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Virilization in Bilateral Macronodular Adrenal Hyperplasia Controlled by Luteinizing Hormone

Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine and Gonda Diabetes Center (M.O.G., A.J.V.H.) and Department of Pathology and Laboratory Medicine (D.W.D., P.S.), University of California Los Angeles School of Medicine, Los Angeles, California 90095; and Department of Obstetrics, Gynecology, and Women’s Health (X.L., Z.L., C.V.R.), University of Louisville Health Sciences Center, Louisville, Kentucky 40292

Address all correspondence and requests for reprints to: Mark O. Goodarzi, M.D., UCLA School of Medicine, Division of Endocrinology, Diabetes, and Hypertension, 200 UCLA Medical Plaza, Suite 530, Los Angeles, California 90095-7065. E-mail: mgoodarzi{at}mednet.ucla.edu.

We report a case of a virilized 59-yr-old woman with elevated serum testosterone levels and bilateral macronodular adrenal hyperplasia. The patient underwent laparoscopic right adrenalectomy, after which the elevated testosterone level transiently normalized. The immediate postoperative depression of the testosterone level suggested that the process was driven by gonadotropins that were suppressed by the stress of surgery. The excised right adrenal mass contained testosterone by immunohistochemistry and LH receptor mRNA by in situ hybridization. The recurrence of hyperandrogenemia suggested that the enlarged left adrenal was also secreting testosterone. The serum testosterone level increased in response to im injection of human chorionic gonadotropin, suggesting control by aberrant LH receptors. Injection of leuprolide acetate (7.5 mg im) to suppress LH levels resulted in normalization of the testosterone level 12 d later that persisted for several weeks. Ectopic receptors mediating Cushing’s syndrome have been described in several cases of bilateral adrenal hyperplasia and adrenal adenoma. This is the first case to our knowledge in which pure androgen overproduction in adrenal hyperplasia has been shown to be controlled by LH receptors. In our patient, the control of androgen secretion by LH may explain the postmenopausal onset of virilization and the transient postoperative normalization of the serum testosterone level.

Abbreviations: hCG, Human chorionic gonadotropin; SSC, saline sodium citrate.

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