CONTEXT Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and metabolic risks. Recent studies report glucocorticoid co-secretion 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 PA patients according to cortisol co-secretion. METHODS We performed oral-glucose-tolerance-tests (OGTT) and complete testing for hypercortisolism (1mg-dexamethasone-suppression-test (DST), late-night-salivary-cortisol (LNC), 24hour-urinary-free-cortisol (UFC)) in 161 newly diagnosed PA patients of the German Conn Registry. 76 of 161 patients were reevaluated at follow-up. We compared our results to a population-based sample from the KORA-F4 study matched to the PA participants (3:1) by sex, age, and BMI. 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 pathological DST exhibited significantly higher 2h plasma glucose in OGTT and were significantly more often diagnosed with T2DM than patients with normal DST (20% vs. 0.8%, p<0.0001) and matched controls from the KORA study (20.6% vs. 5.9%.; p=0.022). PA patients without ACS tended to have higher homeostatic-model-assessmentof-insulin-resistance (HOMA-IR) than KORA control subjects (p=0.05). CONCLUSION ACS appears frequently in PA patients and is associated with impaired glucose metabolism, which could increase the risk of T2DM. PA itself seems to enhance insulin resistance.

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