What is the role of the rapid ACTH stimulation test in the workup of Addison disease?

Updated: Mar 11, 2020
  • Author: George T Griffing, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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The diagnosis of adrenocortical insufficiency rests on the assessment of the functional capacity of the adrenal cortex to synthesize cortisol. This is accomplished primarily by use of the rapid ACTH stimulation test (Cortrosyn, cosyntropin, or Synacthen). [2]

  • ACTH, through complex mechanisms, activates cholesterol esterase enzymes and leads to the release of free cholesterol from cholesterol esters. It also activates the 20,22-desmolase enzyme, which catalyzes the rate-limiting step in adrenal steroidogenesis and increases the NADPH (nicotinamide adenine dinucleotide phosphate) levels necessary for the various hydroxylation steps in steroidogenesis.

  • Within 15-30 minutes of ACTH infusion, the normal adrenal cortex releases 2-5 times its basal plasma cortisol output.

  • Although ACTH stimulation is not normally the major stimulus for aldosterone production, it increases aldosterone production to peak levels within 30 minutes. This response, however, is affected by dietary sodium intake.

  • An increase in the plasma cortisol and aldosterone levels above basal levels after ACTH injection reflects the functional integrity of the adrenal cortex.

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