SAT-069 A Case of Congenital Hypoaldosteronism Due to Aldosterone Synthase Deficiency Misdiagnosed as Classic Congenital Adrenal Hyperplasia

Background: The clinical presentation of congenital hypoaldosteronism due to aldosterone synthase (aka corticosterone methyloxidase; CMO) deficiency varies with age and infants present with signs/symptoms of isolated mineralocorticoid deficiency. Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is characterized by combined glucocorticoid, mineralocorticoid deficiency and androgen excess. Clinical Case: A 6.8 y/o Female was referred for genetic testing for classic 21OHD CAH. Past History: Birth weight/length: 7.9 lbs/20 inches at term, uncomplicated pregnancy. Normal female genitalia. She presented within the 1(st) week of life with poor feeding and poor weight gain. Newborn screen - normal. Inpatient admission at 1 month for failure to thrive. Initial workup significant for Na 127 mg/dL (135 - 145), K 6.5 mg/dL (3.4 - 5.3), mildly elevated random 17hydroxyprogesterone (17OHP) 241 ng/dL (32 - 139) and cortisol 11.6 mcg/dL. She was diagnosed with CAH and initiated on hydrocortisone and fludrocortisone therapy. Medications: Hydrocortisone 2.5 mg twice daily (6.3 mg/m2/day), fludrocortisone 50 mcg daily. Family History: Non-contributory, mid-parental height 154.9 cm. Physical exam: Height 115.6 cm (20(th) %ile), weight 19.8 kg (18(th) %ile), BP 109/65 mmHg (95(th)/ 84(th) %ile). Well-appearing with no cushingoid features. Genital/pubertal exam: Prepubertal, normal female external genitalia. Laboratory tests: ACTH stimulation test was performed which showed - 0min: 17OHP 19 ng/dL, Cortisol 8 mcg/dL; 60min: 17OHP 155 ng/dL (<1000), Cortisol 23.4 mcg/dL (normal response >18), ruling out the diagnosis of classic 21OHD CAH. Hydrocortisone was discontinued. Further workup (holding fludrocortisone for 48hrs) showed mildly elevated plasma renin activity 3.5 ng/mL/hr (0.8 - 2), low aldosterone 1.8 ng/dL (3.5 - 124), normal 18-hydroxycorticosterone 11 ng/dL (6 - 85). 18-hydroxycorticosterone/aldosterone ratio 6.1 (ratio <10) - suggesting the diagnosis of CMO type I deficiency (1). Targeted genetic testing for CYP11B2 revealed a novel homozygous frameshift alteration in exon 3: p.Phe157Serfs*108 (c.451_469dup), a pathogenic variant predicted to lead to protein truncation and loss of function. Conclusions: This case demonstrates that the clinical presentation of isolated mineralocorticoid deficiency often overlaps features of combined glucocorticoid and mineralocorticoid deficiency. Normal newborn screen along with absence of virilization in a female infant should alert a clinician to consider isolated mineralocorticoid axis defects. The gold standard ACTH stimulation test should be performed to rule out classic CAH and avoid unnecessary glucocorticoid replacement and its long-term side effects. Reference: 1. Root AW, Disorders of aldosterone synthesis, secretion, and cellular function. Curr Opin Pediatr. 2014 Aug;26(4):480-6.