Graves' disease, sometimes called Basedow's disease, though the Irish physician has a right to the name by priority, is often called exophthalmic goitre, because this term is descriptive of the two most marked symptoms. It must not be forgotten, however, that there are cases in which there is no exophthalmos and even no goitre, at least no enlargement of the thyroid gland that can be demonstrated externally. It is said that in these cases there must be an enlargement of the thyroid bound down by fascia and concealed by other structures of the neck so that it does not appear externally. It is probable, however, that there are cases of true Graves' disease without enlargement of the thyroid yet with the characteristic tremor, rapid heart and the mental symptoms of the affection.

Etiology.—The symptoms of the affection often develop after a period of excitement or worry, or at critical times in life, if sorrow or misfortune proves a burden. Responsibility sometimes has a like effect. I have seen a woman patient on several occasions in the last fifteen years develop marked symptoms of Graves' disease when she was placed in a position of responsibility involving worry, while in the intervals when pursuing a simple ordinary life without trouble of mind no symptoms were present. Occasionally a fright seems to be at least a predisposing cause for the development of the symptoms. Emotional strains, mental stresses, play a large part in occasioning Graves' disease, though the cause of it is probably deeper in some structural defect. In recent years nearly all the medical attention has become concentrated on the idea that the disease is primarily due to hyperthyroidization. More detailed study, however, has shown that other ductless glands are probably also concerned in the etiology. The adrenals particularly seem to be associated closely with the thyroid and Graves' disease may be due to some disturbance of the co-ordination between these glandular systems. The thymus gland is usually {501} persistent in these cases and this must represent something in the affection and at one time the use of thymus substance for therapeutic purposes seemed to confirm this idea. The parathyroids have also been called into question and their use in therapeusis seems to justify this to some extent, though probably we know too little about them to be able to say anything definite in the matter.

Even though the affection may be due directly to hypersecretion of the thyroid, it is possible that the mental and nervous state may be closely concerned in the etiology. Some patients have had an enlarged thyroid for years, without any symptoms of Graves' disease. Then during a time of stress and worry or anxiety and responsibility symptoms of the affection develop. The circulation of the thyroid is under the control of the cervical sympathetic. It is possible that this may be affected by states of mind to such an extent as to cause an increase of the circulation in the thyroid and as a consequence more of the thyroid secretion may get into the blood stream and produce its effect. Under these circumstances anything that would allay the excited mental condition and thus neutralize the unfavorable effect of the cervical sympathetic would cure or at least relieve Graves' disease.

The affection is about five times as frequent among women as it is among men. This has sometimes been attributed to the fact that there seems to be some more or less direct correlation between the sex organs in women and the ductless gland systems. It has often been pointed out that the thyroid is likely to be engorged at the time of menstruation and, indeed, there are those who have attributed some of the symptoms of tremulousness, irritability, and tiredness at this time to over-functioning of the gland. In women who have borne a child the thyroid is usually somewhat enlarged. Good authorities in obstetrics have insisted that they could pick out of a group of women in evening dress, those who had borne children, from the appearance of their necks. Probably this is an exaggeration, but there is no doubt that the thyroid is intimately related to the genital functions in women. It has been said that a direct connection could be traced between disappointments in love or in sexual matters and the development of Graves' disease. To put much stress on this would easily lead to mistaken conclusions, though it represents a principle that should be recalled in certain cases of the affection. The frequency with which slighter disturbances of the thyroid occur in connection with the common genital incidents of female life and their comparative insignificance for health or strength, should make for the holding of a not too serious prognosis in the affection.

Symptomatology.—There are four cardinal symptoms of the disease: rapid heart action, tremor, enlargement of the thyroid, and exophthalmos. At least two of these are largely dependent on mental influences. There are certain accompanying symptoms that are of importance and supposed to be connected directly with the disease, though oftener they can be traced to the influence of the state of the patient's mind upon the organism. Emaciation is common. It is due to the fact that the appetite is likely to be seriously disturbed by anxiety and solicitude. Anemia develops as a consequence and there may be slight fever which is sometimes inanition fever. Attacks of vomiting and diarrhea occur intermittently and sometimes there is constipation. The disturbance of eating consequent upon the affections seems largely {502} responsible for these. The disturbance of the vascular system gives rise to flashes of heat and cold and often to profuse perspiration. Certain of the symptoms of the menopause can be compared rather strikingly with those of Graves' disease and have been attributed to the disturbance of the external secretion of the ovaries which are now known to act as ductless glands as well as genital organs.

