From the Guidelines
Adrenal insufficiency in children is primarily caused by congenital adrenal hyperplasia, autoimmune destruction of the adrenal glands, and other conditions that impair cortisol and aldosterone production, with approximately 25% of children with septic shock having absolute adrenal insufficiency, as noted in the 2013 study by 1.
Causes of Adrenal Insufficiency
The causes of adrenal insufficiency in children can be categorized into several groups, including:
- Congenital adrenal hyperplasia (CAH), a genetic disorder affecting steroid hormone production
- Autoimmune destruction of the adrenal glands (Addison's disease)
- Infections like tuberculosis or fungal infections
- Hemorrhage into the adrenal glands
- Medications that inhibit cortisol synthesis, such as ketoconazole or etomidate
- Pituitary gland disorders affecting ACTH production (secondary adrenal insufficiency)
- Abrupt withdrawal of long-term steroid therapy
- Rare causes, including adrenal hypoplasia congenita, adrenoleukodystrophy, and familial glucocorticoid deficiency
Diagnosis and Treatment
According to the 2014 consensus statement by 1, the diagnosis of primary adrenal insufficiency (PAI) should be considered in all patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, and treatment should never be delayed by diagnostic procedures. The recommended treatment involves hormone replacement therapy with hydrocortisone (15-25 mg daily in split doses for adults, and 6-10 mg/m² of body surface area for children) and fludrocortisone (50-200 µg daily) for aldosterone replacement.
Management of Adrenal Insufficiency
In cases of suspected acute adrenal insufficiency, treatment with hydrocortisone should be initiated promptly, as noted in the 2009 study by 1. The dose of hydrocortisone can be titrated to resolution of shock, using between 2 mg/kg and 50 mg/kg/day as a continuous infusion or intermittent dosing. Children with adrenal insufficiency should wear medical alert identification and caregivers should have injectable hydrocortisone available for emergencies. Early diagnosis and proper management are essential to prevent life-threatening adrenal crisis, as highlighted in the studies by 1, 1, and 1.
From the Research
Causes of Adrenal Insufficiency in Children
- Primary adrenal insufficiency (PAI) is a heterogeneous group of disorders characterized by an impaired production of cortisol and other steroid hormones by the adrenal cortex 2
- Most causes of PAI in childhood are inherited and monogenic in origin, and are associated with significant morbidity and mortality whenever diagnosis and treatment are delayed 2
- Congenital adrenal hyperplasia (CAH) accounts for most cases of PAI in childhood, followed by abnormalities in the development of the adrenal gland, resistance to adrenocorticotropin hormone action, and adrenal destruction 2
- Other causes of adrenal insufficiency in children include autoimmune Addison's disease, tuberculosis, HIV, adrenoleukodystrophy, adrenal hypoplasia congenita, and syndromes such as triple A and IMAGe 3
- Exogenous corticosteroid therapy withdrawal or poor adherence to scheduled corticosteroid dosing with long-standing treatment can also cause acquired adrenal insufficiency in children 4
Specific Causes of Adrenal Insufficiency
- Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common primary adrenal insufficiency in children and adolescents 5
- CAH is characterized by androgen excess secondary to impaired steroidogenesis in the adrenal glands 5
- Adrenoleukodystrophy is a genetic disorder that can cause adrenal insufficiency in children, and is characterized by elevated very long chain fatty acids 3
- Autoimmune adrenal insufficiency is another cause of primary adrenal insufficiency in children, and is characterized by the presence of autoantibodies 3
Diagnosis and Treatment
- Early and accurate diagnosis of adrenal insufficiency is crucial to allow appropriate management and genetic counseling for the family 2
- The use of genome-wide, next-generation sequencing approaches has opened new avenues for identifying novel genetic causes of PAI in children 2
- Treatment of adrenal insufficiency in children typically involves glucocorticoid replacement with hydrocortisone, as well as mineralocorticoid and salt replacement in some cases 5
- Increased stress doses of corticosteroids may be necessary during acute illness, trauma, or procedures 5