Adrenal Steroid Metabolites and Bone Status in Patients with Adrenal Incidentalomas and Hypercortisolism

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2023 Aug 5

PMID 37543511

Authors

Hiroshi Nakao

Maki Yokomoto-Umakoshi

Kohta Nakatani

Hironobu Umakoshi

Masatoshi Ogata

Tazuru Fukumoto

Hiroki Kaneko

Norifusa Iwahashi

Masamichi Fujita

Tatsuki Ogasawara

Yayoi Matsuda

Ryuichi Sakamoto

Yoshihiro Izumi

Takeshi Bamba

Yoshihiro Ogawa

Affiliations

Soon will be listed here.

Abstract

Background: Autonomous cortisol secretion (ACS), resulting from cortisol-producing adenomas (CPA), causes endogenous steroid-induced osteoporosis (SIOP). However, the risk of endogenous SIOP cannot be explained by cortisol excess alone, and how other steroid metabolites affect bone status is unclear.

Methods: ACS was diagnosed as serum cortisol ≥1.8 μg/dL after the 1-mg dexamethasone suppression test (DST-cortisol). Using liquid chromatography tandem mass spectrometry, 21 plasma steroid metabolites were measured in 73 patients with ACS and 85 patients with non-functioning adrenal tumors (NFAT). Expression of steroidogenic enzymes and relevant steroid metabolites were analyzed in some of CPA tissues.

Findings: Discriminant and principal component analyses distinguished steroid profiles between the ACS and NFAT groups in premenopausal women. Premenopausal women with ACS exhibited higher levels of a mineralocorticoid metabolite, 11-deoxycorticosterone (11-DOC), and lower levels of androgen metabolites, dehydroepiandrosterone-sulfate, and androsterone-glucuronide. In premenopausal women with ACS, DST-cortisol negatively correlated with trabecular bone score (TBS). Additionally, 11-DOC negatively correlated with lumbar spine-bone mineral density, whereas androsterone-glucuronide positively correlated with TBS. The CPA tissues showed increased 11-DOC levels with increased expression of CYP21A2, essential for 11-DOC synthesis. Adrenal non-tumor tissues were atrophied with reduced expression of CYB5A, required for androgen synthesis.

Interpretation: This study demonstrates that unbalanced production of adrenal steroid metabolites, derived from both adrenal tumor and non-tumor tissues, contributes to the pathogenesis of endogenous SIOP in premenopausal women with ACS.

Funding: JSPS KAKENHI, Secom Science and Technology Foundation, Takeda Science Foundation, Japan Foundation for Applied Enzymology, AMED-CREST, JSTA-STEP, JST-Moonshot, and Ono Medical Research Foundation.

Citing Articles

Multiomics analysis unveils the cellular ecosystem with clinical relevance in aldosterone-producing adenomas with mutations.

Yokomoto-Umakoshi M, Fujita M, Umakoshi H, Ogasawara T, Iwahashi N, Nakatani K Proc Natl Acad Sci U S A. 2025; 122(9):e2421489122.

PMID: 40009643 PMC: 11892633. DOI: 10.1073/pnas.2421489122.

Plasma Steroid Profiling Between Patients With and Without Diabetes Mellitus in Nonfunctioning Adrenal Incidentalomas.

Nakano Y, Yokomoto-Umakoshi M, Nakatani K, Umakoshi H, Nakao H, Fujita M J Endocr Soc. 2024; 8(9):bvae140.

PMID: 39145114 PMC: 11322837. DOI: 10.1210/jendso/bvae140.

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