DUPLICATE HX00017868 1 Columbia ZKnibersfitp CoOese of mv^^tim^ anb ^urgeonis iaef erente Hibrarp Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/acromegalyessaytOOhins ACROMEGALY AN ESSAY TO WHICH WAS AWARDED THE BOYLSTON PRIZE OF HARVARD UNIVERSITY FOR THE YEAR 1898 BY GUY HINSDALE, A.M., M.D., Fellow of the College of Physicians of Philadelphia and of the American Academy of Medicine; Member of the American Neurological Association and Amer- ican Climatological Association; Assistant Physician to the Ortho- pedic Hospital and Infirmary for Nervous Diseases, and to the Presbyterian Hospital in Philadelphia, etc. REPRINTED FROM MEDICINE, 1898 WII,I,IAM M. WARREN, Publisher Detroit \N/. V .—V Nulla autem est alia pro certo noscendi via, nisi quamplurimas et morborum et dissectionum historias, turn aliorum turn proprias collectas habere, et inter se com- parare. MoRGAGNi, Dc Sed. et Cans. Morb. DR. WHARTON SINKLER, WITH THE author's high REGARD FOR HIS CONTRIBUTIONS TO MEDICAL I.ITERATURE AND FOR HIS QUALITIES AS A COLLEAGUE AND CONSULTANT. BOYLSTON MEDICAL PRIZES. These prizes, which are open to public competition, are offered annually for the best dissertations on questions in medical science proposed by the Boylston Medical Committee. At the annual meeting in Boston in 1898, a prize was awarded to Guy Hinsdale, M.D., of Philadelphia, Penn., for an essay on Acromegaly. For 1899 two prizes are offered : — 1. A prize of one hundred and fifty dollars for the best dissertation on The results of Original Work in Anatomy, Physiology, or Pathology. The subject to be chosen by the writer. 2. A prize of one hundred and fifty dollars for the best dissertation on The Results of Original Investigations in the Psychology of 3Iental Disease. Dissertations on these subjects must be sent post-paid to W. F. Whitney, M.D., Harvard Medical School, Boston, Mass., on or before January 1, 1899. For 1900 two prizes are offered : — 1. A prize of one hundred and fifty dollars for the best dissertation on The results of Original Work in Anatomy, Physiology or Pathology. The subject to be chosen by the writer. 2. A prize of one hundred and fifty dollars for the best dissertation on The method of Origin of Serpentine Arteries and the Structural Changes to he found in them. Their Relation to Arterio-ca'pillary Fibrosis, Obliterating Endarteritis and to Endarteritis Deformans. Dissertations on these subjects must be sent to the same address as above on or before January 1, 1900. In awarding these prizes preference will be given to dissertations which exhibit original work, but if no dissertation is considered worthy of a prize, the award may be withheld. Each dissertation must bear in place of its author's name some sentence or device, and must be accompanied by a sealed packet bearing the same sentence or device, and containing within the author's name and residence. Any clew by which the authorship of a dissertation is made known to the committee will debar such dissertation from competition. Dissertations must be written in a distinct and plain hand, and their pages must be bound in book form. All unsuccessful dissertations are deposited with the Secretary, from whom they may be obtained, with the sealed packet unopened, if called for within one year after they have been received. By an order adopted in 1826, the Secretary was directed to publish annually the following votes : — 1. That the Board do not consider themselves as approving the doc- trines contained in any of the dissertations to wliich premiums may be adjudged. 2. That in case of publication of a successful dissertation, the author be considered as bound to print the above vote in connection therewith. The Boylston Medical Committee is appointed by the President and Fellows, and consists of the following physicians : Robert T. Edes, M.D., President ; William F. Whitney, M.D., Secretary ; H. P. Bovr- DiTCH, M.D., Frank W. Draper, M.D., J. Collins Warren, M.D., Samuel G. Webber, M.D., F. H. Williams, M.D., Edward S. Wood, M.D. The address of the Secretary of the Boylston Medical Committee is William F. Whitney, M.D., Harvard Medical School, Boston, Mass. TABLE OF CONTENTS Page History and Definition i SymptomaToi^/._ Patients sometimes have an inordinate thirst, a demand for fluid out of all proportion to even the extraordinary size of some of the subjects. Remington's patient could drink a gallon of beer at once; but he was a large man, six feet two inches in height, and weighed 268 pounds. One of the cases which we record could drink three or four quarts of milk at once. We find a memorandum of 17 patients among 130 in whom polydipsia was a symptom. Increased thirst is doubtless connected with the glycosuria present in many of these cases. Appetite.— 't\i\s is increased more frequently than thirst and is recorded in twenty - five cases. This symptom may exist without increased thirst, and vice versa. In one case it was noted that eating gave great relief to the general discomfort of the patient. Bulimia is thus one of the characteristic signs of acromegaly. SUBJECTIVE SYMPTOMS (ACCESSORY). Hearing, Smell, and Taste.— "Th^ special senses are not generally disturbed, but in exceptional cases affections of smell and hearing are noted. Hearing may be disturbed by bone growth and tinnitus aurium may be a very troublesome symptom. (Cases of Osborne, Barclay-Symmes, and Holsti.) Cardiac Palpitation.— Th:\s has been referred to under the head- ing of the organs of circulation. It is present occasionally, especially in cases where enlargement of the thyroid or thymus is found, or where the great increase of bodily weight, in conjunction with muscular fatigue, overtaxes the heart. GENERAIv PSYCHIC SYMPTOMS. Depression.— A.S mentioned at the beginning, the extraordinary changes that occur in the physiognomy and in the hands and feet are a source of great mortification and mental distress to the unfor- tunate subjects. The mind is naturally affected, and depression of the spirits is the natural outcome of the progress of this grotesque 28 ACROMEGALY disease. The temper may be irritable, and impulses of a suicidal or homicidal nature are recorded (Osborne, Pick, Haskovec). The memory is, as a rule, unaffected. In cases in which the headaches are violent and of long duration, and in which muscular feebleness, lassitude and inability to pursue the usual avocations mark the advance of the disease, it is but natural that profound mental depression should ensue. In the latest stage coma ushers in the fatal termination. The Nervous System. — In a few cases we have organic changes which may be more or less connected with the disturbances of the pituitary gland. Epilepsy is one of these and has been observed by Marinesco. Drs. Raymond and Souques have reported a case of acromegaly of many years' standing in a man aged 54, who in the last three years had developed Jacksonian epilepsy lim- ited to the right upper extremity and right side of the face. They stated that the pituitary gland, in their opinion, constituted a cere- bral tumor capable of exciting from a distance the cortical psycho- motor centers. Marinesco's case was that of a woman aged 32, who had had epilepsy at 22, the attacks occurring three or four times a week. At the age of 25 she