University of Virginia Library

Graves' Disease

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 rôle.

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.

FIG. 15
A: Section of Human Cerebellum—Normal (x310). B: Section of Human Cerebellum Showing Effect of Exophthalmic Goiter (x310). The Effect of Excessive Activation of the System with Thyroid Secretion is Shown by the Loss of Cytoplasm and the Degeneration of the Purkinje Cells.

[Description: Black-and-white photographs showing sections of human cerebellum under various conditions.]

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

FIG. 16—TYPICAL CASE OF EXOPHTHALMIC GOITER SHOWING CHARACTERISTIC FACIES.

[Description: Black-and-white photograph of woman with bulging eyes.]

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 reëstablishment 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[7] has worn off.[8] It is necessary, therefore,

not to venture too far in serious cases. Since the adoption of this new method (anoci-association) my operative results have been so vastly improved that I now rarely regard any case of Graves' disease as inoperable, at least to the extent of contraindicating a double ligation (Fig. 17).

If we believe that, in accordance with the law of phylogenetic association, a continuous stimulation of both the brain and the thyroid gland, accelerated by summation,

plays a rôle in the establishment of the pathologic interaction seen in Graves' disease, then it is but the next step to assume that if the nerve connection between the brain and the thyroid be severed, or if the lobe be excised and the patient reinforced by a sojourn in a sanatorium or in some environment free from former noci-associations, he may be restored to normal health, provided that the brain-cells, the heart, or other essential organs have not suffered irreparable damage. There are still many missing links in the solution of this problem, and the foregoing hypotheses are not offered as final, although from the viewpoint of the surgeon many of the phenomena of this disease are explicable.