Rare Causes of Pediatric Primary Adrenal Insufficiency: An Observational Cohort Study.

OBJECTIVE

Primary adrenal insufficiency (PAI) is a rare, chronic condition responsible for life-threatening complications and is usually due to 21-hydroxylase deficiency. Identifying other rare causes is crucial to ensure optimal management. The objective of this study was to describe rare causes of pediatric PAI.

METHODS

An observational, retrospective, single-center, cohort study.

RESULTS

Of 172 patients under 18 years diagnosed with PAI in 1980-2023: 113 with 21-hydroxylase deficiency and 59 (34%) with rare causes of PAI including monogenic diseases (n = 38, 64%), auto-immune disorders (n = 15, 25%), and bilateral adrenal hemorrhage (n = 3). Median follow-up was 7.6 years. The mortality was 6 of 59 (10%), with myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital phenotypes and enteropathy syndrome as the most common cause. Acute adrenal crisis occurred in 26 (45%) patients, usually due to poor treatment adherence. Excess weight was common (16/59, 27%). Among 37 available data, puberty was normal in 26 (72%), early in 6 (17%), and delayed in 5 (14%). Growth outcomes were satisfactory of 28 (48%) patients who attained their adult height, median final height was -1.1 standard deviation score (SDS) in males and -0.4 SDS in females and median height in the 27 patients still growing was -0.4 SDS.

CONCLUSION

The wide range of rare causes of PAI raises diagnostic challenges. In most cases, however, the cause can be determined, allowing optimal therapy. Phenotypic characteristics-including age at PAI onset, growth patterns, pubertal development, and body mass index-vary according to the underlying genotype (i.e., myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital phenotypes and enteropathy syndrome Triple A syndrome, and NNT deficiency). Targeted monitoring of these features is therefore essential.