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ACTH stimulation test

IV/IM admin of cosyntropin (250 μg), with collection of serum & measurement of cortisol at baseline & 30–60 min post stimulation.

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.




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