What is the evaluation approach for a patient with hypertension and an elevated Aldosterone (Aldosterone) to Plasma Renin Activity (PRA) ratio, suggestive of primary hyperaldosteronism?

From the Guidelines

For a patient with hypertension and an aldosterone-to-plasma renin activity (PRA) ratio of 22, further evaluation for primary hyperaldosteronism is warranted, as this condition is associated with increased cardiovascular morbidity and mortality, and proper diagnosis allows for targeted treatment that can improve quality of life and reduce the risk of complications. The next step should be confirmatory testing with either a saline suppression test, oral sodium loading test, or captopril challenge test, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. Before these tests, interfering medications should be discontinued: spironolactone and eplerenone for 4-6 weeks; diuretics, ACE inhibitors, and ARBs for 2 weeks; and beta-blockers, central alpha-2 agonists, and NSAIDs for 1-2 weeks. During the saline suppression test, 2 liters of normal saline is infused over 4 hours, with failure to suppress aldosterone below 10 ng/dL confirming the diagnosis, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.

If primary hyperaldosteronism is confirmed, adrenal imaging with CT or MRI should be performed to distinguish between an aldosterone-producing adenoma and bilateral adrenal hyperplasia. For patients with unilateral disease, adrenal vein sampling may be necessary to confirm lateralization before considering surgical treatment, as recommended by the 2024 ESC guidelines 1. This evaluation pathway is important because primary hyperaldosteronism is present in approximately 5-10% of hypertensive patients and is associated with increased cardiovascular morbidity beyond that explained by blood pressure elevation alone, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1. Proper diagnosis allows for targeted treatment with either surgical removal of an adenoma or medical management with mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, which can improve blood pressure control and reduce the risk of complications, as recommended by the 2024 ESC guidelines 1.

Some key points to consider in the evaluation and management of primary hyperaldosteronism include:

• The aldosterone-to-renin ratio is a useful screening test, but it should be interpreted with caution and in the context of other clinical and laboratory findings, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.
• Confirmatory testing is necessary to establish the diagnosis of primary hyperaldosteronism, as recommended by the 2024 ESC guidelines 1.
• Adrenal imaging and adrenal vein sampling are important tools in the evaluation of primary hyperaldosteronism, as they can help distinguish between unilateral and bilateral disease, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.
• Targeted treatment with either surgical removal of an adenoma or medical management with mineralocorticoid receptor antagonists can improve blood pressure control and reduce the risk of complications, as recommended by the 2024 ESC guidelines 1.

From the FDA Drug Label

1. 4 Primary Hyperaldosteronism 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 patient's Aldosterone to PRA ratio of 22 suggests primary hyperaldosteronism.

• Evaluation of primary hyperaldosteronism in a patient with hypertension involves confirming the diagnosis and identifying the underlying cause.
• Spironolactone may be used for the treatment of primary hyperaldosteronism, but the provided information does not directly address the evaluation process 2.
• The diagnosis of primary hyperaldosteronism typically involves biochemical testing, including the aldosterone to PRA ratio, and imaging studies to identify any underlying adrenal abnormalities 2.
• The patient's hypertension and elevated aldosterone to PRA ratio suggest the need for further evaluation to confirm the diagnosis of primary hyperaldosteronism 2.

From the Research

Evaluation of Primary Hyperaldosteronism

The patient's condition, with hypertension and an Aldosterone to PRA ratio of 22, suggests the need for further evaluation for primary hyperaldosteronism.

• The aldosterone-to-renin ratio (ARR) is a practical and informative initial test for screening primary aldosteronism (PA) 3.
• A ratio greater than 75 has been suggested as a sensitive indicator for aldosterone-producing adenomas 4, but the patient's ratio of 22 is below this threshold.
• However, guidelines recommend wider screening for PA in hypertensive patients, and further confirmatory tests are necessary to diagnose PA 3.
• Confirmatory tests include oral salt loading, saline infusion, captopril challenge, and fludrocortisone suppression test 3, 5.
• The saline infusion test (SIT) and the fludrocortisone suppression test (FST) are two commonly used confirmatory tests, with the SIT leading to a stronger suppression of aldosterone than the FST 5.
• The diagnosis of primary aldosteronism is crucial, as it can lead to adverse cardiovascular, renal, and metabolic effects, and treatment differs depending on the subtype of PA 3, 6.

Diagnostic Approach

• The patient's evaluation should include a comprehensive diagnostic approach, involving screening with ARR, followed by confirmatory tests to establish the diagnosis of PA 3, 6.
• Imaging studies, such as high-resolution CT and MRI scans, can help differentiate between aldosterone-producing adrenal adenoma (APA) and zona glomerulosa hyperplasia (IHA) 4.
• Adrenal venous sampling (AVS) may be necessary to lateralize aldosterone production and guide treatment decisions 6.

Treatment Considerations

• Treatment of primary aldosteronism depends on the subtype, with surgical intervention considered for patients with APA, and medical management with mineralocorticoid receptor antagonists for those with IHA or bilateral hyperaldosteronism 4, 6.
• The goal of treatment is to prevent the long-term sequelae of hypertension and normalize aldosterone levels 4, 6.