Blood pressure and its associations in 554 children and young people with congenital adrenal hyperplasia

Neil R. Lawrence; Irina Bacila; Joseph Tonge; Jeremy Dawson; Gary S. Collins; Zi Qiang Lang; Jillian Bryce; Malika Alimussina; Minglu Chen; Salma Rashid Ali; Safwaan Adam; Erica L.T. Van Den Akker; Tânia Aparecida Sartori Sanchez Bachega; Federico Baronio; Niels Holtum Birkebæk; Walter Bonfig; Hedi Claahsen - Van Der Grinten; Martine Cools; Eduardo Correa Costa; Miguel Debono; Liat De Vries; Christa E. Flück; Gabriella Gazdagh; Ayla Güven; Sabine E. Hannema; Violeta Iotova; Hetty J. Van Der Kamp; Ruth Krone; Sofia Leka-Emiri; María Clemente-León; Corina Raducanu Lichiardopol; Renata L. Markosyan; Tatjana Milenkovic; Mirela Costa De Miranda; Uta Neumann; John Newell-Price; Şükran Poyrazoǧlu; Ursina Probst-Scheidegger; Gianni Russo; Luisa De Sanctis; Sumudu Nimali Seneviratne; Marianna Rita Stancampiano; Rieko Tadokoro-Cuccaro; Ajay Thankamony; Ana Vieites; Malgorzata Wasniewska; Diego Yeste; Jeremy Tomlinson; S. Faisal Ahmed; Nils Krone

doi:10.1093/ejendo/lvaf060

Blood pressure and its associations in 554 children and young people with congenital adrenal hyperplasia

Neil R. Lawrence
, Irina Bacila
, Joseph Tonge
, Jeremy Dawson
, Gary S. Collins
, Zi Qiang Lang
, Jillian Bryce
, Malika Alimussina
, Minglu Chen
, Salma Rashid Ali
, Safwaan Adam
, Erica L.T. Van Den Akker
, Tânia Aparecida Sartori Sanchez Bachega
, Federico Baronio
, Niels Holtum Birkebæk
, Walter Bonfig
, Hedi Claahsen - Van Der Grinten
, Martine Cools
, Eduardo Correa Costa
, Miguel Debono

Liat De Vries, Christa E. Flück, Gabriella Gazdagh, Ayla Güven, Sabine E. Hannema, Violeta Iotova, Hetty J. Van Der Kamp, Ruth Krone, Sofia Leka-Emiri, María Clemente-León, Corina Raducanu Lichiardopol, Renata L. Markosyan, Tatjana Milenkovic, Mirela Costa De Miranda, Uta Neumann, John Newell-Price, Şükran Poyrazoǧlu, Ursina Probst-Scheidegger, Gianni Russo, Luisa De Sanctis, Sumudu Nimali Seneviratne, Marianna Rita Stancampiano, Rieko Tadokoro-Cuccaro, Ajay Thankamony, Ana Vieites, Malgorzata Wasniewska, Diego Yeste, Jeremy Tomlinson, S. Faisal Ahmed, Nils Krone^*

^*Corresponding author for this work

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

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Abstract

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) affects approximately 1 in 15 000 individuals. We leveraged the power of multicentre registry data to assess the trend and predictors of blood pressure (BP) within children and young persons with 21OHD to inform monitoring strategies. Method: Data from the International CAH Registry in patients younger than 20 years was compared to normative values. Values of BP were modeled to create reference curves, multiple change point analysis applied to quantify the difference with normative data. Covariate adjustment was informed by a directed acyclic graph, prior to joint outcome regression modeling to accurately assess predictors of BP. Results: A total of 6436 visits within 554 patients (52.5% females) showed BP-Standard deviation scores (SDS) were higher at younger ages. Patients under five years had systolic BP-SDS of 1.6 (Q1:0.6-Q3:2.7) decreasing to 1.0 (Q1:0.2-Q3:1.8) over 5 years, equating to 31.0% over the 95th centile decreasing to 15.0%. Higher doses of fludrocortisone were associated with a small increase in systolic BP equivalent to 1.2 mmHg with every 100 g extra fludrocortisone. Renin of 100 U/mL was associated with 4.6 mmHg lower systolic BP than a renin of 1 U/ mL, higher 17OH-progesterone and androstenedione also predicted lower systolic and diastolic BP (P < .05). Conclusion: Higher BP in children with 21OHD is common and particularly pronounced at a younger age, but may not be attributable to excessive mineralocorticoid replacement. There is a need to improve our understanding of the determinants of this raised BP as well as its long-term effects. The Author(s) 2025.