had an attack of giddiness, in which she fell from a second floor. Six months later she noticed that her feet were enlarged, and later her hands, face, and abdomen. The menses ceased. Strabismus, polyuria and weakness supervened. Sensibility was preserved in all forms except vision. Examination revealed bitemporal hemianopsia. The urine contained forty-eight grammes of sugar per liter. Paraplegia has been observed in acromegaly and was due to pressue of the tumor on both motor tracts in the crura cerebri. In Pershing's case there was also a loss of bladder and rectal control. Syringomyelia has been found coincident with acromegaly by Holschewnikoff, Frederick Peterson, and Bassi. In the first case, however, it should be noted that there was no affection of the thy- roid and thymus or of the pituitary bodj^; although, on the other hand, the hands were large and hypertrophied and the skin covering them was thickened in the superficial and deeper layers, and the bones of the hands showed small exostoses. The second case has not yet come to autopsy. Bassi 's was a remarkable case, in which syringomyelia and solitary tubercle in the cerebellum were associated with cephalic acromegaly. It is greatly to M. Bassi' s credit that he was able to diasrnosticate all three of these affections intra vitam, and he was ACROMEGALY 29 fully corroborated at the autopsy. It would appear that the syr- ingomyelia antedated the acromegaly and cerebellar tubercle. Glioma of the brain and apoplexy were noted by Pel in a case of acromegaly. Tinnitus may be caused by the pressure of the growth upon the carotid arteries. Paresthesias and pains in the extremities, according to Maxi- milian Sternberg, are frequent in acromegaly. On this account many cases have been treated and considered as cases of rheuma- tism. Pressure on the brachial plexus and the trigeminus due to bone changes has been noted (Ascher). Great sensitiveness to cold is recorded in several cases, and, on the other hand, one case, that of Rolleston, had a subjective sense of heat even in the coldest weather and felt obliged to wear thin clothing. The pains are consequent on the extraordinary tissue changes and are sometimes described as giving the sensation of the bones being torn apart. The symptom-complex which we designate as acromegaly may be tabulated in the following manner, as M. Sternberg has done, or in the synoptical chart which has been used in our analysis of the cases comprised in the appendix (not included in the present pub- lication) : 1. Objective symptoms: {a) Constant. — Enlarged hands and feet; lengthening of face; enlarged eyelids; excessive enlargement of nose; prominence of cheek bones; enlarged lips; enlarged chin; prominent jaw; kyphosis; thickening of bones of thorax; abdominal respiration. ((^) Inconstant. — Prominence of supraorbital arch; exophthalmus; optic nerve atrophy; hemianopsia; impaired hearing; anosmia; dis- ordered taste; enlarged larynx; depth and roughness of voice; Erb's dulness; atrophy of testicles; enlargement of penis; enlargement of abdomen; atrophy of muscles; reflexes; enlargement of heart; increased rate of pulse; varicose veins; enlarged lymphatic glands; impotence; sweats; polyuria; glycosuria; disordered sensibility; pig- mentation; warts and moles. 2. Subjective signs: (a) Constant. — Eoss of sexual instinct; polyphagia; polydipsia. ((^) Inconstant. — Headaches; palpitation; dyspnea; paresthesia; vasomotor neuroses. 3. General and psychic symptoms: General weakness and ennui; melancholia. Varieties of Acromegaly. — Three distinct varieties or forms of acromegaly have been differentiated by M. Sternberg. They are as follows: 30 ACROMEGALY 1. A benign form. Duration, about fifty years; changes, slight. 2. The usual chronic form. Duration, eight to thirty years. 3. An acute malignant form. Duration, three to four years. In this form the pituitary is sarcomatous. COURSE — DURATION. The course of acromegaly is essentially slow. In its onset it is insidious, and for that reason it is always difficult or impossible to fix the exact date of its inception. In the case of women we may be guided somewhat by the time at which menstruation ceased, and in this sex any change that may occur in the size of the hands and feet will be more readily noted and remembered. There is diffi- culty, also, in making any positive statements as to the arrest of the disease, should this occur. It is found that five or ten years or €ven longer may elapse before menstruation is disturbed. There is some variation as to the member which is first affected. Although the hands are probably the first to be affected, in one case (Kanthack's) the starting-point was the left foot, and the second toe grew to an enormous size. In Tamburini's case the disease started in the feet, involving next the head and then the upper -extremities. The occurrence of prognathism, while common in acromegaly, is not always noticed by the patients. Figs. 18 and 19 show the general progress of the disease. The £rst photograph was taken eight years before the disease first appeared; the second was taken about fifteen years after its origin, but, as we have intimated, its onset was so gradual and insidious that neither she nor her relatives can state accurately just when the trouble began. Although the progressive nature of the disease must be recog- nized, it is quite likely that arrest will be more frequently recorded as its nature and treatment are better understood. The case of Costanzo and a recently published case by Vinke are probably as encouraging as any that have been presented. The latter patient was treated with thyroid and pituitary extracts, alone and combined -with each other, and remained under treatment for five months. The results in both instances are recorded in the chapter on Treatment. It would thus appear that appropriate treatment may be followed "by an actual diminution in the size of the hypertrophied limbs. Two stages in the course of acromegaly have been differentiated, -viz., the erethic stage and the cachectic stage (Gauthier). ACROMEGALY 31 The phenomena of erethism which characterizes the first stage embraces, first, a painful hyperesthesia which manifests itself in headaches and rheumatic pains; second, a hypertrophy of the mus- cular fibers which may give to patients a muscular power greater than usual; third, palpitation of the heart accompanying the hyper- trophy of that organ; and finally the polyphagia and polyuria which may be considered to be connected with an crethic state of the respective organs. The second stage is characterized by a cachexia or a period of decadence. The stage of increase has abated and the phenomena of erethism have disappeared. Muscular atrophy and cardiac dilata- tion and a consequent enfeeblement of the circulation render the patient quite helpless. It is in this stage that bleeding from the nose may ensue, and progressive debility marks the period of decline, which ends in syncope. Epistaxis may also occur early. Tamburini has designated the stage in which the visual functions are interfered with and in which headaches develop as " /« phase hypophysaire. ' ' The duration of acromegaly may cover as much as ten, twenty or thirty years. When death occurs it is usually by syncope