Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision)

doi:10.1297/cpe.2022-0009

. 2022;31(3):116-143.

doi: 10.1297/cpe.2022-0009. Epub 2022 Apr 10.

Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision)

Tomohiro Ishii^{1

2}, Kenichi Kashimada^{1

3}, Naoko Amano^{2

4

5}, Kei Takasawa^{3

4}, Akari Nakamura-Utsunomiya^{4

6}, Shuichi Yatsuga^{4

7}, Tokuo Mukai^{1

8}, Shinobu Ida^{1

9}, Mitsuhisa Isobe^{10

11}, Masaru Fukushi^{10

12}, Hiroyuki Satoh^{13

14}, Kaoru Yoshino^{13

15}, Michio Otsuki^{16

17}, Takuyuki Katabami^{16

18}, Toshihiro Tajima^{4

19}

Affiliations

¹ Differences of Sex Development (DSD) and Adrenal Disorders Committee, Japanese Society for Pediatric Endocrinology.
² Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
³ Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
⁴ Committee on Mass Screening, Japanese Society for Pediatric Endocrinology.
⁵ Department of Pediatrics, Saitama City Hospital, Saitama, Japan.
⁶ Department of Pediatrics, Hiroshima Prefectural Hospital, Hiroshima, Japan.
⁷ Department of Pediatrics, Fukuoka University School of Medicine, Fukuoka, Japan.
⁸ Department of Pediatrics, Asahikawa Red Cross Hospital, Asahikawa, Japan.
⁹ Department of Gastroenterology and Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan.
¹⁰ Japanese Society for Neonatal Screening.
¹¹ Saitama City Institute of Health Science and Research, Saitama, Japan.
¹² Sapporo Immuno Diagnostic Laboratory (IDL), Sapporo, Japan.
¹³ Japanese Society for Pediatric Urology.
¹⁴ Division of Urology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
¹⁵ Department of Urology, Aichi Children's Health and Medical Center, Obu, Japan.
¹⁶ Japan Endocrine Society.
¹⁷ Department of Endocrinology, Tokyo Women's Medical University, Tokyo, Japan.
¹⁸ Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University School, Yokohama Seibu Hospital, Yokohama, Japan.
¹⁹ Department of Pediatrics, Jichi Medical University Tochigi Children's Medical Center, Tochigi, Japan.

PMID: 35928387
PMCID: PMC9297175
DOI: 10.1297/cpe.2022-0009

Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision)

Tomohiro Ishii et al. Clin Pediatr Endocrinol. 2022.

. 2022;31(3):116-143.

doi: 10.1297/cpe.2022-0009. Epub 2022 Apr 10.

Authors

Affiliations

¹ Differences of Sex Development (DSD) and Adrenal Disorders Committee, Japanese Society for Pediatric Endocrinology.
² Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
³ Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
⁴ Committee on Mass Screening, Japanese Society for Pediatric Endocrinology.
⁵ Department of Pediatrics, Saitama City Hospital, Saitama, Japan.
⁶ Department of Pediatrics, Hiroshima Prefectural Hospital, Hiroshima, Japan.
⁷ Department of Pediatrics, Fukuoka University School of Medicine, Fukuoka, Japan.
⁸ Department of Pediatrics, Asahikawa Red Cross Hospital, Asahikawa, Japan.
⁹ Department of Gastroenterology and Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan.
¹⁰ Japanese Society for Neonatal Screening.
¹¹ Saitama City Institute of Health Science and Research, Saitama, Japan.
¹² Sapporo Immuno Diagnostic Laboratory (IDL), Sapporo, Japan.
¹³ Japanese Society for Pediatric Urology.
¹⁴ Division of Urology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
¹⁵ Department of Urology, Aichi Children's Health and Medical Center, Obu, Japan.
¹⁶ Japan Endocrine Society.
¹⁷ Department of Endocrinology, Tokyo Women's Medical University, Tokyo, Japan.
¹⁸ Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University School, Yokohama Seibu Hospital, Yokohama, Japan.
¹⁹ Department of Pediatrics, Jichi Medical University Tochigi Children's Medical Center, Tochigi, Japan.

