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Adrenocorticotropin-Independent Bilateral Macronodular Adrenal Hyperplasia: An Unusual Cause of Cushing’s Syndrome^*

Departments of Medicine, Surgery, and Radiology, University of Connecticut Health Center (C.D.M., J.R., R.A.K., G.R.R., D.M.M.) Farmington, Connecticut 06032
The Departments of Medicine and Pathology, Vanderbilt University Medical Center (C.R.D., D.L.P., D.N.O.) Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: Carl D. Malchoff, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06032.

Inappropriate ACTH secretion with bilateral diffuse or macronodular adrenal hyperplasia is the most common cause of Cushing’s syndrome. This report describes a patient with Cushing’s syndrome and feminization due to ACTH-independent bilateral macronodular adrenal hyperplasia. A 47-yrold black man presented with Cushingoid features, diabetes mellitus, hypertension, impotence, and gynecomastia. Urinary cortisol and 17-hydroxycorticosteroid excretion were 94 nmol/mmol creatinine (normal, <32) and 5.8 µmol/mmol creatinine (normal, 0.6–3.6), respectively. Both decreased by less than 30% after administration of dexamethasone (8 and 16 mg/day), and urinary 17-hydroxycorticosteroid excretion did not increase after metyrapone (750 mg, orally, every 4 h for six doses). Plasma ACTH was undetectable (<1 pmol/L) and was not stimulated by administration of metyrapone or ovine CRH. Serum testosterone was 5.2 nmol/L (normal, 7–30), FSH was 5 U/L (normal, 3–18), LH was 2.8 U/L (normal, 1.5–9.2), and estrone was 767 pmol/L (normal, 55–240). Both adrenal glands were enlarged, with a total weight of 86 g (normal, 8–10), and contained multiple nodules (diameter, >0.5 cm) composed of two active cell types, one of which was also observed between the nodules. Cushing’s syndrome with feminization due to ACTH-independent bilateral macronodular adrenal hyperplasia is an unusual process of unknown etiology that should be included with the other known causes of Cushing’s syndrome.

^* This work was supported by the Centers of Excellence Program, Department of Higher Education, State of Connecticut Award to the Clinical Research Center, University of Connecticut Health Center, and in part by USPHS Grants 2-R01-DK-33334 from the NIDDK and 2-R01-CA-11685 from the NCI.

Received July 11, 1988.

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