Adiposity rebound and height velocity in patients with congenital adrenal hyperplasia

Neil R Lawrence; Irina Bacila; Joseph Tonge; Chamila Balagamage; Jeremy Dawson; Gary S Collins; Zi-Qiang Lang; Jillian Bryce; Malika Alimussina; Minglu Chen; Salma R Ali; Nadia Amin; Nermine H Amr; Fathima A Anverdeen; Tânia Bachega; Magdalena Banaszak-Ziemska; Federico Baronio; Niels Holtum Birkebæk; Walter Bonfig; María Clemente-León; Martine Cools; Justin H Davies; Liat de Vries; Christiaan de Bruin; Heba Elsedfy; Christa E Flück; Antony Fu; Gabriella Gazdagh; Alina German; Evelien Gevers; Evgenia Globa; Ayla Güven; Sabine E Hannema; Violeta Iotova; Dominika Janus; Hayat El Kaddouri; Hetty J van der Kamp; Ruth Krone; Nina Lenherr-Taube; Otilia Marginean; Renata Markosyan; Inas Mazen; Harriet Miles; Mirela Costa de Miranda; Klaus L Mohnike; Cheryl Morris; Anuja Natarajan; Uta Neumann; Marek Niedziela; Rita Ortolano; Alegria Ferri Perez; Şükran Poyrazoğlu; Ursina Probst-Scheidegger; Tabitha Randell; D Aled Rees; Gianni Russo; Mariacarolina Salerno; Luisa De Sanctis; Valérie Schwitzgebel Luscher; Sumudu Nimali Seneviratne; Savitha Shenoy; Margarett Shnorhavorian; Marianna Rita Stancampiano; Rieko Tadokoro-Cuccaro; Ajay Thankamony; Agustini Utari; Ana Vieites; Malgorzata Wasniewska; Diego Yeste; Jeremy W Tomlinson; S Faisal Ahmed; Nils Krone

doi:10.1093/ejendo/lvag050

Adiposity rebound and height velocity in patients with congenital adrenal hyperplasia

Neil R Lawrence
, Irina Bacila
, Joseph Tonge
, Chamila Balagamage
, Jeremy Dawson
, Gary S Collins
, Zi-Qiang Lang
, Jillian Bryce
, Malika Alimussina
, Minglu Chen
, Salma R Ali
, Nadia Amin
, Nermine H Amr
, Fathima A Anverdeen
, Tânia Bachega
, Magdalena Banaszak-Ziemska
, Federico Baronio
, Niels Holtum Birkebæk
, Walter Bonfig
, María Clemente-León

Martine Cools, Justin H Davies, Liat de Vries, Christiaan de Bruin, Heba Elsedfy, Christa E Flück, Antony Fu, Gabriella Gazdagh, Alina German, Evelien Gevers, Evgenia Globa, Ayla Güven, Sabine E Hannema, Violeta Iotova, Dominika Janus, Hayat El Kaddouri, Hetty J van der Kamp, Ruth Krone, Nina Lenherr-Taube, Otilia Marginean, Renata Markosyan, Inas Mazen, Harriet Miles, Mirela Costa de Miranda, Klaus L Mohnike, Cheryl Morris, Anuja Natarajan, Uta Neumann, Marek Niedziela, Rita Ortolano, Alegria Ferri Perez, Şükran Poyrazoğlu, Ursina Probst-Scheidegger, Tabitha Randell, D Aled Rees, Gianni Russo, Mariacarolina Salerno, Luisa De Sanctis, Valérie Schwitzgebel Luscher, Sumudu Nimali Seneviratne, Savitha Shenoy, Margarett Shnorhavorian, Marianna Rita Stancampiano, Rieko Tadokoro-Cuccaro, Ajay Thankamony, Agustini Utari, Ana Vieites, Malgorzata Wasniewska, Diego Yeste, Jeremy W Tomlinson, S Faisal Ahmed, Nils Krone^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVE: Adiposity rebound is the first rise in BMI that occurs after the initial decrease during infancy. Early adiposity rebound, before age 5, is a risk factor for later obesity and metabolic problems. We investigated adiposity rebound in children with Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (CAH).

