Today, I review, link to, and excerpt from Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline. [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 9, September 2025, Pages 2453–2495, https://doi.org/10.1210/clinem/dgaf284.
All that follows is from the above resource.
Abstract
Primary aldosteronism (PA), a primary adrenal disorder leading to excessive aldosterone production by one or both adrenal glands, is a common cause of hypertension. It is associated with an increased risk of cardiovascular complications compared with primary hypertension. Despite effective methods for diagnosing and treating PA, it remains markedly underdiagnosed and undertreated.
ObjectiveTo develop an updated guideline that provides a practical, clinical approach to identifying and managing PA to improve diagnosis rates and encourage targeted treatment.
MethodsThe Guideline Development Panel (GDP), composed of a multidisciplinary panel of clinical experts and experts in systemic review methodology, used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to define 10 questions related to the diagnosis and treatment of PA. Systematic reviews were conducted for each question. The GDP used the GRADE Evidence to Decision (EtD) framework to consider contextual factors, such as stakeholder values and preferences, costs and required resources, cost-effectiveness, acceptability, feasibility, and the potential impact on health equity.
ResultsWe suggest that all individuals with hypertension be screened for PA by measuring aldosterone and renin and determining the aldosterone to renin ratio, and that subsequent clinical care be guided by the results. We suggest that individuals with PA receive PA-specific therapy, either medical or surgical. In individuals who screen positive for PA, we suggest (1) commencement of PA-specific medical therapy in individuals who do not desire or are not candidates for surgery and in situations where the probability of lateralizing PA (excess aldosterone produced by one adrenal) is low based on screening results; and (2) aldosterone suppression testing in situations when screening results indicate an intermediate probability for lateralizing PA and individualized decision making confirms a desire to pursue eligibility for surgical therapy. In those who test positive by aldosterone suppression testing, and in those in whom screening results show a high probability of lateralizing PA (obviating the need for aldosterone suppression testing), we suggest adrenal lateralization with computed tomography scanning and adrenal venous sampling prior to deciding the treatment approach (medical vs surgical). In all individuals with PA and an adrenal adenoma, we suggest performing a 1-mg overnight dexamethasone suppression test. We suggest the use of mineralocorticoid receptor antagonists (MRAs) over epithelial sodium-channel (ENaC) inhibitors in the medical treatment of PA. We suggest the use of spironolactone over other MRAs, given its lower cost and greater availability; however, all MRAs, when titrated to equivalent potencies, are anticipated to have similar efficacy in treating PA. Thus, MRAs with greater mineralocorticoid receptor specificity and fewer androgen/progesterone receptor-mediated side effects may be preferred in some situations. In individuals receiving MRA therapy, we suggest monitoring renin and, in those whose hypertension remains uncontrolled and renin is suppressed, titrating the MRA to increase renin.
ConclusionThese recommendations provide a practical framework for the diagnosis and treatment of PA. They are based on currently available literature and take into consideration outcomes that are important to key stakeholders. The goal is to increase identification of individuals with PA and, by initiating PA-specific medical or surgical therapy, improve blood pressure control and reduce PA-associated adverse cardiovascular events. The guidelines also highlight important knowledge gaps in PA diagnosis and management.
List of Recommendations
Question 1. Should care that includes primary aldosteronism screening be applied to all individuals with hypertension, compared with care without screening?
Recommendation 1In all individuals with hypertension, we suggest screening for primary aldosteronism (PA) (2 | ⊕⊕OO).
Technical remarks:
This is a conditional recommendation, with implementation depending on contextual factors such as available resources, local expertise, and healthcare system capacity, which may affect feasibility and prioritization.
This recommendation emphasizes care that is informed and guided by screening, with a positive screening result serving as the critical first step in the care process for individuals with PA.
PA screening includes measurement of serum/plasma aldosterone concentration and plasma renin (concentration or activity) with determination of the aldosterone to renin ratio (ARR). Potassium is also assessed—not for screening itself—but to aid in the accurate interpretation of aldosterone (refer to Question 3).
