Contemporary global management of 21-hydroxylase deficiency congenital adrenal hyperplasia in early infancy: a multi-national registry study

David B N Lim; Jillian Bryce; Salma R Ali; Xanthippi Tseretopoulou; Niels H Birkebaek; Sabine E Hannema; Ariadna Campos-Martorell; Maria Clemente; Uta Neumann; Christa E Flück; Sara Metzger; Ruth E Krone; Alina German; Federico Baronio; Pascal Barat; Marine Delagrange; Vanessa Vautier; Ana Vieites; Rodolfo Rey; Heba Elsedfy; Navoda Atapattu; Sumudu N Seneviratne; Martine Cools; Tulay Guran; Zehra Yavas Abali; Antony Fu; Dominika Janus; Savitha Shenoy; Malgorzata Wasniewska; Roberto Coco; Gianni Russo; Marianna Rita Stancampiano; Walter Bonfig; Mariacarolina Salerno; Hedi L Claahsen-van der Grinten; Bas P H Adriaansen; Chiara Mozzato; Laura Guazzarotti; Marek Niedziela; Magdalena Banaszak-Ziemska; Judith van Eck; Tania Bachega; Mirela C Miranda; Otilia Marginean; Jessica Munarin; Luisa De Sanctis; Ursina Probst-Scheidegger; Nina Lenherr-Taube; Daniel Konrad; Michele O'Connell; Aneta Gawlik-Starzyk; David E Sandberg; Margarett Shnorhavorian; Nils Krone; S Faisal Ahmed; Justin H Davies

doi:10.1093/ejendo/lvag004

Contemporary global management of 21-hydroxylase deficiency congenital adrenal hyperplasia in early infancy: a multi-national registry study

David B N Lim
, Jillian Bryce
, Salma R Ali
, Xanthippi Tseretopoulou
, Niels H Birkebaek
, Sabine E Hannema
, Ariadna Campos-Martorell
, Maria Clemente
, Uta Neumann
, Christa E Flück
, Sara Metzger
, Ruth E Krone
, Alina German
, Federico Baronio
, Pascal Barat
, Marine Delagrange
, Vanessa Vautier
, Ana Vieites
, Rodolfo Rey
, Heba Elsedfy

Navoda Atapattu, Sumudu N Seneviratne, Martine Cools, Tulay Guran, Zehra Yavas Abali, Antony Fu, Dominika Janus, Savitha Shenoy, Malgorzata Wasniewska, Roberto Coco, Gianni Russo, Marianna Rita Stancampiano, Walter Bonfig, Mariacarolina Salerno, Hedi L Claahsen-van der Grinten, Bas P H Adriaansen, Chiara Mozzato, Laura Guazzarotti, Marek Niedziela, Magdalena Banaszak-Ziemska, Judith van Eck, Tania Bachega, Mirela C Miranda, Otilia Marginean, Jessica Munarin, Luisa De Sanctis, Ursina Probst-Scheidegger, Nina Lenherr-Taube, Daniel Konrad, Michele O'Connell, Aneta Gawlik-Starzyk, David E Sandberg, Margarett Shnorhavorian, Nils Krone, S Faisal Ahmed, Justin H Davies

Southampton University Hospital
Royal Hospital for Children & Queen Elizabeth University Hospital
Aarhus University Hospital
Vall d'Hebron Research Institute (VHIR)
Paediatric Endocrinology Section
Vall d'Hebron Hospital Universitari
Growth and Development Research Group
Clinic for Paediatric Endocrinology and Diabetes
Paediatric Respiratory Medicine, University Children's Hospital of Bern, University of Bern, Bern, Switzerland.
Birmingham Women's and Children's Nhs Foundation Hospital
Haemek Medical Center
Paediatric Intensive Care Unit
Pediatric Onco-Hematology Department, University Hospital Center of Bordeaux, Bordeaux, France
Hospital de Niños Dr. Ricardo Gutiérrez
Ain Shams University Hospitals
Lady Ridgeway Hospital for Children
University of Colombo
Ghent University Hospital
Marmara University
Princess Margaret Hospital
University Children's Hospital
Leicester Children's Hospital
University of Messina
IRCCS San Raffaele Scientific Institute
Technical University of Munich and Helmholtz Zentrum München
Federico II University, Italy
Radboud University Medical Centre
University Hospital of Padua
University of Medical Sciences Poznan
Erasmus University Medical Center-Sophia Children's Hospital
University of São Paulo, São Paulo, Brazil
Victor Babes University of Medicine and Pharmacy
Regina Margherita Children's Hospital
Department of Paediatric Neurology
University of Zurich
Royal Children's Hospital Brisbane
Medical University of Silesia in Katowice
University of Michigan Medical School
Seattle Children's Hospital
University of Sheffield