DESIGN: Longitudinal observational registry study.

METHODS: Height, weight, and BMI from patients younger than 20 years in the I-CAH Registry was described by non-linear mixed-effects models. Covariates of glucocorticoid dose, mineralocorticoid dose, 17-Hydroxyprogesterone were assessed on growth and bone age.

RESULTS: A total of 10 261 visits within 573 patients (43.6% male) showed significant variation in age at latest peak height velocity [8.4 years (SD = 3.0) in boys; 9.0 years (SD = 1.6) in girls]. Peak height velocity was more blunted in boys [7.7 cm/year (SD = 1.4)] than girls [7.4 cm/year (SD = 1.3)] in comparison to normative values. Adiposity rebound occurred earlier than age 5 years in 82% of the cohort, mean age 3.7 years (SD = 1.3) in boys and 3.9 years (SD = 0.9) in girls. Girls prescribed higher doses of glucocorticoid were associated with heavier weight in adolescence and earlier adiposity rebound. Bone age was increasingly advanced in those prescribed higher doses in both sexes.

CONCLUSIONS: There is a large variation in the timing of adiposity rebound and SITAR-estimated latest peak height velocity in children with CAH. In addition to identifying individuals with CAH who may be at risk of adverse cardiometabolic outcomes these metrics may serve as early surrogate outcomes in future research investigating early-life treatment strategies.

Original language	English
Pages (from-to)	467-481
Number of pages	15
Journal	European Journal of Endocrinology
Volume	194
Issue number	4
DOIs	https://doi.org/10.1093/ejendo/lvag050
Publication status	Published - Apr 2026

Keywords

Humans
Adrenal Hyperplasia, Congenital/physiopathology
Male
Female
Child
Adiposity/physiology
Body Height/physiology
Child, Preschool
Longitudinal Studies
Adolescent
Glucocorticoids/therapeutic use
Registries
Body Mass Index
Infant
Young Adult

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10.1093/ejendo/lvag050Licence: CC BY

lvag050Final published version, 10.1 MBLicence: CC BY

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Lawrence, N. R., Bacila, I., Tonge, J., Balagamage, C., Dawson, J., Collins, G. S., Lang, Z.-Q., Bryce, J., Alimussina, M., Chen, M., Ali, S. R., Amin, N., Amr, N. H., Anverdeen, F. A., Bachega, T., Banaszak-Ziemska, M., Baronio, F., Birkebæk, N. H., Bonfig, W., ... Krone, N. (2026). Adiposity rebound and height velocity in patients with congenital adrenal hyperplasia. European Journal of Endocrinology, 194(4), 467-481. https://doi.org/10.1093/ejendo/lvag050

@article{f4921b178f1e48f4bcb1a294f28d535c,

title = "Adiposity rebound and height velocity in patients with congenital adrenal hyperplasia",

abstract = "OBJECTIVE: Adiposity rebound is the first rise in BMI that occurs after the initial decrease during infancy. Early adiposity rebound, before age 5, is a risk factor for later obesity and metabolic problems. We investigated adiposity rebound in children with Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (CAH).DESIGN: Longitudinal observational registry study.METHODS: Height, weight, and BMI from patients younger than 20 years in the I-CAH Registry was described by non-linear mixed-effects models. Covariates of glucocorticoid dose, mineralocorticoid dose, 17-Hydroxyprogesterone were assessed on growth and bone age.RESULTS: A total of 10 261 visits within 573 patients (43.6\% male) showed significant variation in age at latest peak height velocity [8.4 years (SD = 3.0) in boys; 9.0 years (SD = 1.6) in girls]. Peak height velocity was more blunted in boys [7.7 cm/year (SD = 1.4)] than girls [7.4 cm/year (SD = 1.3)] in comparison to normative values. Adiposity rebound occurred earlier than age 5 years in 82\% of the cohort, mean age 3.7 years (SD = 1.3) in boys and 3.9 years (SD = 0.9) in girls. Girls prescribed higher doses of glucocorticoid were associated with heavier weight in adolescence and earlier adiposity rebound. Bone age was increasingly advanced in those prescribed higher doses in both sexes.CONCLUSIONS: There is a large variation in the timing of adiposity rebound and SITAR-estimated latest peak height velocity in children with CAH. In addition to identifying individuals with CAH who may be at risk of adverse cardiometabolic outcomes these metrics may serve as early surrogate outcomes in future research investigating early-life treatment strategies.",

