Primary Aldosteronism (PA)

According to the Endocrine Society guidelines of 2016,³ the following patient types should be screened for primary aldosteronism (PA): patients with resistant hypertension and patients who have hypertension with other conditions or family history.

Resistant hypertension (defined as any of the following)

• Blood pressure (BP) >150/100 mmHg on 3 measurements on different days
• BP >140/90 mmHg resistant to 3 conventional hypotensive drugs (including a diuretic)
• BP <140/90 mmHg) on at least 4 antihypertensive drugs

Hypertension with any of the following

• Adrenal incidentaloma
• Sleep apnea
• Family history of early onset hypertension or cerebrovascular accident at a <40 years of age
• First-degree relative with PA
• Spontaneous or diuretic-induced hypokalemia

The 2016 Endocrine Society guidelines recommend using the plasma aldosterone-to-renin ratio (ARR) of ≥30 in at-risk patients to detect cases of PA.³ However, a number of studies have shown that the sensitivity of the ARR test is <50%.^7,9-11

When aldosterone status was measured using 24-hour urinary aldosterone concentration (UAC) rather than ARR, the prevalence of PA was shown to be higher in hypertensive patients (16% among patients with stage I hypertension, 21% among those with stage II hypertension, and 24% among those with resistant hypertension) and in normotensive patients (10% to 14%).⁷   

Screening rates for PA are extremely low. A key contributor to low screening rates for PA is that the current guideline-supported pathway to diagnosis can take up to 4 to 6 weeks and recommendations can be complicated for providers to follow.³

Other obstacles include limited awareness of PA and the lack of guideline recommendations for primary care physicians (PCP) to assess their hypertensive patients.

Retrospective data suggests that primary aldosteronism (PA) evaluations based on plasma renin activity suppression (<1 ng/mL/h) may be a better index of PA status than the ARR.⁸

The prevalence of PA among hypertensive patients is higher than previously reported, warranting guideline updates to establish who should be screened and what screening test should be used for PA.¹²

Newly released Japanese¹³ and Korean¹⁴ Societies of Endocrinology guidelines endorse screening for PA in all patients presenting with newly diagnosed hypertension. Given the higher prevalence of PA among hypertensives that emerged since 2016, updates in US guidelines may align with these professional societies. 

The aldosterone-to-renin ratio (ARR) is used to screen for primary aldosteronism (PA), but ARR suffers from inconsistent measurements, a complicated workup, and low sensitivity.^7,9-11 Testing for suppressed levels of renin activity (PRA) may offer an alternative to testing for high ARR.

In a Quest study published in 2024, results were obtained for patients tested for PA using plasma aldosterone concentration (PAC) and PRA. Investigators determined how many patients were likely to have PA based on ARR (≥30) versus PRA (<1 ng/mL/h). Substantially more patients who were likely to have primary aldosteronism were identified by measuring PRA (<1 ng/mL/h) versus ARR (≥30).⁸

To better define the patients who tested positive for PRA (<1 ng/mL/h), the authors used an algorithm that sorts them into 3 groups based on PAC as outlined by Vaidya et al.¹⁵  

1. PRA ≥1 ng/mL/hr or PRA <1 ng/mL/hr with PAC<5 ng/dL suggests PA is unlikely.
2. PRA <1 ng/mL/hr with PAC of 5 to15 ng/dL suggests PA is likely, until proven otherwise.
3. PRA <1 ng/mL/hr with PAC >15 ng/dL suggests overt PA.

If one considers patients with PAC ≥5 ng/dL as positive or overt positive, and <5 ng/dL negative for PA, then 30.7% of the 94,829 patients in the cohort were positive (ie, had PRA <1 ng/mL/min and PAC ≥5 ng/dL), compared to 13.2% of patients with ARR ≥30.⁸

The testing pathway of the Plasma Renin Activity Reflex to Aldosterone test begins with testing plasma renin activity. The full algorithm is depicted in this Figure. 

If PRA is <1 ng/mL/hr, aldosterone levels are then measured. The components of this reflex test can be ordered separately (see table below).