Original language	English
Pages (from-to)	529-539
Number of pages	11
Journal	European Journal of Endocrinology
Volume	192
Issue number	5
DOIs	https://doi.org/10.1093/ejendo/lvaf060
Publication status	Published - 1 May 2025

Keywords

Bayesian analysis
blood pressure
congenital adrenal hyperplasia
glucocorticoids
statistical modeling

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10.1093/ejendo/lvaf060Licence: CC BY

lvaf060Final published version, 0.98 MBLicence: CC BY

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Lawrence, N. R., Bacila, I., Tonge, J., Dawson, J., Collins, G. S., Lang, Z. Q., Bryce, J., Alimussina, M., Chen, M., Ali, S. R., Adam, S., Van Den Akker, E. L. T., Bachega, T. A. S. S., Baronio, F., Birkebæk, N. H., Bonfig, W., Claahsen - Van Der Grinten, H., Cools, M., Costa, E. C., ... Krone, N. (2025). Blood pressure and its associations in 554 children and young people with congenital adrenal hyperplasia. European Journal of Endocrinology, 192(5), 529-539. https://doi.org/10.1093/ejendo/lvaf060

@article{2127a1eb1f9a48619e8c58d2fa274d17,

title = "Blood pressure and its associations in 554 children and young people with congenital adrenal hyperplasia",

abstract = "Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) affects approximately 1 in 15 000 individuals. We leveraged the power of multicentre registry data to assess the trend and predictors of blood pressure (BP) within children and young persons with 21OHD to inform monitoring strategies. Method: Data from the International CAH Registry in patients younger than 20 years was compared to normative values. Values of BP were modeled to create reference curves, multiple change point analysis applied to quantify the difference with normative data. Covariate adjustment was informed by a directed acyclic graph, prior to joint outcome regression modeling to accurately assess predictors of BP. Results: A total of 6436 visits within 554 patients (52.5\% females) showed BP-Standard deviation scores (SDS) were higher at younger ages. Patients under five years had systolic BP-SDS of 1.6 (Q1:0.6-Q3:2.7) decreasing to 1.0 (Q1:0.2-Q3:1.8) over 5 years, equating to 31.0\% over the 95th centile decreasing to 15.0\%. Higher doses of fludrocortisone were associated with a small increase in systolic BP equivalent to 1.2 mmHg with every 100 g extra fludrocortisone. Renin of 100 U/mL was associated with 4.6 mmHg lower systolic BP than a renin of 1 U/ mL, higher 17OH-progesterone and androstenedione also predicted lower systolic and diastolic BP (P < .05). Conclusion: Higher BP in children with 21OHD is common and particularly pronounced at a younger age, but may not be attributable to excessive mineralocorticoid replacement. There is a need to improve our understanding of the determinants of this raised BP as well as its long-term effects. The Author(s) 2025.",

keywords = "Bayesian analysis, blood pressure, congenital adrenal hyperplasia, glucocorticoids, statistical modeling",

