Aldosterone’s Resurgence in Hypertension: a Primary Care Primer

Primary, autonomous secretion of aldosterone-or primary hyperaldosteronism-has a prevalence of 5% to 20% in hypertensive persons and may be the cause of resistant hypertension.¹ Although primary aldosteronism is often perceived as a subspecialty disease (nephrology, endocrinology, interventional radiology), primary care clinicians can conduct an initial screening if this diagnosis is suspected.
A recent publication outlines a simple approach, and explains how to proceed with screening, confirmation, and classification of hyperaldosteronism in hypertensive patients.¹

Screening
What findings should lead you to screen for excess aldosterone?
• Difficult to control, resistant, or refractory hypertension may be a signal that there is unregulated, excess aldosterone.^1,2 Since aldosterone increases potassium excretion, patients with either hypokalemia and/or hypokalemic metabolic alkalosis and high urine chloride excretion may have elevated, unresponsive aldosterone secretion.
• Patients with hypertension who also have an adrenal incidentaloma should be screened.²
• A family or personal history of earlier life onset of target organ injury from hypertension may also be a marker for aldosterone excess syndromes. More recent studies have implicated aldosterone in the hypertension and complications of diabetes, metabolic syndrome, and obstructive sleep apnea.²

During screening, patients should only be taking a few selected antihypertensive agents that do not alter the renin-angiotensin-aldosterone axis: dihydropyridine calcium channel blockers, terazosin, and/or doxazosin. After screening, patients can resume their usual regimen for blood pressure control.
Screening includes Plasma Renin Concentration (PRC) and Plasma Aldosterone Concentration (PAC), drawn preferably in the morning. The ratio of aldosterone to renin is then calculated (ARR). Autonomous aldosterone excretion is suspected when the ARR demonstrates an increased aldosterone to renin ratio of >65 pmol/mIU.³

Confirmation
There are 3 confirmatory tests:
• The Saline Infusion Test (SIT)
• The Captopril Challenge Test (CCT)
• The Fludrocortisone Suppression Test (FST).1 

A recent review recommends the CCT based on safety and ease of performance.1 The SIT necessitates the administration of 2 liters of normal saline intravenously over 4 hours. The rationale is that volume loading with saline will lower aldosterone secretion if it is not autonomous. That is a lot of fluid in a short period of time. The FST is complicated and takes 4 days to complete! If aldosterone is not suppressed as a consequence of ingesting fludrocortisone, a mineralocorticoid, it suggests that the elevated aldosterone is autonomous and not regulated by either volume or mineralocorticoids.

With the CCT (n=280 in the study),1 patients take 50 mg of captopril at 9 AM, sitting or standing, and blood is drawn for PRC and PAC at 0 and 2 hours. Captopril, an ACEI, should increase renin (which is low in primary, excess aldosterone syndromes) by decreasing angiotensin II, thereby also decreasing aldosterone. If it does not, it suggests that the renin suppression and aldosterone excess are autonomous.

Classification
Specialists can assist with classification. Hyperaldosteronism from a benign aldosterone-producing tumor can be localized by CT scanning and adrenal venous sampling for aldosterone (higher on the side of the tumor). Adrenal hyperplasia is usually bilateral and does not demonstrate a tumor on CT; it does not have unilateral, excess secretion of aldosterone. Unilateral hyperplasia and glucocorticoid remedial varieties are less common.

In short, some or all of the workup for hyperaldosteronism can be performed by primary care physicians. Since aldosterone has become a pivotal hypertensive hormone, screening with or without confirmation should be part of primary care practice.

References:

1. Song Y, Yang S, He W, et al. Confirmatory tests for the diagnosis of primary aldosteronism. Hypertension. 2018; 71:118-124.
2. Monticone S, Viola A, Tizzani D, et al. Primary aldosteronism: who should be screened? Horm Metab Res. 2012; 44:163-169.
3. Mourtzinis G, Ebrahimi A, Gustafsson H, et al. Aldosterone to renin ratio as a screening instrument for primary aldosteronism in a middle-aged population with atrial fibrillation. Horm Metab Res. 2017;49:831-837.