Pseudohyperaldosteronism is characterized by a clinical picture of
hyperaldosteronism with suppression of plasma
renin activity and
aldosterone. Pseudohyperaldosteronism can be due to a direct
mineralocorticoid effect, as with
desoxycorticosterone, fluorohydrocortisone, fluoroprednisolone,
estrogens, and the ingestion of high amounts of
glycyrrhetinic acid. A block of 11-hydroxysteroid-dehydrogenase type 2 (11HSD2), the
enzyme that converts
cortisol into
cortisone, at the level of epithelial target tissues of
aldosterone, is involved in other cases. This mechanism is related either to a mutation of the gene, which encodes 11HSD2 (
apparent mineralocorticoid excess syndrome and some cases of low
renin hypertension) or to an acquired reduction of the activity of the
enzyme due to
glycyrrhetinic acid,
carbenoxolone, and grapefruit juice. In other cases saturation of 11HSD2 may be involved as in severe
Cushing's syndrome and chronic
therapy with some
corticosteroids. Recently, an activating mutation of the
mineralocorticoid receptor gene has been described. Another genetic cause of pseudohyperaldosteronism is the syndrome of Liddle, which is due to a mutation of the gene encoding for beta and gamma subunits of the
sodium channels.