K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension.

Endocrine tumors such as aldosterone-producing adrenal adenomas (APAs), a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown. We identify two recurrent somatic mutations in and near the selectivity filter of the potassium (K(+)) channel KCNJ5 that are present in 8 of 22 human APAs studied. Both produce increased sodium (Na(+)) conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium (Ca(2+)) entry, the signal for aldosterone production and cell proliferation.

A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism.

Context: Primary aldosteronism is a leading cause of secondary hypertension (HTN), but the mechanisms underlying the characteristic renin-independent secretion of aldosterone remain unknown in most patients.

Objectives: We report a new familial form of aldosteronism in a father and two daughters. All were diagnosed with severe HTN refractory to medical treatment by age 7 yr.