Etiology of primary adrenal insufficiency in children: a 29-year single-center experience

Abstract

Background Primary adrenal insufficiency (PAI) in children is a rare condition and potentially lethal. The clinical characteristics are non-specific. It may be manifested as a chronic condition or crisis. The etiologies of PAI in children are different from the adult population. Therefore, diagnostic investigation becomes challenging. Methods A retrospective study was conducted at The First Affiliated Sun Yat Sen University Pediatric Endocrine unit between September 1989 and July 2016. Results A total of 434 patients (237 males, 197 females) were identified as having PAI. Congenital adrenal hyperplasia (CAH) was the most frequent etiology (83.4%, n = 362, male:female = 174:188), of which 351 (97.2%) were 21-hydroxylase deficiency (21-OH) CAH. Non-CAH etiology accounted for 11.3% (n = 49, male:female = 47:2), of which 46 (93.9%) were of non-autoimmune. The etiologies of the 49 cases were adrenoleukodystrophy (ALD; n = 22), X-linked adrenal hypoplasia congenital (X-AHC; n = 20), autoimmune polyglandular syndrome (APS; n = 3), triple A syndrome (n = 2), steroidogenic factor 1 (SF-1) gene mutation (n = 1) and adrenalectomy (n = 1). The etiology was not identified for 23 patients (5.3%, male:female =16:7). Clinical symptoms were in accordance with the incidence of genital ambiguity (42.6%), digestive symptoms (vomiting and diarrhea) (35.5%), failure to thrive (26.5%), gonadal-associated symptom (premature puberty, sexual infantilism and amenorrhea) (21.2%), hyperpigmentation (9.7%), adrenal crisis (AC; 4.1%), neurological symptoms (3.2%), fatigue (2.5%) and prolonged jaundice (2.1%). Through physical examination, 58.5% were found to have hyperpigmentation. Conclusions This study spanned 29 years at our institution. The etiology of PAI in children was mostly of congenital forms, which exhibits a wide spectrum of clinical characteristics. For etiological diagnosis, chromosomal karyotyping is recommended for female phenotype patients.

Beyond the adrenals: Organ manifestations in inherited primary adrenal insufficiency in children

“…TART, gonadal insufficiency), and heart diseases. Proper diagnosis of unknown cases of PAI is therefore important to adequately control long-term treatment and follow-up in such patients (2,3,4,5).…”

“…Up to 90% of cases of PAI in adults in Western countries are caused by autoimmune destruction of the adrenal cortex (1). In contrast, PAI is caused mostly due to genetic defects in children (2,3).…”

Metabolic and Endocrine Challenges

“…However, an increasing number of reports highlight AC being triggered by drugs such as opioids, etomidate, and new chemotherapy regimens, as well as immunotherapy. [135][136][137] By far the largest group of patients at risk are those with chronic steroid medication (up to 3% of the population), who often develop adrenal suppression over time, and therefore may not be able to increase their endogenous cortisol levels sufficiently during acute stress/illness. 138 This population continues to increase worldwide for several reasons: better and thorough diagnosis and increased incidence of autoimmune diseases in adults and children, increased number of immunosuppressed patients due to transplantations, progressive use of corticosteroids with chemotherapy, and, generally, an increase in survival of patients accompanied with chronic disease and the potential for development of complications.…”

Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected

“…In general, the above clinical findings of neonates with PAI are non-specific, misdiagnosis and delayed diagnosis are likely to result in potentially life-threatening adrenal crisis. The most common cause of PAI in the neonatal period is congenital adrenal hyperplasia (CAH), which occurs in approximately 1 of 14,200 live births (1,2). 21-hydroxylase deficiency (21-OHD) caused by mutations in the CYP21A2 gene represents 95-99% of cases of CAH (3).…”