Thyroid hormones and TSH were assessed before and after steroid replacement in 10 consecutive patients with nontuberculous primary adrenal insufficiency in order to study the numerous interactions between corticosteroids and thyroid function. Although none had clinical features of thyroid disease, 6 showed increased levels of plasma TSH before treatment in association with a wide range of circulating thyroid hormone levels. In 1 patient with positive thyroid autoantibodies, biochemical features of primary hypothyroidism resolved after steroid replacement, although TSH excess has persisted. In 5 patients, 2 of whom had adrenal insufficiency due to metastatic carcinoma, TSH decreased to normal after steroid replacement, and in 3 of these, the TSH decrease occurred without a change in normal circulating thyroid hormone levels, consistent with a direct influence of glucocorticoids on TSH release. Steroid treatment did not cause inverse changes in T₃ and rT₃, suggesting that physiological levels of adrenal steroids are not major determinants of T₄ deiodination. The capacity of T₄-binding globulin showed no significant change.

These findings suggest two reasons why a high plasma TSH level in untreated adrenal insufficiency can be an unreliable index of thyroid failure. Firstly, thyroid function can return towards normal after corticosteroid replacement. Alternatively, TSH may be increased as a direct result of steroid deficiency without thyroid malfunction. Hence, when TSH is assessed in adrenal insufficiency, a distinction must be made between values obtained before and after adrenal replacement.