This is not due to 
 
124 
 
 vaso-constriction in the gland vessels, as Ed- 
 munds held, but is independent of the systemic 
 blood pressure. This action persists when the 
 blood pressure is below normal. This inhibition 
 by the pituitar}^ and suprarenals ensues when the 
 pancreas is stimulated by the action of hydro- 
 chloric acid in the duodenum.^ 
 
 Parchtner, in a castrated male calf 1 1 months 
 old, found a diminution of oxygen taken into the 
 system from 12 to 15 per cent. He confirms 
 Loewy and Richter's results.^ 
 
 In castrated female dogs Loewy and Richter 
 found that ovarian feeding elevated the amount 
 of oxygen taken into the system by the lungs 
 even above normal. Even in male castrated 
 dogs oophorin increased the oxygen used up 
 above normal, while in the non-castrate oophorin 
 showed no increased using up of oxygen by the 
 animal. In young animals castration causes a 
 slow ossification and a slow calcification com- 
 pared with non-castrates. In two cases of 
 osteomalacia before castration there was a 
 deficiency of 0.39, comparing the CaO ingested 
 with the CaO excreted. After castration there 
 was an excess of calcium -t-5.78 retained, com- 
 paring the calcium ingested with the calcium 
 egested (Gold th wait. Painter, Osgood and Mac- 
 Crudden^). 
 
 In a fat person Steyrer has showTi in thyroid- 
 
 • Archives of Internal Med., Vol. 5, No. 5, p. 466. 
 - Oppenheim's Handbuch Biochemie, Band 4, 2 Halfte p. 
 201. 
 
 3 Ibid., p. 206. 
 
125 
 
 feeding that there was a fall of weight — the 
 nitrogenized substances were spared but the fats 
 were used up causing a minus balance of C, 
 compared with carbon ingested.^ 
 
 Secretory Nerves in the Thyroid. — Asher and 
 Flack^ have shown that on irritating the superior 
 laryngeal nerve which dilates the blood vessels 
 of the thyroid that there was an increased 
 secretion of some substance by the thyroid which 
 augments the excitability of the nervus depressor. 
 During the irritation of the laryngeal nerves 
 by electricity, the same dose of adrenalin elevates 
 the blood pressure more if the depressors have 
 been ligated previously. Von Cyon stated that 
 iodothyrin excited the nervus depressor. Falta, 
 by metabolism experiments, has shown that the 
 adrenals and thyroid assist each other by their 
 respective secretions. 
 
 I have indicated in the following table a 
 provisional relation of some of the glands with 
 an internal secretion upon each other. 
 
 Thymus 
 
 Thyroid 
 
 Pars anterior 
 
 Hypophysis 
 
 
 O 
 
 Hypophysis 
 
 O 
 
 HH 
 
 o > 
 
 
 
 o 
 
 3 
 
 5^ 
 
 
 k 
 
 > 
 
 >— 1 
 
 ^ 3 
 
 
 'S 
 
 5* 
 
 n 
 
 
 
 0'_ 
 
 
 n 
 
 ition 
 > 
 
 CO 
 
 o i 
 
 ' 
 
 > 
 
 bition 
 
 > 
 
 ■-1 
 
 
 ^ 
 
 
 ^ 
 
 Testis 
 
 Hypophysis 
 
 Testis Ovary 
 
 Parathyroid 
 
 Pig. 19. 
 
 1 Oppenheim's Handbuch Biochemie, Band 4, 2 Halfte, p. 234. 
 
 2 Zentralblait fiir Physiologie Band, XXIV, No. 6, p. 211. 
 
126 
 
 Pathology. 
 
 Deficiency of parathyroid secretion produces 
 tetany. 
 
 Excess of secretion by thyroid produces 
 Basedow's disease. 
 
 Deficiency of thyroid secretion produces in 
 child cretinism, in adult myxedema. 
 
 Parhon^ gives the following parallel of symp- 
 toms between Basedow's disease and mxye- 
 dema. 
 
 Basedow's disease. 
 
 Frequent hypertrophy of 
 thyroid gland. 
 
