Cortisol measurements are essential for the interpretation of adrenal venous samplings (AVS) in primary aldosteronism (PA). Cortisol cosecretion may influence AVS indices. We aimed to investigate whether cortisol cosecretion affects non-ACTH stimulated AVS results. A retrospective cohort study was conducted at a tertiary referral center. We analyzed 278 PA patients who underwent non-ACTH stimulated AVS and had undergone at least a 1-mg dexamethasone suppression test (DST). Subsets underwent additional late-night salivary cortisol (LSC) and/or 24-hour urinary free cortisol (UFC) measurements. Patients were studied from 2013-2020 with follow-up data of 6 months following adrenalectomy or mineralocorticoid antagonist therapy initiation. We analyzed AVS parameters including adrenal vein aldosterone/cortisol ratios, selectivity, lateralization (LI) and contralateral suppression indices and post-operative ACTH-stimulation. We classified outcome according to PASO criteria. 18.9% had a pathological DST result (1.9-5 µg/dl: n=44 (15.8%); > 5 µg/dl: n=8 (2.9%)). Comparison of AVS results stratified according to the 1-mg DST (≤ 1.8 vs. >1.8 µg/dl: p=0.499; ≤ 1.8 vs. 1.8 ≤ 5 vs. > 5 µg/dl: p=0.811) showed no difference. Lateralized cases with post DST serum cortisol values > 5 µg/dL had lower LI (≤ 1.8 µg/dL: 11.11 [5.36; 26.76] vs. 1.9-5 µg/dL: 11.76 [4.9; 31.88] vs. > 5 µg/dL: 2.58 [1.67; 3.3]; p=0.008). PASO outcome was not different according to cortisol cosecretion. Marked cortisol cosecretion has the potential to influence non-ACTH stimulated AVS results. While this could result in falsely classified lateralized cases as bilateral, further analysis of substitutes for cortisol are required to unmask effects on clinical outcome.
