IMPE Abstracts

Background: Aldosterone synthase is a cytochrome P450 enzyme encoded by the CYP11B2 gene and responsible of the conversion of dehydrocorticosterone to aldosterone through three enzymatic steps: addition of the 11b-hydroxyl group to form corticosterone, 18-hydroxylation to form 18-hydroxycorticosterone, and 18-dehydrogenation to form aldosterone. Two types of aldosterone synthase deficiency have been reported: type I related to defects in 18-hydroxilation, and type II related to defects in 18-dehydrogenation, respectively. In both, failure to thrive and variable degrees of salt wasting appear early in infancy.

Case report: A female 4-month-old baby was admitted to our institution because of failure to thrive, and poor feeding, without fever, diarrhea or vomiting. Born full-term with adequate birth weight (3400 grams) by c-section. Second child from healthy non-consanguineous parents, without relevant family history. 17OHprogesterone determination in the neonatal screening was normal. On admission baby was reactive, vital, with signs of dehydration (dry skin and mucous membranes, skin folds). Physical exam revealed weight 3700 grams, normal female genitalia. Blood tests showed hyponatremia (105 mEq/L), hyperkalemia (6.1 mEq/L), hypochloremia (80 mEq/L), metabolic acidosis (HCO3 16 mmol/l), normal glycemia and renal function, increased urea (54 mg/dl). After blood sampling to perform diagnostic tests, hydrocortisone was administered IV in push and the patient continued with hydrocortisone treatment until results were available. Abdominal ultrasound showed normally shaped and sized adrenal glands and kidneys with no alterations in the urinary track. Pretreatment hormone determinations were as follows: cortisol 24 mg/dl, ACTH 11 pg/l, aldosterone 165.1 pg/ml (reference range: 117-1253). Plasma renin activity was not available in pretreatment sample, but, under treatment, proved it to be increased (66.1, reference range <15 ng/ml/h). With gradual normalization of metabolic profile, IV hydrocortisone was switched to oral fludrocortisone with good response and tolerance. At 3.8 years-old, her body length was 91 cm (-2.6 SDS), weight 14 kg (-1 SDS) and growth velocity 11.4 cm/y. Molecular study of the CYP11B2 gene revealed the presence of variants in compound heterozygous form (c.428G>C and c.826C>G) not previously reported and classified as of uncertain significance by ACMG.

Conclusion: Aldosterone synthase deficiency is a very infrequent and life-threatening disorder. Congenital adrenal hyperplasia due to 21 hydroxilase deficiency and other forms of adrenal failure must be consider in the differential diagnosis. A key step to allow an early and accurate diagnosis is to obtain a blood sample before therapy is begun.