Adrenal crises in children with adrenal insufficiency: epidemiology and risk factors

Abstract

The aim of the study was to assess the epidemiology and risk factors of adrenal crises (AC) in children with adrenal insufficiency (AI). Children diagnosed with AI between 1990 and 2017 at four Israeli pediatric endocrinology units were studied. Demographic and clinical data were retrieved retrospectively from their files. The study population consisted of 120 children (73 boys, 47 girls) and comprised 904 patient years. Median age at diagnosis was 0.3 years (0–17.5). Thirty-one AC events in 26 children occurred during the study period, accounting for a frequency of 3.4 crises/100 patient years. Fifty-two percent of AC events occurred at presentation. The significant risk factors for developing AC were the following: younger age at diagnosis (P = 0.003), primary AI vs. secondary AI (P = 0.016), specific diagnosis of autoimmune AI, adrenal hypoplasia congenita and salt wasting congenital adrenal hyperplasia (P < 0.001), mineralocorticoid treatment (P < 0.001), and recurrent hospital admissions (P > 0.001). After applying a stepwise logistic regression model, only the group of diagnoses, including salt wasting CAH, AHC, and Addison’s disease, remained significant predictor of AC (OR 17.5, 95% CI 4.7–64.9, P < 0.001). There was no AC-associated mortality during the study period.

Conclusions: Since significant percent of AC events occurred at presentation, measures to increase the awareness to signs and symptoms of AI among primary care physicians should be taken. Efforts to prevent AC should be focused on younger patients, especially those with primary AI.

What Is Known:
• Diagnosis and long-term management of pediatric patients with adrenal insufficiency (AI) remain a challenge.
• Adrenal crises (AC) pose life-threatening emergencies in affected youngsters. Studies on the rate and risk factors of AC in children with AI are scarce, and they were done mainly on children with congenital adrenal hyperplasia (CAH).
What Is New:
• The rate of AC was relatively low and there was no AC-associated mortality during the study period.
• Children with primary AI were at higher risk for AC than children with secondary AI. Specifically, children with salt wasting CAH, adrenal hypoplasia congenita, and Addison’s disease at the highest risk.

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Abbreviations

AC:

Adrenal crises

ACTH:

Adrenocorticotrophic hormone

AHC:

Adrenal hypoplasia congenita

AI:

Adrenal insufficiency

ALD:

Adrenoleukodystrophy

CAH:

Congenital adrenal hyperplasia

CI:

Confidence interval

OR:

Odds ratio

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Acknowledgments

We thank Pearl Lilos for the statistical analysis and Esther Eshkol for professional English editing.

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Authors

Contributions

OE and NW: Study design, literature search, data analysis and interpretation, writing the manuscript

YL: Data collection and analysis, literature search

AO: Study design, data analysis, and interpretation

AZ, MR, ASD, and ASB: Data collection, analysis, and interpretation

All authors were involved in the preparation of the manuscript, critically reviewed the manuscript, and approved the final manuscript as submitted.

Corresponding author

Correspondence to Ori Eyal.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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This study was approved by the medical ethics committee of each participating center; the requirement for informed consent was waived.

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Eyal, O., Levin, Y., Oren, A. et al. Adrenal crises in children with adrenal insufficiency: epidemiology and risk factors. Eur J Pediatr 178, 731–738 (2019). https://doi.org/10.1007/s00431-019-03348-1

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Keywords

  • Pediatric
  • Epidemiology
  • Adrenal insufficiency
  • Adrenal crisis