Interpret Saline Infusion Test for Primary Aldosteronism

STEP 1 — Gather Information

• Obtain post‑infusion plasma aldosterone concentration (PAC) from the saline infusion test (2 L of 0.9% saline over 4 h, recumbent or seated).
• Confirm baseline cortisol is lower than post‑infusion cortisol (for seated SIT) to exclude an ACTH effect.
• Verify patient has a positive ARR, hypertension (sustained BP >150/100 mm Hg or resistant), and has discontinued mineralocorticoid receptor antagonists for ≥4 weeks.
• Ensure no severe uncontrolled hypertension, cardiac arrhythmia, severe hypokalemia, or renal insufficiency that would contraindicate the test.

STEP 2 — Rule In / Rule Out

• If post‑infusion PAC ≤ 5 ng/dL (≤ 140 pmol/L) → rule out primary aldosteronism (PA unlikely).
• If post‑infusion PAC ≥ 10 ng/dL (≥ 280 pmol/L) → rule in primary aldosteronism (very probable PA).
• If post‑infusion PAC is between 5 ng/dL and 10 ng/dL (140–280 pmol/L) → proceed to Step 3 (indeterminate range).

STEP 3 — Classify or Stratify

• For indeterminate PAC (5–10 ng/dL), apply the cutoff of 6.8 ng/dL (190 pmol/L) that offers the best sensitivity/specificity trade‑off.
• PAC < 6.8 ng/dL → lower probability of PA (consider repeat SIT or alternative confirmatory test).
• PAC ≥ 6.8 ng/dL → higher probability of PA (proceed to subtype testing).

STEP 4 — Decide

• PAC ≤ 5 ng/dL: Exclude PA; no further confirmatory testing needed; manage hypertension conventionally.
• PAC ≥ 10 ng/dL: Diagnose PA; proceed to adrenal venous sampling (AVS) for lateralization and subtype classification.
• PAC 5–10 ng/dL:
  • If PAC < 6.8 ng/dL: Repeat SIT or perform fludrocortisone suppression test (FST) to clarify.
  • If PAC ≥ 6.8 ng/dL: Proceed to AVS for lateralization.

Clinical Guardrails / Mimics / Pitfalls

• Do not perform SIT in patients with severe uncontrolled hypertension, cardiac arrhythmia, severe hypokalemia, or renal insufficiency.
• Avoid interpreting SIT without confirming adequate sodium status and withdrawal of interfering medications (MRAs, ACE‑I/ARBs, β‑blockers, NSAIDs) for at least 2–4 weeks.
• Recumbent SIT has lower sensitivity; prefer seated SIT when available for better diagnostic accuracy.
• Do not rely solely on SIT if baseline cortisol is not suppressed (risk of false‑positive due to ACTH surge).
• Indeterminate results (5–10 ng/dL) should not be used to definitively rule in or out PA without additional testing.

Concrete Clinical Example

A 48‑year‑old patient with resistant hypertension and a positive ARR undergoes a seated saline infusion test. Post‑infusion PAC measures 7.2 ng/dL (202 pmol/L). Since the value lies between 5–10 ng/dL, the 6.8 ng/dL cutoff is applied: PAC ≥ 6.8 ng/dL indicates higher probability of PA. The clinician proceeds to adrenal venous sampling for lateralization, which later confirms unilateral aldosterone‑producing adenoma.

Source: The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2016, DOI:10.1210/jc.2015-4061