Use Low-Dose Corticotropin Test Only When Standard Test Unavailable
STEP 1 — Gather Information
Collect clinical features suggestive of PAI (e.g., unexplained fatigue, hypotension, hyponatremia, hyperpigmentation, salt craving) and verify whether the standard 250 µg corticotropin for stimulation testing is unavailable due to shortage.
→ If standard corticotropin is unavailable due to shortage, proceed to Step 2; otherwise, perform the standard corticotropin stimulation test.
STEP 2 — Rule In / Rule Out
Administer a low-dose (1 µg) corticotropin stimulation test (IV or IM) and measure serum cortisol at 30 or 60 minutes post‑dose.
→ If peak cortisol <500 nmol/L (18 µg/dL) (assay‑dependent), rule in PAI; if peak cortisol ≥500 nmol/L, rule out PAI.
STEP 3 — Classify or Stratify
If PAI is ruled in, order 21‑hydroxylase autoantibody testing to assess for autoimmune etiology.
→ Send serum for 21‑hydroxylase antibody assay.
STEP 4 — Decide
If PAI is confirmed, initiate glucocorticoid and mineralocorticoid replacement; if PAI is ruled out, pursue alternative diagnoses for the presenting symptoms.
→ Start hydrocortisone 15–25 mg daily in divided doses and fludrocortisone 50–100 µg daily.
Clinical Guardrails / Mimics / Pitfalls
Do not use the low‑dose test when the standard corticotropin is available; avoid relying on the low‑dose test alone in critically ill patients without corroborating ACTH; be aware of assay‑specific cortisol cutoffs and CBG‑related false‑low results; do not use this test for population‑based screening.
Concrete Clinical Example
A 45‑year‑old woman with progressive fatigue, weight loss, and salt craving has a baseline cortisol of 120 nmol/L and elevated ACTH; owing to a nationwide corticotropin shortage, a low‑dose (1 µg) test is performed, yielding a 60‑minute cortisol of 380 nmol/L (<500 nmol/L). PAI is diagnosed, and she is started on hydrocortisone 20 mg daily and fludrocortisone 100 µg daily.
Source: Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2016, DOI:10.1210/jc.2015-1710