VOL. XVIII.

ORIGINAL ARTICLES.

SOME OBSERVATIONS ON DISEASE OF THE THYROID, WITH AN ANALYSIS OF 28 CASES.

BY HENRY G. WEBSTER, M.D.

Presented at a meeting of the Brooklyn Pathological Society Jan. 14, 1904.

My excuse for burdening you with a paper on . a topic which is by no means new is not that I have anything startling or original to offer, but that recent publications have attracted my attention to the thyroid gland and its functions, and, on looking up the subject, I find a number of cases, 31 in all, that have not as yet been published and an analysis of which may be useful. I am indebted to the kindness of Drs. Pilcher, Fowler, Bogart, Butler and Matheson of the Methodist Hospital for permission to use the records of cases occurring in their services.

It is only in recent years, especially since the advent of thyroid preparations in the treatment of cachexia strumipriva as indicated by Reverdin, and more recently in the cure of myxedema, that the thyroid has possessed any but a surgical interest; but latterly, parallel investigation of the pituitaries, thymus, adrenals, and parathyroid glands, of the pancreas, spleen, liver, kidneys, testes, ovaries, intestines, parotids, and even of the leucocytes tends to show a correllation of the internal secretions of these organs that bids fair, if substantiated, to revolutionize our conceptions of physiology and therapeutics.

By way of introduction to the subject, a brief glance at the accepted facts in regard to the gland is permissible.

Anatomically, it consists of two lateral lobes and a connecting isthmus, the former lying to either side of the trachea on a level with and below the thyroid cartilage, the isthmus being in front of the second and third tracheal rings. Not infrequently a third lobe, the pyramid, rises mesially from the isthmus to the hyoid bone. sometimes is separate. Four smaller bodies, almost always paired, the parathyroids, lie external to the lateral thyroid lobes. In passing it should

It

No. 4.

be emphasized that in all probability these parathyroid bodies are independent physiological entities, quite distinct in structure and function from the thyroid gland, and, according to Benjamins, of great physiological importance. Accessory thyroids are not infrequent, notably in the substance of the tongue and about the hyoid bone.

Histologically the thyroid consists of a loose connective tissue stroma rich in blood vessels and continuous with the capsule. Its interstices contain irregular cavities lined with a single layer of cuboidal epithelium and containing a colloid substance believed to be a secretion of the epithelial cells. Abundant lymph spaces also occur.

The gland is developed from the primary branchial cavity in close approximation with the pituitary bodies. In the foetus it is small, developing with adolesence as the thymus shrinks, and tending to atrophy after middle life. The nerve supply is from the vagus and sympathetic systems. The blood supply is particularly noteworthy, the total amount being estimated at almost that of the brain.

The gland is subject to a variety of pathological changes. Its structure permits of either hypertrophy of the connective tissue, vascular or glandular portions, resulting in hypertrophy, hyperplasia, congestion, cystic degeneration or atrophy. Primary inflammatory and suppurative. conditions are infrequent, but may result from bacterial invasion in infectious diseases like typhoid, or variola, or from trauma. Malignant neoplasms occur, sometimes as metastases, rarely as primary growths. Roger Williams notes primary carcinoma in 1 in 1,043 and sarcoma once in 1,266 cases. The sarcomas are usually spindle cell, and death has almost always followed operation by a very few days (Tippany and Laurier). Wells has reported three cases of neoplasm comprising both carcinoma and sarcoma with simple and combined metastases.

It seems evident that the gland supplies an internal secretion, acting either generally through the body or locally in the gland. That the former is the more reasonab'e supposition may be argued from the effect of thyroid substance supplied to subjects in whom d'sease or interference has de

stroyed the organ, as well as from the results of transplantation of the gland, and from the excess of efferent over afferent blood supply.

acid).

