Initial Laboratory Testing for Primary Hyperaldosteronism
The aldosterone-to-renin ratio (ARR) is the preferred initial screening test for primary hyperaldosteronism, measured from morning samples after the patient has been ambulatory for at least 2 hours and seated for 5-15 minutes. 1, 2
Screening Test: Aldosterone-to-Renin Ratio (ARR)
Sample Collection Requirements
The most recent Endocrine Society guideline 2 and Hypertension Canada 2020 guidelines 1 specify standardized collection conditions:
- Timing: Morning samples after patient has been ambulatory (sitting, standing, or walking) for at least 2 hours
- Patient position: Seated for 5-15 minutes before blood draw
- Potassium status: Correct hypokalemia before testing
- Sodium intake: Should be liberalized (not restricted)
Medication Management Before Testing
Critical medications to withdraw 4-6 weeks before testing 1, 2:
- Aldosterone antagonists (spironolactone, eplerenone)
- Potassium-sparing diuretics (amiloride, triamterene)
- Potassium-wasting diuretics (thiazides, loop diuretics)
If results are non-diagnostic, withdraw these medications 2 weeks before repeat testing 1:
- β-blockers
- Centrally acting α₂-agonists (clonidine, methyldopa)
- Angiotensin receptor blockers (ARBs)
- ACE inhibitors
- Direct renin inhibitors
- Dihydropyridine calcium channel blockers
Medications that can be continued 1: Slow-release verapamil, diltiazem, hydralazine, prazosin, doxazosin, terazosin
Important caveat: Oral contraceptives can cause false-positive results with direct renin concentration. Discontinue 1 month before testing or use plasma renin activity instead 1.
Interpretation of ARR Results
The 2020 Hypertension Canada guidelines 1 provide method-specific cutoffs based on how renin is measured:
| Renin Method | ARR Cutoff (Higher Sensitivity) | ARR Cutoff (Higher Specificity) |
|---|---|---|
| Plasma renin activity (ng/mL/h) | >555 pmol/L per ng/mL/h | >750 pmol/L per ng/mL/h |
| Direct renin concentration (mIU/L) | >60 pmol/L per mIU/L | >91 pmol/L per mIU/L |
| Direct renin concentration (ng/L) | >100 pmol/L per ng/L | >144 pmol/L per ng/L |
The older guidelines 3, 4 used a single cutoff of >550 pmol/L/ng/mL/h for plasma renin activity or >140 pmol/L/ng/L for renin mass, but the 2020 guideline recognizes that optimal cutoffs remain undefined and provides options based on desired sensitivity versus specificity.
When Confirmatory Testing Can Be Skipped
The 2025 Endocrine Society guideline 2 introduced important exceptions where you can proceed directly to treatment without confirmatory testing:
Skip confirmatory testing if the patient has 2:
- Resistant hypertension or hypertension with hypokalemia AND
- Plasma renin activity <0.2 ng/mL/h or direct renin concentration <2 mU/L AND
- Plasma aldosterone >15 ng/dL (>416 pmol/L) by LC-MS/MS or >20 ng/dL (>554 pmol/L) by immunoassay
This represents a significant shift from older guidelines that universally required confirmatory testing. The rationale is that in these cases, the risk of false-negative confirmatory tests exceeds the risk of false-positive screening results.
Also skip confirmatory testing for 2:
- Individuals from families with germline mutations causing familial hyperaldosteronism
- Cases where likelihood of lateralizing PA is very low (normokalemia + aldosterone <11 ng/dL by immunoassay or <8 ng/dL by LC-MS/MS)
Additional Initial Labs to Order
While not explicitly stated in the guidelines, you should simultaneously obtain:
- Serum potassium: Hypokalemia supports the diagnosis but is present in only a minority of PA cases
- Basic metabolic panel: To assess renal function and electrolytes
- Plasma aldosterone concentration: Absolute value matters, not just the ratio
- Plasma renin activity OR direct renin concentration: Choose based on local laboratory availability
Common Pitfalls to Avoid
Don't screen patients on interfering medications without recognizing the limitation: β-blockers are particularly problematic and can cause false positives. The 2025 guideline 2 suggests PA is likely if aldosterone is >10-15 ng/dL by immunoassay despite β-blocker use.
Don't forget about chronic kidney disease: Renin decreases with nephron loss, leading to increased false-positive rates in CKD patients 2.
Don't assume a negative screen rules out PA forever: Rescreen if the patient develops worsening hypertension, new hypokalemia, or atrial fibrillation 2.
Don't use random timing for blood draws: The standardized collection protocol is critical for accurate interpretation.
Next Steps After Positive Screening
If the ARR is positive and confirmatory testing is indicated (i.e., the patient doesn't meet criteria to skip it), proceed to one of the following confirmatory tests 1:
- Saline infusion test: 2L normal saline IV over 4 hours (contraindicated in severe uncontrolled hypertension or heart failure)
- Oral sodium loading: >200 mmol/day sodium for 3 days with 24-hour urinary aldosterone measurement
- Captopril suppression test: 25-50 mg captopril with aldosterone measured at baseline and 1-2 hours post-dose
- Fludrocortisone suppression test: Less commonly used
The choice between these tests depends on local expertise, patient contraindications, and institutional preference, as there is no definitive evidence favoring one over another 5, 6.