With the exception of the enlargement of the thyroid and the exophthalmos, all of the symptoms of Graves' disease are of a kind that can be produced in states of excitement with nothing more present than a functional neurotic condition. It is true that the tremor is characteristic and differs from that of hysterical patients, being finer and at the rate of a little more than eight to the second. The rapid heart action, however, and the disturbance of the general circulation which causes flushing and pruritus and the sense of nervousness, as if the patients were in a constant state of fright, are always characteristically neurotic. The changes in disposition, often in the line of irritability, sometimes with severe mental depression, seem in many cases to be only a mental reaction to the patient's solicitude. The weakness of the limbs which sometimes amounts to a giving away of the legs, is connected with the tremor, but seems to be neurotic rather than of any more serious character. In spite of all our study of the affection its place among the neuroses must still be reserved for it, at least as regards many cases, and its treatment must be conducted with that idea in mind.

Diagnosis.—The disease is easy to recognize when fully developed. At the beginning of cases, however, and in certain abortive types of the affection which the French have called formes frustes, the diagnosis may be difficult. Usually the first symptom is tremor and this of itself will often serve, especially in association with general symptoms of nervousness, to make the diagnosis. Tremor with tachycardia puts the case beyond doubt, as a rule, though of course it must not be forgotten that hysteria may simulate rather closely this much of the disease.

The abortive types of the affection are important because they masquerade as forms of psychoneurosis, hysteria, and the like, though the patients are not suggestible, have very definite, not variable, symptoms and get better and worse according to the variations in the underlying affection. Occasionally they seem to be associated with certain other forms of neurotic conditions, especially those with vascular disturbances. There may be tinglings in the ends of the fingers, occasionally with suffusion, erythromelalgia—Weir Mitchell's disease—and even a tendency to the white "dead fingers" as the French call them, of Raynaud's disease. It seems not unlikely that further study will show that many of these affections involving disturbances of the vasomotor system are connected in some special way.

Prognosis in Young Patients.—Some of the cases, especially in young people, are likely to seem quite discouraging and apparently to justify even a serious operation. I have in mind a young woman seen some fifteen years ago when she was about seventeen. The prominence of the eyes, the enlargement of the thyroid, the tremor and the rapid heart were all marked. The symptoms had been growing worse for over a year and the outlook was serious. Ten years later I saw her in another city in perfectly normal health, married and happy and the mother of two healthy children. The only trace {503} apparently of the disturbance of the thyroid to be noted in the family was that her children got their teeth very late, her first child, a boy, not cutting his first tooth until after he was fifteen months old. In every other way, however, the boy was perfectly well, rugged and strong, having passed through his summers without any serious disturbance and not being a particularly nervous or excitable child. Such complete relief from symptoms after the condition had been so grave would ordinarily have seemed quite out of the question. It emphasizes the fact that for Graves' disease as it occurs among young growing people, where perhaps the thyroid does not grow in proper proportion to the rest of the body, but for some reason overgrows, the prognosis of the case may seem to be much worse than it really is.

Treatment.—The story of the various methods of treatment that have been reported as successful for Graves' disease serve to show very well how much the affection must depend upon psychic and neurotic conditions, for most of them have been positive in action at the beginning when their suggestive influence was strong, and quite inert after they had lost their novelty and their power to influence the mind. Sometimes even slight operations as on the nose, the removal of polyps, or of a spur on the septum, or an enlarged turbinate, have been found to bring relief of the symptoms of Graves' disease even in marked cases. Operations upon the tonsils have had a like effect and even shortening of the uvula has been reported as curative. A generation ago applications of iodin to the goiter were reported to have good effects. In lancing the goiter, sometimes evidently a cyst was punctured, but sometimes the lance was only followed by a slight issue of blood, yet the affection was favorably modified. More serious operations have followed by complete relief of symptoms for a time, though relapses are not infrequent and occasionally the patient was not relieved, though apparently all the conditions present were similar to those of other patients in whom the operation produced excellent results.

The medical treatment of Graves' disease demonstrates interestingly the power of suggestion. About fifteen years ago a distinguished English observer announced that he was getting good results in the treatment of Graves' disease by the administration of thyroid substance. At that time our present theories with regard to hyperthyroidization as the etiology of the affection had not been formulated, though some vague connection between the thyroid secretion and the symptoms had been accepted. A number of patients were improved by taking thyroid. Other observers found, however, that not only were their patients not improved, but they seemed to be worse as the result of the thyroid feeding. The English physician therefore was asked to say exactly how he obtained his material and prepared it for his patients. Organo-therapy was then new and it was found that the orders given to the butcher for thyroid had been filled by him according to the directions by furnishing portions of a large gland situated in the neck of the calf. This was the thymus, and not the thyroid. Thymus was then deliberately used for a while and there were some reported good successes while the treatment was new and strongly suggestive. After a time it proved to be of no avail.

