Unique Sex Steroid Profiles in Estrogen-Producing Adrenocortical Adenoma Associated With Bilateral Hyperaldosteronism

Abstract

Because of its rarity, our understanding of steroidogenesis in estrogen-producing adrenocortical adenoma, including the response to adrenocorticotropic hormone (ACTH) stimulation, remains limited. A 65-year-old man was referred to us because of primary aldosteronism and a right adrenal tumor. Endocrinological evaluations revealed secondary hypogonadism due to hyperestrogenemia. Adrenal venous sampling (AVS) and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated bilateral hyperaldosteronism and a right estrogen-producing adrenocortical tumor. He subsequently underwent right unilateral adrenalectomy, which resulted in clinical remission of hypogonadism. Subsequent histopathological analysis identified a right estrogen-producing adrenocortical adenoma and multiple, concomitant adrenocortical micronodules. Sequential evaluation of steroid profiles using LC-MS/MS revealed unique hormone production, including adrenal androgens, and less responsiveness to ACTH in the right estrogen-producing adrenocortical adenoma as compared to the nonneoplastic adrenal cortex. This case study revealed unique profiles of steroid production in estrogen-producing adrenocortical adenoma associated with concomitant primary aldosteronism. Sequential steroid profiling analysis using LC-MS/MS in combination with AVS can contribute to the diagnosis of various adrenal disorders.

Keywords: ACTH; LC-MS/MS; adrenal venous sampling; estrogen-producing adrenocortical adenoma; primary aldosteronism.

Figure 1.

Immunohistochemical staining of the resected adrenal gland. A to L, Right adrenal tumor and M to O, adjacent adrenal gland. A, Hematoxylin-eosin (×200); B, 17α-hydroxylase (diffuse, ×200); C, 3β-hydroxysteroid dehydrogenase (partial, ×200); D, 17β-hydroxysteroid dehydrogenase 5 (focal, ×200); E, aromatase (focal, ×200); F, CYP11B1 (partial, ×200); G, dehydroepiandrosterone-sulfotransferase (diffuse, ×200); H, steroid sulfatase (diffuse, ×200); I, 5α reductase 1 (diffuse, ×200); J, 5α reductase 2 (diffuse, ×200); K, estrogen sulfotransferase (diffuse, ×200); L, aldosterone synthase (CYP11B2) (negative, ×200); M, Hematoxylin-eosin (×200); N, CYP11B2 (focal, ×200); O, dehydroepiandrosterone-sulfotransferase (diffuse, ×200).

Figure 2.

The steroidogenesis pathway of sex hormones. In this patient, immunohistochemical staining of the resected adrenal gland revealed expression of all the steroidogenic enzymes related to estrogens and their precursors, androstenedione and testosterone, in the estrogen-producing adenoma. Analysis of steroid profiles in peripheral and adrenal venous samples indicated that 11-oxygenated androgens were mainly secreted in the nontumoral adrenal cortex, although tumor cells partially showed CYP11B1 expression. 11-β-hydroxy-androstenedione; 11-OHAD, 11-OHT, 11-hydroxytestosterone; 11-ketoAD, 11-ketoandrostenedione;11-ketoT, 11-ketotestosterone; A4, androstenedione; A5, 5-androstene-3β,17β-diol; DHEA, dehydroepiandrosterone; DHEA-S, dehydroepiandrosterone sulfate; DHT, dihydrotestosterone; E1, estrone; E2, estradiol; T, testosterone.