Question 2. Should primary aldosteronism–specific therapy (medical or surgical) vs nonspecific antihypertensive therapy be used in individuals with primary aldosteronism?
Recommendation 2In individuals with hypertension and primary aldosteronism (PA), we suggest PA-specific therapy (medical or surgical) (2 | ⊕⊕OO).
Technical remarks:
In individuals with lateralizing PA who are not surgical candidates or do not desire surgery and in individuals with bilateral PA, medical treatment with mineralocorticoid receptor antagonists (MRAs) should be considered preferable over nonspecific antihypertensive therapy.
In individuals with lateralizing PA who are surgical candidates and desire surgery, unilateral adrenalectomy should be considered preferable over nonspecific antihypertensive therapy.
Question 3. Should aldosterone (serum/plasma, or urine), renin (concentration or activity), and the aldosterone to renin ratio vs hypokalemia (unprovoked or diuretic-induced) be used for screening for primary aldosteronism in individuals with hypertension?
Recommendation 3In individuals with hypertension, we suggest primary aldosteronism (PA) screening with serum/plasma aldosterone concentration and plasma renin (concentration or activity) (2 | ⊕⊕OO).
Technical remarks:
Screen for PA by measuring serum/plasma aldosterone and plasma renin (concentration or activity) in the morning with individuals seated and avoiding dietary sodium restriction during the few days prior to screening. Potassium should be measured alongside renin and aldosterone—not for screening itself but to aid in the accurate interpretation of aldosterone—as low potassium may lead to a falsely low aldosterone.
If screening results are negative and the patient has hypokalemia, potassium should be corrected to within the laboratory reference range and screening should be repeated.
Manage interfering medications depending on individual safety and feasibility. The Guideline Development Panel outlined both minimal-withdrawal and no-withdrawal strategies of interfering medications before screening (Tables 6 and 7, Fig. 1).
A positive screen meets both of the following conditions in most circumstances:
Renin is low/suppressed (hallmark of diagnosis) and aldosterone is inappropriately high relative to renin: indicative of PA if plasma renin activity (PRA) is ≤1 ng/mL/h or direct renin concentration (DRC) is ≤8.2 mU/L AND serum/plasma aldosterone concentration is ≥10 ng/dL (≥277 pmol/L) when measured by immunoassay or ≥7.5 ng/dL (≥208 pmol/L) when measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS)
Elevated aldosterone to renin ratio (ARR): indicative of PA if the aldosterone [ng/dL] to PRA [ng/mL/h] ratio is >20 or aldosterone [pmol/L] to DRC [mU/L] ratio is >70 when aldosterone is measured by immunoassay; the ARR indicative of PA is about 25% lower when aldosterone is measured by LC-MS/MS). (Fig. 1 and Table 5 for ARR cut points for differing assays and units).
The aldosterone, renin, and ARR values above are provided for guidance. However, as with many diagnostic tests based on continuous variables, the sensitivity and specificity depend on the selected threshold. Aldosterone and renin levels are further influenced by individual variability, local laboratory assays, and other factors. Where possible, clinicians should rely on local laboratory cut points, as assays may vary. No cut point is perfect—each carries a trade-off between false positives and false negatives. Therefore, results should be interpreted within the context of the patient’s pretest probability for PA, along with potential interfering medications and conditions.
If the individual’s initial screen is negative and factors are present that could have led to a false-negative result (eg, hypokalemia or medications), the test should be repeated on a different day, preferably after correcting hypokalemia (where present) and withdrawing interfering medications if safe and feasible (for 4 weeks for mineralocorticoid receptor antagonists [MRAs], epithelial sodium-channel [ENaC] inhibitors [eg, amiloride, triamterene], and other diuretics; and 2 weeks for angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]), which raise renin or lower aldosterone. For the most accurate determination of potassium, measure plasma potassium in blood collected slowly with a syringe and needle (preferably not using a vacuum-sealed blood collection tube to minimize the risk of spuriously raising potassium). During collection, avoid fist clenching, wait at least 5 seconds after tourniquet release (if used) to achieve insertion of needle, and ensure separation of plasma from cells within 30 minutes of collection.
