ESPE Yearbook of Paediatric Endocrinology

Nat Rev Endocrinol. 2020; 16(10): 578–589.https://pubmed.ncbi.nlm.nih.gov/32724183/

In this review, the authors discuss the pathogenesis and treatment of primary aldosteronism (PA), the most frequent form of secondary hypertension (affecting 5% of patients with hypertension in primary care and 10–20% of those referred to specialist care). The pathophysiological basis of PA is autonomous aldosterone production (autonomous from its physiological regulators and inappropriate to the salt and blood volume status of the individual) from the adrenal gland, which leads to hypertension, hypokalemia and metabolic alkalosis. Patients with PA are at higher risk for cardiovascular disease compared to patients with essential hypertension matched for age and blood pressure. In most cases, PA is attributed to a unilateral aldosterone-producing adenoma (APA) or to bilateral adrenal hyperplasia. Many cases of PA are sporadic, while ~6% have a familial form of the disease. Familial forms of hyper-aldosteronism (FH-I, FH-II and FH-III) result from germline mutations. In unilateral APA, somatic mutations are found in the same genes that are associated with familial forms of primary aldosteronism, and the use of next generation sequencing increases the detection of mutations. Most genetic abnormalities increase intracellular calcium signaling in the adrenal zona glomerulosa, increasing aldosterone production, and making it autonomous. The underlying mechanisms leading to activation of calcium signaling are different for each type of channel and pump. PA is curable. However, it is largely underdiagnosed, and this prevents patients from receiving appropriate targeted treatments and results in cardiovascular complications. New approaches are currently being developed to achieve more rapid and precise diagnosis, for more efficient targeted treatment in mutation carriers, and improved management of affected family members.