ESPE Abstracts

Introduction: Apparent mineralocorticoid excess (AME) is rare cause of endocrine hypertension. 11 alpha hydroxysteroid dehydrogenase(HSD) type 2 enzyme metabolises cortisol to cortisone, thereby inhibiting cortisol acting at mineralocorticoid receptor(MR). In AME, this enzyme is defective resulting in unmetabolised cortisol causing MR activation with resultant hypokalemic metabolic alkalosis and hypertension.

Case presentation: Patient is 2 year girl born at 36 weeks gestation with birth weight 1.26 kgs, following pregnancy complicated with severe IUGR and oligohydramnios. Parents were non consanguineous. She presented with 3 day history of lethargy, headache and right hemiparesis. There was a year’s history of polyuria and polydipsia. Evaluation revealed short stature (73 cm, -4.15 SDS), poor weight gain (7 kg, -4.12 SDS) BP 157/95 mmHg (> 99th centile). Investigations revealed metabolic alkalosis (pH7.5, bicarb25.9 mmol/l) hypokalemia (3.0 mmol/l), normal serum sodium (145 mmol/l), suppressed renin (<0.5 mIU/ml)and low plasma aldosterone(1.31 ng/dl) , no urinary electrolyte losses (Na 29 mmol/l, K 17 mmol/l), normal renal function (urea 24 mg/dl, creatinine 0.3 mg/dl). Echocardiogram -severe left ventricular hypertrophy, Ultrasound-left nephrocalcinosis and MRI brain-acute infarct in left thalamus and capsuloganglionic region. Whole exome sequencing reported homozygous missense variation in exon 3 of HSD11B2 gene (chr16:g.67436005A>G; Depth: 29x) resulting in amino acid substitution of Glycine for Aspartic acid at codon 176 (p.Asp176Gly; ENST00000326152.6). The p.Asp176Gly variant has not been reported in 1000 genomes and gnomAD databases and has minor allele frequency of 0.001% in Medgenome internal database. InIIn silico predictions of the variant are probably damaging by PolyPhen-2 (HumDiv), and damaging by SIFT and LRT. The reference codon is conserved across species. Parents’ target gene analysis is awaited. Maximum doses of 3 antihypertensives (Spironolactone 10 mg/kg/day, labetalol and ramipril) were required to control the BP just above 99th centile. Polyuria settled within few days and potassium supplements were stopped after a month. Dexamethasone 0.25 mg had dramatic response and helped to gradually wean down the anti-hypertensives. Blood pressure improved after addition of small dose of Amiloride 0.15 mg/kg/day to Spironolactone 1.5 mg/kg/day

Conclusion: This novel mutation reflects severe phenotype. Hypertension with hypokalemic alkalosis and suppressed plasma renin and aldosterone should make one think of Liddle syndrome or AME. Further delineation can done by urine cortisol/cortisone ratio or genetics. Dexamethasone, Spironolactone and Amiloride are drugs of choice for control of hypertension and hypokalemia.