A number of biological remedies were tried after this. Personally, after having made some studies of the parathyroids while in Virchow's laboratory, I resolved to try material from those glands. The first two patients to whom {504} the material was given, with a careful explanation of the theory on which it was administered, proceeded to obtain relief from their symptoms and an intermission in their disease. Just as soon as I purposely omitted to explain to patients how much might be expected from this new remedy and failed to make suggestions founded on the parathyroids, no improvement was noted. In the first two cases this had been more or less necessary in order to determine whether the patients could stand the doses suggested, which began very low and were gradually increased. The material seemed to have no ill effects, however, and a definite dosage could be used without the necessity of taking patients into one's confidence.

A number of serums of one kind or another were reported as beneficial for Graves' disease. It was admitted that they did not benefit all the cases, but that in certain cases they did much good. Practically all of these were strikingly more efficient in their discoverers' hands than when used by anyone else. Thyroids were removed from animals and after some time serum from these animals, supposed to be of lower thyroid content, was injected into human beings with the idea of reducing the hyperthyroidization or perhaps neutralizing it by some substance present in the serum. One very interesting observation on most of these cases deserves remark. The animals deprived of their thyroids, such as goats and sheep, lived on absolutely unhurt by the operation, and as one experimenter expressly noted, sold for more money after being kept for a year under observation than they had cost him before dethyroidization.

Most of our biological remedies for Graves' disease then are strongly reminiscent of the therapy of the affection in older times. It was particularly for Graves' disease, or at least for nervous symptoms closely resembling Graves' disease—those of fright, nervousness, irritability and tremor—that various more or less terrifying procedures and particularly deterrent substances were employed in medicine. These patients, for instance, were cured by the touch of a hanged criminal, and particularly by the touch of their goiter to the mark on his neck. It was especially for them that Usnea, the moss gathered from the skull of a criminal who had been hanged, was of benefit when administered internally. Mummy as a remedial substance remained in common use until well on into the latter half of the eighteenth century in England.

In older times a dead snake wrapped around the neck was said to be an excellent remedy for goiter and especially those cases of goiter that caused symptoms of fright and nervousness. Evidently anything that produces a strong effect upon the patient's mind may prove helpful. Perhaps the suggestion enables the mind to control the cervical sympathetic and by that means the circulation in the thyroid gland, thus lessening the amount of blood that flows through and therefore the amount of secretion that is carried out. There is no doubt but that the sympathetic is largely under the influence of the emotions and that through it very important effects may be worked out in various structures. There seems no other possible explanation for the uniformly reported success of remedies when their suggestive power is strong and their failure quite as invariably later even in the same cases.

Operations.—In recent years operations for the removal of portions of the enlarged thyroid have become popular and some very successful results have been reported. Those of us who know how easy it is to influence the minds of {505} patients in Graves' disease favorably hesitate as yet to pronounce definitely with regard to the indication for operation except under such conditions of pressure in the neck or projection of the eyeballs as may lead to serious symptoms. Not all the operators have been as successful as some who made a specialty of the affection. I have personal information which shows a number of unsuccessful cases after operation and the records of conservative surgeons as published indicate this. Unfortunately, a great many cases have been reported within a few months as cured; if they were comparatively without symptoms, surgical intervention is considered to have been eminently successful. For, be it noted, very few are entirely without symptoms, even after operation.

Dr. William H. Thompson in his book on "Graves' Disease" points out that even so good an operator and so thoroughly conservative a surgeon as Kocher reports cases of Graves' disease as cured, which are still exhibiting symptoms that would make the medical clinician hesitate to agree with him and, indeed, rather lead him to expect that under the stress of worry and excitement there may be redevelopment of the symptoms. As the number of cases operated upon has increased there has been a growing feeling that relapses might be expected in certain cases even after removal of large portions of the thyroid gland. The fact of the matter is that we do not understand as yet what is the underlying pathological significance of the symptoms grouped under the term Graves' disease. When there are severe symptoms, as extreme exophthalmos, greatly enlarged thyroid pressing upon the important neck structures, or serious disturbance of nutrition, an operation is always needed; but as yet we cannot be sure that it will produce even complete or lasting relief.

