Part 31

TABLE 15 _Showing Weights of Animals, of Their Thyroid Bodies and the Relation of These Weights Per Kilogram._ ═════════════════════════════╤═════════════╤═════════════╤═════════════ │Grams of Body│ Grams of │ Grams of │ │ Thyroid │ Thyroid per │ │ │Kilo of Body ─────────────────────────────┼─────────────┼─────────────┼───────────── Primates: │ │ │ Woolly Monkey │ 2,370│ 2.│ .84 Lagothrix lagotricha │ │ │ Carnivora: │ │ │ Wild Cat │ 8,180│ 2.│ .24 Felis ruffus │ │ │ Silver Fox │ 3,325│ 4.│ 1.2 Canis chama │ │ │ Kamchatkan Bear │ 31,800│ 22.│ .63 Ursus beringiana │ │ │ Lynx │ 9,500│ 1.│ .1 Felis canadensis │ │ │ Jaguar │ 29,500│ 16.│ .54 Felis onca │ │ │ Rodentia: │ │ │ Ground Squirrel │ 550│ 2.│ 3.6 Xerus capensis │ │ │ Ungulata: │ │ │ Zebra │ 340,000│ 64.│ .19 Equus burchelli │ │ │ Giraffe │ 384,000│ 45.│ .12 Giraffa camelopardalis │ │ │ Barasingha Deer │ 56,800│ 8.│ .14 Cervus duvanceli │ │ │ Kashmir Deer │ 56,800│ 20.│ .35 Cervus cashmirianus │ │ │ Urial │ 22,700│ 2.5│ .11 Ovis vignei │ │ │ Marsupialia: │ │ │ Kangaroo │ 18,000│ 10.│ .55 Macropus robustus (?) │ │ │ Tasmanian Devil │ 3,120│ 4.│ .13 Sarcophilus ursinus │ │ │ Wombat │ 26,000│ 7.│ .27 Phascolomys mitchelli │ │ │ Wallaby │ 3,360│ 3.│ .9 Genus and species (?) │ │ │ Edentata: │ │ │ Anteater │ 3,300│ 2.│ .6 Myrmecophaga tetradactyla│ │ │ Accipitres: │ │ │ Wedgetailed Eagle │ 2,300│ 1.│ .43 Aquila audax │ │ │ Struthiones: │ │ │ Rhea │ 18,000│ 5.│ .27 Rhea americana │ │ │ Emu │ 36,300│ 23.│ .63 Dromæus novæ-hollandiæ │ │ │ ─────────────────────────────┴─────────────┴─────────────┴─────────────

ANATOMY.

The minute anatomy of the normal thyroid is fully given in text-books, and is doubtless pictured in the minds of all but students of the subject as a fixed and definite affair. Such is not the case. There is certainly a variation in gross size under conditions of seasonal and sexual activity, and it would seem acceptably demonstrated that changes in diet, especially where meat is concerned, are associated with swellings or shrinkage of the glands. These gross changes must be due to alterations in histology. In youth also the bulk is larger, a condition due to cellular activity, while as middle age advances the thyroid becomes smaller and more balanced in its colloid and cellular proportions. I need not detail the ultimate constituents of the gland, but it is well to emphasize a few points which must be taken into consideration in microscopical diagnosis. In the first place, the lobules or acini are not all of the same size in normal organs. This is especially true in the normal adult gland but may be so in youth. The cells which form the inner lining of the acinus are low cuboidal in shape but the elements which lie under them are oval and do not change with hyperplasia of the former. The colloid which fills the glandular spaces is very susceptible to mechanical and chemical agencies. In material preserved in alcohol it may be shrunken away from the cells or heavily vacuolated, while in tissue preserved a long while in any liquid it may be found contracted or broken. Large vacuolated or vesicular cells are characteristic of the human parathyroid; this type is by no means so prominent in the lower animals, and in the few examples studied closely the arrangement is less definitely glandular than in man.

The avian thyroid is distinct from the mammalian in the delicacy of its fibrous framework and the flatter character of its epithelia. Acini are usually of more uniform size. Capsular vessels are prominent but internal vascularity is less in birds than in mammals and their goitres are not solid.

PHYSIOLOGY.

