Abstract
Most adrenocortical carcinomas (ACCs) produce excessive amounts of steroid hormones including aldosterone, cortisol, and steroid precursors. However, aldosterone- and cortisol-producing cells in ACCs have not yet been immunohistochemically described. We present a case of ACC causing mild primary aldosteronism and subclinical Cushing’s syndrome. Removal of the tumor cured both conditions. In order to examine the expression patterns of the steroidogenic enzymes responsible for adrenocortical hormone production, 10 tumor portions were immunohistochemically analyzed for aldosterone synthase (CYP11B2), 11β-hydroxylase (CYP11B1, cortisol-synthesizing enzyme), 3β-hydroxysteroid dehydrogenase (3βHSD, upstream enzyme for both CYP11B2 and CYP11B1), and 17α-hydroxylase/C17-20 lyase (CYP17, upstream enzyme for CYP11B1, but not for CYP11B1). CYP11B2, CYP11B1, and 3βHSD were expressed sporadically, and their expression patterns varied significantly among the different tumor portions examined. The expression of these enzymes was random and not associated with each other. CYP17 was expressed throughout the tumor, even in CYP11B2-positive cells. Small tumor cell populations were aldosterone- or cortisol-producing cells, as judged by 3βHSD coinciding with either CYP11B2 or CYP11B1, respectively. These results suggest that the tumor produced limited amounts of aldosterone and cortisol due to the lack of the coordinated expression of steroidogenic enzymes, which led to mild clinical expression in this case. We delineated the expression patterns of steroidogenic enzymes in ACC. The coordinated expression of steroidogenic enzymes in normal and adenoma cells was disturbed in ACC cells, resulting in the inefficient production of steroid hormones in relation to the large tumor volume.
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Acknowledgments
We thank Dr. Takeshi Yamazaki at Hiroshima University for providing us with the anti-3βHSD antibody; Mr. Shinya Sasai at Tachikawa Hospital for his technical assistance with immunohistochemistry; as well as funding support from the Japan Society for the Promotion of Science (KAKENHI-Grants to T.U [#23791043], K.N [#26893261], and KM [#26461387]), the Suzuken Memorial Foundation (to KN), Yamaguchi Endocrine Research Foundation (to KN), Okinaka Memorial Institute for Medical Research (to KN), Federation of National Public Service Personnel Mutual Aid Associations (to KN), NIH HL27255 (to CEG-S), and Initiative for Rare and Undiagnosed Diseases (IRUD) by AMED (to YK).
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Toyoyoshi Uchida and Koshiro Nishimoto contributed equally to this work.
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Uchida, T., Nishimoto, K., Fukumura, Y. et al. Disorganized Steroidogenesis in Adrenocortical Carcinoma, a Case Study. Endocr Pathol 28, 27–35 (2017). https://doi.org/10.1007/s12022-016-9441-8
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DOI: https://doi.org/10.1007/s12022-016-9441-8