Use Morning Cortisol and ACTH as Preliminary Test for PAI
STEP 1 — Gather Information
Collect morning plasma cortisol (drawn 6–10 AM) and plasma ACTH; assess clinical signs suggestive of PAI (e.g., hypotension, hyponatremia, hyperkalemia, fatigue, weight loss, hyperpigmentation). If corticotropin stimulation test is not feasible, proceed.
STEP 2 — Rule In / Rule Out
Apply cutoff: morning cortisol ≤140 nmol/L (5 µg/dL) AND ACTH >2× upper limit of reference range (or elevated per assay). If both criteria met, rule in possible PAI; if cortisol >140 nmol/L or ACTH not elevated, rule out PAI for now and consider alternative diagnoses.
STEP 3 — Classify or Stratify
If ruled in, classify as preliminary suggestive of primary adrenal insufficiency; note that confirmatory corticotropin stimulation test should be performed when feasible. If ruled out, consider other causes of adrenal insufficiency or non-adrenal etiologies.
STEP 4 — Decide
If preliminary test suggestive, initiate stress-dose glucocorticoid therapy if patient is acutely ill or adrenal crisis suspected, and arrange for corticotropin stimulation test as soon as possible; otherwise, schedule confirmatory test and educate patient on adrenal crisis prevention.
Clinical Guardrails / Mimics / Pitfalls
Do not rely solely on this preliminary test for definitive diagnosis; avoid using in community-based screening; beware of estrogen-containing medications that raise CBG and cortisol, which may falsely normalize cortisol; remember that ACTH assays vary and a single elevated ACTH may be spurious; do not delay definitive testing when corticotropin stimulation becomes available.
Concrete Clinical Example
A 58‑year‑old woman presents with fatigue, postural hypotension, and serum sodium 128 mmol/L. Morning cortisol is 110 nmol/L (4 µg/dL) and ACTH is 85 pmol/L (reference <45 pmol/L). Corticotropin stimulation test is delayed due to equipment unavailability. Preliminary test meets criteria (cortisol ≤140 nmol/L, ACTH >2× ULN), so she is started on hydrocortisone 15 mg morning, 10 mg afternoon and referred for prompt stim test.
Source: Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2016, https://doi.org/10.1210/jc.2015-1710
TODO: consider adding scripts/calc.py for the enda-preliminary-cortisol-acth-test calculator