What is the significance of an elevated aldosterone (aldosterone) to renin (renin) ratio and how is primary aldosteronism treated?

From the Guidelines

An elevated aldosterone to renin ratio (ARR) is a significant finding that suggests primary aldosteronism, a condition where the adrenal glands produce excessive aldosterone independently of the renin-angiotensin system, and treatment should be initiated with mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, or laparoscopic adrenalectomy for unilateral disease, as recommended by the 2024 ESC guidelines 1. The aldosterone to renin ratio (ARR) is the primary screening test for primary aldosteronism (PA), a condition that affects 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension 1. Key points to consider in the diagnosis and treatment of primary aldosteronism include:

• The ARR is currently the most accurate and reliable means of screening for primary aldosteronism, with a cutoff value of 30 when plasma aldosterone concentration is reported in nanograms per deciliter (ng/dL) and plasma renin activity in nanograms per milliliter per hour (ng/mL/h) 1.
• Treatment for primary aldosteronism depends on whether it's unilateral (typically an aldosterone-producing adenoma) or bilateral (idiopathic hyperaldosteronism), with laparoscopic adrenalectomy being the preferred treatment for unilateral disease, and medical therapy with mineralocorticoid receptor antagonists being the mainstay of treatment for bilateral disease or patients who cannot undergo surgery 1.
• Spironolactone (25-100 mg daily) is the first-line agent for medical therapy, though eplerenone (50-100 mg daily) may be used if spironolactone causes intolerable side effects like gynecomastia or sexual dysfunction 1.
• Patients should be monitored for hyperkalemia, especially when starting therapy or adjusting doses, and blood pressure control often requires additional antihypertensive medications, with lifestyle modifications including sodium restriction (<2.4g/day) also being important 1. Some of the key considerations in the management of primary aldosteronism include:
• The importance of screening for primary aldosteronism in patients with hypertension at increased risk, such as those with adrenal incidentaloma or a history of early onset hypertension and/or cerebrovascular accident at a young age 1.
• The need for confirmatory testing, such as the intravenous saline suppression test or oral salt-loading test, to confirm the diagnosis of primary aldosteronism 1.
• The role of adrenal venous sampling in determining whether the increased aldosterone production is unilateral or bilateral in origin, and guiding treatment decisions 1.

From the FDA Drug Label

Spironolactone tablets are indicated in the following settings: Short-term preoperative treatment of patients with primary hyperaldosteronism. Long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery Long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).

The significance of an elevated aldosterone to renin ratio is indicative of primary hyperaldosteronism, a condition where the adrenal glands produce too much aldosterone. This condition can lead to hypertension and hypokalemia.

• Treatment of primary hyperaldosteronism involves surgery to remove the affected adrenal gland(s) or medical therapy with aldosterone antagonists such as spironolactone.
• Spironolactone is used for long-term maintenance therapy in patients with primary hyperaldosteronism who are not candidates for surgery or have bilateral adrenal hyperplasia.
• The dosage of spironolactone for primary hyperaldosteronism is 100 mg to 400 mg daily, as determined by the individual patient's response 2, 2.

From the Research

Significance of Elevated Aldosterone to Renin Ratio

• The aldosterone to renin ratio (ARR) is used as a screening test for primary aldosteronism, a condition characterized by excess production of aldosterone, a hormone that regulates blood pressure 3, 4, 5.
• An elevated ARR suggests that the aldosterone level is high relative to the renin level, which can indicate primary aldosteronism 6, 7.
• However, the sensitivity and specificity of the ARR as a screening test have been found to vary widely, with some studies reporting limited ability to identify patients with primary aldosteronism 7.

Treatment of Primary Aldosteronism

• Treatment of primary aldosteronism typically involves surgery to remove the affected adrenal gland or glands, or medication to control blood pressure and aldosterone levels 4, 5.
• In some cases, patients with primary aldosteronism may be treated with antialdosterone medications, such as spironolactone, to control blood pressure and reduce aldosterone levels 4.
• The choice of treatment depends on the underlying cause of the primary aldosteronism, as well as the patient's overall health and medical history.

Diagnostic Challenges

• The diagnosis of primary aldosteronism can be challenging, as the condition often presents with non-specific symptoms, such as high blood pressure and hypokalemia (low potassium levels) 3, 6.
• The ARR is not a perfect screening test, and further diagnostic testing, such as adrenal imaging and confirmatory testing, may be necessary to confirm the diagnosis 7, 5.
• The variability in ARR performance highlights the need for careful interpretation of test results and consideration of other diagnostic factors to ensure accurate diagnosis and effective treatment of primary aldosteronism 7.