How is gain of function mutation of mineralocorticoid receptor (MR) differentiated from hyperaldosteronism?

Updated: Sep 08, 2020
  • Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London); Chief Editor: Robert P Hoffman, MD  more...
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Gain of function mutation of mineralocorticoid receptor (MR)

An even less common autosomal-dominant cause of mineralocorticoid hypertension is associated with an activating mutation, resulting in the substitution of leucine for serine at codon 810 (S810L) in the human mineralocorticoid receptor. In this case, mineralocorticoid receptor antagonists, such as progesterone, develop agonist properties, whereas cortisone, rather than being inactive at the mineralocorticoid receptor, is actually an agonist. This gain of function mutation of the mineralocorticoid receptor results in early onset hypertension in men and gestational hypertension in women. Both spironolactone and eplerenone are not only unable to block the constitutive activity of the mutant MRS810L, but paradoxically activate this mutant receptor, exacerbating the hypertension. The patients, on the other hand, respond to amiloride acting downstream at the epithelial sodium channel. [20]

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