Many patients have been greatly benefited by operation, some of them perhaps permanently, but we need more of the after-history of these patients covering a long period of time, to be sure that the results flow entirely from the operation. There was a time when operations were reported as doing quite as much good for epilepsy as they are now for Graves' disease. As we have pointed out, a number of operative procedures that had nothing to do with the underlying basic pathology of the disease have proved the occasion for considerable improvement or sometimes what might be called a cure for a prolonged period. We can be sure, as a rule, that patients will be benefited immediately after operations. The rest, with care, the strong suggestion, the aroused feeling of expectancy, the confidence in the surgeon, all this would do much of itself. It remains to be seen how much more than this the operation does.

General Condition.—The treatment of patients suffering from Graves' disease consists largely in having them take up some occupation that, while reasonably absorbing, does not make too great a demand upon them. Often when they complain most of their symptoms they are below normal weight and the first indication is to have them brought back to it. I have seen such cases over and over again almost entirely without symptoms when they were up to normal weight and with a good many symptoms when they were below normal. It would be easy to theorize as to why this is so, but the observation is the most important consideration for practical purposes, and we are not yet in possession of enough scientific knowledge with regard to the thyroid or {506} its possible connection with other organs that have an internal secretion, to be able to say anything definite about it.

After weight and nutrition the most important indication is sleep. It is impossible for patients to get along with less than eight or nine hours of sleep. Most of them are much better if they have nine or ten every night. Late hours are particularly prejudicial to them. They are tired if they have been on their feet all day and they should be encouraged to take more sleep than others. Sleep is one of the most important considerations for sufferers from the abortive forms of Graves' disease and they must be encouraged to take it in the quantity that they need. This can only be decided by their feeling.

Diversion of Mind.—Much more than other nervous people these patients need encouragement and require diversion of mind. They are prone to be discouraged, rather tired, and easily tempt themselves into a routine in which there is little recreation and no diversion. For them more than for most other patients it is necessary to prescribe that twice every week they shall have some engagement different from their ordinary routine to which they look forward for several days. This looking forward to a break in the routine does much to make life more livable for them and must be encouraged in every way. As to what the diversion is to be must depend entirely on the character of the individual. Some find complete diversion of mind in the theater or even in vaudeville. Others are bored by this after a while and need other recreations. I have known people who were bored by the theater find an evening a week spent in helping a poor person or an afternoon devoted to a visit to a hospital ward or to an ailing friend an excellent diversion. Some of those who do not care for the theater like music and are helped by it. As a rule, however, one must be careful about the indulgence of music for neurotic people since it seems to exert a serious emotional strain on many of them and as the phrase goes "takes a good deal out of them." This is particularly true for younger people who have a passion for music. Older people may be trusted more in this matter and the attendance on concert and opera, which is looked upon as a social duty by some, giving them an opportunity to greet friends and to display their gowns and jewels, is a harmless diversion of mind.

Mental Treatment.—Graves' disease is, then, as we have said, especially likely to be influenced by the patient's state of mind. Nothing disturbs patients more than the declaration sometimes made by physicians that their condition is incurable or that they will have to doctor for it for many years. This must be avoided because our present knowledge does not justify any such positive declarations. Most cases of Graves' disease, while not particularly amenable to treatment by specific drugs, are very much improved if the patient's general health is brought up to the best standard and if all sources of worry and emotion are eliminated, as far as possible. Nothing is more serious for them, however, than the suggestion that they will not get well. Probably no one has ever seen a mild case of Graves' disease that did not improve so much as to be practically well after the lapse of some time. Recurrences take place, but if all sources of worry and irritation of the digestive tract and over-tiredness are removed, then patients will stay free from their symptoms for surprisingly long periods. Old people do not have these {507} favorable remissions so much as the young, but under twenty there can be, as a rule, definite promise of decided improvement and sometimes of results that seem like complete cure. For patients under thirty there is every reason to think that if they are in a run-down condition when the disease is first noted remissions of symptoms can be looked for lasting for long periods, during which they will be comparatively well.

Diet Suggestions.—The changes in diet necessary to bring improvement in Graves' disease are different for individual patients. Prof. Mendel, in Berlin, found in his extensive experience that meat does not seem to be disposed of well by these patients and acts somewhat as an irritant. He reduces the meat taken and usually allows it at but one meal. If patients get on well as vegetarians, meat is gradually eliminated from their diet. On the other hand, there are patients who seem to develop Graves' disease during a vegetarian diet. Very often it will be found that there is an intermittent constipation and diarrhea in these cases, and that the bowels will act much better if a certain amount of meat is given, and then the symptoms of Graves' disease remit, as a rule. As in most of the major neuroses, as is known so well in epilepsy, any irritative condition of the digestive tract will surely revive neurotic manifestations and make many of the major neuroses much worse than they were before.{508}