The physiological value of the thyroid-parathyroid complex has been the subject of extensive study and voluminous literature without exhaustion of the possibilities, but with the result that we are possessed of knowledge explaining certain phases of abnormality, even if the normal functions be not unexceptionally demonstrated. The accepted alterations of functions are hypothyroidism—inadequate physiology, and hyperthyroidism—excessive activity. Absence or atrophy of the thyroid bodies is usual in hypothyroidism, while enlargements, collectively called goitre, commonly accompany excessive function. Exemplifying the former, cretinism is the result of failure of normal function and development during fetal life while myxedema is the expression of the disappearance of thyroid secretion after it has once been operative; the latter may occur in infancy after nursing has ceased, or at any time that the thyroid may atrophy, during some of the forms of goitre for example. Hyperthyroidism may express itself, with or without visible enlargement of the thyroid body, in nervousness, gastrointestinal disturbances, tachycardia, loss of weight and exophthalmos. The first group, which might be called athyroidism, is often associated with alterations in the bony skeleton in the form of chondrodystrophy or of rickets, while some degree of osseous change is observed with myxedema. Goitre, be it simple or exophthalmic, may be followed by cardiac enlargement or by myocarditis.

The character of the thyroid secretion is not known except that it is influenced by the availability of iodine in the diet, but there are some other as yet unexplained features. The normal thyroid fed to cretins or persons suffering with myxedema, has the power to improve the condition apparently by supplying iodine and the other essential elements. Iodine is an important constituent of the gland, being present in combination with protein. Its quality varies indirectly with the amount of colloid and of hyperplasia (Marine). The administration of this element is beneficial in colloid goitre but is harmful in the toxic variety. Even though the administration of thyroid extract may relieve athyroidism, this procedure in normal animals fails to produce typical pictures of hyperthyroidism. Carnivora fed thyroid gland do not show toxic symptoms until excessive amounts are given, whereas herbivorous varieties are much more sensitive to this feeding.[44] Tachycardia, nervousness and exophthalmos are not produced by these experiments, an interesting observation since these signs are not recorded in wild animals, and only vaguely reported by veterinarians. Man is apparently very sensitive to thyroid dysfunction.

On the other hand, meat-eating animals are more sensitive to excision of the thyroid body than are grain eaters.[45] Chemical studies have shown that the thyroid is concerned in basal metabolism since this is increased in hyperthyroidism and decreased in myxedema; nitrogen output is much elevated.

Thyroid physiology stands probably in some relation to the cardiac mechanism since in simple colloid or simple hyperplastic goitre if of long duration, cardiac enlargement and disease may be greater than the excess work occasioned by the mere physical bulk of the enlarged gland in the neck would seem to warrant. A detoxicating function has been ascribed to the gland, but Murray discredits this on the ground that congestion occurs in infectious disease of warm blooded animals but not in snakes. He thinks the gland more likely stands in some connection with the thermoregulatory mechanism.

It is evident from the foregoing that the thyroid is closely related to protein metabolism, and that this is in some way connected with the ability the body possesses to use iodine in the food if it can get it. Feeding of meat to fish was found by Marine to increase the size of the thyroid. With all this in mind it is not astonishing that two-thirds of our cases of thyroid abnormalities were found in the order Carnivora.

The anatomical changes of the human thyroid that precede or accompany the various clinical pictures cannot be said to be uniform to a degree that one can even approximately predict in every case what will be found at operation, at autopsy or by the microscope. Furthermore, much discussion has existed upon the importance of the several changes, the association with clinical phenomena and the nomenclature. I shall not enter the academic discussion with our material because so much has depended, in human medicine, upon symptoms, signs and chemistry—data that we cannot adduce. Upon many occasions I have seen animals with very evident goitres, but have not been able to detect bulging of the eyes or especial nervousness. One striped hyena carried his mass for several years. It swelled up occasionally and seemed to cause dyspnœa. At one examination of the beast, to see if anything could be done for him, a large cyst broke under the examining hand, whereupon a deep inspiration was heard and relief was apparent. This handling was repeated twice, these times with the purpose of breaking cysts and when this was successful disappearance of the dyspnœa was observed. However, a similar attempt upon another hyena and a wolf failed possibly because no large thin-walled cyst was present. These and the case of the lion cub (page 170) are the only instances in which the enlarged thyroid seemed to have given serious difficulty, and the symptoms were probably due to pressure. Many, indeed most, enlarged thyroids have been found at autopsy, when the Garden personnel was unaware of their existence. Interesting notes of familial cretinism will be found under the appropriate heading.