keywords = "Humans, Adrenal Hyperplasia, Congenital/physiopathology, Male, Female, Child, Adiposity/physiology, Body Height/physiology, Child, Preschool, Longitudinal Studies, Adolescent, Glucocorticoids/therapeutic use, Registries, Body Mass Index, Infant, Young Adult",

author = "Lawrence, \{Neil R\} and Irina Bacila and Joseph Tonge and Chamila Balagamage and Jeremy Dawson and Collins, \{Gary S\} and Zi-Qiang Lang and Jillian Bryce and Malika Alimussina and Minglu Chen and Ali, \{Salma R\} and Nadia Amin and Amr, \{Nermine H\} and Anverdeen, \{Fathima A\} and T{\^a}nia Bachega and Magdalena Banaszak-Ziemska and Federico Baronio and Birkeb{\ae}k, \{Niels Holtum\} and Walter Bonfig and Mar{\'i}a Clemente-Le{\'o}n and Martine Cools and Davies, \{Justin H\} and \{de Vries\}, Liat and \{de Bruin\}, Christiaan and Heba Elsedfy and Fl{\"u}ck, \{Christa E\} and Antony Fu and Gabriella Gazdagh and Alina German and Evelien Gevers and Evgenia Globa and Ayla G{\"u}ven and Hannema, \{Sabine E\} and Violeta Iotova and Dominika Janus and \{El Kaddouri\}, Hayat and \{van der Kamp\}, \{Hetty J\} and Ruth Krone and Nina Lenherr-Taube and Otilia Marginean and Renata Markosyan and Inas Mazen and Harriet Miles and \{de Miranda\}, \{Mirela Costa\} and Mohnike, \{Klaus L\} and Cheryl Morris and Anuja Natarajan and Uta Neumann and Marek Niedziela and Rita Ortolano and Perez, \{Alegria Ferri\} and {\c S}{\"u}kran Poyrazoğlu and Ursina Probst-Scheidegger and Tabitha Randell and Rees, \{D Aled\} and Gianni Russo and Mariacarolina Salerno and \{De Sanctis\}, Luisa and Luscher, \{Val{\'e}rie Schwitzgebel\} and Seneviratne, \{Sumudu Nimali\} and Savitha Shenoy and Margarett Shnorhavorian and Stancampiano, \{Marianna Rita\} and Rieko Tadokoro-Cuccaro and Ajay Thankamony and Agustini Utari and Ana Vieites and Malgorzata Wasniewska and Diego Yeste and Tomlinson, \{Jeremy W\} and Ahmed, \{S Faisal\} and Nils Krone",

