Intratumoral Steroid Profiling of Adrenal Cortisol-Producing Adenomas by Liquid Chromatography- Mass Spectrometry.

Jun 7, 2021

Contributor: James P Teuber,Kazutaka Nanba,Adina F Turcu,Xuan Chen,Lili Zhao,Tobias Else,Richard J Auchus,William E Rainey,Juilee Rege

Intratumoral Steroid Profiling of Adrenal Cortisol-Producing Adenomas by Liquid Chromatography- Mass Spectrometry.

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 adrenal 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.
Copyright © 2021. Published by Elsevier Ltd.

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About The Expert

James P Teuber

Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA.

Kazutaka Nanba

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, 612-8555, Japan; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA.

Adina F Turcu

Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA.

Xuan Chen

Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, 612-8555, Japan; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA.

Lili Zhao

Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, 612-8555, Japan; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA.

Tobias Else

Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA.

Richard J Auchus

Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA.

William E Rainey

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA.

Juilee Rege

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109, USA. Electronic address: juilee@umich.edu.

References

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