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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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