Does a 27-year-old male on Lisinopril (Zestril) with elevated plasma renin activity and a low Aldosterone-to-Renin Ratio (ARR) require further evaluation for primary aldosteronism?

From the Guidelines

Further evaluation for primary aldosteronism is not necessary in this 27-year-old male taking Lisinopril 20mg, as the plasma renin activity is elevated and the aldosterone-to-renin ratio (ARR) is well below the screening threshold. The patient's laboratory values are consistent with the expected effect of an ACE inhibitor like Lisinopril, which typically increases renin levels, as noted in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. This medication interferes with the renin-angiotensin-aldosterone system by blocking the conversion of angiotensin I to angiotensin II, leading to a compensatory increase in renin production, as discussed 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. The low ARR in this case effectively rules out primary aldosteronism, as this condition is characterized by autonomous aldosterone production with suppressed renin levels, resulting in an elevated ARR, as stated in the 2024 ESC guidelines 1. Key points to consider in the evaluation of primary aldosteronism include:

• The aldosterone-to-renin ratio (ARR) is the most accurate and reliable means of screening for primary aldosteronism, with a commonly used 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.
• The diagnosis of primary aldosteronism generally requires a confirmatory test, such as an intravenous saline suppression test or oral salt-loading test, as noted in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.
• The management of primary aldosteronism depends on its subtype, particularly on adrenal lesions being unilateral or bilateral, as discussed in the 2024 ESC guidelines 1. Given the patient's elevated plasma renin activity and low ARR, no further evaluation for primary aldosteronism is necessary, and the patient's current treatment with Lisinopril can be continued, as the laboratory values suggest an appropriate physiological response to the ACE inhibitor therapy rather than pathological aldosterone excess, as supported by the 2024 ESC guidelines 1.

From the FDA Drug Label

Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity. The patient is on Lisinopril, which increases plasma renin activity by removing the negative feedback of angiotensin II on renin secretion. Given that the patient has elevated plasma renin activity and a low Aldosterone-to-Renin Ratio (ARR), this is consistent with the expected effects of Lisinopril. Therefore, further evaluation for primary aldosteronism is not necessarily required based on the information provided, as the low ARR can be a result of the medication rather than an indication of primary aldosteronism 2 2.

From the Research

Evaluation for Primary Aldosteronism

The patient in question is a 27-year-old male on Lisinopril (Zestril) with elevated plasma renin activity and a low Aldosterone-to-Renin Ratio (ARR). To determine if further evaluation for primary aldosteronism is required, we need to consider the following points:

• Primary aldosteronism is a common form of secondary hypertension, and its diagnosis can lead to improved or cured hypertension or targeted pharmacotherapy 3.
• The ARR is a useful screening test for primary aldosteronism, but it can be affected by antihypertensive therapy 4.
• A low ARR in a patient with elevated plasma renin activity may not be indicative of primary aldosteronism, as the ARR can be influenced by various factors, including medication and renal function 5.

Considerations for Further Evaluation

Given the patient's low ARR and elevated plasma renin activity, further evaluation for primary aldosteronism may not be necessary. However, the following points should be considered:

• The patient's age and the presence of hypertension may still warrant screening for primary aldosteronism, especially if the patient has resistant hypertension or a family history of hypertension 6.
• The use of Lisinopril, an ACE inhibitor, may affect the interpretation of the ARR, and a washout period may be necessary to accurately assess the patient's aldosterone and renin levels 4.
• If further evaluation is deemed necessary, an aldosterone suppression test or measurement of 24-hr urinary aldosterone may be required to confirm the diagnosis of primary aldosteronism 3, 7.

Key Points to Consider

• The ARR is not a definitive diagnostic test for primary aldosteronism, and further evaluation is necessary to confirm the diagnosis.
• Antihypertensive therapy can affect the interpretation of the ARR, and a washout period may be necessary to accurately assess the patient's aldosterone and renin levels.
• The patient's age, hypertension, and family history may still warrant screening for primary aldosteronism, despite a low ARR.