PMID: 35928387
PMCID: PMC9297175
DOI: 10.1297/cpe.2022-0009

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 CAY21A2 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.

Keywords: 21-hydroxylase deficiency; congenital adrenal hyperplasia; guideline; neonatal mass screening.

2022©The Japanese Society for Pediatric Endocrinology.

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Conflict of interest statement

In accordance with the regulations related to the Conflict of Interest (COI) of the Japanese Society for Pediatric Endocrinology, none of the working committee members had COI regarding the guidelines in the past 3 years.

Figures

**Fig. 1.**
Steroidogenesis in 21-hydroxylase deficiency. DOC: deoxycorticosterone, 17-OHP: 17-hydroxyprogesterone, DHEA: dehydroepiandrosterone, DHEA-S: dehydroepiandrosterone sulfate, ZG: zona glomerulosa, ZF: zona fasciculata, ZR: zona reticularis.

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References

1. Suwa S. Nationwide survey of neonatal mass-screening for congenital adrenal hyperplasia in Japan. Screening 1994;3: 141–51. doi: 10.1016/0925-6164(94)90022-1 - DOI
1. Pang SY, Wallace MA, Hofman L, Thuline HC, Dorche C, Lyon IC, et al. . Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics 1988;81: 866–74. - PubMed
1. Suwa S. Congenital adrenal hyperplasia. Jpn J Pediatr Med 1994;12: 1967–72(in Japanese).
1. Fujieda K. History of current status of neonatal mass screening for congenital adrenal hyperplasia. Jpn J Pediatr Med 2001;33: 1674–8(in Japanese).
1. Suwa S, Igarashi Y, Kitagawa T, Shimozawa K, Tsuruhara T, Matsuura N, et al. . Diagnostic handbook of congenital adrenal hyperplasia (21-hydropxylase deficiency) identified by neonatal mass screening. J Jpn Pediatr Soc 1989;93: 1632–3(in Japanese).

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[1] Suwa S. Nationwide survey of neonatal mass-screening for congenital adrenal hyperplasia in Japan. Screening 1994;3: 141–51. doi: 10.1016/0925-6164(94)90022-1 - DOI

[2] Suwa S. Nationwide survey of neonatal mass-screening for congenital adrenal hyperplasia in Japan. Screening 1994;3: 141–51. doi: 10.1016/0925-6164(94)90022-1 - DOI

[3] Pang SY, Wallace MA, Hofman L, Thuline HC, Dorche C, Lyon IC, et al. . Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics 1988;81: 866–74. - PubMed

[4] Pang SY, Wallace MA, Hofman L, Thuline HC, Dorche C, Lyon IC, et al. . Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics 1988;81: 866–74. - PubMed

[5] Suwa S. Congenital adrenal hyperplasia. Jpn J Pediatr Med 1994;12: 1967–72(in Japanese).

[6] Suwa S. Congenital adrenal hyperplasia. Jpn J Pediatr Med 1994;12: 1967–72(in Japanese).

[7] Fujieda K. History of current status of neonatal mass screening for congenital adrenal hyperplasia. Jpn J Pediatr Med 2001;33: 1674–8(in Japanese).

[8] Fujieda K. History of current status of neonatal mass screening for congenital adrenal hyperplasia. Jpn J Pediatr Med 2001;33: 1674–8(in Japanese).

[9] Suwa S, Igarashi Y, Kitagawa T, Shimozawa K, Tsuruhara T, Matsuura N, et al. . Diagnostic handbook of congenital adrenal hyperplasia (21-hydropxylase deficiency) identified by neonatal mass screening. J Jpn Pediatr Soc 1989;93: 1632–3(in Japanese).

[10] Suwa S, Igarashi Y, Kitagawa T, Shimozawa K, Tsuruhara T, Matsuura N, et al. . Diagnostic handbook of congenital adrenal hyperplasia (21-hydropxylase deficiency) identified by neonatal mass screening. J Jpn Pediatr Soc 1989;93: 1632–3(in Japanese).

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Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision)

Affiliations

Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision)

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

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