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

Abstract

OBJECTIVE: Management of 21-hydroxylase deficiency (21-OHD) congenital adrenal hyperplasia (CAH) in early infancy is challenging, with extent of variation in management unclear.

DESIGN AND METHODS: Using the I-CAH Registry, we retrospectively reviewed management over the first 90 days of life of 154 infants with 21-OHD born in 2018-2023, across 33 centers in 18 countries.

RESULTS: Of 154 infants (92 female, 62 male), 136 were diagnosed postnatally, with median (10th centile, 90th centile) presentation age of Day 4 (0, 20.8). At initial hospital discharge, median doses of hydrocortisone (HC), fludrocortisone (FC), and salt were 17 (11.4, 39.6) mg/m2/day, 100 (50, 200) mcg/day and 3.5 (1.6, 8.7) mmol/kg/day, and at Day 90 (D90) 14.5 (8.7, 24.1) mg/m2/day, 100 (50, 200) mcg/day, and 2.1 (1.0, 5.2) mmol/kg/day, respectively. Hyponatremia, hyperkalemia, and hypoglycemia were reported in 70.0%, 71.9%, and 13.0% of infants, respectively. At D90, hyponatremia and hyperkalemia were reported in 7.4% and 28.6%, respectively. At D90, BP measurements were recorded in 30.5%, amongst whom 31.9% had hypertension reported. Median total hospitalization duration over 90 days was 9 days (2, 24). Adrenal crises were associated with 40. 6% of hospitalization episodes. Percentages (males:females) of cases seen by a pediatric endocrinologist, psychologist, pediatric endocrine nurse specialist, and surgeon by D90 were 95.9% (58:84), 33.3% (9:35), 42.1% (20:36), and 23.8% (0:35), respectively.

CONCLUSIONS: Contemporary management of CAH in early infancy varies considerably. Hypertension and hyperkalemia are frequently reported. Our data may help inform development of quality indicators for benchmarking CAH care in infancy.

Original language	English
Pages (from-to)	123-135
Number of pages	13
Journal	European Journal of Endocrinology
Volume	194
Issue number	2
DOIs	https://doi.org/10.1093/ejendo/lvag004
Publication status	Published - 1 Feb 2026

Keywords

21-hydroxylase deficiency
benchmarking
congenital adrenal hyperplasia
early infancy
quality of care
treatment variation

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10.1093/ejendo/lvag004

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Lim, D. B. N., Bryce, J., Ali, S. R., Tseretopoulou, X., Birkebaek, N. H., Hannema, S. E., Campos-Martorell, A., Clemente, M., Neumann, U., Flück, C. E., Metzger, S., Krone, R. E., German, A., Baronio, F., Barat, P., Delagrange, M., Vautier, V., Vieites, A., Rey, R., ... Davies, J. H. (2026). Contemporary global management of 21-hydroxylase deficiency congenital adrenal hyperplasia in early infancy: a multi-national registry study. European Journal of Endocrinology, 194(2), 123-135. https://doi.org/10.1093/ejendo/lvag004