note = "{\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Endocrinology.",

year = "2026",

month = apr,

doi = "10.1093/ejendo/lvag050",

language = "English",

volume = "194",

pages = "467--481",

journal = "European Journal of Endocrinology",

issn = "0804-4643",

publisher = "Oxford University Press",

number = "4",

}

Lawrence, NR, Bacila, I, Tonge, J, Balagamage, C, Dawson, J, Collins, GS, Lang, Z-Q, Bryce, J, Alimussina, M, Chen, M, Ali, SR, Amin, N, Amr, NH, Anverdeen, FA, Bachega, T, Banaszak-Ziemska, M, Baronio, F, Birkebæk, NH, Bonfig, W, Clemente-León, M, Cools, M, Davies, JH, de Vries, L, de Bruin, C, Elsedfy, H, Flück, CE, Fu, A, Gazdagh, G, German, A, Gevers, E, Globa, E, Güven, A, Hannema, SE, Iotova, V, Janus, D, El Kaddouri, H, van der Kamp, HJ, Krone, R, Lenherr-Taube, N, Marginean, O, Markosyan, R, Mazen, I, Miles, H, de Miranda, MC, Mohnike, KL, Morris, C, Natarajan, A, Neumann, U, Niedziela, M, Ortolano, R, Perez, AF, Poyrazoğlu, Ş, Probst-Scheidegger, U, Randell, T, Rees, DA, Russo, G, Salerno, M, De Sanctis, L, Luscher, VS, Seneviratne, SN, Shenoy, S, Shnorhavorian, M, Stancampiano, MR, Tadokoro-Cuccaro, R, Thankamony, A, Utari, A, Vieites, A, Wasniewska, M, Yeste, D, Tomlinson, JW, Ahmed, SF & Krone, N 2026, 'Adiposity rebound and height velocity in patients with congenital adrenal hyperplasia', European Journal of Endocrinology, vol. 194, no. 4, pp. 467-481. https://doi.org/10.1093/ejendo/lvag050

TY - JOUR

T1 - Adiposity rebound and height velocity in patients with congenital adrenal hyperplasia

