Endocrine Abstracts

Definition: High blood pressure due to excessive activation of mineralocorticoid receptors (MR).

Consequences of an excess in MR activation are an excess in sodium and water retention, an expansion of plasma volume and a depletion of exchangeable body potassium.

Laboratory hallmarks of mineralocorticoid hypertension are a suppressed renin secretion and a tendency to develop hypokalemia.

Causes: The most frequent cause is Primary Aldosteronism (PA). PA is caused by an excessive autonomous secretion of aldosterone due to either a single adrenal adenoma or bilateral adrenal hyperplasia. Rare sporadic causes are monolateral hyperplasia and carcinoma. Rare genetic causes are Glucocorticoid Responsive Aldosteronism (GRA) and Familiar Aldosteronism type II. The overall estimated frequency of PA is around 10%. All these forms are characterized by an increased plasma aldosterone/plasma renin (activity) ratio. Confirmatory tests are fludrocortisone or saline suppression test. Differential diagnosis between adenoma and bilateral hyperplasia is based on radiology (CT or NMR) and adrenal venous catheterization.

The group characterized by stimulation of MR by abnormal ligands encompasses Pseudohyperaldosteronism (caused by the intake of drugs containing 9-alpha-fludrocortisone), the syndrome of Apparent Mineralocorticoid Excess (due to 11βHSD type 2 deficiency), Congenital Adrenal Hyperplasia (11-hydroxylase or 17-hydroxylase deficiency), DOC secreting tumors. In this group renin and aldosterone secretion are both suppressed.

Finally, mineralocorticoid hypertension may be due to Activating Mutations of MR (whereby the receptor loses its specificity and become sensitive to other steroids such as progesterone) or to mutations in amiloride-sensitive sodium channels (ENaC) (Liddle Syndrome) leading to their increased constitutive expression. Also these two forms are characterized by suppression of both renin and aldosterone levels.