@article{582178feb8144d379636a203a5519075,

title = "Contemporary global management of 21-hydroxylase deficiency congenital adrenal hyperplasia in early infancy: a multi-national registry study",

abstract = "OBJECTIVE: Management of 21-hydroxylase deficiency (21-OHD) congenital adrenal hyperplasia (CAH) in early infancy is challenging, with extent of variation in management unclear.DESIGN AND METHODS: Using the I-CAH Registry, we retrospectively reviewed management over the first 90 days of life of 154 infants with 21-OHD born in 2018-2023, across 33 centers in 18 countries.RESULTS: Of 154 infants (92 female, 62 male), 136 were diagnosed postnatally, with median (10th centile, 90th centile) presentation age of Day 4 (0, 20.8). At initial hospital discharge, median doses of hydrocortisone (HC), fludrocortisone (FC), and salt were 17 (11.4, 39.6) mg/m2/day, 100 (50, 200) mcg/day and 3.5 (1.6, 8.7) mmol/kg/day, and at Day 90 (D90) 14.5 (8.7, 24.1) mg/m2/day, 100 (50, 200) mcg/day, and 2.1 (1.0, 5.2) mmol/kg/day, respectively. Hyponatremia, hyperkalemia, and hypoglycemia were reported in 70.0\%, 71.9\%, and 13.0\% of infants, respectively. At D90, hyponatremia and hyperkalemia were reported in 7.4\% and 28.6\%, respectively. At D90, BP measurements were recorded in 30.5\%, amongst whom 31.9\% had hypertension reported. Median total hospitalization duration over 90 days was 9 days (2, 24). Adrenal crises were associated with 40. 6\% of hospitalization episodes. Percentages (males:females) of cases seen by a pediatric endocrinologist, psychologist, pediatric endocrine nurse specialist, and surgeon by D90 were 95.9\% (58:84), 33.3\% (9:35), 42.1\% (20:36), and 23.8\% (0:35), respectively.CONCLUSIONS: Contemporary management of CAH in early infancy varies considerably. Hypertension and hyperkalemia are frequently reported. Our data may help inform development of quality indicators for benchmarking CAH care in infancy.",

keywords = "21-hydroxylase deficiency, benchmarking, congenital adrenal hyperplasia, early infancy, quality of care, treatment variation",

author = "Lim, \{David B N\} and Jillian Bryce and Ali, \{Salma R\} and Xanthippi Tseretopoulou and Birkebaek, \{Niels H\} and Hannema, \{Sabine E\} and Ariadna Campos-Martorell and Maria Clemente and Uta Neumann and Fl{\"u}ck, \{Christa E\} and Sara Metzger and Krone, \{Ruth E\} and Alina German and Federico Baronio and Pascal Barat and Marine Delagrange and Vanessa Vautier and Ana Vieites and Rodolfo Rey and Heba Elsedfy and Navoda Atapattu and Seneviratne, \{Sumudu N\} and Martine Cools and Tulay Guran and \{Yavas Abali\}, Zehra and Antony Fu and Dominika Janus and Savitha Shenoy and Malgorzata Wasniewska and Roberto Coco and Gianni Russo and Stancampiano, \{Marianna Rita\} and Walter Bonfig and Mariacarolina Salerno and \{Claahsen-van der Grinten\}, \{Hedi L\} and Adriaansen, \{Bas P H\} and Chiara Mozzato and Laura Guazzarotti and Marek Niedziela and Magdalena Banaszak-Ziemska and \{van Eck\}, Judith and Tania Bachega and Miranda, \{Mirela C\} and Otilia Marginean and Jessica Munarin and \{De Sanctis\}, Luisa and Ursina Probst-Scheidegger and Nina Lenherr-Taube and Daniel Konrad and Michele O'Connell and Aneta Gawlik-Starzyk and Sandberg, \{David E\} and Margarett Shnorhavorian and Nils Krone and Ahmed, \{S Faisal\} and Davies, \{Justin H\}",

