Long-Term Cortisol Exposure and Associations with Height and Comorbidities in Turner Syndrome

Abstract

Context: Turner syndrome (TS) usually manifests in traits as short stature and premature ovarian failure. Many patients also have an increased risk of cardiometabolic disorders and psychological distress, which are features that overlap with those of a prolonged state of hypercortisolism. Objective: To investigate whether TS is associated with increased long-term cortisol concentrations as measured in scalp hair and whether these are linked to cardiometabolic and psychological parameters. Design: Prospective observational case-control study. Setting: Academic outpatient TS expertise center. Participants: Fifty-five patients with TS (53% 45,X karyotype), and 110 age-matched female community control subjects from the general population-based Lifelines cohort study. Main Outcome Measures: Hair cortisol concentrations (HCC), anthropometrics, biochemical parameters, and psychological questionnaires for perceived stress (Perceived Stress Scale-14), fatigue (Checklist Individual Strength-20), and health-related quality of life (RAND-36). Results: Compared with control subjects, patients with TS had higher HCC [geometric mean, 3.51 pg/mg (95% CI, 2.64 to 4.65) vs 2.39 pg/mg (2.13 to 2.68); P = 0.003] and a worse cardiometabolic profile in terms of fasting glucose, and triglycerides. HCC was only associated with total cholesterol levels (standardized β = 0.294; P = 0.047) and was not associated with the psychological outcomes. A higher HCC was inversely associated with height only in patients with TS (standardized β = -0.307; P = 0.023). Conclusion: Patients with TS are chronically exposed to higher cortisol levels, which is associated with short stature and increased total cholesterol levels, and potentially contributes to the known elevated cardiovascular disease risk.