New-onset diabetes mellitus risk associated with concurrent autonomous cortisol secretion in patients with primary aldosteronism

Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA patients) is not uncommon. This work aimed to determine the effect of cortisol levels on incident new-onset type 2 diabetes mellitus (NODM) in PA patients. Using the prospectively designed observational TAIPAI cohort, the PA patients were grouped by cortisol level after an overnight low-dose dexamethasone suppression test (1-mg DST). Of the 476 PA patients, 387 (43.7% men; mean age 52.8 years) did not have baseline DM. After a mean follow-up of 4.3 ± 2.9 years, 32 patients (8.3%) developed NODM. The cutoff value obtained via a generalized additive model showed that a serum cortisol level ≥ 2.65 µg/dL after 1-mg DST was a risk factor for developing NODM (HR, 3.5, p = 0.031) by Cox proportional- hazards model.. In PA patients with a higher body mass index (>25 kg/m 2 ; HR, 3.16), lower estimated glomerular filtration rate (<90 ml/min/1.73 m 2 ; HR, 3.18), longer hypertension duration (>7 years; HR, 3.34), and higher waist-to-hip ratio (>0.9; HR, 3.07), a concomitant cortisol level ≥ 2.65 μg/dL after 1-mg DST were more likely to develop NODM. The high-cortisol group of patients with aldosterone-producing adenoma (APA) using mineralocorticoid receptor antagonist (MRA) was associated with an increased risk of NODM (HR, 5.72). Our results showed that PA patients with a concomitant cortisol level ≥ 2.65 µg/dL after 1-mg DST, independent of the aldosterone level, had a higher incidence of NODM. Such PA patients should be carefully evaluated and managed to achieve better glucose control and prevent metabolic syndrome.