Iranian Journal of Medical Sciences

Document Type : Original Article(s)


1 Department of Child Health, Faculty of Medicine, University Sumatera Utara, Medan, Indonesia

2 Department of Child Health, Faculty of Medicine, University Indonesia Jakarta, Indonesia



Background: Children with Congenital Adrenal Hyperplasia (CAH) have a higher chance of hypertension. The likelihood of hypertension is higher in CAH children who get fludrocortisone medication and have an over-suppression. Plasma renin activity (PRA) is a sensitive indicator when the fludrocortisone dose is insufficient. The objective of this study is to assess the relationship between plasma renin activity with hypertension in 21-hydroxylase-deficient (21-OHD) CAH children. 
Methods: This cross-sectional observational analytical study was conducted in 2019 at the Pediatric Endocrinology Outpatient Clinic in Dr. Cipto Mangunkusumo Hospital (RSCM), Jakarta, Indonesia. The subjects were 21-OHD CAH children, aged >6 months to 18 years who had already taken hydrocortisone with or without fludrocortisone for at least 6 months, and were divided into hypertension and non-hypertension groups. The subjects were selected by a consecutive sampling method. Data was analyzed using SPSS software (version 23.0) with unpaired t test analysis and multiple logistic regression test. Statistical significance was achieved if P<0.05.
Results: Forty 21-OHD CAH patients were included, and 20 subjects (50%) had hypertension. A higher incidence of hypertension was found in salt-wasting CAH than in simple virilizing types (59.3% vs 30.8%). There was a significant mean difference in PRA levels between hypertension and non-hypertension groups in salt-wasting patients (P=0.016). A significant difference between the last dose of hydrocortisone with the number of hypertension patients in salt-wasting patients (P=0.032) was found, and low PRA levels showed a 1.09 times higher risk of hypertension. 
Conclusion: Children with salt-wasting CAH with low PRA levels had a higher risk of getting hypertension.


  1. Dörr HG, Odenwald B, Nennstiel-Ratzel U. Early diagnosis of children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency by newborn screening. International Journal of Neonatal Screening. 2015;1:36-43. doi: 10.3390/ijns1010036.
  2. Witchel SF. Congenital Adrenal Hyperplasia. J Pediatr Adolesc Gynecol. 2017;30:520-34. doi: 10.1016/j.jpag.2017.04.001. PubMed PMID: 28450075; PubMed Central PMCID: PMCPMC5624825.
  3. Mallappa A, Merke DP. Management challenges and therapeutic advances in congenital adrenal hyperplasia. Nat Rev Endocrinol. 2022;18:337-52. doi: 10.1038/s41574-022-00655-w. PubMed PMID: 35411073; PubMed Central PMCID: PMCPMC8999997.
  4. Aditiawati, Utari A, Triningsih E. Hiperplasia adrenal kongenital. In: Batubara J, Tridjaja B, Pulungan D, editors. Buku Ajar Endokrinologi Anak. 2nd ed. Badan Penerbit Ikatan Dokter Anak Indonesia; 2017. p. 379-418.
  5. Podgorski R, Aebisher D, Stompor M, Podgorska D, Mazur A. Congenital adrenal hyperplasia: clinical symptoms and diagnostic methods. Acta Biochim Pol. 2018;65:25-33. doi: 10.18388/abp.2017_2343. PubMed PMID: 29543924.
  6. Raghupathy P. Disorders of adrenocortical biosynthesis. In: Desai M, Menon P, Bhatia V, editors. Pediatric Endocrine Disorders. 3rd ed. Hyderabad: Universities Press (India) Private Ltd; 2014. p. 227-38.
  7. Mansur A, Vaidya A, Turchin A. Using Renin Activity to Guide Mineralocorticoid Receptor Antagonist Therapy in Patients with Low Renin and Hypertension. Am J Hypertens. 2023;36:455-61. doi: 10.1093/ajh/hpad032. PubMed PMID: 37013957; PubMed Central PMCID: PMCPMC10345476.
  8. Pizon T, Rajzer M, Wojciechowska W, Drozdz T, Drozdz D, Rojek M, et al. Plasma renin activity, serum aldosterone concentration and selected organ damage indices in essential arterial hypertension. Arch Med Sci. 2021;17:9-18. doi: 10.5114/aoms.2018.73333. PubMed PMID: 33488850; PubMed Central PMCID: PMCPMC7811306.
  9. Bonfig W, Roehl FW, Riedl S, Dorr HG, Bettendorf M, Bramswig J, et al. Blood Pressure in a Large Cohort of Children and Adolescents With Classic Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency. Am J Hypertens. 2016;29:266-72. doi: 10.1093/ajh/hpv087. PubMed PMID: 26071487.
  10. Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian J Psychol Med. 2013;35:121-6. doi: 10.4103/0253-7176.116232. PubMed PMID: 24049221; PubMed Central PMCID: PMCPMC3775042.
  11. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents. Pediatrics. 2017;140. doi: 10.1542/peds.2017-1904. PubMed PMID: 28827377.
  12. Pediatric Z-score calculator [Internet]. BMI Z-score calculator Children’s Hospital of Philadelphia. [cited 13 April 2020]. Available from:
  13. Yang Y, Zhang M, Yu J, Pei Z, Sun C, He J, et al. Nationwide Trends of Pediatric Obesity and BMI z-Score from 2017-2021 in China: Comparable Findings From Real-World Mobile- and Hospital-Based Data. Front Endocrinol (Lausanne). 2022;13:859245. doi: 10.3389/fendo.2022.859245. PubMed PMID: 35721754; PubMed Central PMCID: PMCPMC9204322.
  14. Maccabee-Ryaboy N, Thomas W, Kyllo J, Lteif A, Petryk A, Gonzalez-Bolanos MT, et al. Hypertension in children with congenital adrenal hyperplasia. Clin Endocrinol (Oxf). 2016;85:528-34. doi: 10.1111/cen.13086. PubMed PMID: 27105393.
  15. Subbarayan A, Dattani MT, Peters CJ, Hindmarsh PC. Cardiovascular risk factors in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin Endocrinol (Oxf). 2014;80:471-7. doi: 10.1111/cen.12265. PubMed PMID: 23751160; PubMed Central PMCID: PMCPMC4204515.
  16. Hoyer-Kuhn H, Huebner A, Richter-Unruh A, Bettendorf M, Rohrer T, Kapelari K, et al. Hydrocortisone dosing in children with classic congenital adrenal hyperplasia: results of the German/Austrian registry. Endocr Connect. 2021;10:561-9. doi: 10.1530/EC-21-0023. PubMed PMID: 33909597; PubMed Central PMCID: PMCPMC8183617.
  17. Ajish TP, Praveen VP, Nisha B, Kumar H. Comparison of different glucocorticoid regimens in the management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Indian J Endocrinol Metab. 2014;18:815-20. doi: 10.4103/2230-8210.141358. PubMed PMID: 25364676; PubMed Central PMCID: PMCPMC4192987.
  18. Hashemi Dehkordi E, Khaheshi S, Mostofizadeh N, Hashemipour M. Cardiovascular Risk Factors in Children and Adolescents with Congenital Adrenal Hyperplasia. Adv Biomed Res. 2021;10:19. doi: 10.4103/abr.abr_219_20. PubMed PMID: 34476227; PubMed Central PMCID: PMCPMC8378445.
  19. Bonfig W, Schwarz HP. Blood pressure, fludrocortisone dose and plasma renin activity in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency followed from birth to 4 years of age. Clin Endocrinol (Oxf). 2014;81:871-5. doi: 10.1111/cen.12498. PubMed PMID: 24818525.