The effect of certain endocrine glands on myasthenia gravis

Abstract

S INCE Thomas Willis' first description of myasthenia gravis in 1672, each of the glands of internal secretion have been thought by some investigators to be related either to the cause or the course of this disease. The pertinent literature on this subject up to the last decade has been reviewed by McEachern I and Goni. 2 I t may be stated at the outset that ten years later there is still no convincing evidence that myasthenia gravis is a specific type of endocrinopathy. However, it is possible to demonstrate that certain hormonal principles of the thyroid, adrenal and pituitary glands are able to modify the altered neuromuscular transmission seen in these patients. While the precise mechanisms of this action are still obscure, it is believed that this may well prove to be a fruitful avenue of approach to an understanding of the basic pathophysiology of myasthenia gravis. In addition to the influence of pregnancy and menstruation on this disease (which is the subject of another presentation at this conference), perhaps the most interesting relationship is between the thyroid and myasthenia gravis. In discussing this we must first eliminate those patients with thyrotoxic and exophthalmic ophthalmoplegia ''3,4 who do not have true myasthenia gravis. This leaves a much smaller group--perhaps two dozen or so well documented cases--in which there is coincident hyperthyroidism and true myasthenia. 5,6'34 Most of the patients have been women between the ages of twenty to fifty-nine years who have shown characteristic improvement in their myasthenia with prostigmin. ® In four instances in which the myasthenia preceded the thyrotoxicosis, the onset of the latter resulted in improvement in two of the myasthenics, while t reatment of the hyperthyroidism made the myasthenia worse. This interesting see-saw relationship, originally commented on by McEachern, 5 has also been recently described by Maclean and Wilson. 6 Levitt 1~ urges combined thyroidectomy and thymectomy in these cases and reports good results in six patients with thyrotoxicosis and myasthenia gravis so treated. The cases described by Laurent 7 and Waldenstr6m 8 and designated as acute thyrotoxic bulbar palsy or acute thyrotoxic encephalomyopathy are quite likely fulminant cases of myasthenia gravis associated with hyperthyroidism. Tha t there is some over lap between these and the previously described cases is indicated by the sudden death (in respiratory failure) of three of twenty-one reported cases of chronic thyrotoxic myopathy 3,9,1° and the observation of McEachern and Ross 3 that prostigmin produced significant improvement in some but not all of these same cases. Finally, the interesting association between hypothyroidism and myotonia, the mir ror image of myasthenia gravis as far as neuromuscular transmission is concerned, may be ment ioned? ~ Three interesting laboratory observations are worth mentioning in connection with the thyroid gland. Tickner 12 is said to have found significant increase in serum cholinesterase levels in 50 per cent of thirty-five patients with thyrotoxicosis. Rawson t3 has reported that the thyrotropic factor (TSH) of the adenohypophysis is inactivated not only by iodides and thyroxine but also by thymus tissue. Finally, focal collections of lymphocytes ( lymphorrhages) are quite common in extraocular and somatic muscles in hyperthyroidism as well as in myasthenics. 14 Nevertheless it is the rare patient with myasthenia gravis who will show any obvious clinical signs of thyrotoxicosis or any demonstrable alteration in the basal metabolism rate or serum cholesterol values. I f there is a report of