In situ metabolomics of aldosterone-producing adenomas

• DOI: 10.1172/jci.insight.130356
• Publication Date: 2019-09-04T15:01:02Z
• Authors: Masanori Murakami; Yara Rhayem; Thomas Kunzke; Na Sun; Annette Feuchtinger; Philippe Ludwig; Tim Matthias Strom; Celso Gomez-Sanchez; Thomas Knösel; Thomas Kirchner; Tracy Ann Williams; Martin Reincke; Axel Karl Walch; Felix Beuschlein
• Keywords: Adenoma; Adult; Male; Calcium Channels, L-Type; Genotype; Hydrocortisone; 10265 Clinic for Endocrinology and Diabetology; 610 Medicine & health; 2700 General Medicine; Cohort Studies; 03 medical and health sciences; Hyperaldosteronism; Endocrinology; Hypertension; Humans; Metabolomics; Aldosterone; 0303 health sciences; Endocrinology ; Hypertension; Middle Aged; Adrenal Cortex Neoplasms; ddc:; Phenotype; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Adrenocortical Adenoma; Mutation; Steroid 11-beta-Hydroxylase; Female

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