The syndrome of apparent
mineralocorticoid excess (
AME) is an autosomal recessive disorder characterized by
hypertension,
hypokalemia, low
renin, and
hypoaldosteronism. It is caused by deficiency of 11β-hydroxysteroid
dehydrogenase, which results in a defect of the peripheral metabolism of
cortisol to
cortisone. As a consequence, the serum
cortisol half-life (T½) is prolonged,
ACTH is suppressed, and serum
cortisol concentration is normal. The hormonal diagnosis of the disorder is made by the increased ratio of urine-free
cortisol to
cortisone. In patients with
AME, this ratio is 5-18, while in normal individuals it is <0.5. These studies suggest that an abnormality in
cortisol action or metabolism results in
cortisol behaving as a potent
mineralocorticoid and causing the syndrome of
AME. We report three siblings - two female and one male - with the syndrome of apparent
mineralocorticoid excess who presented with
hypertension,
hypokalemia, low
renin, and low
aldosterone levels. The finding of abnormally high ratios of 24-h urine-free
cortisol to
cortisone in our three patients (case 1, 8.4; case 2, 25; and case 3, 7.5) confirmed the diagnosis of
apparent mineralocorticoid excess syndrome in these children. They were treated with oral
potassium supplements. The addition of
spironolactone resulted in a decrease in blood pressure, rise in serum
potassium and a gradual increase in plasma
renin activity in all three. In this study, the genetic testing of those three siblings with the typical clinical features of
AME has detected missense mutation c.662C>T (p.Arg208Cys) in exon 3 of the HSD11B2 gene in the homozygous state.