Confirm PAI Diagnosis with Corticotropin Stimulation Test
STEP 1 — Gather Information
Collect history of suggestive symptoms (fatigue, weight loss, hypotension, hyponatremia, hyperkalemia, fever, abdominal pain, hyperpigmentation, hypoglycemia in children), vital signs, baseline morning cortisol and ACTH if available, review recent glucocorticoid use, and assess for acute adrenal crisis or contraindications to testing. If the patient is hemodynamically unstable or requires immediate steroids, proceed to emergency treatment; otherwise, move to stimulation testing.
STEP 2 — Rule In / Rule Out
Is the patient’s condition stable enough to safely undergo corticotropin stimulation testing without delaying life‑saving glucocorticoids?
- Yes: Proceed to administer the standard 250 µg cosyntropin (or ACTH) stimulation test.
- No: Give immediate stress‑dose intravenous hydrocortisone (100 mg) and postpone confirmatory testing until the patient is stabilized.
STEP 3 — Classify or Stratify
Measure serum cortisol 30–60 minutes post‑stimulation.
- Peak cortisol < 500 nmol/L (18 µg/dL) (assay‑specific cutoff may apply) → consistent with primary adrenal insufficiency.
- Peak cortisol ≥ 500 nmol/L → makes PAI unlikely; consider alternative diagnoses.
STEP 4 — Decide
If the stimulation test confirms PAI (low cortisol), initiate glucocorticoid replacement (hydrocortisone 15–25 mg/day in divided doses) and assess for mineralocorticoid deficiency; if normal, investigate other causes of symptoms and avoid unnecessary steroid therapy.
Clinical Guardrails / Mimics / Pitfalls
Do not test in patients currently on exogenous glucocorticoids, as this suppresses the response; avoid reliance on basal cortisol alone; recognize that estrogen, pregnancy, critical illness, or CBG abnormalities can alter cortisol interpretation and may require adjusted cutoffs; the low‑dose (1 µg) test is reserved for corticotropin shortage and is not preferred for PAI confirmation; never delay emergency hydrocortisone in suspected adrenal crisis pending test results.
Concrete Clinical Example
A 48‑year‑old woman reports 3 months of progressive fatigue, 4 kg weight loss, orthostatic hypotension, and new hyperpigmentation of palmar creases. Morning cortisol is 190 nmol/L (borderline) and ACTH is mildly elevated. She is afebrile, hemodynamically stable, and not on steroids. A standard 250 µg cosyntropin test yields a peak cortisol of 340 nmol/L at 60 minutes (< 500 nmol/L cutoff). This confirms PAI; she is started on hydrocortisone 20 mg daily (10 mg AM, 5 mg noon, 5 mg early evening) and fludrocortisone 100 µg daily, with education on stress dosing and a steroid emergency card.
Source: Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2016, DOI:10.1210/jc.2015-1710