Clinical Guidelines for the Diagnosis and Treatment of 21-hydroxylase Deficiency (2021 Revision)

Overview

Journal Clin Pediatr Endocrinol

Specialty Pediatrics

Date 2022 Aug 5

PMID 35928387

Authors

Tomohiro Ishii

Kenichi Kashimada

Naoko Amano

Kei Takasawa

Akari Nakamura-Utsunomiya

Shuichi Yatsuga

Tokuo Mukai

Shinobu Ida

Mitsuhisa Isobe

Masaru Fukushi

Hiroyuki Satoh

Kaoru Yoshino

Michio Otsuki

Takuyuki Katabami

Toshihiro Tajima

Affiliations

Soon will be listed here.

Abstract

Congenital adrenal hyperplasia is a category of disorders characterized by impaired adrenocortical steroidogenesis. The most frequent disorder of congenital adrenal hyperplasia is 21-hydroxylase deficiency, which is caused by pathogenic variants of and is prevalent between 1 in 18,000 and 20,000 in Japan. The clinical guidelines for 21-hydroxylase deficiency in Japan have been revised twice since a diagnostic handbook in Japan was published in 1989. On behalf of the Japanese Society for Pediatric Endocrinology, the Japanese Society for Mass Screening, the Japanese Society for Urology, and the Japan Endocrine Society, the working committee updated the guidelines for the diagnosis and treatment of 21-hydroxylase deficiency published in 2014, based on recent evidence and knowledge related to this disorder. The recommendations in the updated guidelines can be applied in clinical practice considering the risks and benefits to each patient.

Citing Articles

Subcutaneous route is a reliable alternative for ACTH-stimulated steroid profiling.

Dhananjaya M, Revanasiddappa S, Kansal N, Lila A, Sarathi V Endocrine. 2025; .

PMID: 39862361 DOI: 10.1007/s12020-025-04172-4.

Newborn screening for congenital adrenal hyperplasia: Utility of liquid chromatography with tandem mass spectrometry as a secondary test.

Tajima T Clin Pediatr Endocrinol. 2025; 34(1):13-18.

PMID: 39777132 PMC: 11701021. DOI: 10.1297/cpe.2024-0069.

Adrenal crisis during a trip in a young child with septo-optic dysplasia.

Takahashi M, Sato T, Nakano S, Hamada J, Ishii T, Hasegawa T Clin Pediatr Endocrinol. 2024; 33(2):101-103.

PMID: 38572384 PMC: 10985012. DOI: 10.1297/cpe.2023-0067.

Acute Adrenal Insufficiency Caused by Mental Stress in a Patient With Adrenocorticotropic Hormone Deficiency.

Sueoka H, Ikegawa K, Hasegawa Y Cureus. 2023; 15(3):e36933.

PMID: 37131577 PMC: 10148941. DOI: 10.7759/cureus.36933.

Monitoring treatment in pediatric patients with 21-hydroxylase deficiency.

Itonaga T, Hasegawa Y Front Endocrinol (Lausanne). 2023; 14:1102741.

PMID: 36843618 PMC: 9945343. DOI: 10.3389/fendo.2023.1102741.

References

Schoer M, Nguyen P, Merritt D, Wesevich V, Hollander A . The Role of Patient Advocacy and the Declining Rate of Clitoroplasty in 46,XX Patients With Congenital Adrenal Hyperplasia. Clin Pediatr (Phila). 2018; 57(14):1664-1671. DOI: 10.1177/0009922818803407. View

Simunkova K, Jovanovic N, Rostrup E, Methlie P, Oksnes M, Nilsen R . Effect of a pre-exercise hydrocortisone dose on short-term physical performance in female patients with primary adrenal failure. Eur J Endocrinol. 2015; 174(1):97-105. DOI: 10.1530/EJE-15-0630. View

Sircili M, Bachega T, Madureira G, Gomes L, Mendonca B, Denes F . Surgical Treatment after Failed Primary Correction of Urogenital Sinus in Female Patients with Virilizing Congenital Adrenal Hyperplasia: Are Good Results Possible?. Front Pediatr. 2016; 4:118. PMC: 5081340. DOI: 10.3389/fped.2016.00118. View

Metwalley K, El-Saied A . Bone mineral status in Egyptian children with classic congenital adrenal hyperplasia. A single-center study from Upper Egypt. Indian J Endocrinol Metab. 2014; 18(5):700-4. PMC: 4171895. DOI: 10.4103/2230-8210.139236. View

