Perform early morning serum cortisol test for central AI diagnosis
STEP 1 — Gather Information
Collect clinical history suggestive of adrenal insufficiency (fatigue, weight loss, hypotension, hyponatremia, hyperpigmentation), ensure patient is fasting and has abstained from glucocorticoids for at least 18–24 hours after the last hydrocortisone dose or longer for synthetic glucocorticoids, and note estrogen therapy that may increase cortisol‑binding globulin. Obtain a serum cortisol sample drawn between 8 and 9 AM.
STEP 2 — Rule In / Rule Out
If serum cortisol is <3 µg/dL, adrenal insufficiency is likely (rule in). If serum cortisol is >15 µg/dL, adrenal insufficiency is unlikely (rule out). If cortisol is between 3 and 15 µg/dL, proceed to an ACTH stimulation test.
STEP 3 — Classify or Stratify
Perform a low‑dose (1 µg) or standard‑dose (250 µg) ACTH stimulation test and measure cortisol at 30 and 60 minutes. A peak cortisol <18.1 µg/dL (500 nmol/L) confirms adrenal insufficiency; a peak ≥18.1 µg/dL excludes adrenal insufficiency.
STEP 4 — Decide
If adrenal insufficiency is confirmed, initiate physiologic glucocorticoid replacement (e.g., hydrocortisone 15–20 mg daily in divided doses) and provide stress‑dose education. If adrenal insufficiency is ruled out, pursue alternative diagnoses for symptoms. If results remain indeterminate, repeat testing under standardized conditions.
Clinical Guardrails / Mimics / Pitfalls
Do not use random cortisol levels; avoid testing during acute illness or stress which can falsely elevate cortisol; recognize that estrogen therapy increases total cortisol via CBG, potentially masking insufficiency; ensure adequate glucocorticoid washout period to avoid suppression; remember that low cortisol may also occur in critical illness unrelated to adrenal insufficiency.
Concrete Clinical Example
A 45‑year‑old woman with secondary amenorrhea, fatigue, and hypotension undergoes workup for suspected adrenal insufficiency. An 8 AM serum cortisol is 2.8 µg/dL (<3), prompting immediate initiation of hydrocortisone 15 mg daily and stress‑dose counseling.
Source: Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2016, doi:10.1210/jc.2016-2118