ACTH-independent production of 11-oxygenated androgens and glucocorticoids in an adrenocortical adenoma

in European Journal of Endocrinology
Authors:
Takuya KitamuraDepartment of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

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Amy R BlinderDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA

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Kazutaka NanbaDepartment of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute

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https://orcid.org/0000-0002-6475-5141
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Mika TsuikiDepartment of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

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Mutsuki MishinaDepartment of Urology

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Hiroshi OkunoDepartment of Urology

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Koki MoriyoshiDepartment of Diagnostic Pathology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

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Yuto YamazakiDepartment of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Hironobu SasanoDepartment of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Keisuke YoneyamaAska Pharma Medical Co. Ltd., Fujisawa, Japan

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Aaron M UdagerDepartment of Pathology
Michigan Center for Translational Pathology
Rogel Cancer Center

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William E RaineyDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan, USA

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Akihiro YasodaClinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

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Noriko Satoh-AsaharaDepartment of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute

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Tetsuya TagamiDepartment of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute

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Correspondence should be addressed to K Nanba; Email: knamba@umich.edu

*(T Kitamura and A R Blinder contributed equally to this work)

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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.

Significance statement

Due to its rarity, biochemical and histologic characteristics of androgen and glucocorticoid co-secreting adrenocortical adenomas are largely unknown. Herein, we report a case of adrenocortical adenoma that caused marked hyperandrogenemia and mild autonomous cortisol secretion. In this study, we investigated serum steroid profiles using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and histologic characteristics of the resected tumor. LC-MS/MS revealed highly elevated levels of 11-oxygenated androgens which have not been well studied in adrenal tumors. The expression patterns of steroidogenic enzymes determined by immunohistochemistry supported the results of steroid profiling and suggested the capacity of the tumor cells to produce 11-oxygenated androgens. Measurement of 11-oxygenated steroids should facilitate a better understanding of androgen-producing adrenocortical neoplasms.

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