Cognition in patients with mild autonomous cortisol secretion at baseline and post-adrenalectomy

Abstract

Objectives The impact of mild autonomous cortisol secretion (MACS) on cognition is incompletely characterized. We aimed to assess cognition in patients with MACS, identify factors associated with lower cognition, and determine the impact of adrenalectomy on cognition. Methods We conducted a cross-sectional study (4/2019 to 10/2022) and a longitudinal cohort study (10/2021-9/2023) of adults with MACS and referent subjects. Cognition was assessed with NIH Toolbox Cognition Battery and reported as standardized T-scores (adjusted for age, sex, race/ethnicity, and education) for fluid, crystallized, and total composite cognition. Participants were assessed with urine steroid profiling (liquid chromatography-tandem mass spectrometry), frailty index, Beck Depression Inventory (BDI), Short Form-36 (SF36). Results A total of 84 patients (median age 57 years, 67% women) and 201 referent subjects (median age 63 years, 58% women) were included. Patients with MACS demonstrated lower mean (SD) total composite (50.9 (9.3) vs 55.4 (8.9), P<0.001) and fluid composite T-score (49.3 (10.6) vs 55.2 (10.2), P<0.001), but not crystallized composite T-score (52.3 (8.4) vs 54.0 (8.4), P=0.130) when compared to referent subjects. Multivariable analysis adjusted for age, sex, BDI, SF36, frailty index, total glucocorticoids, and androgens demonstrated that MACS status was associated with lower cognition. When cognition was reassessed in 37 patients post-adrenalectomy and 31 referent subjects, adjusted group differences of cognition change were similar except for a higher comparative increase in attention and executive functioning in patients with MACS. Conclusion Patients with MACS demonstrate lower cognition than referent subjects. Adrenalectomy for MACS had a minor positive impact on cognition.