According to Baumann, this secretion, which may be the colloid alone or in some combination, has the following physical characteristics: It is dependent on an iodine compound, iodothyroidin, a substance having no proteid reaction, containing much nitrogen, and 5% phosphorus in organic combination (possibly nucleic acid). Gautier has found arsenic, but believes the iodin to be the active component. It is prepared from the fresh gland by boiling with suphuric acid, or treating with artificial gastric fluids. Only a part is free iodin, the remainder being combined with an albumin and a globulin. Chittenden has shown that it passes through the stomach unchanged. Thyroid extract has been used with good results in the treatment of myxedema, cretinism, exophthalmic goitre, simple goitre, obesity, agalactia, alopecia, psoriasis, insanity, the nervous and circulatory disturbances of the menopause and puberty, acromegaly, and muscular atrophy. To these may be added a long list comprising almost the entire practice of medicine, where the gland has failed to work. The most constant results accrue in myxedema and after ablation of the thyroid, though even here it sometimes fails. The dose may be put down as the equivalent of one lobe from a young sheep daily, more or less. would seem that the best results should follow ne use of a preparation containing as much of the gland as possible, and preserved so as to prevent contamination by bacteria and such putrefactive agents. However, Baumann claims remarkably good results from his thyroidin.

A brief review of the physiological action of thyroid secretin as related in the literature shows the accepted belief to be that administration of the gland or its extract produces, 1st. increased metabolism with corresponding increase of the nitrogen coefficient, resulting in increased temperature and loss of weight; 2d. growth of the skeleton in the young; 3d. increased activity of the mucous membranes, skin and kidneys; while in excess it produces the untoward results outlined in three of the cases to be mentioned, and which Notthaft, quoted by Sajous, classifies as follows: 1. Rapid loss of weight. 2. Dyspnoea with swelling of the neck. 3. Exophthalmos with Stellwag's and von Graef's signs. 4. Thyroid enlarged, pulsation, and a thrill. 5. Tremor of tongue and fingers. 6. Apex displaced outward, pulse 120. 7. Cough. 8. Mental depression. 9. Polyuria and glycosuria.

Because of the appearance of a similar train of symptoms in connection with an enlarged gland in Graves' disease it is generally stated that this argues an excessive thyroid secretion as one of the primary causes of this little understood condition. This is, of course, taking for granted that the thyroid is the storm centre, and leaves out of consideration the relation of that gland to the other organs furnishing internal secretions. We should expect, if the thyroid secretion is uniform in its physiological effect, to find always a rise of temperature, rapid pulse and increased respiration; whereas reference to the cases to be cited shows marked subnormal temperature in four and a low average in some of the rest. Operative interference, too, as indicated in the series of cases of simple goitre, may produce sudden and extreme depression of temperature, as in cases 5 and 9, suggesting that interference with. the thyroid produces some untoward results in allied structures.

Turning now to a consideration of the cases at hand, we find a series of 13 of goitre treated surgically, 3 medically, 12 of exophthalmic goitre, of which 2 were subjected to operation, and 3 of obesity treated by thyroid extract-32 in all.

Taking up first the goitre cases: There were 4 males and 12 females, 30 per cent. and 70 per cent. The ages ran from 19 to 49 years, both limits in women. Of predisposing causes in the family history there are not many-one patient told of carcinoma in the family and one of rheumatism. If the number of years' duration of the disease be subtracted from the patients' ages at the time of coming under treatment we find that with one exception all commenced under 30 and after 12 years, the average age being 21. One patient reported the tumor as present since early childhood. One traced the growth to her first pregnancy. The occupations and places of residence have been so varied that conclusions on these points are valueless. Diseases of childhood, too, while sometimes reported, are mostly noted as negative. The pathologist's reports show 3 to have been cystic, 6 hypertrophic, 3 vascular, and 2 mixed. Of the 3 medical cases 2 were hypertrophic and I hyperplastic. The right lobe showed the greater enlargement in 9 instances, the left in 4, and the growth was more nearly symmetrical in 4.

