Primary aldosteronism: New insights into familial forms

Primary aldosteronism (PA) is characterized by autonomic aldosterone production, usually leading to severe hypertension and hypokalaemia. PA is a heterogeneous condition caused by sporadic adrenal adenoma, bilateral adrenal hyperplasia or rare familial forms. Familial aldosteronism type 1 is caused by a hybrid gene that codes for an ACTHsensitive form of aldosterone synthase. Familial aldosteronism type 3 was recently recognized as a new form of PA caused by mutation in KCNJ5. The clinical manifestations vary from lifethreatening PA and pronounced adrenal hyperplasia to milder forms. In addition to germline mutations in KCNJ5, somatic KCNJ5 mutations are present in about 40% of aldosteroneproducing adrenal adenomas. Mutations in three other genes are also regularly observed. All these mutations cause increased aldosterone synthase activity, eventually leading to PA. In patients under 20 with PA, familial forms must be excluded before proceeding to adrenalectomy.