Quality of life burden in Cushing’s syndrome: baseline results from the PROMPT study

Objective Cushing’s syndrome (CS) is associated with marked impairment in quality of life (QoL). This analysis aimed to comprehensively describe QoL impairment in participants of the PROMPT study using two validated instruments: the CushingQoL and the Tübingen Cushing’s Disease Quality of Life Inventory (CD-25). Methods Cross-sectional analysis used baseline questionnaires from PROMPT (NCT02297945), a prospective study of metyrapone in 49 adults with confirmed endogenous CS. Item- and domain-level analyses were conducted for the CushingQoL (0-100; higher = better QoL) and CD-25 (0-100; higher = worse QoL). Subgroups: sex (15 males, 34 females) and biochemical UFC severity (31 moderate and 16 severe). Results Patients reported substantial impairment in QoL. The mean CushingQoL score was 41.2 (95%CI 35.6-46.7), with greater physical (36.8) than psychosocial (45.5) burden. The CD-25 score was 39.8 (95%CI 32.7-46.9), with bodily restrictions (48.6) and eating behaviour (44.7) most severely affected. Worry about future health (75.5%) and physical appearance (73.5%) were the most prevalent individual concerns. The two instruments were strongly inversely correlated (r= −0.81, p<0.001). Females reported clinically worse psychosocial QoL compared with males (CushingQoL psychosocial: 41.7 vs 54.2, −12.2 points; CD-25 depression: 39.5 vs 26.9, + 12.6 points), despite similar biochemical severity. No meaningful differences in overall QoL scores were observed between patients with moderate versus severe hypercortisolism. Conclusions Uncontrolled CS is associated with profound multidomain QoL impairment dominated by psychological distress, largely independent of biochemical disease severity. Women reported clinically meaningful worse psychosocial outcomes than men. Disease-specific, item-level QoL assessment may add information not captured by biochemical parameters in patients with active CS.