Maaloul Ines, Aloulou Hajer, Bessghaier Wissem, Ameur Salma Ben, Chabchoub Imen, Khalfallah Rania, Kamoun Hassen, Morel Yves, Kamoun Thouraya
Department of Pediatrics, Hedi Chaker Hospital, Sfax, Tunisia; Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia.
Department of Pediatrics, Hedi Chaker Hospital, Sfax, Tunisia; Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia.
Arch Pediatr. 2025 Jan 27. doi: 10.1016/j.arcped.2024.10.010.
Primary adrenal insufficiency (PAI) is a rare but potentially life-threatening condition. Congenital adrenal hyperplasia (CAH) is the most common cause of PAI in children. To date, numerous non-CAH causes have been identified through genetic analysis but they remain poorly characterized.
We aimed to describe the clinical presentation, etiology, genetic analysis, and long-term outcome of non-CAH PAI in children.
We retrospectively collected clinical and laboratory data from patients with non-CAH PAI who were followed up during a period of 33 years (1988-2020) at the pediatric department of a university hospital center in southern Tunisia.
We identified 52 patients with non-CAH PAI (35 boys and 17 girls). The mean age at diagnosis was 4.8 years (0.05-18.7 years). Hyperpigmentation was the most frequent symptom at diagnosis (92.3%), followed by asthenia (84.6%), weight loss (57.7%), recurrent vomiting (53.8%), and dehydration (42.3%). The most prominent biochemical findings were hyponatremia (60.4%), hypoglycemia (35.4%), and hyperkalemia (16.6%). A total of 21patients (40.4%) presented with adrenal crisis at disease onset. The most common causes of non-CAH PAI were inherited genetic conditions and included Allgrove syndrome (n=15), X-linked adrenoleukodystrophy (n=10), autoimmune polyglandular syndrome (APS) type 2 (n=2), familial glucocorticoid deficiency type 1 (n=1), MCM4 mutation responsible for DNA repair defect (n=1), SF1 deficiency (n=1), APS type 1 (n=1), and autoimmune PAI (n=3). The cause of PAI remained unknown in 34.6% of cases. During follow-up, 24 patients (46.2%) presented with statural growth delay, and eight patients (15.4%) developed obesity.
Allgrove syndrome was the most common etiology of non-CAH PAI in our study, followed by X-linked adrenoleukodystrophy. Today, advanced molecular analysis can be useful for diagnostic investigations, especially in patients with no specific diagnostic features.
原发性肾上腺皮质功能减退症（PAI）是一种罕见但可能危及生命的疾病。先天性肾上腺皮质增生症（CAH）是儿童PAI最常见的病因。迄今为止，通过基因分析已确定了许多非CAH病因，但对其特征仍了解甚少。
我们旨在描述儿童非CAH PAI的临床表现、病因、基因分析及长期预后。
我们回顾性收集了突尼斯南部一家大学医院中心儿科在33年（1988 - 2020年）期间随访的非CAH PAI患者的临床和实验室数据。
我们确定了52例非CAH PAI患者（35例男孩和17例女孩）。诊断时的平均年龄为4.8岁（0.05 - 18.7岁）。色素沉着是诊断时最常见的症状（92.3%），其次是乏力（84.6%）、体重减轻（57.7%）、反复呕吐（53.8%）和脱水（42.3%）。最突出的生化检查结果是低钠血症（60.4%）、低血糖（35.4%）和高钾血症（16.6%）。共有21例患者（40.4%）在疾病发作时出现肾上腺危象。非CAH PAI最常见的病因是遗传性疾病，包括阿尔格罗夫综合征（n = 15）、X连锁肾上腺脑白质营养不良（n = 10）、自身免疫性多内分泌腺综合征（APS）2型（n = 2）、家族性糖皮质激素缺乏1型（n = 1）、负责DNA修复缺陷的MCM4突变（n = 1）、SF1缺乏（n = 1）、APS 1型（n = 1）和自身免疫性PAI（n = 3）。34.6%的病例中PAI的病因仍不明。在随访期间，24例患者（46.2%）出现身材生长迟缓，8例患者（15.4%）出现肥胖。
在我们的研究中，阿尔格罗夫综合征是非CAH PAI最常见的病因，其次是X连锁肾上腺脑白质营养不良。如今，先进的分子分析对诊断性研究可能有用，尤其是对无特异性诊断特征的患者。