If the individual’s initial screen is negative and the pretest probability of PA is moderate to high (eg, hypokalemia and/or resistant hypertension) or renin is suppressed with aldosterone of 5 to 10 ng/dL (138 to 277 pmol/L) by immunoassay, the test should be repeated on a different day.
If the individual’s initial screen is positive, but they are receiving medications (eg, β-adrenergic blockers and centrally acting α2-agonists [eg, clonidine, α-methyldopa]) that can lower renin and thereby cause false-positive results, the test should be repeated after withdrawing those medications for 2 weeks if it is safe and feasible. Consider potential false positives induced by β-adrenergic blockers when aldosterone is 10 to 15 ng/dL (277-416 pmol/L) by immunoassay or 7.5 to 10 ng/dL (208-277 pmol/L) by LC-MS/MS; if aldosterone is above these concentrations, PA is likely despite being on β-adrenergic blockers.
If screening hypertensive patients with chronic kidney disease, renin decreases proportionately to nephron loss, except in cases where there is renal ischemia from renal artery stenosis where renin will be elevated. Aldosterone can also be elevated in chronic kidney disease, leading to overall increases in false-positive testing.
If all initial screening is negative, consider re-screening in the future if a patient develops:
Unexplained worsening of hypertension or resistant hypertension
New spontaneous or diuretic-induced hypokalemia
Atrial fibrillation in the absence of structural heart disease or hyperthyroidism
Question 4. Should care guided by aldosterone suppression testing vs no aldosterone suppression testing be used in individuals with positive primary aldosteronism screen before initiating primary aldosteronism–specific therapy (medical or surgical)?
Recommendation 4In individuals who screen positive for primary aldosteronism (PA), we suggest aldosterone suppression testing in situations when screening results suggest an intermediate probability for lateralizing PA and individualized decision making confirms a desire to pursue eligibility for surgical therapy (2 | ⊕OOO).
Figure 1.How to screen for PA in individuals with hypertension. This figure diagrams the process of screening for PA in individuals with hypertension. For individuals whose screening indicates likely PA, the next steps are diagrammed in Fig. 2, Algorithm for the Management of Adults with Hypertension in Whom PA is Likely Based on Aldosterone, Renin, and ARR. *Blood is obtained in seated position in the morning; ideally without venous stasis (release tourniquet after venipuncture and wait at least 5 seconds before withdrawing blood) to avoid factitious rises in potassium. **The aldosterone, renin, and ARR values provided in this figure and in greater detail in Table 5 are for guidance. However, as with many diagnostic tests based on continuous variables, the sensitivity and specificity depend on the selected threshold. Aldosterone and renin levels are further influenced by individual variability, local laboratory assays, and other factors. Where possible, clinicians should rely on local laboratory cut points, as assays may vary. No cut point is perfect—each carries a trade-off between false positives and false negatives. Therefore, results should be interpreted within the context of the patient’s pretest probability for PA, along with potential interfering medications and conditions. ***Consider potential false positive induced by β-adrenergic blockers when aldosterone <15 ng/dL (< 415 pmol/L) by immunoassay, <10 ng/dL (< 277 pmol/L) by LC-MS/MS. #Drospirenone in OCPs is an MRA. ##Amiloride and triamterene are ENaC inhibitors.
Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II–receptor blocker; CCB, calcium-channel blocker; DRC, direct renin concentration; ENaC, epithelial sodium-channel; HRT, hormone-replacement therapy; LC-MS/MS: liquid chromatography–tandem mass spectrometry; MRA, mineralocorticoid antagonist; OCP, oral contraceptive; PRA, plasma renin activity; SGLT2, sodium-glucose cotransporter 2.Technical remarks:Situations in which aldosterone suppression testing may be helpful include:
In individuals with an intermediate probability of having lateralizing PA who are willing and able to undergo surgical adrenalectomy (Fig. 2).