 Excess of sudorific secre- 
 tion, skin smooth and 
 moist. 
 
 Electric resistance dimin- 
 ished. 
 
 Sensation of heat, quite 
 painful. 
 
 Temperature of body fre- 
 quently above normal. 
 
 Diarrhea frequent. 
 
 Nutritive exchanges fre- 
 quently exaggerated. 
 
 Growth accelerated. 
 
 Enchondral ossification pre- 
 cocious. 
 
 Irritability increased, psy- 
 chic lability. 
 
 Emotional instability. 
 
 Myxedema. 
 
 Absence or frequent 
 atrophy of thyroid. 
 
 Deficiency of sudorific 
 secretion, skin dry, after- 
 wards wrinkled. 
 
 Electric resistance in- 
 creased. 
 
 Continual sensation of 
 cold. 
 
 Temperature of the body 
 below normal. 
 
 Constipation frequent. 
 
 Nutritive exchanges dimin- 
 ished. 
 
 Growth slow. 
 
 Enchondral ossification 
 
 retarded. 
 
 Psychic apathy. 
 
 Henry J. Berkeley^ has found that patients 
 
 1 Les Secretions Internes, 1909. 
 
 ^ Folia Neuro-hiologica, Nov., 1908, p. 157. 
 
127 
 
 with katatonia have their mental integrity- 
 restored by partial thyroidectomy. 
 
 In Basedow's disease, we have increased 
 destruction of proteid. This augmented met- 
 abolism of proteid can be reduced to normal 
 by large doses of carbohydrates and fats for 
 some time. Carbohydrates and fats in the nor- 
 mal man reduces the metabolism of proteid. 
 
 In Basedow's disease, by giving large doses 
 of sugar we can produce alimentary glycosuria. 
 Quite often we have Basedow's disease and 
 glycosuria combined. By the use of thyroid 
 tablets we have occasional diabetes, probably 
 due to a latent disposition to diabetes. 
 
 Diabetes can ensue from hyperfunction of 
 thyroid, or excessive action of adrenaUn. In 
 some severe cases of diabetes in the young the 
 thyroid could not be felt. Falta found in dogs 
 with the thyroid and pancreas removed a strong 
 diabetes. It is well known that disease of pan- 
 creas produces diabetes. 
 
 The diabetes which ensues during pregnancy 
 in nervous cases and ends after deUvery is very 
 probably due to hyperhypophysy. The pro- 
 motion of activity of the chromaffine tissue 
 by the thyroid also is contributory. 
 
 Tumors of adrenals have been observed by 
 Grawitz to produce diabetes, perhaps due to 
 hyperactivity of the adrenals. 
 
 Deficiency of adrenalin produces Addison's 
 disease. 
 
128 
 
 Hyperhypophysy produces in the child giant- 
 ism, in the adult acromegaly. 
 
 Hypohypophysy produces dwarfs and in- 
 fantilism. 
 
 Gross lesions of the pituitary have been found 
 in at least four cases of adiposis dolorosa. 
 
 If ovarian insufficiency or thyroid insufficiency 
 supervene before hyperhypophysy, then we have 
 Dercum's disease. 
 
 Delille^ makes the following symptoms for 
 diseases of the hypophysis: 
 
 Hypohypophysy. 
 Hypotension 
 Tachycardia 
 
 Painful sensations of heat 
 Diminished quantity of 
 
 urine 
 Anorexia 
 
 Asthenia 
 
 Nutrition changes, emacia- 
 tion, in certain cases 
 obesity 
 
 Trophic troubles 
 
 Psychic troubles 
 
 Insomnia 
 
 Mental and physical back- 
 wardness 
 
 Less resistance to infec- 
 tions 
 
 Signs of special intracranial 
 compression by a tumor 
 of pituitary 
 
 » L'Hjpophyse, 1909. 
 
