Intratumoral steroid profiling of adrenal cortisol-producing adenomas by liquid chromatography- mass spectrometry.

Abstract

Endogenous Cushing syndrome (CS) is an endocrine disorder marked by excess cortisol production rendering patients susceptible to visceral obesity, dyslipidemia, hypertension, osteoporosis and diabetes mellitus. Adrenal CS is characterized by autonomous production of cortisol from cortisol-producing adenomas (CPA) via adrenocorticotropic hormone-independent mechanisms. A limited number of studies have quantified the steroid profiles in sera from patients with CS. To understand the intratumoral steroid biosynthesis, we quantified 19 steroids by mass spectrometry in optimal cutting temperature compound (OCT)-embedded 24 CPA tissue from patients with overt CS (OCS, n = 10) and mild autonomous cortisol excess (MACE, n = 14). Where available, normal CPA-adjacent adrenal tissue (AdjN) was also collected and used for comparison (n = 8). Immunohistochemistry (IHC) for CYP17A1 and HSD3B2, two steroidogenic enzymes required for cortisol synthesis, was performed on OCT sections to confirm the presence of tumor tissue and guided subsequent steroid extraction from the tumor. LC-MS/MS was used to quantify steroids extracted from CPA and AdjN. Our data indicated that CPA demonstrated increased concentrations of cortisol, cortisone, 11-deoxycortisol, corticosterone, progesterone, 17OH-progesterone and 16OH-progesterone as compared to AdjN (p < 0.05). Compared to OCS, MACE patient CPA tissue displayed higher concentrations of corticosterone, 18OH-corticosterone, 21-deoxycortisol, progesterone, and 17OH-progesterone (p < 0.05). These findings also demonstrate that OCT-embedded tissue can be used to define intra-tissue steroid profiles, which will have application for steroid-producing and steroid-responsive tumors.

• Authors: James P Teuber, Kazutaka Nanba, Adina F Turcu, Xuan Chen, Lili Zhao, Tobias Else, Richard J Auchus, William E Rainey, Juilee Rege
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 212 Pg. 105924 (09 2021) ISSN: 1879-1220 [Electronic] England
• PMID: 34089832 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Steroids
• 3 beta-hydroxysteroid dehydrogenase type II
• Progesterone Reductase
• CYP17A1 protein, human
• Steroid 17-alpha-Hydroxylase

Topics

• Adenoma (blood, metabolism)
• Adrenal Cortex Neoplasms (blood, metabolism)
• Adult
• Chromatography, Liquid
• Cushing Syndrome (blood, metabolism)
• Female
• Humans
• Male
• Middle Aged
• Progesterone Reductase (metabolism)
• Steroid 17-alpha-Hydroxylase (metabolism)
• Steroids (blood, metabolism)
• Tandem Mass Spectrometry