Figure 2.Algorithm for the management of adults with hypertension in whom PA is likely based on aldosterone, renin, and ARR. Patients who are likely to have PA, but have no desire for surgical adrenalectomy, or have contraindications to undergoing surgery, can be offered MRA therapy without further testing. MRA therapy is highly effective in PA. In addition, in studies of hypertensive individuals, MRAs have been consistently shown to be superior to alternative medication classes at lowering BP when renin is low or when the ARR is high (19–22). For patients who are interested in the possibility of, and capable of undergoing, unilateral adrenalectomy, probabilistic and shared decision making should be pursued. When the probability of lateralizing PA is low, patients can be offered MRA therapy without further testing. When the probability of lateralizing PA is high, cross-sectional adrenal imaging with CT and AVS can be pursued to adjudicate the possibility of lateralizing PA. When the probability of lateralizing PA is intermediate, or uncertain, shared decision making is advised. When possible, aldosterone suppression testing may be considered to steer the direction of management in individuals willing and able to undergo testing. In interpreting the aldosterone suppression test one should consider the possibility of false negatives (23–27). When aldosterone suppression testing is not available or desired, MRA therapy can be initiated. Approximate values for aldosterone and renin are provided for guidance. *See Fig. 3. Initiating and Following MRA Therapy. #False negatives may occur, may be impacted by local study conditions, and should be considered when deciding on whether to proceed to AVS testing.
Abbreviations: HTN, hypertension; CVA, cerebrovascular accident; MRA, mineralocorticoid antagonist.Situations in which aldosterone suppression testing is not required prior to initiating PA-specific therapy include (Fig. 2):
In individuals with resistant hypertension or hypertension with hypokalemia and overt biochemical evidence of renin-independent aldosterone production (plasma renin activity [PRA] <0.2 ng/mL/h or direct renin concentration [DRC] <2 mU/L and plasma aldosterone concentration >15 ng/dL [>416 pmol/L] via liquid chromatography–tandem mass spectrometry [LC-MS/MS] assay or >20 ng/dL [>554 pmol/L] via immunoassay), aldosterone suppression testing is not recommended due to the risk of false-negative results, which may exceed the risk of false-positive screening results.
Individuals unwilling or unable to pursue adrenal venous sampling and adrenalectomy can be empirically treated with mineralocorticoid receptor antagonists (MRAs) based on screening results, without aldosterone suppression testing. Aldosterone suppression testing may still provide value in some cases for further documenting the diagnosis.
Aldosterone suppression testing is unnecessary in individuals from families with germline mutations associated with familial hyperaldosteronism. Genetic screening is recommended for all first-degree relatives of individuals with familial hyperaldosteronism and for individuals with young-onset PA (<20 years) to enable early diagnosis and treatment.
Aldosterone suppression testing can also be avoided if the likelihood of lateralizing PA is so low that pursuing a formal diagnosis of PA is not justifiable (eg, normokalemia + plasma/serum aldosterone <∼11ng/dL [<∼305 pmol/L] [immunoassay] or <∼8 ng/dL [<∼222 pmol/L] [LC-MS/MS]).
Question 5. Should primary aldosteronism–specific medical therapy vs surgical therapy be used in individuals with diagnosed primary aldosteronism?
Recommendation 5In individuals with primary aldosteronism (PA), we suggest medical therapy or surgical therapy with the choice of therapy based on lateralization of aldosterone hypersecretion and candidacy for surgery (2 | ⊕OOO).
Technical remarks:
Surgical therapy by total unilateral adrenalectomy, usually by the laparoscopic approach, is mainly offered to individuals with lateralizing PA who choose to pursue the surgical option (Fig. 2).
Lifelong medical therapy that includes a mineralocorticoid receptor antagonist (MRA) is usually offered to individuals with bilateral PA or lateralization status unknown (refer to Question 6 for definition of lateralization) and to those who are not surgical candidates or who decline the surgical option (Fig. 2).