author = "Lawrence, \{Neil R.\} and Irina Bacila and Joseph Tonge and Jeremy Dawson and Collins, \{Gary S.\} and Lang, \{Zi Qiang\} and Jillian Bryce and Malika Alimussina and Minglu Chen and Ali, \{Salma Rashid\} and Safwaan Adam and \{Van Den Akker\}, \{Erica L.T.\} and Bachega, \{T{\^a}nia Aparecida Sartori Sanchez\} and Federico Baronio and Birkeb{\ae}k, \{Niels Holtum\} and Walter Bonfig and \{Claahsen - Van Der Grinten\}, Hedi and Martine Cools and Costa, \{Eduardo Correa\} and Miguel Debono and \{De Vries\}, Liat and Fl{\"u}ck, \{Christa E.\} and Gabriella Gazdagh and Ayla G{\"u}ven and Hannema, \{Sabine E.\} and Violeta Iotova and \{Van Der Kamp\}, \{Hetty J.\} and Ruth Krone and Sofia Leka-Emiri and Mar{\'i}a Clemente-Le{\'o}n and Lichiardopol, \{Corina Raducanu\} and Markosyan, \{Renata L.\} and Tatjana Milenkovic and \{De Miranda\}, \{Mirela Costa\} and Uta Neumann and John Newell-Price and {\c S}{\"u}kran Poyrazoǧlu and Ursina Probst-Scheidegger and Gianni Russo and \{De Sanctis\}, Luisa and Seneviratne, \{Sumudu Nimali\} and Stancampiano, \{Marianna Rita\} and Rieko Tadokoro-Cuccaro and Ajay Thankamony and Ana Vieites and Malgorzata Wasniewska and Diego Yeste and Jeremy Tomlinson and Ahmed, \{S. Faisal\} and Nils Krone",

year = "2025",

month = may,

day = "1",

doi = "10.1093/ejendo/lvaf060",

language = "English",

volume = "192",

pages = "529--539",

journal = "European Journal of Endocrinology",

issn = "0804-4643",

publisher = "Oxford University Press",

number = "5",

}

Lawrence, NR, Bacila, I, Tonge, J, Dawson, J, Collins, GS, Lang, ZQ, Bryce, J, Alimussina, M, Chen, M, Ali, SR, Adam, S, Van Den Akker, ELT, Bachega, TASS, Baronio, F, Birkebæk, NH, Bonfig, W, Claahsen - Van Der Grinten, H, Cools, M, Costa, EC, Debono, M, De Vries, L, Flück, CE, Gazdagh, G, Güven, A, Hannema, SE, Iotova, V, Van Der Kamp, HJ, Krone, R, Leka-Emiri, S, Clemente-León, M, Lichiardopol, CR, Markosyan, RL, Milenkovic, T, De Miranda, MC, Neumann, U, Newell-Price, J, Poyrazoǧlu, Ş, Probst-Scheidegger, U, Russo, G, De Sanctis, L, Seneviratne, SN, Stancampiano, MR, Tadokoro-Cuccaro, R, Thankamony, A, Vieites, A, Wasniewska, M, Yeste, D, Tomlinson, J, Ahmed, SF & Krone, N 2025, 'Blood pressure and its associations in 554 children and young people with congenital adrenal hyperplasia', European Journal of Endocrinology, vol. 192, no. 5, pp. 529-539. https://doi.org/10.1093/ejendo/lvaf060

TY - JOUR

T1 - Blood pressure and its associations in 554 children and young people with congenital adrenal hyperplasia

AU - Lawrence, Neil R.

AU - Bacila, Irina

AU - Tonge, Joseph

AU - Dawson, Jeremy

AU - Collins, Gary S.

AU - Lang, Zi Qiang

AU - Bryce, Jillian

AU - Alimussina, Malika

AU - Chen, Minglu

AU - Ali, Salma Rashid

AU - Adam, Safwaan

AU - Van Den Akker, Erica L.T.

AU - Bachega, Tânia Aparecida Sartori Sanchez

AU - Baronio, Federico

AU - Birkebæk, Niels Holtum

AU - Bonfig, Walter

AU - Claahsen - Van Der Grinten, Hedi

AU - Cools, Martine

AU - Costa, Eduardo Correa

AU - Debono, Miguel

AU - De Vries, Liat

AU - Flück, Christa E.

AU - Gazdagh, Gabriella

AU - Güven, Ayla

AU - Hannema, Sabine E.

AU - Iotova, Violeta

AU - Van Der Kamp, Hetty J.

AU - Krone, Ruth

AU - Leka-Emiri, Sofia

AU - Clemente-León, María

AU - Lichiardopol, Corina Raducanu

AU - Markosyan, Renata L.

