Prevalence of cortisol cosecretion in patients with primary aldosteronism: role of metanephrine in adrenal vein sampling

Context: Adrenal venous sampling (AVS) is the gold standard procedure for subtype diagnosis in patients with primary aldosteronism (PA). Cortisol is usually adopted for the normalization of aldosterone levels in peripheral and adrenal samples. However, asymmetrical cortisol secretion can potentially affect the lateralization index, leading to subtype misdiagnosis. Objective: We aimed to assess the prevalence of asymmetrical cortisol secretion in patients undergoing AVS and whether variations in adrenal vein cortisol might influence AVS interpretations. We then evaluated the use of metanephrines for the normalization of aldosterone levels for lateralization index. Design, patient, setting and main outcome measures: We retrospectively included 101 patients with PA who performed AVS: 49 patients underwent unstimulated AVS, while 52 patients underwent both, unstimulated and cosyntropin stimulated AVS. Eighty-eight patients had bilateral successful AVS according to metanephrine ratio. We assessed the prevalence of asymmetrical cortisol secretion through the cortisol-to-metanephrine (C/M) lateralization index (LI). We then evaluated whether the use of aldosterone-to-metanephrine (A/M) LI can improve the diagnostic accuracy of AVS compared to aldosterone-to-cortisol (A/C) LI. Results: Asymmetrical cortisol secretion is present in 18% of patients with PA. Diagnosis with A/M LI and A/C LI is discordant in 14% of patients: 9% had a diagnosis of UPA with A/M LI instead of BiPA with A/C LI and 5% had a diagnosis of BiPA with A/M LI instead of UPA. Conclusions: The assessment of metanephrine levels in AVS is useful for the determination of selectivity and lateralization, allowing an accurate diagnosis, especially in patients with asymmetrical cortisol secretion.