Muthusamy K, Elamin M, Smushkin G, Murad M, Lampropulos J, Elamin K . Clinical review: Adult height in patients with congenital adrenal hyperplasia: a systematic review and metaanalysis. J Clin Endocrinol Metab. 2010; 95(9):4161-72. DOI: 10.1210/jc.2009-2616. View

Nidal S, Kocherov S, Jaber J, Levi-Khademi F, Farkas A, Chertin B . Sexual function and voiding status following one stage feminizing genitoplasty. J Pediatr Urol. 2020; 16(1):97.e1-97.e6. DOI: 10.1016/j.jpurol.2019.11.017. View

New M, Carlson A, Obeid J, Marshall I, Cabrera M, Goseco A . Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies. J Clin Endocrinol Metab. 2001; 86(12):5651-7. DOI: 10.1210/jcem.86.12.8072. View

van der Kamp H, Oudshoorn C, Elvers B, van Baarle M, Otten B, Wit J . Cutoff levels of 17-alpha-hydroxyprogesterone in neonatal screening for congenital adrenal hyperplasia should be based on gestational age rather than on birth weight. J Clin Endocrinol Metab. 2005; 90(7):3904-7. DOI: 10.1210/jc.2004-2136. View

Pussard E, Travers S, Bouvattier C, Xue Q, Cosson C, Viengchareun S . Urinary steroidomic profiles by LC-MS/MS to monitor classic 21-Hydroxylase deficiency. J Steroid Biochem Mol Biol. 2019; 198:105553. DOI: 10.1016/j.jsbmb.2019.105553. View

10.

Burgu B, Duffy P, Cuckow P, Ransley P, Wilcox D . Long-term outcome of vaginal reconstruction: comparing techniques and timing. J Pediatr Urol. 2008; 3(4):316-20. DOI: 10.1016/j.jpurol.2006.09.008. View

11.

Kosel S, Burggraf S, Fingerhut R, Dorr H, Roscher A, Olgemoller B . Rapid second-tier molecular genetic analysis for congenital adrenal hyperplasia attributable to steroid 21-hydroxylase deficiency. Clin Chem. 2004; 51(2):298-304. DOI: 10.1373/clinchem.2004.042416. View

12.

Subbarayan A, Dattani M, Peters C, Hindmarsh P . Cardiovascular risk factors in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin Endocrinol (Oxf). 2013; 80(4):471-7. PMC: 4204515. DOI: 10.1111/cen.12265. View

13.

Powell D, Newman K, Randolph J . A proposed classification of vaginal anomalies and their surgical correction. J Pediatr Surg. 1995; 30(2):271-5; discussion 275-6. DOI: 10.1016/0022-3468(95)90573-1. View

14.

Woodcock T, Barker P, Daniel S, Fletcher S, Wass J, Tomlinson J . Guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency: Guidelines from the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK. Anaesthesia. 2020; 75(5):654-663. DOI: 10.1111/anae.14963. View

15.

Gurian E, Kinnamon D, Henry J, Waisbren S . Expanded newborn screening for biochemical disorders: the effect of a false-positive result. Pediatrics. 2006; 117(6):1915-21. DOI: 10.1542/peds.2005-2294. View

16.

Matsubara Y, Ono M, Miyai K, Takizawa F, Takasawa K, Onishi T . Longitudinal analysis of growth and body composition of Japanese 21-OHD patients in childhood. Endocr J. 2012; 60(2):149-54. DOI: 10.1507/endocrj.ej12-0123. View

17.

Charmandari E, Matthews D, Johnston A, Brook C, Hindmarsh P . Serum cortisol and 17-hydroxyprogesterone interrelation in classic 21-hydroxylase deficiency: is current replacement therapy satisfactory?. J Clin Endocrinol Metab. 2001; 86(10):4679-85. DOI: 10.1210/jcem.86.10.7972. View

18.

Rivkees S, Crawford J . Dexamethasone treatment of virilizing congenital adrenal hyperplasia: the ability to achieve normal growth. Pediatrics. 2000; 106(4):767-73. DOI: 10.1542/peds.106.4.767. View

19.

Mullis P, Hindmarsh P, Brook C . Sodium chloride supplement at diagnosis and during infancy in children with salt-losing 21-hydroxylase deficiency. Eur J Pediatr. 1990; 150(1):22-5. DOI: 10.1007/BF01959473. View

20.

Bonfig W, Pozza S, Schmidt H, Pagel P, Knorr D, Schwarz H . Hydrocortisone dosing during puberty in patients with classical congenital adrenal hyperplasia: an evidence-based recommendation. J Clin Endocrinol Metab. 2009; 94(10):3882-8. DOI: 10.1210/jc.2009-0942. View