Supra-physiological dose stimulates the pituitary & releases cortisol from the adrenal cortex, as long as the adrenal cortex has a functional reserve.
Factors
affecting ACTH stim test interpretation:
- Falsely negative or normal in mild disease or disease of recent onset.
- Most common- false-positive test is seen in recent use of corticosteroids
- Exogenous steroids lead to both baselines &adrenal responsiveness to cosyntropin.
- Propofol impairs adrenal steroidogenesis
- Midazolam, morphine, and fentanyl blunt the HPA axis, thereby interfering with corticosteroid metabolism.
- Metyrapone, etomidate, ketoconazole, megesterol, & mitotate interfere with cosyntropin function.
- Rifampin & phenytoin may increase cortisol metabolism.
In females, response to ACTH may be affected OCs which increase CBG levels.
- Salivary cortisol response can be useful as their measurement is a surrogate for serum free cortisol & are not affected by OCs
- Opioid receptors are present in the pituitary gland & hypothalamus, & opioids may impact HPA function.
- Nenke et al studied 17 pts treated with long-term opioids. Five of the 17 (29%) were found to have evidence of AI, with cortisol levels of <5 μg/dL.