ter- minating a progressive cachexia. Death has occurred, however, during an epileptic convulsion. ANATOMY. The discovery of acromegaly has awakened great interest in the anatomy and physiology of the pituitary body. Indeed, it was not until 1890 that the announcement was made that the pituitary body is the seat of such marked alteration as to suggest that it is the/ons et origo mali. To Souza-L^eite belongs the credit of this observation. Up to that point, the pituitary body, or hypophysis cerebri, as it is termed, was regarded with indifference. Descartes had made its neighbor, the pineal gland, world-famous, as the supposed anatom- ical seat of the soul; but the pituitary body, as that name implies, was relegated, in the minds of anatomists, to the humble duty of secreting the nasal mucus. It remained contented with this igno- minious office until its emancipation in the early part of the present decade, and during these latter years it has attracted universal attention and assumed gigantic functions. The pituitary body, hypophysis cerebri (German, Hirnanhang), is a reddish - gray, extremely vascular mass, situated in the sella turcica. It is oval in shape and weighs from five to ten grains. 32 ACROMEGALY Boyce has made a careful study of the gland, based on an examination of one hundred brains of insane subjects, dying of intercurrent affections. The weight averages .5 gramme, ranging usually from .3 to .6 gramme, the size, apparently, bearing no relation to age, and more particularly to sex or general nutrition, or to the size of the brain. The hypophysis is held in place by a process of the dura derived from the inner wall of the cavernous sinus. There is a small hole in the center for the passage of the infundibulum. ^ The two lobes are separated from each other by a fibrous lamina. The anterior is somewhat the larger, oblong, with a concavity behind, in which the round posterior lobe is received. The anterior lobe, of a dark yellowish-gray color, is developed from the ectoderm of the buccal, or primary oral, cavity, and resem- bles somewhat, in microscopic structure, the thyroid body. It con- sists of isolated vesicles and slightly convoluted tubular alveoli lined by columnar or ciliated epithelium and united by loose vascular connective tissue. A majority of the acini are solid; they occasionally contain a colloid material, similar to that found in the tubules of the thyroid body. Their walls are surrounded by a close network of lymphatics and capillary blood-vessels. Only a few of the acini at the edge of the smaller lobe are hollow. This portion of the gland is related to the alimentary tract, and it is the part that is especially liable to disease. The posterior and smaller lobe is developed by an outgrowth from the embryonic brain and during fetal life contains a cavity which communicates, through the infundibulum, with the cavity of the third ventricle. In the adult it becomes firmer and more solid, and consists of sponge-like connective tissue arranged in the form of reticulating bundles between which are branched cells, closely resembling bipolar or multipolar ganglion cells. This portion is evidently vestigial or rudimentary in man. In the lower animals the two lobes are quite distinct, and it is only in the mammalia that they become connected. The hypophysis thus assumes a much more prominent feature in the brains of the lower animals than in the case of man. It is not strictly a ductless gland, but its secretion is poured through an imperfect system of ducts opening between the dura and pia mater. The accompanying illustrations show the position and compara- tive size of the embryonic hypophysis in the sheep and the chicken. 1 For the anatomical description, see Gray's Anatomy and a description by Philip Stohr. ACROMEGALY 33 e;mbryoi.ogy. The pituitary and thyroid bodies start as pouches from the wall of the oral cavity — but growing dorsad, the hypophysis is embraced between the ossifying centers at the base of the skull and is thus included within the cranial cavity. Andriezen states that it originally "poured its secretion into the current of a water- vascular system which, beginning at the mouth, irrigated the cerebral ven- tricles and central spinal canal of the earliest vertebrates. The main function of this system must have been respiratory, but the pituitary gland probably furnished some substance necessary for the proper nutrition of the nerve tissue, which it now nourishes less directly through the blood and lymph" (Pershing). Andriezen, after tracing the development of the pituitary body in the lower vertebrates through the amphibia to mammals and man, shows that its related size does not keep pace with the increased growth of the nervous system, an indication probably that having attained the acme of its activity in lower vertebrates, it is, in higher forms, already beginning to show signs of diminishing activity, though, of course, still functionally active even in man.^ There is, as Andriezen states, an obvious parallelism between the thyroid and the pituitary, not only in their early evolution in vertebrate animals, but also a physiological relationship. Thus we can explain the enlargement of the pituitary which has been observed by Stieda, Rogowitsch, Hofmeister, and Gley, after thy- roidectomy. But Andriezen notes that it must be remembered, however, that ' ' the pituitary belongs both anatomically and physio- logically to the central nervous system, while the thyroid belongs to the respiratory function of the blood-vascular system and thereby to the tissues generally." All of these investigations point to the important trophic influ- ence of the pituitar}^ gland on the central nervous system. Just how this operates, we are as yet unable to state; even the observa- tions on the experimental destruction of the pituitary by Horsley in 1886, and by Gley, Marinesco and others in 1892-93, appear nega- tive; but such experiments are liable to defects which do not permit too positive conclusions. Granted that Andriezen is correct in his own conclusions that the pituitary gland exercises a trophic action 1 Rogowitsch has found that after thyroidectomy in dogs, the pituitarj' gland becomes swollen, the cells vacuolated and ultimately disintegrated. Bourneville and Brecon state that in sporadic cretinism, where the thyroid gland is lost, the pituitary body has been found to be enlarged. Boyce and Beadles found, in a case of myxedema, that the acini and extra-acinar tissues were filled with colloid-like material cells and that the cells were increased in size. Abram found changes in the pituitary in a case of carcinoma of the thyroid. 34 ACROMEGALY Sheep StriaiujTi thse. Sup. rrjxx Inf-, cochltcu Sheep Fig. 20.— (After Dr. Alec Fraser, qcLTiqliXt> ACROMEGALY 35 on the nerve tissues, enabling them to take up and assimilate oxygen from the blood -stream and to destroy and render innocuous the waste products of the metabolism, and these two functions are intimately related — in fact, really one process — so that an adequate assimilation of oxygen by the nerve tissues secures an adequate destruction (by oxidation) of the waste products. Thus we ma}^ expect, a priori, that the results which would follow removal or destruction of the pituitary body would be those due first to a malassimilation of oxygen by the nerve tissues, and simultaneously, in the second place, to an insufficient destruction and consequent accumulation of waste products. In this way there ensues a rapid nutritional failure and death of the central nervous system. The results would, therefore, be: 1. Depression and apathy (the commencing failure of activity in the nerve centers). 