Graves Disease





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 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 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 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 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 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 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 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.





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