Impaired Glucose Metabolism in Primary Aldosteronism Is Associated With Cortisol Cosecretion

Context: Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and metabolic risks. Recent studies report glucocorticoid cosecretion as a relevant phenotype of PA, which could contribute to associated risks, including type 2 diabetes mellitus (T2DM). The relationship between autonomous cortisol secretion (ACS) and glucose metabolism in PA has not been investigated. Objective: To evaluate the prevalence of impaired glucose homeostasis in patients with PA according to cortisol cosecretion. Design: We performed oral glucose tolerance tests (OGTTs) and complete testing for hyper-cortisolism [1-mg dexamethasone suppression test (DST), late-night salivary cortisol, 24-hour urinary free cortisol] in 161 newly diagnosed patients with PA of the German Conn Registry. Seventy-six of 161 patients were reevaluated at follow-up. We compared our results to a population-based sample from the Cooperative Health Research in the Region of Augsburg (KORA)-F4 study matched to the participants with PA (3:1) by sex, age, and body mass index. Results: At the time of diagnosis, 125 patients (77.6%) had a pathological response in at least one of the Cushing screening tests; T2DM was diagnosed in 6.4% of these 125 cases. Patients with a pathological DST exhibited significantly higher 2-hour plasma glucose in OGTTs and were significantly more often diagnosed with T2DM than were patients with a normal DST (20% vs 0.8%, P < 0.0001) and matched controls from the KORA study (20.6% vs 5.9%, P = 0.022). Patients with PA without ACS tended to have higher homeostatic model assessment of insulin resistance levels than did KORA control subjects (P = 0.05). Conclusion: ACS appears frequently in patients with PA and is associated with impaired glucose metabolism, which could increase the risk of T2DM. PA itself seems to enhance insulin resistance.