 Hyperhypophysy. 
 Hypertension 
 Polyuria 
 Glycosuria 
 Emaciation 
 
 Obesity by an indirect 
 
 action 
 Red blood corpuscles, 
 
 normal or above normal 
 Acromegaly 
 
 Giantism 
 Psychic troubles 
 Sleepiness 
 
 Nearly always genital in- 
 sufficiency 
 Frequent hypothjToidism 
 
 Signs of special intra- 
 cranial compression by 
 a tumor of pituitary 
 
129 
 
 Striimpell thinks sclerodermia is due to hy- 
 pohypophysy. Lafond confirms it. Leman and 
 Van Wart suggest a hyperhy^ophysy and hy- 
 pohypophysy of the anterior and posterior 
 part of the pituitary, making thus four classi- 
 fications of disease in this part. 
 
 Therapeutics. 
 
 In deficiency or loss of an internal secretion 
 we substitute by giving the gland by the mouth. 
 In excessive internal secretion of a gland we 
 can overcome it by its antagonizing gland. 
 
 Bell and Schober have used the extract of 
 the mammary gland in uterine myoma and 
 obtained a diminution of the tumor and a cessa- 
 tion of the hemorrhages. 
 
 Mykertschianz^ found mammin (Poehl), an 
 extract of the mammary gland cause the 
 disappearance of uterine fibroma in 2 cases 
 a diminution of fibromas in 21 cases, and no 
 action in 3 cases. The hemorrhage and pain 
 were diminished. He also found mammin use- 
 ful in chronic metritis. 
 
 The thyroid has been used to restrain metror- 
 rhagia. It cures cretinism and myxedema. 
 It also relieves obesity of pale people but not 
 those with a high color. 
 
 Osteomalacia has been cured in many cases 
 by ovarian castration. 
 
 Adrenalin has been locally applied to stop 
 hemorrhages by its local vaso-constriction. It 
 
 ' Meunchener Med. Woch., Aug. 9, 1910, p. 1705. 
 
I30 
 
 has also been used in congestions of the con- 
 junctiva and of the nasal mucous membrane. 
 It has been used in asthmas of cardiac and 
 renal origin with good eflfect. Here the vaso- 
 dilation of the coronary arteries and its tonic 
 action on the cardiac muscle may come into play. 
 
 In bronchial asthma it has been applied locally 
 to the nasal mucous membrane, and given 
 internally. Internally it may act upon the 
 broncho-constrictor muscles of the bronchi as 
 an inhibitor, or as a stimulant upon the broncho- 
 dilators, or if there is congestion of the bronchial 
 mucous membrane in these cases it would reduce 
 the congestion. 
 
 It has been found after the removal of fluids 
 from the pleural or peritoneal cavities that 
 injection of adrenalin prevents its reaccumulation. 
 In pneumonia of adults and children it has been 
 used to prevent the debility of the muscular 
 structure of the heart. In these cases it raises 
 the peripheral resistance by the vaso-constric- 
 tion and makes the left ventricle produce more 
 work. Pulmonary edema in these states is 
 not produced by its use. 
 
 In Addison's disease it improves but does not 
 cure, as usually the lesions are of an incurable 
 nature, being either tubercular or malignant. 
 Used by the mouth in the lower animals in large 
 doses it causes no perceptible increase of. blood 
 pressure. The surest way to its activity is sub- 
 cutaneously, intramuscularly and intravenously. 
 Adrenalin in patients with arterio-sclerosis and 
 
131 
 
 high blood pressure must be used with great care. 
 Wiggers^ has studied the effect upon internal 
 hemorrhages, and has arrived at the conclusion 
 that adrenalin increases the quantity of blood 
 in the pulmonary veins as well as in the arteries, 
 and that its use in pulmonary hemorrhage 
 can not be looked upon as favorable. Small 
 doses of adrenalin, according to Wiggers, that 
 do not slow the heart generally cause no rise 
 of pulmonary venous and arterial pressure, 
 or only a feeble rise, even though the systemic 
 pressure rises appreciably. Pressure measure- 
 ments, however, give no accurate estimate 
 of the blood contents of these vessels, for out- 
 flow records show that this is decidedly increased 
 by adrenalin. This increase is not due, according 
 to Wiggers, to a "back effect" from the systemic 
 rise, for the pressure in the left auricle falls. 
 It is not due to constriction of the pulmonary 
 vessels, for the venous pressure should then 
 fall and not rise. It is probably due to the fact 
 that the total volume of blood thrown out by 
 the augmented contraction of the right ventricle 
 is not entirely forced ahead to be utilized in 
 the feeding of the left heart, but instead is stored 
 in the distensible pulmonary veins. Wiggers 
 advises in intestinal hemorrhages not large doses, 
 but small ones, 0.025 milligram, his so-called 
 "therapeutic doses," which produce a rise of 
 blood pressure and a diminished bleeding from 
 the intestinal vessels. In these cases a high 
 
