Graded Electrolyte Disturbances Across the Spectrum of Autonomous Cortisol Secretion in Patients with Adrenal...

Background/Objectives: Autonomous cortisol secretion (ACS), including mild autonomous cortisol secretion (MACS), nonfunctioning adrenal tumors (NFAT), and overt Cushing's syndrome (CS), is common in patients with adrenal incidentaloma (AI). Although ACS has been linked to adverse cardiometabolic outcomes, its association with renal function and electrolyte homeostasis has not been well characterized. To examine the associations of different degrees of ACS with renal function and serum electrolyte profiles in patients with AI. Methods: This retrospective single-center study included 575 adult patients with AI who underwent an overnight low-dose dexamethasone suppression test (LDDST). Patients were classified as having NFAT (n = 30), MACS (n = 236), or overt CS (n = 309) according to biochemical findings and clinical presentation. Clinical characteristics, hormonal parameters, estimated glomerular filtration rate (eGFR), and serum electrolyte levels were collected. Multivariable regression analyses were performed after adjustment for age, sex, tumor size, body mass index, hypertension, diabetes mellitus, smoking status, and alcohol consumption. Results: Compared with the NFAT and MACS groups, patients with overt CS were younger and predominantly female (84.5%), more frequently hypertensive, and had the highest serum and urinary free cortisol, the lowest ACTH, and the most pronounced electrolyte disturbances, with higher serum sodium and lower serum potassium (all p < 0.001). A pattern of electrolyte alterations was observed across the spectrum of cortisol autonomy (CS ≈ MACS > NFAT). Compared with NFAT, cortisol-secreting tumors were associated with higher serum sodium levels and lower serum potassium and calcium levels (p < 0.001). These associations remained significant after multivariable adjustment (p < 0.001). By contrast, although median eGFR differed among groups and tended to be higher in cortisol-secreting tumors, ACS was not significantly associated with clinically overt renal impairment based on categorical eGFR analysis. Conclusions: In patients with AI, increasing degrees of ACS are associated with alterations in electrolyte homeostasis, particularly involving sodium, potassium, and calcium. In contrast, no clear association was identified between ACS and clinically overt renal impairment in this cross-sectional cohort. Routine monitoring of electrolyte balance may be warranted in patients with cortisol-secreting adrenal tumors.