Clinical Features of 57 Patients with Lipoid Congenital Adrenal Hyperplasia: Criteria for Nonclassic Form Revisited

Tomohiro Ishii; Toshihiro Tajima; Kenichi Kashimada; Tokuo Mukai; Yusuke Tanahashi; Noriyuki Katsumata; Junko Kanno; Takashi Hamajima; Kenichi Miyako; Shinobu Ida; Tomonobu Hasegawa

doi:10.1210/clinem/dgaa557

Clinical Features of 57 Patients with Lipoid Congenital Adrenal Hyperplasia: Criteria for Nonclassic Form Revisited

J Clin Endocrinol Metab. 2020 Nov 1;105(11):dgaa557. doi: 10.1210/clinem/dgaa557.

Authors

Tomohiro Ishii^{1

2

3}, Toshihiro Tajima^{1

4}, Kenichi Kashimada^{1

2

5}, Tokuo Mukai^{1

2

6}, Yusuke Tanahashi^{1

7}, Noriyuki Katsumata^{1

8}, Junko Kanno^{2

9}, Takashi Hamajima^{2

10}, Kenichi Miyako^{2

11}, Shinobu Ida^{2

12}, Tomonobu Hasegawa^{1

3}

Affiliations

¹ Research Committee on Disorders of Adrenal Hormones, Research on Intractable Diseases, Health and Labour Sciences Research Grants, Tokyo, Japan.
² Disorders of Sex Development and Adrenal Disorders Committee, the Japanese Society for Pediatric Endocrinology, Fushimi-ku, Kyoto, Japan.
³ Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
⁴ Department of Pediatrics, Jichi Medical University Tochigi Children's Medical Center, Shimotsuke, Tochigi, Japan.
⁵ Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
⁶ Department of Pediatrics, Asahikawa-Kosei General Hospital, Asahikawa, Hokkaido, Japan.
⁷ Department of Pediatrics, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
⁸ Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
⁹ Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
¹⁰ Department of Endocrinology and Metabolism, Aichi Children's Health and Medical Center, Obu, Aichi, Japan.
¹¹ Department of Endocrinology and Metabolism, Fukuoka Children's Hospital, Fukuoka, Fukuoka, Japan.
¹² Department of Pediatric Gastroenterology and Endocrinology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan.

PMID: 32835366
DOI: 10.1210/clinem/dgaa557

Abstract

Context: Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. Classic (CLCAH) and nonclassic (NCLCAH) forms were reported as total and partial deficiencies, respectively, of adrenal and gonadal steroid hormones. The rarity of LCAH has precluded large-scale epidemiological and clinical investigations.

Objective: To determine the epidemiological and clinical characteristics of 2 forms of LCAH.

Design: A multicenter cross-sectional cohort study in Japan on December 1, 2017.

Participants: Fifty-seven patients with LCAH (median age, 23.7 years; range, 0.0-47.5 years).

Main outcome measures: Patient demographics, STAR genotype, Quigley grade, endocrinological and imaging data, treatment, and prognosis.

Results: Fifty-three and 4 patients fulfilled definite and probable diagnostic criteria for LCAH, respectively. When NCLCAH was defined as either Quigley grade 1 in XY karyotype, no episode of salt losing or requirement of fludrocortisone, or onset of primary adrenal insufficiency (PAI) at 1 year or older, patients were divided into groups of 43 patients with CLCAH (75.4%), 11 with NCLCAH (19.3%), and 3 with unclassified LCAH (5.3%). All of the patients with CLCAH and 7/11 NCLCAH (63.6%) were treated with fludrocortisone. CLCAH was diagnosed at a significantly younger age than NCLCAH (median, 0.0 vs 4.0 years). STAR-Arg272Cys or -Met225Thr was identified only in NCLCAH (8/11, 72.7%).

Conclusions: We demonstrated the relative proportions and clinical and molecular characteristics of NCLCAH and CLCAH in Japan. These criteria for NCLCAH correspond to all previously published cases and our cases whose masculinization of the external genitalia, ability of mineralocorticoid production, and onset of PAI were described.

Keywords: STAR; Japan; classic form; lipoid congenital adrenal hyperplasia; nonclassic form; steroidogenic acute regulatory protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adrenal Hyperplasia, Congenital / diagnosis*
Adrenal Hyperplasia, Congenital / drug therapy
Adrenal Hyperplasia, Congenital / genetics
Adult
Child
Child, Preschool
Cross-Sectional Studies
Disorder of Sex Development, 46,XY / diagnosis*
Disorder of Sex Development, 46,XY / drug therapy
Disorder of Sex Development, 46,XY / genetics
Female
Fludrocortisone / therapeutic use*
Humans
Infant
Infant, Newborn
Japan
Middle Aged
Mineralocorticoids / therapeutic use*
Mutation*
Phenotype*
Phosphoproteins / genetics*
Prognosis
Young Adult

Substances

Mineralocorticoids
Phosphoproteins
steroidogenic acute regulatory protein
Fludrocortisone

Supplementary concepts

Lipoid congenital adrenal hyperplasia