Symptoms. Each patient applied primarily for the relief of an unsightly deformity which caused dyspnoea in 5 cases, and pain with dyspnoea in 2. Palpitation without tachycardia was complained of twice, while sleeplessness and huskiness of

Hemanalyses appear in 3 cases and anemia is mentioned without an analysis once. Of the 3, the erythrocytes were reduced to 42, 334, and 44 millions respectively, with correspondingly low Hb per cent. In 2 the leucocytes were normal, and in I increased.

Of changes in the urine, calcium oxalate is noted twice before operation, uric acid once, trace of albumin alone once, and trace of albumin with casts once. Only once was albumin noted post operative with ether as the anesthetic.

In the operative cases as a rule there was little to note in regard to the pulse, although cardiac murmurs were noted five times and displacement of the apex once. After operation, however, there were marked irregularities.

Case I ran an average temperature of 100.5 for 6 days.

2. Died of shock immediately after operation. 3. Ran an average temperature of 100.5 for 5 days and an irregular pulse, average 90, with free serous discharge.

cially as the occurrence is noted repeatedly in the cases of exophthalmic goitre. They do not seem to have been followed by the reactionary high temperature associated with chill, but in some instances a moderate increase in the pulse rate is noted. The occurrence is possibly due to nerve injury, and yet taken in connection with the other irregular symptoms like tetany, delirium, sudden and marked irregularities in the pulse, all noted frequently in the exophthalmic cases, seems to me to be directly due to interference with the glandular functions.

Medication in all this series of cases but one was directed to the upbuilding of the patient's general health rather than specifically against the disease, though it is reasonable to suppose that many of the cases had received such special treatment before their hospital residence.

One death-immediately after operation from hemorrhage and shock-makes the death rate about 8 per cent.

Of the direct and remote results, one died, as just stated; one developed cachexia strumipriva, which later yielded to treatment; the rest recov

5. Pulse rose to 100 twelve hours after operation. On the ninth day fell to 50. The temperature fell to 97 twelve hours post op.

6. Irregular pulse with moderate sero-sanguinous discharge.

7. Pulse averaged 135 for 3 days; never under 95. Temperature 102 for 3 days. Thereafter averaged high. On the 5th day symptoms of tetany with dizziness, nervousness, etc.

8. Pulse irregular and rapid under ether. Both pulse and temperature irregular and high after operation.

9. Temperature fell to 97.4 post op.

10. Pulse ran up to 130 during the operation. Afterward both pulse and temperature were irregularly high.

II, 12 and 13. Ran irregular and high pulses after operation.

A reference to the literature brings up the question of thyroid fever complicating partial ablation of the gland. In this condition as described there is high fever with disproportionately low pulse and respiration. Ordinarily the greater the amount of discharge the higher the fever, retention being present, as I understand it. Case 4 Case 4 was the only one in whom retention was noted, and with him the temperature was not pronounced, but he developed delirium. The marked remissions of temperature are interesting, espe

and vomiting was produced in 2, difficulty in swallowing in 1, and hoarseness in 2.

The three cases treated medically are chiefly interesting from the failure of thyroid extract to benefit the tumor in one, while in the other two complete cures resulted. The failure occurred in a woman of 30, in whom there had been a steady increase in the tumor for 3 years, and although the mass was soft and elastic and seemed favorable, no improvement resulted. She eventually submitted to operation at a New York hospital and has experienced complete relief. The others, also women, 18 and 24 respectively, had been afflicted for much shorter periods-6 and 14 months-and both responded promptly to thyroid treatment, with occasional courses of KI, the treatment being continued for 3 months in each case. This bears out the statements of Baumann and others that as high as 60 per cent. of cures may be expected in young subjects treated by the thyroid method.

Of the cases of exophthalmic goitre, we find a list of 12, 2 men and 10 women. The ages range from 14 to 54, though the greater number are between 20 and 30. Four are single, 6 married, 2 widowed. Four show some family history of communicable disease-tuberculosis and heart disease in one; uric acid habit, rheumatism and melancholia in another; rheumatism in a third; and a family history of nervousness in a fourth.