2. Muscular weakness, the first peripheral effect. 3. lyoss of fine coordination and equilibrium. 4. The development of twitchings and irregular contractions or spasms of the muscles. 5. Deficient heat production and subnormal temperature. 6. A wasting of the body tissues, in relation to the more rapid failure of the central nervous system. 7. A probable compensatory polypnea or dyspnea, the peripheral indication of the failure of the nerve centers to assimilate oxygen. 8. A rapid progress toward death. ^ PATHOLOGY. Although, as we have noted, the hypophysis has been observed slightly enlarged in myxedema and cretinism, it remains true that in acromegaly we have the only disease in which the pituitary attains any considerable size. Gauthier remarks that the hyp- ophysis is a veritable anpov and, consequently, especiallj' liable to hypertrophy, just as in the case of other terminal points in the economy. I, however, do not lay much stress upon such a con- struction of the anatomy of the hypoph3'sis, as I believe whatever pathological changes it undergoes are entirely referable to cellular and developmental characteristics and have no relation to gross physical form. We have to deal with the remarkable fact in acromegaly that the pituitary body has a tendency to increase pari passu with the 1 For a fuller account of the histology of the pituitarj- body, reference is made to the works of Luschka, Langen, Flesch, Dostoiewsky, r,othringer, Rogowitsch, Andriezen (1894), Berkley (1894), Schouemann, Slieda, W. Krause (1876), W. Muller (1S71), and Haller (1S96). 36 ACROMEGALY Fig. 21. -Base of the skull of the American giant, showing enlarged pituitary fossa, com- pared with normal skull from the collection of Dr. George McClellan. development of the affection. The expansile power, coincident with hypertrophy, is able to deform and hollow out the bone by reason of its great vascularity and proliferative power. The sella turcica is dilated into a cavity of corresponding size. In an extreme case the growth presses on the optic commissure, the cavernous sinus, and on the carotid artery; on the third and fourth nerves; slightly on the ophthalmic division of the fifth nerve; on the uncinate convolu- tion of the temporo-sphenoidal lobe; in some cases, on the olfactory tract; on the posterior surface of the orbital convolutions; on the under surface of the crura; on a part of the internal capsule and thalamus, and even on the anterior surface of the pons. In Roxburgh's and Collis' case the enlarged pituitary had so pressed upon both optic tracts and the chiasm as to cause a total disappearance of the left tract and partial destruction of the right. The dura of the sella turcica presented an irregularly eroded and vascular appearance, and the irregularities were filled with an. extension of the pituitary growth. ACROMEGALY 37 Enlargement of the pituitary fossa is, in general, a fair means of determining the size of the pituitary body. In my case (the giant) the extreme antero-posterior diameter is 2.7 centimeters as against .8 to 1.2 centimeters in the normal skull. This is 4.5 millimeters larger than Thomson's and Broca's cases, and the lateral diameter is 42 millimeters as against 28 millimeters in the normal. In Rothmell's case the pituitary body was enlarged to the size of a hen's egg and weighed 476 grains (32 grammes). We cannot overlook the fact, however, that dilatation of the pituitary fossa by itself is not a certain proof of acromegaly. There is, in the Musee Dupuytren, a skull in which this fossa measures eighteen millimeters in antero-posterior diameter in which there was evidently no acromegaly, as the face is normal and there is no hypertrophy of the bones of the skull. The specimen originally showed a tumor lying between the brain and the skull. Sarcoma and Other Ttcmors of the Pituitary Gland. — In one of Mosse's cases the hypophysis was found to be replaced by a " fascic- ulated sarcoma" weighing 36 grammes (540 grains). The thyroid gland had undergone cystic degeneration; the thymus, however, had hypertrophied and assumed a pyramidal form. In Striimpell's case, reported in June, 1894, and which had been studied for a long time in the clinic at Erlangen, a tumor of the hypophysis was found having the character of a malignant sarcoma. In Caton's case there was a tumor the size of a Tangierine orange, occupying a much dilated sella turcica and, apparently, sarcomatous. Adenoma of the hypophysis was found in the cases of Pearce Bailey, Boltz, Stroebe, and Tamburini. Boyce and Beadles, Dallemagne, Gauthier, Marino, and Osborne found cystic degeneration. In the description of Roxburgh's and CoUis' case it is stated that, while most of the tumor of the hyp- ophysis had the appearance of a simple hypertrophy, the peripheral and especially the basal portions presented characters midway be- tween those of a glioma and a round -cell sarcoma. In autopsies in acromegaly the hypophysis has always been found to be enlarged or diseased. This position has been challenged on insufficient ground, but is now coming to be accepted as correct. ^ My own independent study and conclusion in this respect is emphatically corroborated by Maximilian Sternberg, who has recently made the unqualified statement: "Die hypophysis . . . ist bei Akromegalie stets erkrankt." He cities forty-seven autop- lAverage weight of hypophysis of man .5 to .6 gramme. 38 ACROMEGALY sies in proof. The list which we present numbers fifty - seven autopsies, the largest number hitherto placed on record. ^ They are as follows: Bailey, 2.2 x 1.6. Henrot, 3x42 cm. De Berg. Holsti, 2.5 x 3 cm. Boltz (i). Lancereaux. (2). Langer-Sternberg. Bonardi. Linsmayer. Bourneville and Regnault (Case I). Marie and Marinesco. Boyce and Beadles. Mosse and Daunic, weight 3.6. Brigidi, 2.8 X 3.8 cm. Osborne. Broca. Packard, 2.5 x 3 cm. Brooks' and Baruch's, 1.5 x 7 cm. Pechadre and I,athuraz. Bury. Pineles. Caton and Paul, size of Tangierine orange. Rolleston, size of walnut. Cepeda. Rothmell, weight 32, size hen's egg. Claus. Roxburgh and CoUis, size of walnut. Comini. Schultze, 4x2 cm. Dallemagne (i), size of pigeon's &%%. Sigurini and Caporiacco, 11x7x6. (2). Smyth, E. J., 5 X 7-5. (3), size of nut. Squance. Dalton. Stroebe, 2.5 x , size of nut. Dana, 3x3 cm., weight 2. Striimpell, 2 x 2.5 cm. Duchesneau. Tamburini, 5.3 x 3.9, weight 2. Fraentzel. Tikhomiroff. Fratnich, 5 x . Thomson, size of walnut. Fritsche and Klebs. UhthoflF. Furnivall. Verga. Gauthier. Wolf, K. (i). Godlee, size of cherry. (2). Griffith. Worcester, weight 58, length 4.6 cm. Hanseman. DIMENSION'S OF PITUITARY FOSSA IN SKELETONS. Regnault 3-i ^ 3.6 .... American Giant (Author's case) 2.7 x 4.2 x 1.2 Irish Giant 3-8 x x 2.8 Byrne, R. C. S. E 2.2 Hutchinson, W 3-i ^ 3-8 .... In Duchesneau' s case the hypophysis contained a wine-colored fluid, which was attributed in part to