PATHOLOGICAL ANATOMY. CLASSIFICATION.

And now to return to the question of morbid anatomy of the thyroid gland, I shall begin by outlining briefly the classification to be used in analyzing our cases, a system which combines those of many pathologists, yet which I believe contains the essentials of all. The changes in the gland being hyperplastic and recessive, at times to a stage of atrophy, no clear cut definite line of demarcation separates all these pictures; instead they must be thought of as merging into one another. When the thyroid enlarges more or less continuously with a maintenance of considerable colloid, the picture is that of COLLOID GOITRE. The gland is pale, gelatinous, tense but resilient and may show large cystic areas with fluid contents. Microscopically studied the acini are overfilled with colloid yet the lining cells are retained but flattened. The cysts may show the ruptured septa of the original acini. Enlarged soft reddish glands are found at times to contain much colloid, nearly every acinus being distended with it, but in such organs the epithelia are high or even reduplicated; the amount of contents is the striking feature. These are termed HYPERPLASIA WITH COLLOID. Hyperplasia may go on with the absorption of colloid, HYPERPLASIA WITHOUT COLLOID. The gland is then a darker body of more solid character, red, dull purple or uniformly pale pink, somewhat dependent upon the blood content. By magnification one sees smaller acini with prominent high cuboidal or cylindrical epithelia and little or no colloid. The increase of cells seems to be due both to an increase in their size and number. As the proliferation increases the lining layer must be accommodated so that it bulges out into the lumen as a bud or papilla which, if it be extensive or universal in the thyroid, gives rise to the ADENOMATOID GOITRE OF PAPILLOMATOUS type. This growth is accompanied by much congestion and small or large hemorrhages may occur, forming cysts containing a blood stained fluid. Grossly such a gland has solid and cystic areas, is mottled red and gray or brown from old pigmentation and is usually of very irregular shape. These forms are more or less uniform and general, but in certain instances the hyperplasia tends to remain in isolated areas or nodules, and in these develop solid masses of thyroid epithelium, sometimes with a small lumen usually devoid of colloid, and a rather rich but loose fibrous supporting tissue, the whole picture resembling the microanatomy of the fetal gland; to these the name fetal adenoma has been given, but since they are not fetal in origin and do not behave like tumors I have called them NODULAR ADENOMATOID HYPERPLASIAS. The next step in hyperplasia would remove it from benign to malignant in pathological character, and the term NEOPLASTIC HYPERPLASIA is used; this must of course be limited to the epithelial growths, since sarcomata, while they occur in the gland, come from other cells.

The changes in atrophy consist in irregular distortion of the gland by fibrous tissue to which may be added large colloid or fluid cysts. There is no uniform finding in the thyroid for the diseases believed to be due to its atrophy, functionally at least, namely cretinism and myxedema. In the former there may be no thyroid, or it may rather closely resemble the normal organ while in the latter definite scarring and distortion is the rule. The gland acini are compressed, the cells vacuolated or crushed out of existence or there may be colloid cysts.

Inflammations occur as swellings of the interstitial tissues and of the acinus cells during many acute infections. Repetitions of this may leave a definite increase of connective tissue with large cells in the acini, a lesion which many observers have looked upon as underlying certain goitres and myxedema.

HYPERPLASIAS.

