PSAT101 Impaired Muscle Function and Health-Related Quality of Life in Patients with Mild Autonomous Cortisol Secretion

BACKGROUND: Cushing syndrome (CS) is recognized to have multisystem morbidity, but data on the effect of mild autonomous cortisol secretion (MACS) are limited. We hypothesized that MACS is associated with impairments in objective measures of muscle strength and self-reported measures of physical and mental functioning. METHODS: We conducted a cross-sectional analysis of a prospective cohort of patients with confirmed hypercortisolism enrolled between 8/01/2019 and 12/31/2021. MACS was defined as serum cortisol greater than 1.8 mcg/dL after the 1 mg dexamethasone suppression test (DST) and lack of typical signs and symptoms of CS. Clinical outcomes were assessed prior to intervention. We measured hand grip strength with hand grip dynamometer and lower extremity muscle function with the chair rise test (number of sit-to-stands completed in 30 seconds). We assessed health-related quality of life with the Short Form-36 (SF-36) questionnaire. Performance was reported using age- and sex-adjusted z-scores based on normative data from the USA population. RESULTS: A total of 81 patients with MACS (median age 55 years, 49% women) and 85 patients with CS (median age 48 years, 51% women—adrenal CS in 14, pituitary CS in 62, and ectopic CS in 9) were enrolled. In the MACS cohort, median cortisol following 1 mg DST was 3.4 µg/dL (IQR 2.6-5.7), DHEA-S 37.0 µg/dL (IQR 21.5-58.5), ACTH 8.1 pg/mL (IQR, 5.6-13.0; normal 10-60), and 24-hour urinary cortisol 25.0 µg/24h (IQR 15.8-43.3, normal <45). In the CS cohort, median cortisol following 1 mg DST was 11.2 µg/dL (IQR 5.1-15.3), 24-hour urinary cortisol 156.0 µg/24h (IQR 65.5-356.5), and late-night salivary cortisol 251.0 ng/dL (IQR 158.8-430.3; normal <100). Z-scores for hand grip strength (0.13 ± 1.1 vs. 0.07 ± 1.1, p=0.73) and chair rise test performance (-0.25 ± 1.3 vs. -0.39 ± 2.0, p=0.63) were similar between patients with MACS and those with CS. On the SF-36 questionnaire, z-scores for all subdomains were negative in both groups. Patients with CS had lower z-scores on physical functioning (-1.71 ± 1.38 vs. -0.97 ± 1.44, p=0.001), role-physical limitation (-1.75 ± 1.19 vs. -1.15 ± 1.17 p =0.002), general health (-1.54 ± 1.16 vs. -1.03 ± 1.07, p=0.004), social functioning (-1.59 ± 1.27 vs. -0.97 ± 1.28, p= 0.002), and vitality subdomains (-1.67 ± 0.87 vs. -1.28 ± 1.11, p=0.01), but similar physical and mental component summary scores compared to patients with MACS. Chair rise test performance correlated with physical but not mental component summary scores. CONCLUSIONS: Patients with MACS have impaired chair rise test performance and health-related quality of life when compared to the general age and sex specific population. Remarkably, when compared to patients with CS, patients with MACS had no significant differences in muscle strength, SF-36 physical component summary score, or SF-36 mental component summary score. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.