Is primary aldosteronism (PA) hypertension hereditary?

From the Guidelines

Primary aldosteronism can have a hereditary component in some cases, with specific genetic forms running in families, such as Familial Hyperaldosteronism (FH), which has several types, including Type I, II, III, and IV, and genetic testing may be warranted if there is a family history of early-onset hypertension, resistant hypertension, or low potassium levels. The most recent and highest quality study, 1, published in 2024, provides guidelines for the management of elevated blood pressure and hypertension, including primary aldosteronism. According to this study, primary aldosteronism is the most common form of secondary hypertension, and its management depends on its subtype, particularly on adrenal lesions being unilateral or bilateral. Some key points to consider in the management of primary aldosteronism include:

• Unilateral primary aldosteronism is distinguished from bilateral primary aldosteronism by adrenal vein sampling or functional imaging with radiolabelled tracers.
• Surgical removal of the offending adrenal gland is typically considered for unilateral primary aldosteronism, unless the patient is older or has co-morbidities of concern.
• Medical treatment is currently based on mineralocorticoid receptor antagonists (MRAs), such as spironolactone or eplerenone.
• The effective dose of spironolactone can be titrated up to 300-400 mg once daily, if necessary.
• Eplerenone is also used, despite being less potent than spironolactone, and has the advantage of causing less gynaecomastia and erectile dysfunction in men.
• Newer agents, such as finerenone and exarenone, and the aldosterone synthase inhibitor baxdrostat, are also being tested for treating primary aldosteronism.
• Genetic testing for germ-line mutations is necessary in familial forms of primary aldosteronism. It is essential to note that the management of primary aldosteronism should prioritize the reduction of morbidity, mortality, and improvement of quality of life, and treatment decisions should be made on a case-by-case basis, taking into account the individual patient's characteristics and medical history. Additionally, lifestyle modifications, such as following a low-sodium diet and maintaining a healthy weight, are also important in the management of primary aldosteronism. Overall, the management of primary aldosteronism requires a comprehensive approach, including accurate diagnosis, appropriate treatment, and lifestyle modifications, to improve patient outcomes and reduce the risk of complications.

From the Research

Primary Aldosterone Hypertension and Heredity

• Primary aldosterone hypertension, also known as primary aldosteronism, is a common cause of secondary hypertension associated with excess cardiovascular morbidities 2.
• The condition is characterized by the excess production of aldosterone by the adrenal cortex, leading to increased morbidity and mortality 3.
• While most cases of primary aldosteronism are sporadic, there are inherited forms of the disease, known as familial hyperaldosteronism, which are caused by germline mutations in specific genes 3, 4, 5.

Genetic Causes of Primary Aldosteronism

• Studies have identified somatic driver mutations in a substantial portion of aldosterone-producing adenomas, including genes such as KCNJ5, CACNA1D, ATP1A1, ATP2B3, and CTNNB1 4, 5.
• Germline variants of CYP11B2, CLCN2, KCNJ5, CACNA1H, and CACNA1D have been reported in different subtypes of familial hyperaldosteronism 4, 5.
• The genetic basis of primary aldosteronism has been clarified in recent years, with more than 90% of aldosterone-producing adenomas carrying somatic mutations in specific genes 5.

Familial Hyperaldosteronism

• Familial hyperaldosteronism is a rare inherited form of primary aldosteronism, caused by germline mutations in specific genes such as KCNJ5, CACNA1H, and CACNA1D 3, 5.
• There are four recognized forms of familial hyperaldosteronism (FH-I to FH-IV), each with a distinct genetic cause 3.
• Genetic testing for inherited forms of primary aldosteronism can help avoid burdensome diagnostic investigations in positive patients 2.