AU - Lawrence, Neil R

AU - Bacila, Irina

AU - Tonge, Joseph

AU - Balagamage, Chamila

AU - Dawson, Jeremy

AU - Collins, Gary S

AU - Lang, Zi-Qiang

AU - Bryce, Jillian

AU - Alimussina, Malika

AU - Chen, Minglu

AU - Ali, Salma R

AU - Amin, Nadia

AU - Amr, Nermine H

AU - Anverdeen, Fathima A

AU - Bachega, Tânia

AU - Banaszak-Ziemska, Magdalena

AU - Baronio, Federico

AU - Birkebæk, Niels Holtum

AU - Bonfig, Walter

AU - Clemente-León, María

AU - Cools, Martine

AU - Davies, Justin H

AU - de Vries, Liat

AU - de Bruin, Christiaan

AU - Elsedfy, Heba

AU - Flück, Christa E

AU - Fu, Antony

AU - Gazdagh, Gabriella

AU - German, Alina

AU - Gevers, Evelien

AU - Globa, Evgenia

AU - Güven, Ayla

AU - Hannema, Sabine E

AU - Iotova, Violeta

AU - Janus, Dominika

AU - El Kaddouri, Hayat

AU - van der Kamp, Hetty J

AU - Krone, Ruth

AU - Lenherr-Taube, Nina

AU - Marginean, Otilia

AU - Markosyan, Renata

AU - Mazen, Inas

AU - Miles, Harriet

AU - de Miranda, Mirela Costa

AU - Mohnike, Klaus L

AU - Morris, Cheryl

AU - Natarajan, Anuja

AU - Neumann, Uta

AU - Niedziela, Marek

AU - Ortolano, Rita

AU - Perez, Alegria Ferri

AU - Poyrazoğlu, Şükran

AU - Probst-Scheidegger, Ursina

AU - Randell, Tabitha

AU - Rees, D Aled

AU - Russo, Gianni

AU - Salerno, Mariacarolina

AU - De Sanctis, Luisa

AU - Luscher, Valérie Schwitzgebel

AU - Seneviratne, Sumudu Nimali

AU - Shenoy, Savitha

AU - Shnorhavorian, Margarett

AU - Stancampiano, Marianna Rita

AU - Tadokoro-Cuccaro, Rieko

AU - Thankamony, Ajay

AU - Utari, Agustini

AU - Vieites, Ana

AU - Wasniewska, Malgorzata

AU - Yeste, Diego

AU - Tomlinson, Jeremy W

AU - Ahmed, S Faisal

AU - Krone, Nils

PY - 2026/4

Y1 - 2026/4

N2 - OBJECTIVE: Adiposity rebound is the first rise in BMI that occurs after the initial decrease during infancy. Early adiposity rebound, before age 5, is a risk factor for later obesity and metabolic problems. We investigated adiposity rebound in children with Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (CAH).DESIGN: Longitudinal observational registry study.METHODS: Height, weight, and BMI from patients younger than 20 years in the I-CAH Registry was described by non-linear mixed-effects models. Covariates of glucocorticoid dose, mineralocorticoid dose, 17-Hydroxyprogesterone were assessed on growth and bone age.RESULTS: A total of 10 261 visits within 573 patients (43.6% male) showed significant variation in age at latest peak height velocity [8.4 years (SD = 3.0) in boys; 9.0 years (SD = 1.6) in girls]. Peak height velocity was more blunted in boys [7.7 cm/year (SD = 1.4)] than girls [7.4 cm/year (SD = 1.3)] in comparison to normative values. Adiposity rebound occurred earlier than age 5 years in 82% of the cohort, mean age 3.7 years (SD = 1.3) in boys and 3.9 years (SD = 0.9) in girls. Girls prescribed higher doses of glucocorticoid were associated with heavier weight in adolescence and earlier adiposity rebound. Bone age was increasingly advanced in those prescribed higher doses in both sexes.CONCLUSIONS: There is a large variation in the timing of adiposity rebound and SITAR-estimated latest peak height velocity in children with CAH. In addition to identifying individuals with CAH who may be at risk of adverse cardiometabolic outcomes these metrics may serve as early surrogate outcomes in future research investigating early-life treatment strategies.

AB - OBJECTIVE: Adiposity rebound is the first rise in BMI that occurs after the initial decrease during infancy. Early adiposity rebound, before age 5, is a risk factor for later obesity and metabolic problems. We investigated adiposity rebound in children with Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (CAH).DESIGN: Longitudinal observational registry study.METHODS: Height, weight, and BMI from patients younger than 20 years in the I-CAH Registry was described by non-linear mixed-effects models. Covariates of glucocorticoid dose, mineralocorticoid dose, 17-Hydroxyprogesterone were assessed on growth and bone age.RESULTS: A total of 10 261 visits within 573 patients (43.6% male) showed significant variation in age at latest peak height velocity [8.4 years (SD = 3.0) in boys; 9.0 years (SD = 1.6) in girls]. Peak height velocity was more blunted in boys [7.7 cm/year (SD = 1.4)] than girls [7.4 cm/year (SD = 1.3)] in comparison to normative values. Adiposity rebound occurred earlier than age 5 years in 82% of the cohort, mean age 3.7 years (SD = 1.3) in boys and 3.9 years (SD = 0.9) in girls. Girls prescribed higher doses of glucocorticoid were associated with heavier weight in adolescence and earlier adiposity rebound. Bone age was increasingly advanced in those prescribed higher doses in both sexes.CONCLUSIONS: There is a large variation in the timing of adiposity rebound and SITAR-estimated latest peak height velocity in children with CAH. In addition to identifying individuals with CAH who may be at risk of adverse cardiometabolic outcomes these metrics may serve as early surrogate outcomes in future research investigating early-life treatment strategies.

KW - Humans

KW - Adrenal Hyperplasia, Congenital/physiopathology

KW - Male

KW - Female

KW - Child

KW - Adiposity/physiology

KW - Body Height/physiology

KW - Child, Preschool

KW - Longitudinal Studies

KW - Adolescent

KW - Glucocorticoids/therapeutic use

KW - Registries

KW - Body Mass Index

KW - Infant

KW - Young Adult

U2 - 10.1093/ejendo/lvag050

DO - 10.1093/ejendo/lvag050

M3 - Article

C2 - 41823987

SN - 0804-4643

VL - 194

SP - 467

EP - 481

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 4

ER -

Adiposity rebound and height velocity in patients with congenital adrenal hyperplasia

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Keywords

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