Inherited, Non-CAH Primary Adrenal Insufficiency in Children: A Genetic and Clinical Profile from a Tertiary Care...

Primary adrenal insufficiency (PAI) results from inadequate adrenal hormone production due to adrenal cortex dysfunction. While congenital adrenal hyperplasia (CAH) is the most common cause in children, non-CAH causes are rare and often associated with specific genetic mutations. This study aims to explore the genetic, clinical, and biochemical spectrum of non-CAH PAI in South Indian children.

This retrospective study reviewed records of children under 18 years diagnosed with PAI at a tertiary care centre between January 2016 and December 2023. Data on clinical presentation, biochemical parameters, genetic findings, and treatment responses were analysed.

Twelve patients (11 index) (7 males, 5 females) with non-CAH PAI were identified, with a median age of 2.5 years at diagnosis. Common symptoms included hyperpigmentation (100%), recurrent infections, gastrointestinal issues, and growth delays. Genetic analysis identified seven distinct mutations: AAAS, MC2R, ABCD1, CYP11A1, NNT, NROB1, and TXNRD2. All 12 patients were initiated on glucocorticoids, and six were also initiated on fludrocortisone.

This study highlights the genetic and clinical spectrum of non-CAH PAI in South India, emphasising the importance of early diagnosis and genetic profiling. The findings suggest a high prevalence of consanguinity and specific mutations, underscoring the need for genetic testing in resource-limited settings. Future research should focus on expanding genetic databases and evaluating long-term outcomes to refine treatment strategies and improve patient care.