the fact that thirty- six hours had elapsed at the time of the autopsy. Claus shows that in his case the autopsy was performed betw^een two and three hours after death, and the fluid found could not be accounted for by cadaveric liquefaction, but must have been due to a process of degeneration of the affected gland. In about 12 per cent, of specimens of hypophysis in acromegaly the disease is a true sarcoma. Tumors of the Hypophysis Without Acromegaly. — Drs. J. M. 1 We intentionally omit the cases of the Hagner brothers and that described by Sarbo; also the case of Somers. In the latter case no examination was made of the brain, and therefore it is not properly included in lists of autopsies in acromegaly. ACROMEGALY 39 Fig. 22. — Sarcoma of pituitary in a case of acromegaly (Striimpell). Anders and Henry W. Cattell, in 1891, reported to the Philadelphia Neurological Society a hemorrhagic tumor of the pituitary body and infundibulum, unattended with any signs of acromegaly. The symptoms in life had been anemia, dizziness, facial neuralgia, inter- nal strabismus, and general weakness and nephritis. Death followed convulsions. In a case which occurred in the practise of Weir Mitchell a large aneurism of an anomalous artery crossing the sella turcica entirely obliterated the hypophysis, but no symptoms of acromegaly ensued. It might be urged, however, that in cases of this class a deficiency of the pituitary for a longer period of time might be followed by symptoms which, it is well known, require considerable periods for their development. Reports by Weir Mitchell and other observers bear out the statement that we may have tumors of the hypophysis without signs of acromegaly. Pearce Bailey has recently reported a case of parenchymatous hypertrophy of the pituitary with death due to hemorrhage into the gland structure. There had been headache, dimness of vision, blindness, and paralysis, but not acromegaly. I have recently observed a fatal case of pleuro - pneumonia in which the autopsy revealed a large tumor of the hypophysis, appar- ently sarcomatous; the case presented no symptom whatever of acromegaly, either clinically or pathologically. It occurred in a 40 ACROMEGALY colored man, a native of North Carolina, 38 years of age. After a short illness he died of double pleural effusion, hypostatic pneu- monia, and pulmonary edema. The heart was hypertrophied; there was pericardial effusion, together with interstitial nephritis, arterio- sclerosis, and fatty infiltration of the liver. The pia mater showed no lesions; dura and calvarium normal. There was no lesion of the convexity of the brain. Occupying the position of the pituitary body was a tumor measuring 3.5 centimeters laterally and three centimeters antero-posteriorly. It had the firmness of brain tissue and fitted the enlarged sella turcica. The walls of the sella were not eroded, excepting as regards the anterior clinoid process on the left side. Microscopic section showed the growth to be a round-cell sarcoma. In the experiments which have been undertaken to see whether acromegaly will follow the destruction of the pituitary body, it is obvious that laboratory experiments of this nature, performed on such small animals as puppies and kittens, for example, are beset with great difficulties in execution; and it would be natural to sup- pose, as Pershing has remarked, that just as a minute remnant of the thyroid left in an operation will prevent the development of myxedema, so a proportionate amount of the pituitary might escape detection and, remaining, defeat the purpose of the experiment. Normal Pituitary in Alleged Acromegaly. — An analysis of the cases in which it has been averred that autopsies do not always reveal changes in the hypophysis tends rather to the casting of doubt on the diagnosis of acromegaly in such instances. Such cases must be very few. In Sarbo's case the patient was both tuberculous and syphilitic, and the jaw, nose and lips do not appear to have been enlarged. The skull was that of a case of true osteitis. The cases of the Hagner brothers, described by Friedreich and Arnold, are doubtful cases also. The jaw, nose, lips and tongue were not enlarged. The}^ had extensive and general enlargement of every bone in the body, due to osteitis. Marie regarded them as cases of hypertrophic pulmonary osteo-arthropathy. In Bonardi's case the pituitary is reported normal. Absence of the Pituitary Gland. — Boyce, in an autopsy on a case of phthisis, discovered that the pituitary gland was absent. Thyroid Gland. — This has been considered previously (see page 13). Thymus Glajid. — This has also been considered previously (see page 15). ACROMEGALY 41 Fig. 23. — Normal and acromegalic skeletons (Osborne). 42 ACROMEGALY Changes in the Spinal Cord and Brain. — Arnold found the periph- eral nerves and the lower part of the cord thickened, with increase of the interstitial connective tissue, with hyaline degeneration of the nervous elements. There was degeneration of the pyramidal tracts, and areas of cerebral softening. Waldo has reported a case where an oval cavity, one centimeter in diameter, was found at the posterior extremity of the right hemisphere, and a second smaller cavity at the posterior part of the second temporo-sphenoidal convolution; also two others at the ante- rior portions of each of the lobes of the cerebellum. They were probably recent and due to emboli. I have already referred to the coexistence of acromegaly and syringomyelia (see page 28). Bone Struchire. — The bone shows an undeniable dilatation of the vascular orifices and an enlargement of the grooves for the course of vessels along the bones (Marie, Broca). Klebs has noticed, in many portions of the affected extremities, the larger size of the arteries and capillaries of the skin, gaping, on section, and infiltrated and surrounded with young neoplastic tissue. This leaves conspicuous vascular canals and osteophytic growths in many of the skeletons, so that, judging from these preparations in muse- ums, we notice strong resemblances to the changes in osteo-arthritis and, in a lesser degree, the appearances in osteitis deformans. We are in need of a good account of the minute bone changes in acromegaly. Other Z"mz^^ minims. 6.30 P.M. Five ounces urine obtained by catheter. 8 P.M. Is in stuporous condition, completely unconscious, pulse very feeble. Given strychnine sulphate ^ grain hypodermically. Temperature 103.8°, pulse 128, respiration 38. 8.15 P.M. Died (December 2, 1896). Circumference of head at level of eyebrows 23^4 inches Circumference of head at subniento-bregmatic 27 inches- >mental 28^ inches. Breadth of base of nose. Breadth across alae. Circumference of occipito-: 154 inches. 2 inches. "'■ '. r ,, 17 inches. Circumference 01 neck ' Circumference of right elbow ^^ inches. Right. Left. Circumference of wrist 75< inches. 7 inches. Circumference of hand at knuckles 10^ inches. io'4 inches. Circumference of base of thumb 3^ inches. s'/s inches. Circumference of last phalanx of thumb yA inches. 3K inches Length of middle finger from articulation of metacarpus AV2 inches. 4-7s Circumference of middle finger SJ^i inches. s/s Length of forefinger 4 inches. 4'^ Circumference of forefinger zA inches. 3H Length of ring finger 4K inches. 