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

year = "2026",

month = feb,

day = "1",

doi = "10.1093/ejendo/lvag004",

language = "English",

volume = "194",

pages = "123--135",

journal = "European Journal of Endocrinology",

issn = "0804-4643",

publisher = "BioScientifica Ltd.",

number = "2",

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Lim, DBN, Bryce, J, Ali, SR, Tseretopoulou, X, Birkebaek, NH, Hannema, SE, Campos-Martorell, A, Clemente, M, Neumann, U, Flück, CE, Metzger, S, Krone, RE, German, A, Baronio, F, Barat, P, Delagrange, M, Vautier, V, Vieites, A, Rey, R, Elsedfy, H, Atapattu, N, Seneviratne, SN, Cools, M, Guran, T, Yavas Abali, Z, Fu, A, Janus, D, Shenoy, S, Wasniewska, M, Coco, R, Russo, G, Stancampiano, MR, Bonfig, W, Salerno, M, Claahsen-van der Grinten, HL, Adriaansen, BPH, Mozzato, C, Guazzarotti, L, Niedziela, M, Banaszak-Ziemska, M, van Eck, J, Bachega, T, Miranda, MC, Marginean, O, Munarin, J, De Sanctis, L, Probst-Scheidegger, U, Lenherr-Taube, N, Konrad, D, O'Connell, M, Gawlik-Starzyk, A, Sandberg, DE, Shnorhavorian, M, Krone, N, Ahmed, SF & Davies, JH 2026, 'Contemporary global management of 21-hydroxylase deficiency congenital adrenal hyperplasia in early infancy: a multi-national registry study', European Journal of Endocrinology, vol. 194, no. 2, pp. 123-135. https://doi.org/10.1093/ejendo/lvag004

TY - JOUR

T1 - Contemporary global management of 21-hydroxylase deficiency congenital adrenal hyperplasia in early infancy

