Question 1: What is primary aldosteronism?

Primary aldosteronism is a disease in which the adrenal gland produces too much aldosterone, a hormone that regulates salt and water balance.1 Excess aldosterone causes the body to retain sodium and lose potassium, leading to high blood pressure (hypertension) and, in some cases, low potassium levels (hypokalemia).1

Question 3: Who should be screened for primary aldosteronism?

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

Primary Aldosteronism (PA)

Q: Question 2: Why should providers screen for primary aldosteronism?

A diagnosis of primary aldosteronism changes the treatment path of hypertensive patients.2 Less than 1% of the patients who are qualified to be screened are being tested.3 Hypertension affects around 50% of American adults.4 Two forms exist. Primary hypertension is caused by an unknown pathophysiologic mechanism. Secondary hypertension is caused by renal, vascular, or endocrine mechanisms. The rate of primary vs secondary hypertension was thought to be approximately 90% vs 10%.3,5,6 However, recent papers indicate that 10% is an underestimate and primary aldosteronism, a form of secondary hypertension, could account for up to 30% of all hypertension cases.7,8 Primary aldosteronism also affects many other systems and organs in the body. It is associated with atrial fibrillation, myocardial infarction, heart failure, stroke, and kidney failure. Other effects of excess aldosterone include insulin resistance, diabetes mellitus, liver fibrosis, and other less frequent manifestations.3,5

Q: Question 4: What are the screening guidelines for PA?

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.

Q: Question 5: What are the emerging data on primary aldosteronism?

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.

Q: Question 6: How does the Plasma Renin Activity Reflex to Aldosterone LC/MS/MS test improve identification of primary aldosteronism?

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 ( 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

Q: Question 7: What is the testing pathway of the Plasma Renin Activity Reflex to Aldosterone LC/MS/MS test?

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). Click on the table to open up (enlarge) in a new window)

Test code: 13817

Primary aldosteronism is a disease in which the adrenal gland produces too much aldosterone, a hormone that regulates salt and water balance.¹

Excess aldosterone causes the body to retain sodium and lose potassium, leading to high blood pressure (hypertension) and, in some cases, low potassium levels (hypokalemia).¹

A diagnosis of primary aldosteronism changes the treatment path of hypertensive patients.²Less than 1% of the patients who are qualified to be screened are being tested.³

Hypertension affects around 50% of American adults.⁴ Two forms exist. Primary hypertension is caused by an unknown pathophysiologic mechanism.

Secondary hypertension is caused by renal, vascular, or endocrine mechanisms. The rate of primary vs secondary hypertension was thought to be approximately 90% vs 10%.^3,5,6 However, recent papers indicate that 10% is an underestimate and primary aldosteronism, a form of secondary hypertension, could account for up to 30% of all hypertension cases.^7,8

Primary aldosteronism also affects many other systems and organs in the body. It is associated with atrial fibrillation, myocardial infarction, heart failure, stroke, and kidney failure. Other effects of excess aldosterone include insulin resistance, diabetes mellitus, liver fibrosis, and other less frequent manifestations.^3,5

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.^7,9-11Testing 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

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

Click on the table to open up (enlarge) in a new window)

References

Vaidya A, Mulatero P, Baudrand R, et al. The expanding spectrum of primary aldosteronism: implications for diagnosis, pathogenesis, and treatment, Endocrine Reviews. 2018:39(6): 1057-1088.
Dogra P, Bancos I, Young WF Jr. Primary aldosteronism: a pragmatic approach to diagnosis and management. Mayo Clin Proc. 2023;98(8):1207-1215.
Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889–1916.
Ostchega Y, Fryar CD, Nwankwo T, Nguyen DT. Hypertension prevalence among adults aged 18 and over: United States, 2017–2018. NCHS Data Brief, no 364. National Center for Health Statistics. 2020. https://www.cdc.gov/nchs/data/databriefs/db364-h.pdf
Savard S, Amar L, Plouin PF, et al. Cardiovascular complications associated with primary aldosteronism: a controlled cross-sectional study. Hypertension. 2013;62(2):331-6.
Young WF Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2019;285(2);126-148.
Vaidya A, Brown JM, Carey RM, et al. The unrecognized prevalence of primary aldosteronism. Ann Intern Med. 2020;173(8):683.
Marcelli M, Caixia B, Funder JW, et al. Comparing ARR versus suppressed PRA as screening tests for primary aldosteronism. Hypertension. 2024;81(10):2071-2081.
Fardella CE, Mosso L, Gómez-Sánchez C, et al. Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology. J Clin Endocrinol Metab. 2000;85(5):1863-1867.
Jansen PM, van den Born BJ, Frenkel WJ, et al. Test characteristics of the aldosterone-to-renin ratio as a screening test for primary aldosteronism. J Hypertens. 2014;32(1):115-126.
Baudrand R, Guarda FJ, Fardella C, et al. Continuum of renin independent aldosteronism in normotension. Hypertension. 2017;69(5):950-956.
Zekarias K, Tessier KM. Screening rate for primary aldosteronism among patients with apparent treatment-resistant hypertension: retrospective analysis of current practice. Endocr Pract. 2022;28(3):271-275.
Naruse M, Katabami T, Shibata H, et al. Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021. Endocr J. 2022;69(4):327-359.
Ha J, Park JH, Kim KJ, et al. 2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism. Endocrinol Metab. 2023;38(6):597-618.
Vaidya A, Hundemer GL, Nanba K, et al. Primary aldosteronism: state-of-the-art review. Am J Hypertens. 2022;35(12):967-988.

This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.

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Primary Aldosteronism (PA)

add Question 1: What is primary aldosteronism?

add Question 2: Why should providers screen for primary aldosteronism?

add Question 3: Who should be screened for primary aldosteronism?

add Question 4: What are the screening guidelines for PA?

add Question 5: What are the emerging data on primary aldosteronism?

add Question 6: How does the Plasma Renin Activity Reflex to Aldosterone LC/MS/MS test improve identification of primary aldosteronism?

add Question 7: What is the testing pathway of the Plasma Renin Activity Reflex to Aldosterone LC/MS/MS test?

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