4/2 inches, inches, inches, inches, inches. 68 ACROMEGALY Right. I.eft. Circumference of ring finger 3 inches. 3 inches. Length of little finger 3^ inches. 33^ inches. Circumference of little finger 2^ inches. 2^ inches. Circumference of groin 20^ inches. 2oJ^ inches. Circumference of knee 15J4 inches. 16 inches. Circumference of calf 14 inches. 14^ inches. Circumference of ankle loj^ inches. 10% inches. Circumference across foot 10^ inches. 10 inches. Breadth across foot 4% inches. 45^ inches. Length of great toe 2j^ inches. 2% inches. Circumference of great toe 4^ inches. 4^ inches. General Description. — Head large, lips thick; eyebrows promi- nent and one hanging; eyelids thick and heavy; cheek bones prominent; space between the eye and malar bone one plane; nose short, thick, and fiat, point of nose blunt and almost globular; tongue broad and thick; teeth good; ears large and prominent; neck short; shoulders broad and square; arm and forearm normal in appearance to wrist; bones at wrist -joint enlarged; hand short, broad, and thick; ends of fingers squared; nails broad, square, flat, and curved at ends, but not thickened; base of digits broad and flat; thighs and pelvis well formed; knee-joints prominent; lower epi- physis of tibia and fibula enlarged and prominent; foot drawn inward and upward, broad and flat; toes short, terminal phalanges broad and square, nails flat and not thickened. General Musculature: Muscles large and soft, small amount of adipose tissue. Face had a peculiar edematous appearance. Chest well formed, abdomen distended and tympanitic. Left pleural cavity contained a few old adhesions; pericardium negative. Heart: small amount of ante-mortem clot in right ventricle; small amount of sur- rounding fat; muscle solid and firm, of a good color; normal; weight 15 ounces. lyungs slightly congested; bronchi congested; bronchial glands slightly enlarged, otherwise negative. Much gaseous disten- tion of intestines. Acute peritonitis, slight degree, most marked about celiac axis, extending over toward left side. In the region slightly above sigmoid flexure was found an area of encysted exu- date, not purulent. Spleen was adherent to cardiac end of stomach and elongated to a length of 6}^ inches; weight 13 ounces. Cap- sule rough, covered by small fibrous masses, granular to the touch, light in color, flabby in consistency, not congested. Pancreas large, tissue very light in color. Stomach distended; large amount of acid-smelling, dark, undigested food; some large masses of cab- bage (?). Stomach wall very normal in appearance, but dilated. Caput coli very much dilated with fecal matter; appendix long, adherent to posterior surface of caecum; no intestinal lesions. Bladder normal in appearance, contained small amount of urine. ACROMEGALY 69 lyiver large and light in color; arteries not thickened; substance friable and not granular; weight 8 pounds i ounce. Gall-bladder distended, duct patulous. Adrenals normal in appearance; right kidney fatty and granular; pelvis of left kidney dilated and dis- tended with urine; pyramids of both kidneys con jested, markings distinct; capsules slightly adherent; vessel walls normal; pelvis dilated; cortex thin; united weight, i>^ pounds. Head: scar the size of a silver half dollar, one and one-half inches to the right of the median line, on a line extending from mastoid process to mas- toid process; skull-cap greatly thickened, cancellous tissue small in amount; acute meningitis with effusion, most extensive over ante- rior lobes. Pituitary Body: Rising from the pituitary fossa and inclining toward the left was found an ovoid red mass, measuring 1.5 centi- meters antero - posteriorly and .7 centimeter vertically. It was attached below, apparently, to the pituitary body. It was of a soft and jelly-like consistence and quite vascular. It pressed directly on the left optic tract, just posterior to the chiasm. The tumor was attached to the hypophysis, which was enlarged to about five times its usual volume. The pituitary fossa was greatly enlarged and the bones comprising its wall were abnormally thin. No adhesions existed between the pituitary body or tumor. SKKLKTON OF A GIANT. Of the person whose skeleton I propose to describe, nothing is known, with the exception of one fact — that he was a native of Kentucky, U. S. A. In the year 1877, Prof. Joseph I^eidy was informed by Prof. A. B. Foote that a body of a giant was offered for sale, provided no questions were asked which might lead to its identification. Arrangements were soon made by Dr. William Hunt through the gentlemen mentioned above, and the body was trans- ferred to Philadelphia, where the skeleton was prepared and mounted by Mr. R. H. Nash. All the persons mentioned are now dead. They were never able to ascertain, or, at least, thought it prudent not to make inquiry as to the antecedents of this giant, whose skeleton, the largest and most interesting in America, now adorns the Miitter Museum of the College of Physicians of Philadelphia. It will be interesting to make a comparison of this skeleton, as a whole, and the individual bones composing it, with some of the famous giants of which we have records, and particularly with skeletons of giants in lyondon and Dublin, and with the acro- megalic skeleton in Edinburgh, which has attracted world-wide 70 ACROMEGALY Fig. 28.— Normal skeleton. Height, 6 feet i inch. (From the private collection of Dr. George McClellan.) Fig. 29.— The American giant. 6 inches. Height, 7 feet ACROMEGALY 71 attention. The author is indebted to Professor Cunningham for measurements of these last named skeletons, and he has endeav- ored so to arrange his description as to conform to the model which Professor Cunningham has given. Not having been furnished with any name for the person whose skeleton I describe, I shall refer to him as the American Giant. Height. — It is probable that the American Giant had attained the age of 22 or 24 at the time of his death. The bones seem to have attained their full development, although the epiphyseal junc- tions are plainly visible in all the long bones. The spine has undergone a kyphoskoliosis which detracts consid- erably from the height which would otherwise exist. Taking the skeletion as we find it, the height is seven feet six inches. This measurement includes suitable artificial intervertebral disks, which were supplied in its preparation. There is a rule formulated by the late Prof. Sir George Humphrey^ by which we may consider the height of any individual, under normal circumstances, to stand in proportion to the length of the femur as 1000 to 275. But in our case, as in other abnormal skeletons, this rule may lead us astray; whatever the error may be in short skeletons or those of moderate height, in the case of giants the disproportionate length of the long bones, particularly those of the lower extremity, used as a basis of calculation, will lead us to a slightly exaggerated estimate of the total height. Applying this rule, however, to the American Giant, we have R. 275:1000: •.6^0:236^ — L. 275:1000: •.666:2421, which equals seven feet eight and three-quarter inches in case we estimate by the right femur, and seven feet and eleven inches in using the left femur. The measurements, therefore, as given in the following table taken from the skeleton itself, doubtless underestimate the size of the giant in life, before kyphosis became extreme. Mm. Ft. In. T. An Austrian, de TExpos. Sc. Anth. de Paris 2550 8 i^% R. Marianne Wehde 2550 8 45^ T. A Kalmuck, Orfila Museum 2530 8 35^ T. A Swedish guard of Frederick II 2520 8 3H R. Chang 2360 7 8K C. Byrne, R.C.S.E 2310 7 7 R. Drasal (Olmutz) 2300 7 6% A. The American Giant 2295 7 6 V. Winkelmeier, born in Upper Austria 2278 7 5f^ R. Thos. Hasler, Bavaria (acromegalic?) 