Leukocyte Telomere Length in Children with Congenital Adrenal Hyperplasia

Christina Raftopoulou, Ozair Abawi, Grit Sommer, Maria Binou, George Paltoglou, Christa E Flück, Erica L T van den Akker, E Charmandari*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numberdgac560
Pages (from-to)443-452
Number of pages10
JournalThe Journal of clinical endocrinology and metabolism
Volume108
Issue number2
DOIs
Publication statusE-pub ahead of print - 1 Oct 2022

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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