Apparent Mineralocorticoid Excess in the Pediatric Population: Report of a Novel Pathogenic Variant of the 11β-HSD2 Gene and Systematic Review of the Literature
Apparent mineralocorticoid excess (AME) is a rare inherited disorder caused by pathogenic variants in the 11β-HSD2 gene resulting in a deficiency of the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme catalyzing the conversion of cortisol to its inactive metabolite, cortisone. Impaired cortisol metabolism results in a mineralocorticoid excess-like state presenting as low renin, low aldosterone hypertension (HTN) and hypokalemia. Typically, AME is diagnosed in early childhood. Medical treatment to control HTN and hypokalemia often is only partially successful. Herein, we systematically review previously reported AME cases in the pediatric population, focusing on presentation, genetic basis, treatment and outcomes. We demonstrate a negative correlation between the ratio of urinary cortisol to cortisone metabolites, and the age of diagnosis (p=0.0051). We also report a novel causative variant of the 11β-HSD2 gene and propose an explanation for failure of the mineralocorticoid receptor antogonist, spironolactone, to control hypertension and hypokalemia in a subgroup of patients.
Adamidis A, Cantas-Orsdemir S, Tsirka A, Abbott MA, Visintainer P, Tonyushkina K. Apparent Mineralocorticoid Excess in the Pediatric Population: Report of a Novel Pathogenic Variant of the 11β-HSD2 Gene and Systematic Review of the Literature. Pediatr Endocrinol Rev. 2019 Mar;16(3):335-358.