The cause of progressive hyperplasias has been ascribed to infection, to chemical substances in water and food, endogenous toxins, heredity and many other factors. While we can add nothing definite in this matter it is worthy of notice that all our animals are exposed to the same general climatic conditions, receive the same water, are fed from the same stocks and many varieties may be in charge of the same keeper. The influence of preëxisting infections cannot of course be measured. Inbreeding or captive breeding seems to have a very definite effect upon thyroid insufficiency as is well known and so sharply emphasized by McCarrison in his reference to intermarriage among certain Moslems; I shall cite the history of a wolf bitch which gave birth to three cretin litters while apparently well but mated to a goitrous male. These facts concerning the etiology are given merely to emphasize the high degree of probability that the distribution of the lesions of the thyroid gland among our specimens indicates the susceptibility of the various orders. This perhaps needs no emphasis for the carnivores, but it does for the marsupials. The literature contains many references to goitre in domesticated ungulates; this would give the impression that they are common among them, and so they may be, but this is not the case for wild ungulates. There being no doubt that the Carnivora have the highest incidence of thyroid enlargement, man being especially prone to it, and since goitre may be induced in fish by feeding meat, the inference is direct that high protein diet stands in some relation to this condition. Thirty-nine of our sixty thyroid lesions occurred in the order Carnivora; all the families of land varieties are represented; 8.1 per cent. of the specimens coming to autopsy showed definite thyroid alterations. However, marsupials have also a decided thyroid vulnerability as indicated by 4 per cent. of the specimens presenting abnormalities at death. Four of the seven cases were among the carnivorous opossums and “devils,” the remaining three being in herbivorous kangaroos. The influence of high protein diet is not evident in birds.

A discussion of the essential pathology can be based upon the accompanying table. In making a diagnosis care was used to exclude mild swelling of the gland seen in acute infectious disease and under conditions of sexual activity. The gross diagnosis was checked by microscopical section, and all but a very few have been reëxamined for the purpose of making the table.

TABLE 16. _Showing Distribution of Lesions in the Thyroid Body by Giving the Number of Cases Met in the Autopsies upon the Various Orders, According to the Classification Given in the Text._

═══════════╤═══════╤═══════╤═══════════╤═══════════╤═══════════ Order │ Cases │Colloid│Hyperplasia│Hyperplasia│ Papillary │ of │Goitre │ with │ without │Adenomatoid │Thyroid│ │ Colloid │ Colloid │Hyperplasia │Disease│ │ │ │ ───────────┼───────┼───────┼───────────┼───────────┼─────────── Carnivora │ 39│ 7│ 6│ 5│ 4 Rodentia │ 1│ │ │ │ Ungulata │ 2│ 1│ │ │ Marsupialia│ 7│ 1│ 1│ 1│ 1 Passeres │ 2│ 2│ │ │ Psittaci │ 2│ │ │ │ 1 Accipitres │ 1│ │ 1│ │ Galli │ 2│ 1│ │ 1│ Alectorides│ 1│ │ 1│ │ Anseres │ 3│ │ 2│ │ ───────────┼───────┼───────┼───────────┼───────────┼─────────── Total │ 60│ 12│ 11│ 7│ 6 ───────────┴───────┴───────┴───────────┴───────────┴───────────

═══════════╤═══════════╤═══════════╤══════╤═══════╤═══════ Order │ Nodular │ Malignant │Mixed │Sarcoma│Atrophy │Adenomatoid│Hyperplasia│Tumors│ │ │Hyperplasia│ │ │ │ │ │ │ │ │ ───────────┼───────────┼───────────┼──────┼───────┼─────── Carnivora │ 9│ 1│ 1│ 1│ 7 Rodentia │ │ │ │ 1│ Ungulata │ │ │ │ │ 1 Marsupialia│ 3│ │ │ │ Passeres │ │ │ │ │ Psittaci │ │ 1│ │ │ Accipitres │ │ │ │ │ Galli │ │ │ │ │ Alectorides│ │ │ │ │ Anseres │ │ │ │ │ ───────────┼───────────┼───────────┼──────┼───────┼─────── Total │ 12│ 2│ 1│ 2│ 8 ───────────┴───────────┴───────────┴──────┴───────┴───────

This rather diversified group of pathological lesions would warrant one to expect a notable number of instances of disease observed during life, suggesting that the thyroid was at fault; such, however, is not the case. In the first place, no case of exophthalmic goitre, as the symptom complex is known in man, has been observed, yet the anatomical alterations, hyperplasia without colloid, and with papillary or solid adenomatoid character, are abundantly represented. For the pathologist to accept a case as toxic goitre I would ask evidence of enlargement of the heart and perhaps in addition degeneration of the myocardium. The animal showing the closest resemblance to the disease in man was a Raccoon-like Dog (_Canis procyonoides_) whose history and notes are given in brief.