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Wada N, Kubo M, Kijima H, Ishizuka T, Saeki T, Koike T, Sasano H. Adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia: immunohistochemical studies of steroidogenic enzymes and post-operative course in two men. Eur J Endocrinol 1996;134:583–7. ISSN 0804–4643

We treated two men with Cushing's syndrome due to adrenocorticotropin (ACTH)-independent bilateral macronodular adrenocortical hyperplasia (AIMAH). In both patients, plasma ACTH was low and plasma cortisol was not suppressed by a high dose of dexamethasone (8 mg) but was remarkably responsive to exogenous ACTH. The adrenal glands were extremely enlarged and contained multiple nodules composed of large clear cells and small compact cells. The immunore-activity of P-450_17α was predominant in the small compact cells, while that of 3β-hydroxysteroid dehydrogenase (3 β-HSD) was observed exclusively in the large clear cells. Among various adrenocortical disorders, differential expression of 3β-HSD and P-450_17α in clear and compact cells has heretofore been demonstrated only in AIMAH. Total adrenalectomy was done for one patient, and partial adrenalectomy for the other. In the former patient, the normal diurnal rhythm of plasma ACTH was restored 11 months postoperatively. In the latter patient, the normal dynamics in the hypothalamic-pituitary-adrenal axis became evident 15 months after surgery. Thus AIMAH is apparently a primary adrenocortical disorder and is not due to abnormalities of the hypothalamus or pituitary.

Mitsumasa Kubo, Department of Medicine II, Hokkaido University School of Medicine, Kita-15, Nishi-7, Kita-Ku, Sapporo 060, Japan

Although excess production of androgens and glucocorticoids has often been observed in adrenocortical carcinomas, adrenocortical adenoma with such hormonal activity is rare. Herein, we report a 41-year-old woman who presented with hyperandrogenemia and mild autonomous cortisol secretion with an undetectable level of adrenocorticotropic hormone. Imaging demonstrated a 6 cm left adrenal tumor. The histologic diagnosis of the resected adrenal tumor was adrenocortical adenoma. Pre- and post-operative serum samples were used for steroid profiling with liquid chromatography-tandem mass spectrometry (LC-MS/MS). LC-MS/MS analysis of pre-operative serum revealed an abnormal buildup of steroid precursors and androgens. Importantly, circulating levels of 11-oxygenated androgens, including 11β-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT), were highly elevated. Both androgen and glucocorticoid levels significantly decreased post-operatively. Immunohistochemical analysis of steroidogenic enzymes and cofactor protein supported the tumor’s ability to directly produce 11OHT and 11KT. This study is the first to describe and characterize an adrenocortical adenoma that co-secretes glucocorticoids and 11-oxygenated androgens.