ABSTRACT
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 ACTH-sensitive 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 life-threatening PA and pronounced adrenal hyperplasia to milder forms. In addition to germline mutations in KCNJ5, somatic KCNJ5 mutations are present in about 40% of aldosterone-producing 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.
Subject(s)
Aldosterone/biosynthesis , G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics , G Protein-Coupled Inwardly-Rectifying Potassium Channels/metabolism , Hyperaldosteronism/genetics , Adrenal Cortex Neoplasms/genetics , Adrenal Cortex Neoplasms/metabolism , Adrenocortical Adenoma/genetics , Adrenocortical Adenoma/metabolism , DNA Mutational Analysis , Germ-Line Mutation , Humans , Hypertension/genetics , Hypertension/metabolism , Hypokalemia/genetics , Hypokalemia/metabolism , MutationABSTRACT
The average systolic blood pressure-lowering effect of antihypertensive monotherapy is no more than 9.1 mmHg and for the diastolic value, 5.5 mmHg. Due to the limited effect of monotherapy, 2 or more antihypertensive agents are required in at least two-third of the hypertensive population. Because of their complementary blood pressure-lowering mechanisms and proven efficacy, it is advisable to initiate a combination of a renin-angiotensin-system (RAS) blocking agent with a RAS-independent agent; the choice of initial agents depends on age, ethnicity and co-morbidity. It is preferable that treatment is started using a stepwise approach: 1 agent is started and a second or third agent is added to the regimen. If the patient's actual blood pressure exceeds the target value by more than 20/10 mmHg, an alternative approach would be to start immediately with 2 agents. Compliance to therapy and the continuation of antihypertensive treatment are notoriously poor; treatment using a combination preparation containing 2 or even 3 different components is therefore preferred.
