Incidence and Risk Factors for Adrenal Crisis in Pediatric-onset Adrenal Insufficiency: A Prospective Study

Mayumi Hosokawa; Yosuke Ichihashi; Yasunori Sato; Nao Shibata; Keisuke Nagasaki; Kento Ikegawa; Yukihiro Hasegawa; Takashi Hamajima; Fusa Nagamatsu; Shigeru Suzuki; Chikahiko Numakura; Naoko Amano; Goro Sasaki; Keiko Nagahara; Shun Soneda; Daisuke Ariyasu; Miwako Maeda; Hotaka Kamasaki; Keiko Aso; Tomonobu Hasegawa; Tomohiro Ishii

doi:10.1210/clinem/dgad753

Incidence and Risk Factors for Adrenal Crisis in Pediatric-onset Adrenal Insufficiency: A Prospective Study

J Clin Endocrinol Metab. 2023 Dec 21:dgad753. doi: 10.1210/clinem/dgad753. Online ahead of print.

Authors

Mayumi Hosokawa^{1

2

3}, Yosuke Ichihashi^{1

2}, Yasunori Sato⁴, Nao Shibata^{1

5}, Keisuke Nagasaki^{1

5}, Kento Ikegawa^{1

6}, Yukihiro Hasegawa^{1

6}, Takashi Hamajima^{1

7}, Fusa Nagamatsu^{1

8}, Shigeru Suzuki^{1

9}, Chikahiko Numakura^{1

10}, Naoko Amano^{1

3}, Goro Sasaki^{1

11}, Keiko Nagahara^{1

12}, Shun Soneda^{1

13}, Daisuke Ariyasu^{1

14}, Miwako Maeda^{1

15}, Hotaka Kamasaki^{1

16}, Keiko Aso^{1

17}, Tomonobu Hasegawa^{1

2}, Tomohiro Ishii^{1

2}

Affiliations

¹ Japanese Multicenter Study for Adrenal Crisis (JMSAC).
² Dept. of Pediatr., Keio Univ. Sch. of Med.
³ Dept. of Pediatr., Saitama City Hosp.
⁴ Dept. of Preventive Medicine and Public Health, Keio Univ. Sch. of Med.
⁵ Dept. of Pediatr., Niigata Univ. Medical and Dental Hosp.
⁶ Dept. of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center.
⁷ Dept. of Endocrinology and Metabolism, Aichi Children's Health and Medical Center.
⁸ Dept. of Pediatr., Kumamoto Univ. Sch. of Med.
⁹ Dept. of Pediatr., Asahikawa Medical Univ.
¹⁰ Dept. of Pediatr., Yamagata Univ. Faculty of Med.
¹¹ Dept. of Pediatr., Tokyo Dental College Ichikawa General Hosp.
¹² Dept. of Pediatr., Showa Univ, Sch. of Med.
¹³ Dept. of Pediatr., St. Marianna Univ., Sch. of Med.
¹⁴ Dept. of Pediatr., Kawasaki Municipal Hosp.
¹⁵ Dept. of Pediatr., Oita Univ. Faculty of Med.
¹⁶ Dept. of Pediatr., Sapporo Medical Univ.
¹⁷ Dept of Pediatr., Toho Univ. Omori Medical Center.

PMID: 38128002
DOI: 10.1210/clinem/dgad753

Abstract

Purpose: To determine the incidence and risk factors for adrenal crisis (AC) in patients with pediatric-onset adrenal insufficiency (AI).

Materials and methods: This multicenter, prospective cohort study conducted in Japan enrolled patients diagnosed with AI at ≤ 15 years of age. The incidence of AC was calculated as events per person-year (PY), and risk factors for AC were assessed using Poisson regression multivariable analysis.

Results: The study population comprised 349 patients (164 male, 185 female) with a total follow-up of 961 PY. The median age at enrollment was 14.3 years (interquartile range [IQR] 8.5-21.2 years), and the median follow-up was 2.8 years (IQR 2.2-3.3 years). Of these patients, 213 (61%) had primary AI and 136 (39%) had secondary AI. Forty-one AC events occurred in 31 patients during the study period. The calculated incidence of AC was 4.27 per 100 PY (95% confidence interval [CI] of 3.15-5.75). Poisson regression analysis identified younger age at enrollment (relative risk [RR] 0.93 [95% CI 0.89-0.97]) and increased number of infections (RR 1.17 [95% CI 1.07-1.27]) as significant risk factors. Female sex (RR 0.99 [95% CI 0.53-1.86]), primary AI (RR 0.65 [95 % CI 0.30-1.41]), or equivalent dosage of hydrocortisone per square meter of body area (RR 1.02 [95% CI 0.96-1.08]) was not a significant risk factor.

Conclusion: A substantial proportion of patients with pediatric-onset AI experience AC. Younger age and an increased number of infections are independent risk factors for developing AC in these patients.

Keywords: adrenal crisis; adrenal insufficiency; incidence; prospective study; risk factor.