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Murakami, M.* ; Sun, N. ; Li, F. ; Feuchtinger, A. ; Gomez-Sanchez, C.* ; Fassnacht, M.* ; Reincke, M.* ; Bancos, I.* ; Walch, A.K. ; Kroiss, M.* ; Beuschlein, F.*

In situ metabolomics of cortisol-producing adenomas.

Clin. Chem. 69, 149-159 (2023)
Postprint DOI PMC
Open Access Green
BACKGROUND: Recent advances in omics techniques have allowed detailed genetic characterization of cortisol-producing adrenal adenoma (CPA). In contrast, the pathophysiology of CPAs has not been elucidated in detail on the level of tumor metabolic alterations. METHODS: The current study conducted a comprehensive mass spectrometry imaging (MSI) map of CPAs in relation to clinical phenotypes and immunohistochemical profiles of steroidogenic enzymes. The study cohort comprised 46 patients with adrenal tumors including CPAs (n = 35) and nonfunctional adenomas (n = 11). RESULTS: Severity of cortisol hypersecretion was significantly correlated with 29 metabolites (adjusted P < 0.05). Adrenal androgens derived from the classic androgen pathway were inversely correlated with both cortisol secretion (rs = -0.41, adjusted P = 0.035) and CYP11B1 expression (rs = -0.77, adjusted P = 2.00E-08). The extent of cortisol excess and tumor CYP11B1 expression further correlated with serotonin (rs = 0.48 and 0.62, adjusted P = 0.008 and 2.41E-05). Tumor size was found to be correlated with abundance of 13 fatty acids (adjusted P < 0.05) and negatively associated with 9 polyunsaturated fatty acids including phosphatidic acid 38:8 (rs = -0.56, adjusted P = 0.009). CONCLUSIONS: MSI reveals novel metabolic links between endocrine function and tumorigenesis, which will further support the understanding of CPA pathophysiology.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cushing Syndrome ; Adrenal Adenoma ; Cortisol ; Metabolome ; Steroidogenic Enzyme; Mass-spectrometry; Adrenal Incidentalomas; Patterns
ISSN (print) / ISBN 0009-9147
e-ISSN 1530-8561
Journal Clinical Chemistry
Quellenangaben Volume: 69, Issue: 2, Pages: 149-159 Article Number: , Supplement: ,
Publisher American Association for Clinical Chemistry
Publishing Place Journals Dept, 2001 Evans Rd, Cary, Nc 27513 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Analytical Pathology (AAP)
CF Pathology & Tissue Analytics (CF-PTA)
Grants NIDDK NIH HHS
NIH HHS