Test for PAI in Acutely Ill Patients with Suggestive Symptoms

STEP 1 — Gather Information

Collect history of acute illness, vital signs (BP, HR, temp), physical exam for volume depletion, hyperpigmentation; order basic labs: serum Na+, K+, glucose, cortisol, ACTH if available.
If any suggestive symptom is present, advance to Step 2; otherwise, consider alternative diagnoses and do not pursue PAI testing.

STEP 2 — Rule In / Rule Out

Assess for presence of unexplained volume depletion, hypotension, hyponatremia, hyperkalemia, fever, abdominal pain, hyperpigmentation, or hypoglycemia (especially in children).
If at least one is present, proceed to Step 3; if none are present, consider other diagnoses and do not test for PAI.

STEP 3 — Classify or Stratify

Determine feasibility of short corticotropin stimulation test (250 µg ACTH).
If feasible, order the test; if not feasible, obtain morning plasma cortisol and ACTH as initial screening.

STEP 4 — Decide

Interpret results: short test peak cortisol <500 nmol/L (18 µg/dL) indicates PAI; morning cortisol <140 nmol/L (5 µg/dL) with ACTH >2× ULN suggests PAI.
If PAI confirmed, initiate stress-dose hydrocortisone and arrange definitive replacement; if not confirmed, exclude PAI and investigate other causes.

Clinical Guardrails / Mimics / Pitfalls

Do not delay empiric stress-dose hydrocortisone in suspected adrenal crisis while awaiting test results; avoid using random cortisol to rule out PAI; be cautious interpreting cortisol in pregnancy, estrogen therapy, or CBG deficiency; do not use dexamethasone for PAI treatment due to lack of mineralocorticoid activity and Cushingoid risk; do not rely solely on symptoms without biochemical confirmation.

Concrete Clinical Example

A 4‑year‑old with fever, vomiting, hypotension, hyponatremia, hyperkalemia, and hypoglycemia. Morning cortisol 80 nmol/L, ACTH 120 pmol/L (elevated). Short ACTH stim test: peak cortisol 300 nmol/L at 60 min (<500). Diagnosis PAI. Patient received IV hydrocortisone 50 mg/m² bolus then continuous infusion, with clinical improvement.

Source: Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2016, DOI:10.1210/jc.2015-1710