Glucocorticoid receptor polymorphism BclI with increased glucocorticoid sensitivity has a positive influence on quality of life in endogenous Cushing's syndrome in remission. Issue 4 (30th March 2023) - Feldkamp, Lara
Abstract: Context: Patients with endogenous Cushing's syndrome (CS) may suffer from a wide range of neuropsychiatric symptoms leading to impaired quality of life (QoL). Objective: Glucocorticoid receptor (GR) polymorphisms are associated with increased ( Bcl I and N363S) or decreased (A3669G and ER22/23EK) GR sensitivity. Hypothesis: GR genotypes may modulate and affect QoL and recovery after remission differently via GR sensitivity. Methods: 295 patients with endogenous CS (81 active, 214 in remission) from 3 centers of the German Cushing's Registry were included for the cross-sectional analysis. All subjects were assessed with three questionnaires (CushingQoL, Tuebingen CD-25, SF-36). For the longitudinal part, 120 patients of them were analyzed at baseline and after 1.5 ± 0.9 yrs of follow-up. DNA samples were obtained from peripheral blood leukocytes for GR genotyping. Results: Patients in remission scored significantly better than patients with active CS in the CushingQoL questionnaire and in the SF-36 sub-categories physical and social functioning, role-physical, bodily pain, and vitality. In cross-sectional analysis, no differences in QoL between minor allele and wildtype carriers were detected for all polymorphisms in active or cured CS. In longitudinal analysis, however, carriers with Bcl I minor allele showed significant improvement in SF-36 sub-categories vitality ( P = .038) and mental health ( P = .013) compared to wildtype carriers (active CS at baseline vs. CS in remission at follow-up). The outcome of the two questionnaires CushingQoL and Tuebingen CD-25 improved significantly in both wildtype and minor allele carriers. Conclusion: Bcl I minor allele carriers initially had the lowest QoL but recovered better from impaired QoL than wildtype carriers.