 ' Archives of Internal Medicine, May, 1909. 
 
132 
 
 blood pressure should be avoided by a study 
 of the rise by the spygmomanometer during 
 the injections. In 1897, I showed that the 
 adrenalin relaxed the intestine, which conduces 
 to a checking of intestinal hemorrhage. 
 
 Heidenhain^ found, as others have, that adren- 
 alin in cases of collapse from weakness of the vaso- 
 motor center in pneumonia, diphtheria and 
 peritonitis gave good results. It must be 
 given subcutaneously or by the vein diluted 
 with salt solution. He also used it in an ap- 
 parently moribund case to tide him over an 
 operation for ileus. 
 
 Kownatzki cured a patient afflicted with 
 osteomalacia by adrenalin.^ 
 
 I have referred to W. N. Berkeley's treatment 
 of paralysis agitans by parathyroid extract. 
 
 Parhon and Urechia have tried the pituitary 
 gland in paralysis agitans and have seen certain 
 symptoms disappear, such as low arterial tension, 
 tachycardia, the sensation of heat, increased 
 perspiration, insomnia, and a diminution of 
 the trembling. However, the rigidity was not 
 modified. 
 
 Dr. A. F. Jaugeas has had good results from 
 the X-rays, in tumors of the hypophysis and 
 thinks they should be tried before any surgical 
 operation is attempted. 
 
 Corpus luteum. — Maits^ concludes from the 
 
 ^ Jourtial Am. Med. Association, p. 2100. 
 
 2 Berlin Klin. Wochenschrift, No. 31. p. 1469. 
 
 3 University of Penna. Medical Bulletin, Vol. XXIII, Nos. 
 5 and 6, p. 275. 
 
133 
 
 use of the extract of human corpus luteum that 
 it has a distinct therapeutic action in osteomalacia 
 in disturbances of the natural and artificial 
 menopause and in hypofunction, due to infantile 
 uterus. 
 
 Antidote. — Falta and IvCovic^ thought adren- 
 alin was an antidote to strychnia, but Hans 
 Januschke,^ in repeating the experiments of Falta 
 and Ivcovie, arrived at the following results: 
 
 (i) Adrenalin is not able to prevent the 
 poisonous action of strychnia on the nervous 
 system of the frog. 
 
 (2) Such adrenalin and strychnia mixtures 
 which remain non-toxic by subcutaneous use 
 in guinea pigs show typical strychnia poisoning 
 by the intravenous use. The view of A. Exner, 
 Meltzer and Auer, that there is a delay in the 
 absorption of the poison in the lymphatics, 
 receives support in his experiments. 
 
 (3) That the diastolic arrest of the frog's 
 heart by strychnia can be caused to beat by 
 adrenalin. This is not specific action but only 
 an irritant action. Similar results can be pro- 
 duced by camphor, barium, strophanthin and 
 atropin, also by mechanical* and electrical irrita- 
 tion. 
 
 Olds^ finds that thyroidectomized rats show 
 the same resistance to morphine-poisoning 
 as normal rats. He does not confirm Reid 
 Hunt's results. 
 
 1 Berlin Klin. Wockenschrifi, 1909, p. 1929. 
 
 2 Wiener Klinische Wochenschrift, 1910. p. 284. 
 
 3 Am. Journal of Physiology, Vol. XXVI. p. 360. . 
 

 O.^