Severe adrenal insufficiency in six neonates with normal newborn screening for CAH.

ABSTRACT

BACKGROUND: Newborn screening (NBS) reduces the risk of mortality in congenital adrenal hyperplasia (CAH), mainly due to the salt-wasting form of 21-hydroxylase deficiency. There is limited knowledge regarding the results of NBS in non-CAH primary adrenal insufficiency (non-CAH PAI). PATIENTS AND METHODS: Clinical and NBS for CAH data of neonates who were diagnosed with non-CAH PAI between January and December 2022 were examined. RESULTS: Patients (n = 6, 4 females) were presented with severe hyperpigmentation (n = 6), hypoglycemia (n = 4), hyponatremia (n = 3), hyperkalemia (n = 1), respiratory distress syndrome (n = 1) between 3rd hour to 2 months of life. All had normal NBS results. The median first-tier 17-hydroxyprogesterone (17OHP) concentration in NBS for CAH was 0.14 ng/mL (range; 0.05-0.85). Molecular studies revealed biallelic mutations in the MC2R (n = 4; 3 homozygous, 1 compound heterozygous), MRAP (n = 1) and STAR (n = 1) genes. Glucocorticoid with or without mineralocorticoid replacement was initiated once the diagnosis of non-CAH PAI was established. CONCLUSION: Neonates with non-CAH PAI have always normal NBS due to persistently low 17OHP, even when these newborn infants are severely symptomatic for adrenal insufficiency. Clinicians should be alert for signs of adrenal insufficiency in neonates, even if the patient has a 'normal' screening for CAH, so as not to delay diagnosis and treatment. This fact should be kept in mind particularly in countries where these conditions are more common than elsewhere.