2270 7 s% A. Henry Alexander Cooper (Yorkshire Giant) 7 5 I,. Innsbruck Giant 2226 7 zVs V. Murphy (Irish), Marseilles Museum 2220 7 3% I,. Berlin (Cat. No. 3040), one of the famous guards of Frederick II 2220 7 2% L. Ivolly, Pomeranian, St. Petersburg 2195 7 2% C. Magrath (Irish Giant), Dublin 2177 7 2"% T., Topinard; C, Cunningham; I,., Langer; R., Ranke; V., Virchow; A., Author. 1 Human Skeleton, 1858, Table IV, page 108. 72 ACROMEGALY Fig. 30.— Americafl giant; posterior aspect. Fig. 31. — American giant; side view. ACROMEGALY 73 Bones. — The Skull: The skull of the American Giant bears a fair proportion to the great size of the skeleton. There has been some discussion among craniologists as to the usual ratio of the size of the skull to that of the skeleton in the case of giants. Virchow maintains that the horizontal circumference and the various diam- eters of the cranium exceed the average. He states, however, that the basis cranii is relatively short. I^anger holds that the head in giants is, as a rule, relatively small. Skull measurement. Cubic capacity, Cc Length, glabella-occipital internal Height, basi-bregmatic binaural over bregma Vertical index Breadth, maximum minimum frontal Cephalic index Horizontal circumference Length of foramen magnum.... Breadth of foramen magnum .. Interzygomatic breadth Intermalar breadth Facial index Orbital width Orbital height Orbital index Palato-maxillary length Palato-maxillary breadth Palato-maxillary index American Irish Byrne, Giant. Giant. R. C. S. E. 2320 1600 1520 234 198 215 195 139 148 78.3 70.2 "68 8 145 155 151 640 78.3 568 70.2 593 51 40 43 39 147 ■156 148 133 ■■'61.5 55.4 52 44 42 42 80 43 97-7 34 81 50 65 61 62 130 101.6 Edinburgh acro- megalic sk. 1580 200 142 71 74 561 33 150 126 54 45 36 67 70 104.4 The measurements, therefore, show that we have to do with a truly gigantic skull, its internal capacity being nearly one -half again as large as in the case of the skeletons in London, Dublin, and Edinburgh. The increased capacity is chiefly due to increased length, by reason of which the skull is classed as dolicho-cephalic. The interzygomatic diameter is slightly under that of the three skulls with which we have compared it. The intermalar breadth, on the other hand, is in excess, due largely to the great develop- ment of the antrum. The frontal sinuses have the following diam- eters: Transverse, 7.5; vertical, 7; antero-posterior, supra-orbital, 2.4. Pituitary fossa. American Giant. Magrath. Edinburgh skeleton. Length. Depth.. Breadth 22.5 28 Face. — The face is large, even in proportion to the large cranium. The air sinu.ses are large and give the great intermalar measure- ment, and the inferior maxilla, slightly prognathous, is massive. 74 ACROMEGALY VERTICAL DEPTH OF FACE (NASION TO CHIN). I,ength of face. Stature. Face-stature index. American Giant Irish Giant Winkelmeier Edinburgh acromegalic Murphy Byrne, R. C. S. E Normal 148 156 149 148 143 137 120 2285 2177 2278 1830 2220 2287 Naso-alveolar length. Naso-alveolar stature index. American Giant 90 96 82 81 73 3-93 4.40 358 4.42 4.26 Irish Giant Byrne, R. C. S. E The mandible is a large bone, as will be seen from the follow- ing measurements: Intercondyloid, 141; intergonial, 113; mento- alveolar, 40; width at angle, 33; width of ramus, 40; angle of ramus, 140°. Fig. 32 — Skull of the American Giant compared with a normal skull. ACROMEGALY 75 Fig. 33. — Skull of the Aniericau Giant compared with normal skull; side view. The coronoid process rises higher than the condyloid process. The lower jaw is prognathous, so that the four incisor teeth project slightly in advance of the corresponding teeth above. All the teeth in both jaws are in place and nearly all are incrusted with tartar. American Giant . Irish Giant Edinburgh skull. Byrne, R. C. S. % Average I^ength of the face from nasion to chin Naso-alveolar length compared with the compared with size size of the cranium. of the cranium. Circumference, 100. circumference, 100. 30 23.1 14.0 27.4 16.8 26.3 14.4 23-1 13-8 22.8 13-8 These indices show that there is a slight excess in both the max- illary and mandibular portions of the face. The alveolar portions of the jaw are perfect, having- undergone no absorption. Relation of maxillary to mandibular portions of the face; sym- physeal height, loo: American Giant, 44; Irish Giant, 47.9; Byrne, R. S. C. K., 50; Edinburgh skull, 56.4. The orbits are extremely capacious. Vertebral Column. — The vertebrae are subject to conspicuous alteration, but they have been so mounted as to give a correct representation of the curves which existed in life. As usual in acromegaly, we find a kyphoskoliosis, in which, however, the cer- vical vertebrae do not partake. Viewed antero- posteriorly, we find a sharp curve in the dorsal 76 ACROMEGALY ^ and lumbar region, with the convexity to the right. The kyphosis reaches its maximum at the ninth thoracic vertebra, resulting in a compression and absorption of the body of that vertebra. The following are the measurements of the anterior surface of the vertebral bodies: Second thoracic, 30 millimeters; third thoracic, 28 millimeters; seventh thoracic, 25 millimeters; ninth thoracic, 10 millimeters; eleventh thoracic, 31 millimeters; first lumbar, 36 mil- limeters; second lumbar, 43 millimeters; third lumbar, 45 millime- ters; fourth lumbar, 47 millimeters; fifth lumbar, 50 millimeters. Greatest width of the first thoracic vertebra, 97 millimeters (3.75 inches). From the atlas to the promontory of the sacrum, 820 millimeters; from the same points in a direct line, 750 millimeters; from the atlas to the tip of the cocc5^x, along the anterior borders of the vertebrae, 1030 millimeters. Viewed laterally, we find the first four thoracic vertebral spines prominent in the convexity; next, the right transverse processes of the sixth, seventh, eighth, ninth, tenth and eleventh vertebrae; then the spinous processes of the twelfth thoracic and the lumbar vertebrae. The great lateral displacement of the vertebrae brings the posterior margin of the right scapula seven centimeters behind the corresponding margin of the left, and in line with the right transverse process of the seventh thoracic vertebra. The lumbar vertebrae are massive. The sacrum is composed of four vertebrae, instead of the usual number, five. Its width is 16 centimeters; length, 13.2. The coccyx consists of three vertebrae, instead of the usual number, four. The ribs are long and narrow, and relatively straight. The seventh and eighth right ribs, measured along the under border, are 45 centimeters and 43.5 centimeters in length; the sixth rib on the left side on the outer side is 43.5 centimeters long; the seventh, measured along the under side, is 43.8 centimeters in length. The sternum has a total length of 23.5 centimeters. It is a large, well-proportioned bone. Manubrium Gladiolus, ist segment. remainder.... Ensiform cartilage Ivcngth. 