What is the appropriate work‑up for a patient with suspected primary hyperaldosteronism?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 20, 2026View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Work-up for Hyperaldosteronism

Who Should Be Screened

Screen all patients with resistant hypertension (BP uncontrolled on ≥3 medications including a diuretic), as primary aldosteronism affects up to 20% of this population and carries dramatically higher cardiovascular risk than essential hypertension. 1

Additional high-risk populations requiring screening include:

  • Severe hypertension (BP >180/110 mmHg) 1
  • Spontaneous or diuretic-induced hypokalemia – though critically, hypokalemia is absent in approximately 50% of primary aldosteronism cases, so normal potassium does not exclude the diagnosis 1, 2
  • Adrenal incidentaloma discovered on imaging 1, 2
  • Family history of early-onset hypertension or stroke before age 40 1, 2
  • Young-onset hypertension in patients <30-40 years without traditional risk factors 1

Patient Preparation Before Testing

Medication Management

Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks before any testing, as they directly interfere with results. 1, 2

When clinically feasible, discontinue interfering medications:

  • Beta-blockers – suppress renin, causing false-positive ARR; stop 2-5 days before testing 1
  • Diuretics – increase renin, causing false-negative ARR; discontinue when possible 1
  • ACE inhibitors/ARBs – increase renin, causing false-negative ARR; withdraw at least 2 weeks before testing 1

Use long-acting calcium channel blockers (verapamil slow-release) and alpha-receptor antagonists (prazosin, doxazosin, hydralazine) as safe alternatives during washout, as they minimally interfere with ARR. 1

If medications cannot be stopped due to severe hypertension, proceed with testing but interpret results in the context of known drug effects. 1

Metabolic Preparation

Ensure potassium repletion before testing, targeting serum potassium 4.0-5.0 mEq/L, as hypokalemia suppresses aldosterone production and causes false-negative results. 1, 2

  • Encourage unrestricted (liberal) salt intake before testing 1
  • Ensure adequate hydration, especially if diuretics were recently used 1

Initial Screening Test: Aldosterone-to-Renin Ratio (ARR)

Blood Collection Protocol

Collect blood in the morning (ideally 0800-1000 hours), with the patient out of bed for at least 2 hours and seated for 5-15 minutes immediately before blood draw. 1, 2

Interpretation Criteria

A positive screening test requires BOTH:

  • ARR ≥20-30 (when aldosterone is in ng/dL and renin activity in ng/mL/h) 1, 2
  • Plasma aldosterone concentration ≥10-15 ng/dL 1, 2

The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 1

Common Pitfalls to Avoid

  • Never rely on hypokalemia alone – it is absent in 50% of cases 1, 2
  • Do not skip screening in normokalemic patients with resistant hypertension 3, 4
  • Recognize that normal aldosterone levels in basal conditions do not exclude hyperaldosteronism – dynamic testing is required 3
  • Consider repeat screening in patients with persistent resistant hypertension despite initial negative testing, as false-negatives occur 5

Confirmatory Testing

All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading. 1, 2

Confirmatory Test Options

Intravenous saline suppression test:

  • Infuse 2L of normal saline over 4 hours
  • Failure to suppress plasma aldosterone below 5 ng/dL confirms the diagnosis 1

Oral sodium loading test:

  • Measure 24-hour urine aldosterone with unrestricted salt intake
  • Elevated urinary aldosterone (>14 μg/24 hours) confirms autonomous secretion 1, 6

Fludrocortisone suppression test:

  • Failure to reduce plasma aldosterone below threshold confirms diagnosis 1

Perform confirmatory testing with unrestricted salt intake and normal serum potassium levels. 1, 2


Subtype Determination

After biochemical confirmation, determine if the disease is unilateral or bilateral, as this dictates treatment – surgery for unilateral disease versus lifelong medical therapy for bilateral disease. 1, 2

Initial Imaging

Obtain non-contrast CT scan of the adrenal glands to identify potential adenomas and exclude adrenocortical carcinoma. 2

Adrenal Venous Sampling (AVS)

AVS is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease, as up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone. 1, 2

Exception: In patients <40 years with imaging showing a single affected gland, AVS may be omitted, as bilateral hyperplasia is rare in this population. 1

AVS should be performed by an experienced radiologist, as it has 95% sensitivity and 100% specificity for lateralization. 1


Referral

Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination and treatment planning. 1, 2


Treatment Based on Subtype

Unilateral Disease (Aldosterone-Producing Adenoma)

Laparoscopic unilateral adrenalectomy is the treatment of choice, improving blood pressure in virtually 100% of patients and curing hypertension in approximately 50%. 1, 2

  • Adrenalectomy normalizes hypokalemia, lowers blood pressure, reduces antihypertensive medication requirements, and improves cardiac and kidney function 1
  • The rate of cure is higher when diagnosis is made early in the disease course 1
  • Even after successful surgery, some patients have residual hypertension due to vascular remodeling from delayed diagnosis 1

Bilateral Disease (Bilateral Adrenal Hyperplasia)

Medical therapy with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of lifelong treatment. 1, 2

Spironolactone is first-line therapy:

  • Start 50-100 mg once daily, titrate up to 300-400 mg once daily if necessary 1
  • Provides significant BP reduction of 25/12 mmHg when added to multidrug regimens 1
  • Low doses (25-50 mg daily) are effective and minimize adverse effects 1

Eplerenone is an alternative:

  • Less potent than spironolactone, requires twice-daily administration 1
  • Fewer anti-androgenic side effects 1

Monitoring During MRA Therapy

Monitor serum potassium within 1 week of MRA initiation and regularly thereafter. 1

  • Risk of hyperkalemia is increased in older patients, those with diabetes, CKD (especially eGFR <45 mL/min), or concomitant use of ACE inhibitors/ARBs/NSAIDs 1, 2
  • Avoid combining MRAs with other potassium-sparing medications or potassium supplements 2
  • Use MRAs with caution in patients with significant renal dysfunction 2

Special Consideration: Empiric Spironolactone in Resistant Hypertension

In patients with resistant hypertension and positive ARR screening (ARR ≥30 with aldosterone ≥10 ng/dL), add spironolactone 25-50 mg daily immediately while awaiting confirmatory testing, as this provides significant blood pressure reduction regardless of whether primary aldosteronism is ultimately confirmed. 1

This approach is justified because spironolactone provides benefit in both true primary aldosteronism and aldosterone-sensitive hypertension. 1


Clinical Impact of Early Diagnosis

Primary aldosteronism causes dramatically worse cardiovascular outcomes than essential hypertension at equivalent blood pressure levels: 1

  • 3.7-fold increase in heart failure
  • 4.2-fold increase in stroke
  • 6.5-fold increase in myocardial infarction
  • 12.1-fold increase in atrial fibrillation

Prompt identification and targeted treatment—either unilateral adrenalectomy or MRA therapy—can reverse aldosterone-mediated target-organ damage and mitigate this excess cardiovascular risk. 1

References

Guideline

Screening for Primary Aldosteronism

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Diagnosis and Treatment of Hyperaldosteronism

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Normokalemic hyperaldosteronism in patients with resistant hypertension.

The Israel Medical Association journal : IMAJ, 2002

Research

A Late Diagnosis of Primary Aldosteronism.

High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension, 2017

Research

Primary aldosteronism. Issues in diagnosis and management.

Endocrinology and metabolism clinics of North America, 1994

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.