By applying the principle of the discharge of nervous energy by
phylogenetic association, and by making the additional hypothesis
that in the discharge of nervous energy the thyroid gland is stimulated
through the nervous system, we can explain many of the phenomena
of Graves' disease and may possibly discover some of the factors
which explain both its genesis and its cure.
In the wild state of animal life in which only the fittest
survive in the struggle for existence, every point of advantage
has its value. An animal engaged in battle or in a desperate
effort to escape will be able to give a better account of itself
if it have some means of accelerating the discharge of energy--
some influence like that of pouring oil upon the kindling fire.
There is evidence, though perhaps it is not conclusive,
that such an influence is exerted by the thyroid gland.
In myxedema, a condition characterized by a lack of thyroid secretion,
there is dulness of the reflexes and of the intellect, a lowered
muscular power, and generally a sluggish discharge of energy.
In Graves' disease there is an excessive production of thyroid secretion.
In this disease the reflexes are increased, the discharge of
energy is greatly facilitated, and metabolism is at a maximum.
The same phenomena occur also after the administration of thyroid
extract in large doses to normal subjects. In the course of
sexual activities there is an increased action of the thyroid,
which is indicated by an increase in its size and vascularity.
That in fear and in injury the thyroid, in cases of Graves'
disease, is probably stimulated to increased activity is indicated
by the increased activity of the thyroid circulation, by an increase
in the size of the gland, by the histologic appearance of activity
in the nuclei of the cells, and by an increase of the toxic symptoms.
Finally, Asher has stated that electric stimulation of the nerve supply
of the thyroid causes an increased secretion. The origin of many cases
of Graves' disease is closely associated with some of the causes
of the discharge of nervous energy, depressive influences especially,
such as nervous shocks, worry and nervous strain, disappointment in love,
business reverses, illness and death of relatives and friends.
The association of thyroid activity with procreation is well known,
hence the coincidence of a strain of overwork or of fear with
the sexual development of maturing girls is obviously favorable
to the incidence of Graves' disease. The presence of a colloid goiter
is a suitable soil for the development of Graves' disease, and I
fully recognize also the evidence that infection or auto-intoxication
may be contributing factors and must be assigned their role.
I have never known a case of Graves' disease to be caused by success
or happiness alone, or by hard physical labor unattended by
psychic strain, or to be the result of energy voluntarily discharged.
Some cases seem to have had their origin in overdosage with thyroid
extract in too vigorous an attempt to cure a colloid goiter.
One of the most striking characteristics of Graves' disease is
the patient's loss of control and his increased susceptibility
to stimuli, especially to trauma and to fear and to the administration
of thyroid extract. It has been shown that the various causes
of the discharge of nervous energy produce alterations in the nervous
system and probably in the thyroid gland. This is especially
true of the fear stimulus, and has been clearly demonstrated
in the brains of rabbits which had been subjected to fear alone
(Fig. 13). Of special interest was the effect of daily fright.
In this case the brain-cells showed a distinct change, although the animal
had been subjected to no fear for twenty-four hours before it was killed
(Fig. 13 C. Now, a great distinction between man and the lower
animals is the greater control man has acquired over his actions.
This quality of control, having been phylogenetically most recently
acquired, is the most vulnerable to various NOCUOUS influences.
The result of a constant noci-integration may be a wearing-out
of the control cells of the brain. In a typical case of Graves'
disease a marked morphologic change in the brain-cells has
been demonstrated (Fig. 15). As has been previously stated,
the origin of many cases of Graves' disease is associated
with some noci-influence. If this influence causes stimulation
of both the brain and the thyroid, its excessive action may cause
impairment of the brain and also hyperplasia of the thyroid.
As self-control is impaired, fear obtains an ascendency and,
_pari passu_, stimulates the thyroid still more actively (Fig. 16).
Finally, the fear of the disease itself becomes a noci-stimulus.
As the thyroid secretion causes an increase in the facility
with which nervous energy is discharged, a pathologic reciprocal
interaction is established between the brain and the thyroid.
The effect of the constantly recurring stimulus of the noci-influence
is heightened by summation. This reciprocal goading may
continue until either the brain or the thyroid is destroyed.
If the original noci-stimulus is withdrawn before the fear of the
disease becomes too strong, and before too much injury to the brain
and the thyroid has been inflicted, a spontaneous cure may result.
Recovery may be greatly facilitated by complete therapeutic rest.
A cure implies the return of the brain-cells to their normal state,
with the reestablishment of the normal self-control and the
restoration of the thyroid to its normal state, when the impulses
of daily life will once more have possession of the final
common path and the noci-influence will be dispossessed.
The discovery of the real cause of a given case of Graves' disease is
frequently difficult because it may be of a painful personal nature.
Of extreme interest is the fact that, in the acute stage,
the patient may be unable to refer to the exciting cause without
exhibiting an exacerbation of the symptoms of the disease.
I presume no case should be regarded as cured until reference
can be made to its cause without an abnormal reaction.
It has been established that in Graves' disease injury to any part
of the body, even under inhalation anesthesia, causes an exacerbation
of the disease. Fear alone may cause an acute exacerbation.
These acute exacerbations are frequently designated "hyperthyroidism"
and are the special hazard of operation.
In applying the principle of anoci-association in operations on
patients with Graves' disease there is scarcely a change in the pulse,
in the respiration, or in the nervous state at the close of the operation.
I know no remedy which can obviate the effect of the inflowing
stimuli from the wound after the cocain[*] has worn off.[t] It
is necessary, therefore,