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

doi:10.1210/clinem/dgac560

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

Pediatrics

Research output: Contribution to journal › Article › Academic › peer-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 language	English
Article number	dgac560
Pages (from-to)	443-452
Number of pages	10
Journal	The Journal of clinical endocrinology and metabolism
Volume	108
Issue number	2
DOIs	https://doi.org/10.1210/clinem/dgac560
Publication status	E-pub ahead of print - 1 Oct 2022

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{ca2d9e065b374f7c9d76076b6dc22d00,

title = "Leukocyte Telomere Length in Children with Congenital Adrenal Hyperplasia",

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.",

author = "Christina Raftopoulou and Ozair Abawi and Grit Sommer and Maria Binou and George Paltoglou and Fl{\"u}ck, {Christa E} and {van den Akker}, {Erica L T} and E Charmandari",

note = "{\textcopyright} 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.",

year = "2022",

month = oct,

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doi = "10.1210/clinem/dgac560",

language = "English",

volume = "108",

pages = "443--452",

journal = "Journal of Clinical Endocrinology and Metabolism",

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T1 - Leukocyte Telomere Length in Children with Congenital Adrenal Hyperplasia

AU - Raftopoulou, Christina

AU - Abawi, Ozair

AU - Sommer, Grit

AU - Binou, Maria

AU - Paltoglou, George

AU - Flück, Christa E

AU - van den Akker, Erica L T

AU - Charmandari, E

PY - 2022/10/1

Y1 - 2022/10/1

N2 - 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.

AB - 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.

U2 - 10.1210/clinem/dgac560

DO - 10.1210/clinem/dgac560

M3 - Article

C2 - 36181470

VL - 108

SP - 443

EP - 452

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

M1 - dgac560

ER -

Leukocyte Telomere Length in Children with Congenital Adrenal Hyperplasia

Abstract

Bibliographical note

UN SDGs

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