Clinical features of hereditary adrenocortical unresponsiveness to adrenocorticotropin (HAUA) in Japan: from a nationwide questionnaire based survey
Abstract
Hereditary adrenocortical unresponsiveness to adrenocorticotropin (HAUA) is a rare congenital disorder characterized by isolated glucocorticoid deficiency with preserved mineralocorticoid production. HAUA encompasses familial glucocorticoid deficiency (FGD) and triple A syndrome (AAAS) and is caused by autosomal recessive defects in ACTH-signaling–related genes, including MC2R, MRAP, AAAS, NNT, TXNRD2, and MCM4. To clarify the current clinical characteristics of HAUA (including FGD and AAAS) in Japan, we conducted a nationwide questionnaire-based survey. The primary survey identified the number of affected patients, and the secondary survey collected detailed clinical information. Fifteen patients were identified from 12 institutions. Detailed clinical data were obtained from nine patients (mean age, 40.6 years). Most patients developed symptoms during childhood [3.75 (0–8) years]. Seven presented with chronic adrenal insufficiency, and two experienced life-threatening events, hypoglycemia or encephalopathy. Genetic confirmation was obtained in four cases. All patients received glucocorticoid replacement therapy (mean hydrocortisone-equivalent dose, 13.0 mg/m2/day). Notably, 50% of adult patients were obese (BMI ≥25 kg/m2), although no clear association between glucocorticoid dose and BMI was observed. Despite the limited cohort size, this study provides detailed clinical information on HAUA (including FGD and AAAS) in Japan and suggests a potential risk of obesity in long-term management.
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BibTeX
@article{tanimoto2026clinical,
title = {{Clinical features of hereditary adrenocortical unresponsiveness to adrenocorticotropin (HAUA) in Japan: from a nationwide questionnaire based survey}},
author = {Eri Tanimoto and Kenichi Kashimada and Bunzo Matsuura and Hideki Yamaguchi and Masafumi Kurajoh and Toshie Segawa and Kenji Ohba and Yuki Abe and Yasunori Wada and Junko Kanno and Yoichiro Oda and Toshihiro Tajima and Hirotaka Shibata and Tomonobu Hasegawa},
journal = {Endocrine Journal},
year = {2026},
month = aug,
doi = {10.1507/endocrj.ej26-0099},
url = {https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0099/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Clinical features of hereditary adrenocortical unresponsiveness to adrenocorticotropin (HAUA) in Japan: from a nationwide questionnaire based survey
AU - Eri Tanimoto
AU - Kenichi Kashimada
AU - Bunzo Matsuura
AU - Hideki Yamaguchi
AU - Masafumi Kurajoh
AU - Toshie Segawa
AU - Kenji Ohba
AU - Yuki Abe
AU - Yasunori Wada
AU - Junko Kanno
AU - Yoichiro Oda
AU - Toshihiro Tajima
AU - Hirotaka Shibata
AU - Tomonobu Hasegawa
PY - 2026
DA - 2026/08/11
JO - Endocrine Journal
DO - 10.1507/endocrj.ej26-0099
UR - https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0099/_article
AB - Hereditary adrenocortical unresponsiveness to adrenocorticotropin (HAUA) is a rare congenital disorder characterized by isolated glucocorticoid deficiency with preserved mineralocorticoid production. HAUA encompasses familial glucocorticoid deficiency (FGD) and triple A syndrome (AAAS) and is caused by autosomal recessive defects in ACTH-signaling–related genes, including MC2R, MRAP, AAAS, NNT, TXNRD2, and MCM4. To clarify the current clinical characteristics of HAUA (including FGD and AAAS) in Japan, we conducted a nationwide questionnaire-based survey. The primary survey identified the number of affected patients, and the secondary survey collected detailed clinical information. Fifteen patients were identified from 12 institutions. Detailed clinical data were obtained from nine patients (mean age, 40.6 years). Most patients developed symptoms during childhood [3.75 (0–8) years]. Seven presented with chronic adrenal insufficiency, and two experienced life-threatening events, hypoglycemia or encephalopathy. Genetic confirmation was obtained in four cases. All patients received glucocorticoid replacement therapy (mean hydrocortisone-equivalent dose, 13.0 mg/m2/day). Notably, 50% of adult patients were obese (BMI ≥25 kg/m2), although no clear association between glucocorticoid dose and BMI was observed. Despite the limited cohort size, this study provides detailed clinical information on HAUA (including FGD and AAAS) in Japan and suggests a potential risk of obesity in long-term management.
SN - 1348-4540
SN - 0918-8959
ER -