The influence of the thyroid on adrenal cortical function.

The evidence is quite conclusive from animal studies that an excess of circulating thyroid hormone results in adrenal enlargement, and hypothyroidism produced by surgical thyroidectomy or by administration of antithyroid drugs results in adrenal atrophy. This subject has been extensively reviewed by Money (1). Studies of adrenal size in patients with thyroid disease coming to autopsy have yielded conflicting reports. Means (2) reported no change in adrenal size in hyperthyroidism, Marine (3) and LeCompte (4) reported a decrease in size of the adrenal, and Holst (5) found enlarged adrenals in some patients with hyperthyroidism. Berkheiser (6) reported an advanced case of hypothyroidism, with atrophy of the adrenals and lipoid depletion. Measurements of adrenal size may not, however, always represent a completely satisfactory "yardstick" for evaluation of adrenal cortical secretory activity (7, 8). In the past few years, several investigators have reported measurements of various plasma and urinary steroid fractions in hyperand hypothyroidism in man. Several investigators have reported on the levels of free urinary corticoids (9-12) in hyperthyroidism, and in myxedema (9, 10). Because of the relatively nonspecific methods of assay used these data are difficult to interpret. Urinary 17-ketosteroids have usually been found to be low in both hyperand hypothyroidism (9-18). Plasma 17,21-dihydroxy-20-ketosteroids have been reported to be normal in these diseases (19-21). Guinea pigs, which excrete a large fraction of the cortisol metabolites as free 17,21-dihydroxy-20-ketosteroids, show an increased excretion of free urinary corticoids after administration of thyroxine (20). In patients with clinical myxedema, the urinary level of the total free and glucuronide conjugated 17,21dihydroxy-20-keteosteroids has been found to be decreased, whereas in hyperthyroidism the level of these urinary steroids is either normal or slightly increased (20). Thyroidectomized rats (22) and cats (23) are reported to survive adrenalectomy better than animals with an intact thyroid, and administration of thyroid to the adrenalectomized cats produced sudden death of the animals. Also, in patients with Addison's disease, acute adrenal cortical failure may be precipitated if thyroid hormone is administered (24, 25). Primary myxedema has been observed in which the presenting findings were those of adrenal cortical insufficiency, and adrenal function returned to normal following thyroid hormone therapy (26). With the advent of new and improved methods for the measurement of certain of the adrenal cortical hormones, and the availability of cortisol4-C14, it has become possible to further study the relationship of the thyroid hormone to adrenal cortical function. These techniques have been applied to a study of the rate of degradation and the rate of synthesis of cortisol in myxedema and thyrotoxicosis, before and after therapy. In this manner, much new information has been gained regarding the state of activity of the adrenal cortex in these diseases.