On the function of the endocrine glands in myotonic muscular dystrophy

Abstract

M YOTONIC muscular dystrophy (myotonia dystrophica, Steinert’s disease) is a disease of unknown cause characterized by familial incidence, inheritance as a dominant trait with variable penetrance [Z], myopathy involving chiefly the distal musculature of the extremities and cranial muscles, the myotonic phenomenon, cataracts and osseous lesions [3,4]. Three other features of myotonic muscular dystrophy that have aroused interest concern the function of the endocrine glands in this disorder. These are testicular atrophy, low basal metabolic rate and the frequent finding of subnormal values for urinary 17-ketosteroids [5,6]. Aside from their intrinsic interest as characteristics of myotonic dystrophy and not of other forms of muscular dystrophy [5], these manifestations have directed attention to the possible role of humoral factors in the pathogenesis of the disease. Testicular atrophy is the most prominent glandular abnormality in myotonic muscular dystrophy [5,6]. The muscular weakness and poor muscle development of eunuchs have raised the possibility of a relationship between androgen deficiency and the muscle wasting which is characteristic of the disorder [7]. It is unlikely that such a relationship would be obligatory, in view of the fact that women have myotonic muscular dystrophy (there is no sexual predisposition) and in males atrophy of the muscles often precedes atrophy of the testes. Nevertheless, several attempts have been made to treat afflicted patients with testosterone [7]. The effects of adrogen therapy upon muscular function, measured by various mechanical indices, have been reported to be beneficial in two instances [7], equivocal or negative in the rest [4,8,9]. The common finding of a low basal metabolic rate has naturally suggested the possibility of reduced thyroid function [4,8]. This possibility is of special interest in view of the reported instances of the myotonic phenomenon occurring in myxedema [70-121, and allegedly disappearing after adequate thyroid replacement therapy [10,12]. The concept of hypothyroidism as an important mechanism of pathogenesis of myotonic dystrophy seems hard to sustain, since this association is very rare; overt hypothyroidism in a patient with myotonic muscular dystrophy has been reported only once [23], and more specific indices of thyroidal function, e.g., thyroidal I13i uptake [S, 73,141, pl asma half-life of administered I13i [14], response to thyrotropin [6,74], and serum precipitable iodine values [ 13,741 are generally normal. The question of reduced adrenal cortical capacity has been raised by pathologic findings [75-171, by the observation of low urinary 17ketosteroid values [4,6,15,78], by the reportedly inadequate response of plasma and urinary steroid levels to stimulation with adrenocorticotropin [9,79], and the frequent improvement of the myotonic phenomenon (but not of the muscular atrophy) following the administration of ACTH or adrenal cortical steroids to patients with the disease [9,2&22]. Whatever the implications of these findings may be, no instance of Addison’s disease has yet been reported in association with myotonia dystrophica [5]. Disorders of other endocrine organs have also been implicated. “Minor abnormalities”