Endocrine activity of the "silent" adrenocortical adenoma is uncovered by response to corticotropin-releasing hormone.

The purpose of this study was to ascertain whether the pituitary-adrenal responses to human corticotropin-releasing hormone (hCRH) in "non-functioning" adrenocortical adenoma would uncover a functional activity in these adrenal nodules. Eleven patients with incidentally discovered "silent" adrenocortical adenoma and eleven controls were studied. The initial clinical and laboratory examination, including an overnight 1 mg dexamethasone suppression test, revealed no abnormalities in any of the subjects. IR-ACTH and serum steroids (F, S, P, 17OHP, 18OHB, and aldosterone) were normal in both controls and patients. After pulse IV injection of 100 micrograms hCRH, the cortisol response was significantly exaggerated (P = 0.01). Stimulated plasma ACTH levels were, however, significantly lower in patients than in controls (P = 0.01), indicating counter-feedback regulation of cortisol. The peak cortisol/peak ACTH ratio (Fmax/ACTHmax) in the patients was significantly elevated (26.8 +/- 4.37 nmol/ng vs. 14.6 +/- 2.16 nmol/ng, P = 0.02). Two further patients with incidentally discovered "pre-Cushing's" adrenocortical adenoma displayed an even higher ratio (43.5 and 45.5 nmol/ng). In established Cushing's syndrome due to an autonomous adrenocortical adenoma, suppression of ACTH and of the ACTH response to hCRH occurs with a very high basal cortisol/basal ACTH ratio. Our findings suggest some functional activity even in clinically "silent" adrenocortical adenoma. Response to hCRH uncovers a continuous spectrum between adrenocortical adenoma, "pre-Cushing's", and Cushing's syndrome.