6.7 cm. 4 8.9 Width. 8.4 4 5-S The thorax is large, but narrow in proportion to its depth. Girth, 109.7 centimeters (43^ inches); antero-posterior diameter, 43 centimeters; lateral diameter, 28 centimeters. ACROMEGALY 77 This corresponds with Langer's observation that in individuals of great stature the thorax is relatively narrow. In this respect the American Giant differs from the Irish Giant, Magrath, whose broad chest and boldly curved ribs give a girth of 132 centimeters (52^ inches). Pelvis. — The pelvis is large and proportionate to the size of the skeleton. The bones are thickened at their borders and bear the marks of periosteal inflammation. Especially is this noticeable in the iliac crests and above the acetabula, which are evidently arthritic. The conformation is of the rachitic type, judging from the increase of the measurement between the anterior superior spines and the crests. Centimeters. Between the anterior superior spines 35.5 Between the crests 33,5 Between the middle points of the ischii 15.5 Antero-posterior diameter of the pelvic inlet 14. Right anterior oblique diameter of the pelvic inlet 17.5 I^eft anterior oblique diameter of the pelvic inlet 17.7 Depth of pelvic cavity Height of pelvis This pelvis is thus somewhat smaller than that of Magrath (Dublin) and of Byrne (R.C.S.E.). The latter have a breadth of 38.6 and 38 centimeters respectively. The cavity of the pelvis is considerably encroached upon by the convexities which mark the position of the acetabula, particularly that of the left side. The acetabula are very deep and separated by thin bone from the pelvic cavity. The bodies of the iliac bones are exceedingly thin. Upper Extremity. — The clavicles: Length, 212 millimeters. The scapulae: Length, acromion to angle, R. 268, L- 268 millimeters; breadth, R. 144, L. 150. The Humeri. — The right humerus is 47.5 centimeters long and has a circular perforation in the olecranon fossa 16 millimeters in diameter. Iiburgh Medical Journal, March, 1898. Ben.son, A.: Dublin Journal of Medical Science, 1895, c, 394-400; British Medical Journal, 1895, P- 949- Berkley, H. J:: Case in a negro, Johns Hopkins Hospital Bulletin, September, 1891. Bertrand, L. E.: Pevue de Med., Paris, 1895, xv, 118. Bettencourt, K.:Jour. de Sc. Med. de Lisbon, 1890, liv, 366. Bier, A.: Mittheil a d. Chir. 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A.: Case showing acromegaly and hypertrophic pulmonary arthropathy, British Medical Journal, July i, 1893, p. 14. Finlayson, James: International Clinics, October, 1896. Flemming, Percy: Trans. Clinical Soc. of I,ondon, 1890. Fournier, J. B. C: "Acrotnegalie et troubles cardio-vasculaires," T/i^se de Paris, 1S96. Foy, G.: " Cheiromegaly," Medical Press and Circular, 1891, lii, 491. Fraenkel, A.: Munchener Med. IVoch., 1897, P- 40i. Fraentzel, O.: Deutsche Med. Woch., 1888, xiv, 651. Franke: Case with temporal hemianopsia, Klin. Monatsbl.f. Augenh., 1896, p. 259. Fratnich, E.: Allgemeine Wiener- Med. Zeitung, 1893, No. 40, and 1892, No. 37; Riv. Veneta di Sc. Med., Venezia, 1892, xvii, 238. Freund, W. A.: Sa7n7nl. Klin. Vort., 1889, Nos. 329 and 330; Rev. de Sciences Medicates, xxxiv, p. 569. Friedreich: Virchow^s Archiv, Bd. xlvii, i858, 83. Hyperostosis, etc. 82 ACROMEGALY ^ Kritsche und Klebs: Ein Beitrag zur Pathologic des Riesenwuchses, Leipzig, 1884. 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Hutchinson, J.: Three cases, Archives of Surgery, London, April, 1891, and 1889-90, i, pp. 141-148. ACROMEGALY 83 Jores: (Bonn.) Jorge, R.: Arch, de psichiat., Turin, 1894, xx, 412. Kalindero: La Roumanie MMicale, 1894, p. 65. Kanthack: British Medical Journal, July 25, 1891. Karg: Archivf. Klin. Chirurg., Bd. xli, p. loi. Keen, W. W. : "Kxcision of Nerves in Acromegaly," International Clinics, Philadelphia, 1893. 3 S., ii, 191. Kerr: Lancet, 1893, ii, 1256. Koscheeff, J.: Protok. Zasaid. Obsh. Vrach. Viatke, 1892, 13-16. Kerner: Vereinsblatt der Pfalzischen Aerzte, Frankenthal, August, 1890. Kinnicutt, F. P.: "Therapeutics of the Internal Secretions," A tnerican Journal of the Medical Sciences, July, 1897. Klebs: Allgem. Path., 1889, ii. Klebs und Fritsche: (Gigantism), Ein Beitrag ztir Pathologie des Rieseiiwuchses, Leipzig, Vogel, 1884. Kojevnikoff, A. G.: Med. Obozr. 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Wadsworth: Boston Medical and Surgical Journal, Jan. i, 1885. Waldo, H.: British Medical Jouriial, 1890, i, 662. Wells, H. Gideon: "The Thyroid Gland and its Congeners," /owrwa/ of the American Medical Associatio7i, 1897, p. 1009. Whyte, J. M.: Lancet, 1893, i, 642. Wilks: Clin. Soc. London, April 13, 1888. Wolf, Kurt: Beitrdge zur Path. Anat., u. s. w., Zeigler, xiii, p. 629. Worcester, W. L.: "Case of Acromegaly with Autopsy," Boston Medical and Surgical Joiirnal, April 23, 1896. Yamasaki, J.: Kyoto Igakkwai Zashi, 1893, No. 72. Zeigler, Ernst; Lehrbuch der Allgemeine Pathologie, u. s. w., Band i. NDEX Abdomen Acromegaly 55, Age Albuminuria 20, Amenorrhea Anatomy Andriezen Animal extracts Apoplexj' Appetite increased Arnold 40, Arteries Arthritis Blood Bones 11, Boyce Brown-Sequard Cardiac palpitation Cerebellum Chin Circulatory organs Costanzo Course and duration Cunningham Dallemagne Dana, C. I, Depression Development, premature Diabetes 20, Diagnosis Electrical reactions Elephantiasis Embryology Epistaxis Erb's sign (thymus) Etiology Exophthalmic goitre 15, Exophthalmus Family form Feet Fingers Foamier Freund Genital organs Giant skeleton Gigantism Glioma Graves' disease Hair Hagner Brothers 40, Hands Headache 5, Hearing Hemianopsia Heredity Hutchinson, Jonathan Hutchinson, Woods 14 Hypophysis 32 66 Hypophysis in myxedema 15 44 Irish Giant 50 67 Joints 18 22 Keen 22 31 Knee-jerk 18 33 Kyphosis 11 59 I^arynx 15 29 lyips 8 27 Macrosomia i 43 Mammse 16 16 Marinesco 28, 61, 63 45 Massalongo 47 21 Megalacria i 42 Mitchell, S. W. (case of aneurism) 39 32 Muscles 18 59 Myxedema 15, 55 27 Myxedema, diagnosis 15 28 Nails 5, 20 II Neck 12 16 Nervous system 28 60 Neurosis, trophic 46 30 Nose 8 50 Ocular symptoms 22 47 Operative treatment 65 13 Optic atrophy 26 27 Osteitis deformans 56 53 Ott's experiments 63 67 Pachyacria i 54 Pain 29 18 Paraplegia 28 56 Pathology 35 33 Paresthesia 29 31 Pituitary body 31 15 Pituitary' extract 61 43 Pituitary fossa 50 50 Prognathism 10 23 Psychic symptoms 27 43 Pulmonary hypertrophic osteo- arthro- 10 pathy 55 5 Pupils 23 16 Race 44 48 Rauzier 55 16 Reflexes 18 69 Respiratory organs 16 50 Rheumatism 56 29 Rogowitsch 33 15 Rolleston 49 20 Roentgen photography 7, 57 43 Sarbo's case 40 5 Sarcoma of hypophysis 37 21 Sensation 21 27 Sex 44 24 Sexual desire 22 43 Skiagraphy 7, 57 53 Skin 20 52 Special senses 27 87 INDEX Spinal cord and brain 42 Spine II Sternberg's table of sj'inptoms 29 Strabismus 23 Symptomatology 3 Syringomyelia 28 Tachj'cardia 16 Tamburini 47 Teeth 8 Temperature 21 Tetranopsia 24 Theories 45 Thirst 27 Thymus 15, 40 Thyroid 13, 40 Thyroid extract 59 Tinnitus aurium 27, 29 Tongue 8 Trauma 44 Treatment 57 Tremor 18 Tumors of the h3^pophysis 38 Urine 20 Varicose veins 16 Vision 23 W