Individuals with mild PA typically have bilateral disease and may bypass adrenal venous sampling (AVS), proceeding directly to medical management, as outlined in the diagnostic algorithm (Fig. 2).
Individuals with multiple comorbidities who may not be good surgical candidates may also proceed directly to medical therapy (Fig. 2).
Question 6. Should care guided by adrenal lateralization with computed tomography scanning and adrenal venous sampling vs computed tomography scanning alone be used for deciding treatment approach in individuals with primary aldosteronism?
Recommendation 6In individuals with primary aldosteronism (PA) considering surgery, we suggest adrenal lateralization with computed tomography (CT) scanning and adrenal venous sampling (AVS) prior to deciding the treatment approach (medical or surgical) (2 | ⊕⊕OO).
Technical remarks:
Individuals with PA who desire and are candidates for adrenalectomy should undergo AVS in order to reliably differentiate lateralizing from bilateral forms.
A potential exception is when the diagnosis of unilateral aldosterone-producing adenoma (APA) is so likely that AVS could be considered unnecessary (eg, individual age <35 years with marked PA with hypokalemia and a > 1.0-cm unilateral adrenal adenoma on CT scanning).
Question 7. Should suppressed renin vs unsuppressed renin be used in individuals with primary aldosteronism receiving primary aldosteronism–specific medical therapy?
Recommendation 7In individuals with primary aldosteronism (PA) receiving PA-specific medical therapy whose hypertension is not controlled and renin is suppressed, we suggest increasing PA-specific medical therapy to raise renin (2 | ⊕OOO).
Technical remarks:
This recommendation applies to individuals with PA receiving aldosterone-directed medical therapy whose blood pressure (BP) remains high. Uncertainty remains as to whether titrating aldosterone-directed medical therapy to raise renin when BP is controlled is efficacious.
The panel does not specify a renin level to target but rather advises titration of aldosterone-directed medical therapy to a rise in renin from pretreatment baseline.
Question 8. Should a dexamethasone suppression test vs no dexamethasone suppression test be used in individuals with primary aldosteronism and adrenal adenoma?
Recommendation 8In individuals with primary aldosteronism (PA) and adrenal adenoma, we suggest a dexamethasone suppression test (2 | ⊕OOO).
Technical remarks:
A dexamethasone suppression test should be performed, and a positive test should prompt further evaluation for Cushing syndrome as detailed in the Endocrine Society Clinical Practice Guidelines.
For the 1-mg overnight dexamethasone suppression test, 1 mg dexamethasone is taken orally at 23:00 to 24:00 with serum cortisol measured at 08:00 to 09:00 the next morning. A serum cortisol >1.8 μg/dL (50 nmol/L) suggests autonomous cortisol secretion (ACS).
For individuals with mild autonomous cortisol secretion, measuring plasma metanephrine during adrenal venous sampling may help lateralize both aldosterone and cortisol secretion, although further research is needed. It will also be important to measure early morning cortisol following adrenal surgery and prepare for a period of possible glucocorticoid insufficiency.
Question 9. Should spironolactone vs other mineralocorticoid receptor antagonists be used for primary aldosteronism–specific medical therapy?
Recommendation 9In individuals with primary aldosteronism (PA) receiving PA-specific medical therapy, we suggest spironolactone over other mineralocorticoid receptor antagonists (MRAs) due to its low cost and widespread availability (2 | ⊕OOO).
Technical remarks:
The recommendation is driven by the availability and low cost of spironolactone vs other MRAs; however, all MRAs, when titrated to equivalent potencies, are anticipated to have similar efficacy in treating PA. MRAs with greater mineralocorticoid receptor specificity and fewer androgen/progesterone receptor-mediated side effects may be preferred.
When initiating an MRA, consider hypertension severity for dosing and potential discontinuation of other antihypertensive medications (Fig. 3).
Monitor potassium, renal function, renin (concentration or activity), and blood pressure response during follow-up to guide MRA dose titration.
Question 10. Should epithelial sodium-channel inhibitors vs mineralocorticoid receptor antagonists (steroidal and nonsteroidal) be used for medical treatment of primary aldosteronism?
