What is the purpose and procedure of the saline loading test in diagnosing primary aldosteronism?

Saline Loading Test for Primary Aldosteronism

Purpose

The saline loading test (also called saline suppression test or saline infusion test) is a confirmatory test used to demonstrate autonomous aldosterone secretion that fails to suppress with sodium loading, thereby confirming the diagnosis of primary aldosteronism after a positive screening aldosterone-to-renin ratio. 1

Primary aldosteronism is defined as inappropriately high aldosterone production that is relatively autonomous and cannot be suppressed with sodium loading, distinguishing it from physiologic aldosterone secretion. 2

When to Perform the Test

• Perform confirmatory testing after a positive screening test (ARR >30 with plasma aldosterone ≥10 ng/dL) in patients with resistant hypertension, hypokalemia, adrenal incidentaloma, or family history of early-onset hypertension. 2, 1
• The test is one of several confirmatory options, including oral sodium loading with 24-hour urine aldosterone measurement or fludrocortisone suppression testing. 1

Patient Preparation

Critical preparation steps include:

• Ensure the patient is potassium-replete before testing, as hypokalemia suppresses aldosterone production and causes false-negative results. 1
• Maintain unrestricted salt intake and normal serum potassium levels during testing. 1
• Withdraw mineralocorticoid receptor antagonists at least 4 weeks before testing. 1
• When feasible, discontinue beta-blockers, centrally acting drugs, and diuretics; substitute with long-acting calcium channel blockers or alpha-receptor antagonists that minimally interfere with testing. 1
• If medications cannot be stopped, interpret results in the context of the specific medications the patient is taking. 1

Standard Procedure

The traditional protocol involves:

• Infuse 2 liters of 0.9% isotonic saline intravenously over 4 hours at a rate of 500 mL/hour. 3, 4
• Collect blood in the morning with the patient out of bed for 2 hours prior and seated for 5-15 minutes immediately before collection. 1
• Measure plasma aldosterone concentration before infusion (baseline) and at 4 hours post-infusion. 3, 4

Test Interpretation

For the standard 4-hour test:

• A plasma aldosterone concentration >140 pmol/L (approximately 5 ng/dL) after 4 hours of saline infusion confirms primary aldosteronism. 5
• More commonly used cutoff: plasma aldosterone >165 pmol/L (approximately 6 ng/dL) at 4 hours indicates autonomous aldosterone secretion. 5
• Failure of aldosterone to suppress below these thresholds despite sodium loading confirms the diagnosis. 4, 6

Important Procedural Variations

Seated vs. Recumbent Position:

• Recent evidence suggests seated saline suppression testing (SSST) is significantly more sensitive than recumbent testing, particularly for posture-responsive forms of primary aldosteronism. 5
• Seated testing detected primary aldosteronism in 96% of confirmed cases compared to only 33% with recumbent testing (P < .001). 5
• Blood should be drawn with the patient in a seated position for optimal sensitivity. 1, 5

Shortened Protocol:

• A 1-hour protocol using only 500 mL of saline has been validated with similar diagnostic performance to the standard 4-hour test. 3
• For the 1-hour test: plasma aldosterone >15 ng/dL confirms primary aldosteronism; <5 ng/dL excludes it. 3
• When 1-hour aldosterone is 5-15 ng/dL (equivocal range), use percentage suppression from baseline: <60% suppression indicates primary aldosteronism with 93.7% sensitivity and 96.7% specificity. 3

Critical Caveats and Limitations

The test has important limitations in normokalaemic patients:

• The saline infusion test shows reasonable sensitivity (91%) and specificity (90%) in hypokalaemic primary aldosteronism but fails to adequately differentiate normokalaemic primary aldosteronism from essential hypertension (sensitivity only 57%). 7
• This is problematic because hypokalemia is absent in the majority of primary aldosteronism cases and has low negative predictive value. 2, 8
• Consider alternative confirmatory tests (captopril challenge, fludrocortisone suppression) if clinical suspicion remains high despite negative saline testing in normokalaemic patients. 4

Next Steps After Positive Confirmatory Testing

• Refer patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination. 2
• Perform non-contrast CT scan of the adrenal glands followed by adrenal vein sampling to differentiate unilateral from bilateral disease. 1, 8
• Adrenal vein sampling is crucial before offering adrenalectomy, as up to 25% of patients might undergo unnecessary surgery based on CT findings alone. 1