Journal
EUROPEAN JOURNAL OF ENDOCRINOLOGY
Volume 188, Issue 4, Pages 366-374Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ejendo/lvad043
Keywords
Cushing's syndrome; cortisol; SF-36; BclI; N363S; A3669G; ER22; 23EK; glucocorticoid
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Patients with endogenous Cushing's syndrome (CS) may experience a wide range of neuropsychiatric symptoms that negatively impact their quality of life (QoL). This study examined the association between glucocorticoid receptor (GR) polymorphisms and QoL in CS patients. The results showed that patients in remission had better QoL compared to those with active CS. In longitudinal analysis, carriers with the BclI minor allele showed significant improvement in QoL compared to wildtype carriers after remission.
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 (BclI 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 BclI 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 BclI minor allele carriers initially had the lowest QoL but recovered better from impaired QoL than wildtype carriers.
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