In situ metabolomics of aldosterone-producing adenomas

Murakami, Masanori; Rhayem, Yara; Kunzke, Thomas; Sun, Na; Feuchtinger, Annette; Ludwig, Philippe; Strom, Tim Matthias; Gomez-Sanchez, Celso; Knösel, Thomas; Kirchner, Thomas; Williams, Tracy Ann; Reincke, Martin; Walch, Axel Karl and Beuschlein, Felix (5. September 2019): In situ metabolomics of aldosterone-producing adenomas. In: JCI Insight, Vol. 4, No. 17, e130356

Abstract

Recent genetic examinations and multisteroid profiles have provided the basis for subclassification of aldosterone-producing adenomas (APAs). The objective of the current study was to produce a comprehensive, high-resolution mass spectrometry imaging (MSI) map of APAs in relation to morphometry, immunohistochemical profiles, mutational status, and clinical outcome. The study cohort comprised 136 patients with unilateral primary aldosteronism. Matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance MSI was conducted, and metabolite profiles were analyzed with genotype/phenotype information, including digital image analysis from morphometry and IHC of steroidogenic enzymes. Distinct molecular signatures between KCNJ5- and CACNA1D-mutated APAs with significant differences of 137 metabolites, including metabolites of purine metabolism and steroidogenesis, were observed. Intratumor concentration of 18-oxocortisol and 18-hydroxycortisol were inversely correlated with the staining intensity of CYP11B1. Lower staining intensity of CYP11B1 and higher levels of 18-oxocortisol were associated with a higher probability of complete clinical success after surgery. The present study demonstrates distinct metabolomic profiles of APAs in relation to tumor genotype. In addition, we reveal an inverse correlation between cortisol derivatives and CYP11B1 and the impact of 18-oxocortisol and CYP11B1 on clinical outcome, which provides unprecedented insights into the pathophysiology, clinical features, and steroidogenesis of APAs.

• Item Type: Journal article
• EU Funded Grant Agreement Number: 694913
• EU Projects: Horizon 2020 > ERC Grants > ERC Advanced Grant > ERC Grant 694913: PAPA - Pathophysiology of Primary Aldosteronism
• Form of publication: Publisher's Version
• Keywords: Endocrinology; Hypertension
• Faculties: Medicine > Medical Center of the University of Munich > Medical Clinic and Outpatient Clinic IV (Endocrinology, nephrology, other sections)
• Subjects: 600 Technology > 610 Medicine and health
• Language: English