AU - Milenkovic, Tatjana

AU - De Miranda, Mirela Costa

AU - Neumann, Uta

AU - Newell-Price, John

AU - Poyrazoǧlu, Şükran

AU - Probst-Scheidegger, Ursina

AU - Russo, Gianni

AU - De Sanctis, Luisa

AU - Seneviratne, Sumudu Nimali

AU - Stancampiano, Marianna Rita

AU - Tadokoro-Cuccaro, Rieko

AU - Thankamony, Ajay

AU - Vieites, Ana

AU - Wasniewska, Malgorzata

AU - Yeste, Diego

AU - Tomlinson, Jeremy

AU - Ahmed, S. Faisal

AU - Krone, Nils

PY - 2025/5/1

Y1 - 2025/5/1

N2 - Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) affects approximately 1 in 15 000 individuals. We leveraged the power of multicentre registry data to assess the trend and predictors of blood pressure (BP) within children and young persons with 21OHD to inform monitoring strategies. Method: Data from the International CAH Registry in patients younger than 20 years was compared to normative values. Values of BP were modeled to create reference curves, multiple change point analysis applied to quantify the difference with normative data. Covariate adjustment was informed by a directed acyclic graph, prior to joint outcome regression modeling to accurately assess predictors of BP. Results: A total of 6436 visits within 554 patients (52.5% females) showed BP-Standard deviation scores (SDS) were higher at younger ages. Patients under five years had systolic BP-SDS of 1.6 (Q1:0.6-Q3:2.7) decreasing to 1.0 (Q1:0.2-Q3:1.8) over 5 years, equating to 31.0% over the 95th centile decreasing to 15.0%. Higher doses of fludrocortisone were associated with a small increase in systolic BP equivalent to 1.2 mmHg with every 100 g extra fludrocortisone. Renin of 100 U/mL was associated with 4.6 mmHg lower systolic BP than a renin of 1 U/ mL, higher 17OH-progesterone and androstenedione also predicted lower systolic and diastolic BP (P < .05). Conclusion: Higher BP in children with 21OHD is common and particularly pronounced at a younger age, but may not be attributable to excessive mineralocorticoid replacement. There is a need to improve our understanding of the determinants of this raised BP as well as its long-term effects. The Author(s) 2025.

AB - Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) affects approximately 1 in 15 000 individuals. We leveraged the power of multicentre registry data to assess the trend and predictors of blood pressure (BP) within children and young persons with 21OHD to inform monitoring strategies. Method: Data from the International CAH Registry in patients younger than 20 years was compared to normative values. Values of BP were modeled to create reference curves, multiple change point analysis applied to quantify the difference with normative data. Covariate adjustment was informed by a directed acyclic graph, prior to joint outcome regression modeling to accurately assess predictors of BP. Results: A total of 6436 visits within 554 patients (52.5% females) showed BP-Standard deviation scores (SDS) were higher at younger ages. Patients under five years had systolic BP-SDS of 1.6 (Q1:0.6-Q3:2.7) decreasing to 1.0 (Q1:0.2-Q3:1.8) over 5 years, equating to 31.0% over the 95th centile decreasing to 15.0%. Higher doses of fludrocortisone were associated with a small increase in systolic BP equivalent to 1.2 mmHg with every 100 g extra fludrocortisone. Renin of 100 U/mL was associated with 4.6 mmHg lower systolic BP than a renin of 1 U/ mL, higher 17OH-progesterone and androstenedione also predicted lower systolic and diastolic BP (P < .05). Conclusion: Higher BP in children with 21OHD is common and particularly pronounced at a younger age, but may not be attributable to excessive mineralocorticoid replacement. There is a need to improve our understanding of the determinants of this raised BP as well as its long-term effects. The Author(s) 2025.

KW - Bayesian analysis

KW - blood pressure

KW - congenital adrenal hyperplasia

KW - glucocorticoids

KW - statistical modeling

UR - https://www.scopus.com/pages/publications/105004757638

U2 - 10.1093/ejendo/lvaf060

DO - 10.1093/ejendo/lvaf060

M3 - Article

C2 - 40184493

AN - SCOPUS:105004757638

SN - 0804-4643

VL - 192

SP - 529

EP - 539

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 5

ER -

Blood pressure and its associations in 554 children and young people with congenital adrenal hyperplasia

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