Baseline Cortisol — The Starting Point Before Stimulation
A morning blood draw sets the reference cortisol level for comparison.
- 6–23: Normal AM cortisol (mcg/dL, wide morning range)
- 8 AM: Sample timing (cortisol peaks diurnally)
- Serum: Draw type (single venous blood tube)
- Reference: Purpose (compares to post-stim value)
Why a baseline draw matters
Establishes each patient's own starting point for comparison.
Diurnal cortisol rhythm
Cortisol naturally peaks near waking, so timing matters.
Cosyntropin — Synthetic ACTH as a Direct Adrenal Challenge
Cosyntropin mimics ACTH, directly asking the adrenal cortex to respond.
- 250 mcg: Standard dose (IV or IM injection)
- ACTH 1–24: Drug identity (synthetic fragment of ACTH)
- Minutes: Onset (rapid adrenal receptor binding)
- 30 & 60 min: Sampling (post-injection cortisol draws)
What cosyntropin does
Synthetic ACTH binds adrenal receptors, bypassing the pituitary.
Why bypass the pituitary
Isolates the adrenal gland itself as the test subject.
Healthy Adrenal Cortex — A Vigorous Cortisol Surge
Intact cortical cells answer ACTH with a strong, rapid cortisol rise.
- >18: Peak cortisol (mcg/dL typical pass threshold)
- 30–60 min: Time to peak (post-cosyntropin)
- >7: Rise magnitude (mcg/dL above baseline)
- Intact: Cell status (zona fasciculata fully functional)
Cellular machinery at work
Steroidogenic cells convert cholesterol to cortisol on demand.
Reading a normal result
A brisk rise proves the gland can still respond.
Addison's Disease — A Gland That Cannot Answer the Call
Autoimmune-destroyed cortex tissue cannot make more cortisol, ACTH or not.
- <18: Peak cortisol (mcg/dL — blunted response)
- Autoimmune: Common cause (~80% of primary cases)
- >90%: Cortex destroyed (before symptoms typically appear)
- High: ACTH level (pituitary compensates, gland can't)
Why stimulation fails
Destroyed tissue simply has no cells left to respond.
Primary vs secondary clue
High baseline ACTH plus no response points to the gland.
Diagnostic Outcome — Confirming Primary Adrenal Insufficiency
An inadequate cortisol rise confirms the problem sits at the adrenal gland.
- ≥18 mcg/dL: Pass threshold (peak cortisol, common cutoff)
- Addison's: Fail result (primary adrenal insufficiency)
- Hormone Rx: Next step (lifelong glucocorticoid replacement)
- High: Test accuracy (gold-standard adrenal function test)
Interpreting the final result
Peak below threshold means the gland itself has failed.
What happens next
Confirmed patients start lifelong glucocorticoid replacement therapy.