Plasma steroid profiling between patients with and without diabetes mellitus in non-functioning adrenal incidentalomas

Abstract

Abstract Context Adrenal incidentalomas (AI), including non-functioning AI (NFAI), are associated with a high prevalence of diabetes mellitus (DM). While NFAI is diagnosed by exclusion when no hormone excess exists, subtle cortisol secretion may exist and contribute to DM development. However, it alone cannot explain the increased risk, and whether other steroid metabolites are involved remains unclear. Purpose To investigate steroid metabolites associated with DM in patients with NFAI using plasma steroid profiles. Methods Using liquid chromatography-tandem mass spectrometry, 22 plasma steroid metabolites were measured in 68 patients with NFAI (31 men and 37 women). Data were adjusted for age before normalization. Results Discriminant analysis showed that plasma steroid profiles discriminated between patients with and without DM in men (n = 10 and = 21, respectively), but not women: 11β-hydroxytestosterone, an adrenal-derived 11-oxygenated androgen, contributed most to this discrimination and was higher in patients with DM than in those without DM (false discovery rate = 0.002). 11β-hydroxytestosterone was correlated positively with fasting plasma glucose (r = 0.507) and hemoglobin A1c (HbA1c) (r = 0.553), but negatively with homeostatic model assessment of β-cell function (HOMA2-B) (r = -0.410). These correlations remained significant after adjusting for confounders, including serum cortisol after the 1-mg dexamethasone suppression test. Bayesian Kernel Machine Regression analysis verified the association of 11β-hydroxytestosterone with HbA1c and HOMA2-B in men. Main conclusions Plasma steroid profiles differed between those with and without DM in men with NFAI. 11β-hydroxytestosterone was associated with hyperglycemia and indicators related to pancreatic β-cell dysfunction, independently of cortisol.