Recommendation 10For individuals with primary aldosteronism (PA) receiving PA-specific medical therapy, we suggest using mineralocorticoid receptor antagonists (MRAs) rather than epithelial sodium-channel (ENaC) inhibitors (amiloride, triamterene) (2 | ⊕OOO).
Figure 3.Initiating and following MRA therapy. This is a general guide and there is a wide range of inter-patient responsiveness to varying doses of MRA. The process of MRA initiation and titration is expected to be multi-step for many patients; each MRA adjustment is followed by an assessment of both BP and biochemical response, then re-entering the treatment algorithm as appropriate. The primary goal of therapy is control of BP. The secondary goal of therapy is achievement of normokalemia. Measurement of renin (as a marker of MR blockade) may assist in the process of MRA dose titration for achieving these goals and possibly reducing other non-MRA antihypertensive drugs.
1. Clinicians may start at a relatively low dose MRA (spironolactone 12.5-25 mg/d or eplerenone 25 mg daily or twice daily). Medically complex or frail individuals and those in whom MRA–drug interactions (eg, with an ACE inhibitor or ARB) are possible may need careful monitoring. For individuals with more severe PA, especially if profound hypokalemia is present, a higher initial dose could be considered (spironolactone 50 mg/d or eplerenone 50 mg twice daily).
2. All individuals should get routine measurement of serum electrolytes, renal function, and renin within 2 to 3 months of starting MRA therapy; more frequent serial measurements may be needed in those with prior severe hypokalemia or renal impairment. Some panelists recommend enquiring about dietary sodium or measuring 24-hour urine sodium at baseline and periodically throughout follow-up as a means of tracking dietary salt restriction; a target of <85.5 mmol/d sodium is recommended (representing <5 g/d salt intake) (6).
3. MRA dose changes to target BP control should occur at 8- to 12-week intervals, and the full drug effect may take up to 3 months in more severe PA forms (28). Typical doses required to de-suppress renin are variable and likely higher than doses used as empiric add-on for resistant hypertension (29) (30); most individuals will achieve renin de-suppression with spironolactone doses (or spironolactone dose equivalents) between 50 and 100 mg/day. Spironolactone may be increased in 25- to 50-mg increments, and eplerenone in 25- to 100-mg increments. With each MRA dose change, repeat electrolytes, renal function, and renin 2 to 3 months later is recommended. When possible, consider off-titration of other anti-hypertensives. Once renin is de-suppressed, and if further BP reduction is required, other non-MRA antihypertensives should be added or uptitrated. If blood pressure is controlled on MRA monotherapy, there is insufficient evidence to suggest further MRA dose increases in response to low renin levels alone.
4. Normalization of serum potassium usually occurs, even with lower-dose MRAs, in the first 3 to 5 days, so it is reasonable to reduce or discontinue any potassium supplements at day 2 to 4 of MRA initiation in all but the most severe hypokalemic cases. Individuals who do require ongoing potassium supplementation require frequent careful monitoring of potassium. Dietary salt restriction is a critical part of determining response to MRA therapy (31); individuals should be explicitly instructed on and assisted with dietary salt reduction strategies. An ongoing high-salt diet is a very common reason for apparent nonresponse to MRA therapy.
5. The glomerular filtration rate (GFR) may decrease in individuals with PA on introduction of PA-targeted medical therapy or with successive titration of MRA (32, 33). The time course of change may be over days to weeks and, in most cases, represents a marker of treatment efficacy as opposed to adverse effect. The natural history of an appropriate treatment-induced decrease in GFR is usually one of eventual long-term stability, anticipating a renal-sparing effect of effective MRA therapy (32, 33). If renal function progressively declines, consider referring to nephrology and discontinuing ACE inhibitors or ARBs.
