From the Guidelines
Primary aldosteronism is most commonly caused by either an aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH), with APA being responsible for approximately 50% of cases and BAH accounting for the remaining 50%. These conditions lead to the overproduction of aldosterone, a hormone that regulates sodium and potassium levels in the body, resulting in hypertension, cardiovascular damage, and kidney damage 1.
Causes of Primary Aldosteronism
- Aldosterone-producing adenoma (APA), also known as Conn's syndrome, is a benign tumor in one adrenal gland that autonomously produces excess aldosterone.
- Bilateral adrenal hyperplasia (BAH) involves both adrenal glands overproducing aldosterone.
- Less common causes include unilateral adrenal hyperplasia, familial hyperaldosteronism (which has several types including glucocorticoid-remediable aldosteronism), adrenocortical carcinoma, and ectopic aldosterone-producing tumors.
- Certain genetic mutations affecting ion channels and enzymes in the adrenal cortex can lead to these conditions, particularly mutations in the KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes, which result in increased intracellular calcium levels in adrenal cells, triggering excessive aldosterone production 1.
Diagnosis and Management
The diagnosis of primary aldosteronism generally requires a confirmatory test (intravenous saline suppression test or oral salt-loading test) after an initial screening with the aldosterone:renin activity ratio, which is currently the most accurate and reliable means of screening for primary aldosteronism 1.
- Patients should have unrestricted salt intake, serum potassium in the normal range, and mineralocorticoid receptor antagonists (e.g., spironolactone or eplerenone) withdrawn for at least 4 weeks before testing.
- If the diagnosis of primary aldosteronism is confirmed, the patient is referred for an adrenal venous sampling procedure to determine whether the increased aldosterone production is unilateral or bilateral in origin.
- Unilateral laparoscopic adrenalectomy is recommended for patients with unilateral aldosterone production, which improves blood pressure in virtually 100% of patients and results in a complete cure of hypertension in about 50% of patients 1.
- For patients with bilateral adrenal hyperplasia or those who cannot undergo surgery, treatment with spironolactone or eplerenone is recommended as the agent of choice 1.
From the Research
Causes of Primary Aldosteronism
The causes of primary aldosteronism can be summarized as follows:
- Unilateral aldosterone-producing adenoma: This is one of the main causes of primary aldosteronism, accounting for approximately one-third of cases 2.
- Bilateral adrenal hyperplasia: This is another major cause, responsible for around two-thirds of cases 2.
- Somatic mutations: These drive autonomous aldosterone production in most adenomas, and have also been identified in nodular lesions adjacent to an aldosterone-producing adenoma and in patients with bilateral disease 3.
- Germline mutations: These cause rare familial forms of aldosteronism, such as familial hyperaldosteronism types 1-4 3.
- Idiopathic hyperaldosteronism: This is characterized by bilateral involvement of the adrenal glands and is a common cause of primary aldosteronism 4.
Key Findings
Some key findings related to the causes of primary aldosteronism include:
- The diagnostic work-up of primary aldosteronism comprises three steps: screening, confirmatory testing, and differentiation of unilateral surgically-correctable forms from medically treated bilateral primary aldosteronism 5.
- Adrenal venous sampling is a key test for reliable subtype identification, but can be bypassed in patients with specific characteristics 3.
- Genetic testing for inherited forms of primary aldosteronism can avoid the need for burdensome diagnostic investigations in positive patients 3.
- The goals of treatment are to normalize both blood pressure and excessive aldosterone production, and to reduce associated comorbidities, improve quality of life, and reduce mortality 3.