Daga Aaditya, Karlekar Manjiri, Lila Anurag, Sarathi Vijaya, Sharma Anima, Memon Saba Samad, Barnabas Rohit, Patil Virendra, Thakker Hemangini, Shah Nalini, Bandgar Tushar
Department of Endocrinology and Metabolism, Seth G S Medical College and KEM Hospital, Mumbai, India.
Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, India.
J Pediatr Endocrinol Metab. 2025 Feb 4;38(4):383-390. doi: 10.1515/jpem-2024-0476. Print 2025 Apr 28.
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.
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.
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 , , and 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 , hypoparathyroidism/candidiasis in autoimmune polyendocrine syndrome-1 and neurodeficit in ALD). Genetics differentiated mutation from suspected ALD in two siblings with neurological deficits. We identified seven novel gene variants. We report the first case of associated with 46,XY gonadal dysgenesis. Adrenal tuberculosis was a unique cause of pediatric PAI.
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.
先天性肾上腺皮质增生症（CAH）以外的小儿原发性肾上腺皮质功能减退症（PAI）病因存在地区差异。鉴于印度的数据有限，本研究旨在描述印度队列中小儿PAI的病因谱、表型和基因型。
我们对1998年至2023年在单一中心发病年龄在20岁之前的PAI患者进行了回顾性研究。在排除数据不完整的患者（n=20）、CAH患者（n=218）和双侧肾上腺切除术患者（n=19）后，我们分析了其余患者的人口统计学、临床、生化和遗传数据。
在54例患者（45例先证者）中，就诊时的中位年龄为6岁（范围0.1-19岁）。常见临床特征包括色素沉着（90.7%）、肾上腺危象（33.3%）和癫痫发作（29.6%）。三分之二患者存在盐皮质激素缺乏，其中各有1例患者分别携带、和突变。肾上腺脑白质营养不良（ALD）是最常见的病因（40%），其次是促肾上腺皮质激素抵抗状态（20%）、早期类固醇生成缺陷（13.3%）、先天性肾上腺发育不全（11.1%）、自身免疫性病因（8.9%）和结核病（4.5%）。遗传学诊断出14/15例无表型线索的患者，并在30例有表型提示的患者中的21例中确诊（先天性无泪症、自身免疫性多内分泌综合征1型中的甲状旁腺功能减退/念珠菌病以及ALD中的神经功能缺损）。遗传学在两名有神经功能缺损的兄弟姐妹中区分了突变与疑似ALD。我们鉴定出7个新的基因变异。我们报告了首例与46,XY性腺发育不全相关的病例。肾上腺结核是小儿PAI的独特病因。
本研究揭示了印度小儿PAI的多种非CAH病因，强调了基因检测对精确诊断的重要性，并提出了针对该地区的诊断算法。
