Insights in non-CAH pediatric primary adrenal insufficiency: a single-center experience from India

Aaditya Daga; Manjiri Karlekar; Anurag Lila; Vijaya Sarathi; Anima Sharma; Saba Samad Memon; Rohit Barnabas; Virendra Patil; Hemangini Thakker; Nalini Shah; Tushar Bandgar

doi:10.1515/jpem-2024-0476

Article

Insights in non-CAH pediatric primary adrenal insufficiency: a single-center experience from India

Aaditya Daga , Manjiri Karlekar , Anurag Lila , Vijaya Sarathi , Anima Sharma , Saba Samad Memon , Rohit Barnabas , Virendra Patil , Hemangini Thakker , Nalini Shah and Tushar Bandgar

Published/Copyright: February 4, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 4

Abstract

Objectives

Pediatric primary adrenal insufficiency (PAI) etiologies beyond congenital adrenal hyperplasia (CAH) show regional variations. Given limited data from India, this study aims to describe the etiological profile, phenotype, and genotype of pediatric PAI in an Indian cohort.

Methods

We conducted a retrospective review of patients with PAI onset before 20 years of age from 1998 to 2023 at a single center. After excluding patients with inadequate data (n=20), CAH (n=218), and bilateral adrenalectomy (n=19), we analyzed demographic, clinical, biochemical, and genetic data of the remaining patients.

Results

Among 54 patients (45 probands), the median age at presentation was 6 years (range 0.1–19). Common clinical features included hyperpigmentation (90.7 %), adrenal crisis (33.3 %), and seizures (29.6 %). Mineralocorticoid deficiency was present in two-third patients including one patient each with AAAS, MRAP, and NNT mutation. Adrenoleukodystrophy (ALD) was the most common cause (40 %), followed by ACTH resistance states (20 %), early steroidogenic defects (13.3 %), congenital adrenal hypoplasia (11.1 %), autoimmune causes (8.9 %), and tuberculosis (4.5 %). Genetics diagnosed 14/15 patients without phenotypic clues and confirmed diagnoses in 21 tested of 30 with phenotypic pointers (alacrimia in AAAS, hypoparathyroidism/candidiasis in autoimmune polyendocrine syndrome-1 and neurodeficit in ALD). Genetics differentiated CYP11A1 mutation from suspected ALD in two siblings with neurological deficits. We identified seven novel gene variants. We report the first case of NNT associated with 46,XY gonadal dysgenesis. Adrenal tuberculosis was a unique cause of pediatric PAI.

Conclusions

This study reveals diverse non-CAH pediatric PAI etiologies in India, emphasizing genetic testing’s importance for precise diagnoses and suggests region-specific diagnostic algorithm.

Keywords: primary adrenal insufficiency; adrenoleukodystrophy; congenital adrenal hypoplasia; NNT ; adrenal tuberculosis

Corresponding author: Dr. Saba Samad Memon, Department of Endocrinology and Metabolism, Seth G S Medical College and KEM Hospital, Parel, Mumbai, 400012, Maharashtra, India, E-mail: sabasamadmemon@gmail.com

Research ethics: Ethical approval was obtained from the Institutional Ethics Committee (EC/OA-198/2021).
Informed consent: Waiver of consent was granted in view of retrospective nature of the study.
Author contributions: All authors contributed to the study conception and design. Data collection and analysis were performed by Aditya Daga. The first draft of the manuscript was written by Aaditya Daga and all authors commented on previous versions of the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: The authors did not receive any funding for the submitted work.
Data availability: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jpem-2024-0476).

Received: 2024-10-04

Accepted: 2025-01-14

Published Online: 2025-02-04

Published in Print: 2025-04-28

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Keywords for this article

primary adrenal insufficiency; adrenoleukodystrophy; congenital adrenal hypoplasia; NNT; adrenal tuberculosis