6. Gynecomastia from spironolactone is dose-related and may appear as early as 1 to 2 months into therapy but more commonly after ≥6 months of treatment. In some cases (especially in younger males) a dose reduction to ≤50 mg per day resolves gynecomastia. Some men may request a switch to a more selective MRA such as eplerenone or other new MRA agents; amiloride is an alternative option (see Question 10). This almost always allows complete resolution of the gynecomastia if it has not already progressed to advanced size.
7. Routine follow-up after MRA dose optimization should generally consist of blood pressure monitoring, along with annual measures of potassium and kidney function. Patients with chronic kidney disease or other risk factors for impaired renal function/electrolyte disorders (eg, combination MRA and ACE inhibitor/ARB drugs) should undergo biochemical monitoring more frequently. Routine repeat renin measures are not necessary unless re-entering the MRA titration algorithm due to incomplete BP/potassium control.
Technical remark:
The recommendation (see Fig. 3) does not apply to clinical conditions in which spironolactone is contraindicated (eg, hyperkalemia, advanced renal impairment, or pregnancy) or if a non-spironolactone MRA were indicated for other non-PA indications (eg, heart failure).
Who Should be Screened for Primary Aldosteronism?
Background
Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension with an estimated prevalence of 5% to 14% of individuals with hypertension seen in primary care (34-36) and up to 30% in referral centers (37-39). PA is particularly prevalent in individuals with specific clinical characteristics or comorbid conditions (Table 3).
Table 3.Prevalence of primary aldosteronism in different subgroups
Setting Prevalence Reference Hypertension in Primary Care 5.9% (range, 3.2-14.0) (34–36, 39) Hypertension in referral centers 7.2% (range, 0.7-21.9) (39) Hypertension in young adults (ages 18-40 years) 16.2% (39) aGrade 1 hypertension 3.9%-15.7% (23, 34) aGrade 2 hypertension 9.7%-21.6% (23, 34, 37) aGrade 3 hypertension 11.9%-19% (34, 37) Resistant hypertension 11.3%-29.1% (23, 40-42) Hypertension and hypokalemia 28.1% (43) Hypertension and adrenal incidentaloma 4.4% (range, 0.4-24.6%) (44) Hypertension and atrial fibrillationb 42.5% (45) Hypertension and type 2 diabetes mellitus 11.3%-19.1% (46, 47) Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure.
aGrades 1, 2, and 3 hypertension refer to the classification of the 2023 European Society of Hypertension guideline (48). Grade 1, SBP 140-159 mmHg and/or DBP 90-99 mmHg; grade 2, 160-179 mmHg and/or DBP 100-109 mmHg; grade 3, SBP ≥180 mmHg and/or DBP ≥110 mmHg.
bIf unexplained by structural heart disease and other conditions like hyperthyroidism.
PA is characterized by excessive production of aldosterone (49), leading to higher blood pressure (BP), renal injury, and an elevated risk of stroke, atrial fibrillation, and other cardiovascular diseases (1, 2). Detection of PA allows the use of specific treatments—such as mineralocorticoid receptor antagonists (MRAs), or adrenalectomy for those with lateralizing disease—that can effectively control BP, correct hypokalemia, and reduce cardiovascular risk (7-9)
Despite the potential benefits of treatment, PA remains underdiagnosed, in part due to limited screening in routine clinical practice (50, 51). Many individuals with PA, even those with high-risk features, such as resistant hypertension and hypokalemia (52), are never identified, leading to suboptimal management of their hypertension and cardiovascular risk. Expanding PA screening to all hypertensive individuals could increase the detection rate, allowing more individuals to benefit from targeted therapies and potentially reducing long-term cardiovascular risks.
However, the benefits of widespread screening must be weighed against certain challenges. The accuracy of screening tests, such as aldosterone concentration, renin concentration or activity, and the aldosterone to renin ratio (ARR), is influenced by various factors, including medication use, dietary sodium intake, and test conditions. False positives can occur, resulting in unnecessary aldosterone suppression testing or even inappropriate PA treatment in individuals without the condition. Access to diagnostic and subtyping tests and the availability of specialized treatments may also undermine the feasibility of universal screening unless alternative strategies are proposed.
