PROGNOSIS IN HYPERTHYROIDISM ARTHUR E. HERTZLER, M.D., F.A.C.S. KANSAS CITY, MISSOURI The term exophthalmic goiter has generally given way to the term hyperthyroidism or thyrotoxicosis, since careful study has shown that exophthalinos is usually absent, and the goiter may be. The only essential feature in the pathogenesis is, that a toxic product, or possibly an excess of a normal one, is produced. All my patients that have come to operation have shown evidence of organic or tinctorial change, which would seem to indicate that the product is always abnormal. In many of these glands a portion may be normal, and, if a thorough examination is not made, the abnormal portion may be overlooked. The most obvious changes are frequently tinctorial, but nearly always there is, in addition, evidence of a more permanent change, as manifest by round-celled infiltration or changes in cell type or of proliferation on the part of the parenchymatous cells. There is reason for believing that the tinctorial changes in the colloid are an exhaustion phenomenon due to over-stimulation continued for prolonged periods. This statement seems warranted, for we are familiar with parallel phenomena in other tissues. If this hypothesis is correct the prompt relief sometimes obtained from rest and sedative treatment is easily understood. The adenoid and papillary proliferation, as well as the round-celled infiltration, may be the secondary result of a perverted secretion due to over-stimulation. Those who are familiar with the pathogenesis of epithelial proliferation induced by sudan III and like drugs will at once perceive a resemblance. The change in reaction on the part of the colloid substance acts as an irritant upon the surrounding tissues, resulting in the changes just mentioned. I have been struck with the parallel changes seen in ovarian cystomas. The glandular and papillary types of goiters are as well marked as in the case of ovarian tumors. In goiters, as in ovarian tumors, the papillary formation exemplifies the greatest deviation from the normal, the glandular the least. In the milder types of goiter there is an increase in colloid which has undergone some changes that result in a changed reaction to stains. The more pronounced cases show, in addition, evidence of cellular irritation. In the pronounced cases of exophthalmic goiter there is an absence of colloid, and the cells assume an active proliferation and papillary formation. These resemble the semimalignant serous cystomas of the ovaries. Whatever may be the significance of the various cell changes there can be no doubt that when cells have so far departed from their normal morphology they are no longer capable of producing a normal secretion. When a gland has undergone such extensive changes, obviously, the control of those factors which were responsible for the initial changes cannot be expected to produce a prompt subsidence of symptoms. We do not know the nature of the changes in the secretion, but, if it is the purpose of the thyroid to produce iodine, then certainly the gland is in a hypo, rather than in a hyper, state, for only a small portion of iodine is found in the pathological, as compared with the normal, gland. As a very general proposition hyperthyroidism may be regarded as a self-limited disease. The manner in which the self-limitation is reached must vary according to the anatomic state in which they find themselves when regression begins. A subsidence of the dominant features of the disease may not presage a return to the normal state. Most likely it is merely a spontaneous obliteration of the pathological process. Certain types, it can well be understood, may arrive at a state of remission with vastly less change than others. In cases in which myxedema follows there is a spontaneous obliteration. Cases are observed in which there is a curious intermixture of symptoms,-partly hyperthyroidism, partly myxedematous. This bears out, what can be easily proved by sections, the fact that some part of the gland remains normal in nearly all cases. In such cases a spontaneous or operative elimination of the diseased part would allow the remaining unaffected portion to carry on the function in a normal manner. In cases which recover clinically only, to be followed subsequently by a relapse, it is usually some other portion of the gland which enlarges. This phase makes it important to determine when a spontaneous remission occurs, whether or not some other organ, which is in any way associated with the function of the thyroid, was previously diseased. If so this lesion should be corrected lest its continued existence stimulate other portions of the gland to abnormal activity. That the thyroid is not equally affected has been almost wholly overlooked by surgeons. This is unfortunate, for it is only when the part of the gland that is diseased is removed, leaving the normal part, can the surgeon be said to have cured his patient. Careful attention must be paid to this phase before the surgeon decides on the plan of operation. Gland in hand, the surgeon should be able to say which is the diseased, and which is the normal, part of the gland. The degree of skill which will enable him to make this operating room diagnosis can be attained only by careful study of his own material in the laboratory. In order to appreciate the degree of recovery possible spontaneously, one must follow the patient for many years. I am able to determine that the cases which I saw in my earlier practice have nearly all of them recovered, or, at least, they have ceased to suffer from pronounced thyrotoxic symptoms. However, while most of them, at least, consider themselves well, there is not lacking evidence of an unbalanced somatic system. They continue to be sensitive to certain nerve stimuli, or they react quickly to certain kinds of physical exertion. Whether these conditions are to be ascribed to thyroid or cardiac degeneration is another matter. Some of these patients have suffered from a succession of relapses and, probably, there is no wholly normal gland left. Some, obviously, have a myocardium that is efficient only for a limited degree of exertion. Some still suffer from some other disease which antedated the primary thyroid disease, and in not a few all these things are complicated or overshadowed by a hereditary neurotic or neuropathic state. It is clear that, in order to determine the subsequent state of our ex-patients, we must examine them ourselves. A written communication from them stating that they are "well" is of limited importance. As in the other self-limiting diseases, our efforts must look, therefore, to the shortening of the process and to preventing a recurrence. Like appdendicitis, hyperthyroidism in running its cycle is subject to certain complications and accidents which must be taken into account. The fundamental factor in the treatment must balance itself against this tendency to complications. Though far simpler and more easily comprehended, appendicitis has not yet reached a state where the universal understanding makes the treatment in all cases less deadly than the disease. This is vastly more apparent in the management of hyperthyroidism. In the first place, the life cycle of the disease is not generally understood, particularly as relates to other diseases; and the difficulties and responsibilities attending surgical treatment are seldom appreciated until experience has forced them home. If spontaneous recoveries are not complete, operative recoveries in certain cases are no better. This is at least true to the degree that the surgon may feel that he is not derelict if he hesitates to operate in all his cases of hyperthyroidism. On the contrary, he is open to censure if he does not weigh all factors before deciding on any kind of operative treatment. There is little in the literature that helps one to solve the many intricate problems. The literature confines itself very largely to consideration of technic and to statistics. Generally speaking, the surgeon who indulges in statistics thereby proclaims himself to be a poor pathologist. We may read that in a given number of cases operated on, r per cent of cases were cured, that y per cent were benefited, and that z per cent were not benefited. Even if these statements were true, they are utterly devoid of helpful information. We are not informed how to determine if a given case will fall into the class, or we would avoid operating; and we would be chary about operating on patients in the y group, unless we felt quite sure the improvement also implied that we prevented the patient from a yet worse state. If cases could be thus accurately prognosticated, most surgeons would confine their efforts to operating on patients in the r group. Even if we had definite information which would make it possible so to group our patients, the question would come up that, the disease being a self-limited one, surely some of the r group would recover without operation. The following discussion is based on my own material. The purpose, primarily, is to determine how constantly one can predict the revelations of the laboratory |