T2 - a multi-national registry study

AU - Lim, David B N

AU - Bryce, Jillian

AU - Ali, Salma R

AU - Tseretopoulou, Xanthippi

AU - Birkebaek, Niels H

AU - Hannema, Sabine E

AU - Campos-Martorell, Ariadna

AU - Clemente, Maria

AU - Neumann, Uta

AU - Flück, Christa E

AU - Metzger, Sara

AU - Krone, Ruth E

AU - German, Alina

AU - Baronio, Federico

AU - Barat, Pascal

AU - Delagrange, Marine

AU - Vautier, Vanessa

AU - Vieites, Ana

AU - Rey, Rodolfo

AU - Elsedfy, Heba

AU - Atapattu, Navoda

AU - Seneviratne, Sumudu N

AU - Cools, Martine

AU - Guran, Tulay

AU - Yavas Abali, Zehra

AU - Fu, Antony

AU - Janus, Dominika

AU - Shenoy, Savitha

AU - Wasniewska, Malgorzata

AU - Coco, Roberto

AU - Russo, Gianni

AU - Stancampiano, Marianna Rita

AU - Bonfig, Walter

AU - Salerno, Mariacarolina

AU - Claahsen-van der Grinten, Hedi L

AU - Adriaansen, Bas P H

AU - Mozzato, Chiara

AU - Guazzarotti, Laura

AU - Niedziela, Marek

AU - Banaszak-Ziemska, Magdalena

AU - van Eck, Judith

AU - Bachega, Tania

AU - Miranda, Mirela C

AU - Marginean, Otilia

AU - Munarin, Jessica

AU - De Sanctis, Luisa

AU - Probst-Scheidegger, Ursina

AU - Lenherr-Taube, Nina

AU - Konrad, Daniel

AU - O'Connell, Michele

AU - Gawlik-Starzyk, Aneta

AU - Sandberg, David E

AU - Shnorhavorian, Margarett

AU - Krone, Nils

AU - Ahmed, S Faisal

AU - Davies, Justin H

PY - 2026/2/1

Y1 - 2026/2/1

N2 - OBJECTIVE: Management of 21-hydroxylase deficiency (21-OHD) congenital adrenal hyperplasia (CAH) in early infancy is challenging, with extent of variation in management unclear.DESIGN AND METHODS: Using the I-CAH Registry, we retrospectively reviewed management over the first 90 days of life of 154 infants with 21-OHD born in 2018-2023, across 33 centers in 18 countries.RESULTS: Of 154 infants (92 female, 62 male), 136 were diagnosed postnatally, with median (10th centile, 90th centile) presentation age of Day 4 (0, 20.8). At initial hospital discharge, median doses of hydrocortisone (HC), fludrocortisone (FC), and salt were 17 (11.4, 39.6) mg/m2/day, 100 (50, 200) mcg/day and 3.5 (1.6, 8.7) mmol/kg/day, and at Day 90 (D90) 14.5 (8.7, 24.1) mg/m2/day, 100 (50, 200) mcg/day, and 2.1 (1.0, 5.2) mmol/kg/day, respectively. Hyponatremia, hyperkalemia, and hypoglycemia were reported in 70.0%, 71.9%, and 13.0% of infants, respectively. At D90, hyponatremia and hyperkalemia were reported in 7.4% and 28.6%, respectively. At D90, BP measurements were recorded in 30.5%, amongst whom 31.9% had hypertension reported. Median total hospitalization duration over 90 days was 9 days (2, 24). Adrenal crises were associated with 40. 6% of hospitalization episodes. Percentages (males:females) of cases seen by a pediatric endocrinologist, psychologist, pediatric endocrine nurse specialist, and surgeon by D90 were 95.9% (58:84), 33.3% (9:35), 42.1% (20:36), and 23.8% (0:35), respectively.CONCLUSIONS: Contemporary management of CAH in early infancy varies considerably. Hypertension and hyperkalemia are frequently reported. Our data may help inform development of quality indicators for benchmarking CAH care in infancy.

AB - OBJECTIVE: Management of 21-hydroxylase deficiency (21-OHD) congenital adrenal hyperplasia (CAH) in early infancy is challenging, with extent of variation in management unclear.DESIGN AND METHODS: Using the I-CAH Registry, we retrospectively reviewed management over the first 90 days of life of 154 infants with 21-OHD born in 2018-2023, across 33 centers in 18 countries.RESULTS: Of 154 infants (92 female, 62 male), 136 were diagnosed postnatally, with median (10th centile, 90th centile) presentation age of Day 4 (0, 20.8). At initial hospital discharge, median doses of hydrocortisone (HC), fludrocortisone (FC), and salt were 17 (11.4, 39.6) mg/m2/day, 100 (50, 200) mcg/day and 3.5 (1.6, 8.7) mmol/kg/day, and at Day 90 (D90) 14.5 (8.7, 24.1) mg/m2/day, 100 (50, 200) mcg/day, and 2.1 (1.0, 5.2) mmol/kg/day, respectively. Hyponatremia, hyperkalemia, and hypoglycemia were reported in 70.0%, 71.9%, and 13.0% of infants, respectively. At D90, hyponatremia and hyperkalemia were reported in 7.4% and 28.6%, respectively. At D90, BP measurements were recorded in 30.5%, amongst whom 31.9% had hypertension reported. Median total hospitalization duration over 90 days was 9 days (2, 24). Adrenal crises were associated with 40. 6% of hospitalization episodes. Percentages (males:females) of cases seen by a pediatric endocrinologist, psychologist, pediatric endocrine nurse specialist, and surgeon by D90 were 95.9% (58:84), 33.3% (9:35), 42.1% (20:36), and 23.8% (0:35), respectively.CONCLUSIONS: Contemporary management of CAH in early infancy varies considerably. Hypertension and hyperkalemia are frequently reported. Our data may help inform development of quality indicators for benchmarking CAH care in infancy.

KW - 21-hydroxylase deficiency

KW - benchmarking

KW - congenital adrenal hyperplasia

KW - early infancy

KW - quality of care

KW - treatment variation

UR - https://www.scopus.com/pages/publications/105029373297

U2 - 10.1093/ejendo/lvag004

DO - 10.1093/ejendo/lvag004

M3 - Article

C2 - 41531283

SN - 0804-4643

VL - 194

SP - 123

EP - 135

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 2

ER -

Contemporary global management of 21-hydroxylase deficiency congenital adrenal hyperplasia in early infancy: a multi-national registry study

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