Raftopoulou, Christina; Abawi, Ozair; Sommer, Grit; Binou, Maria; Paltoglou, George; Flück, Christa E; van den Akker, Erica L T; Charmandari, E (2023). Leukocyte Telomere Length in Children with Congenital Adrenal Hyperplasia. The journal of clinical endocrinology and metabolism, 108(2), pp. 443-452. Oxford University Press 10.1210/clinem/dgac560
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CONTEXT
Exposure to chronic stress and hypercortisolism is associated with decreased leukocyte telomere length (LTL), a marker for biological aging and cardiovascular disease. Children with congenital adrenal hyperplasia (CAH) are treated with glucocorticoids.
OBJECTIVE
To investigate LTL in children with CAH.
DESIGN
Prospective observational cohort study. Patients were followed-up at two visits (mean 4.1 ± 0.7 months apart).
SETTING
Four academic Pediatric Endocrinology Outpatient Clinics.
PATIENTS
Children aged 0-18 years with genetically confirmed CAH.
MAIN OUTCOME MEASURES
At each visit, LTL was determined by quantitative real-time PCR. All subjects underwent detailed clinical and endocrinologic evaluation and were classified as undertreated, optimally treated or overtreated, accordingly. The influence of clinical factors on LTL was investigated using linear mixed models adjusted for age, sex, and BMI-z.
RESULTS
We studied 76 patients, of whom 31 (41%) were girls, 63 (83%) had classic CAH, 67 (88%) received hydrocortisone and 8 (11%) prednisolone. Median age at first visit was 12.0 years (IQR 6.3-15.1), and median BMI-z was 0.51 (IQR -0.12-1.43). LTL was shorter in patients with classic compared to non-classic CAH (-0.29, P = 0.012), in overtreated than in optimally treated patients (-0.07, P = 0.002), and patients receiving prednisolone compared with hydrocortisone (-0.34, P < 0.001). LTL was not associated with undertreatment or daily HC-equivalent dose (P > 0.05).
CONCLUSIONS
LTL is shorter in patients with classic than non-classic CAH, as well as those who are overtreated with hydrocortisone or treated with long-acting glucocorticoids. These findings may be attributed to chronic exposure to supraphysiologic glucocorticoid concentrations, and indicate that LTL may be used as a biomarker for monitoring glucocorticoid treatment.