Background: Primary adrenal insufficiency (PAI) is a rare life-threatening disorder. Data on PAI in children are scanty, with the exception of Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD).
Objective and hypotheses: Evaluate etiology of PAI in a large cohort of children and characterize clinical presentation in subjects with PAI not due to 21-OHD.
Method: Children followed in eight tertiary centers were retrospectively included.
Results: Eight-hundred thirteen children were included; 83.9% patients (n=682) had 21-OHD CAH and were not reviewed further. Different etiologies were found in 16.1% subjects (n=131): 37.4% had autoimmune PAI (42.8% isolated; 57.2% polyendocrine syndromes); 25.9% had steroid biosynthetic defects (DAX1 n=12; 17α-hydroxylase n=1; familial glucocorticoid deficiency n=6; 11β-hydroxylase n=5; 3-3β-hydroxysteroid dehydrogenase n=8; glycerol kinase deficiency n=2); 19% had adrenoleukodystrophy; 6.1% had rare syndromes (Triple A, Pearson); two patients had infections and hemorrhage and in 13 no defined etiology was found. Mean age at diagnosis was 6.8±5.5 years; common signs/symptoms were fatigue (70%), hyperpigmentation (44%), dehydration (31.3%), neurologic signs (29%) and hypotension (28.2%); most common biochemical finding was increased ACTH (86.2%), followed by hypocortisolism (64.1%) and hyponatremia (47.3%) whereas hyperkalemia and hypoglycemia were found in 27.4 and 25.9% of subjects, respectively. Time between onset and diagnosis ranged from 0 to 56 months. Overall mortality was <1% and severe adrenal crisis during a mean follow-up of 10 years were rare.
Conclusion: This large nationwide study document that the most common cause of PAI in childhood is 21-OHD CAH followed by autoimmunity, steroid biosynthetic defects and adrenoleukodystrophy. In non 21-OHD CAH subjects, symptoms at diagnosis are not specific, with the exception of hyperpigmentation; increased ACTH associated to hypocortisolism and hyponatremia are common, while hyperkalemia and hypoglycemia are less frequent. Health outcome in our cohort is favorable with low mortality and incidence of adrenal crisis during follow-up.
10 Sep 2016 - 12 Sep 2016