ACTH Rapid Stimulation Test

The hypothalamus secretes corticotrophin releasing hormone (CRH), which stimulates the pituitary to secrete ACTH. ACTH then stimulates the adrenal gland to produce cortisol. Cortisol exerts negative feedback at both the hypothalamus and the pituitary.

The ACTH (corticotropin) stimulation test is helpful in diagnosing adrenal insufficiency in those patients with equivocal levels of early morning cortisol (5-10 ug/dL). It is performed in the following manner. After obtaining a basal cortisol level, 250 ug of cosyntropin (Corticotropin 1-24 or ACTH 1-24) is given IM or IV.  Plasma samples are then drawn at 30 and 60 minutes. In normal subjects, baseline cortisol levels exceed 5 ug/dL.  Following administration of cosyntropin, plasma cortisol levels should rise at least 7 ug/dL and peak at greater than 18 ug/dL. A normal response rules out primary disorders of the adrenal gland, but does not exclude partial ACTH deficiency with impaired reserve.  

Subsequent measurement of plasma ACTH level, determines whether adrenal insufficiency is primary  (Addison's disease) or secondary. Elevated ACTH levels indicate primary adrenal insufficiency while normal or low levels indicate secondary adrenal insufficiency.  

With the increasing use of steroid replacement therapy for critically ill patients, an important issue is the crossreactivity of steroid medications with the cortisol assay performed in the hospital laboratories. The following table summarizes the degree of crossreactivity with cortisol. This type of study is accomplished by comparing cortisol levels in a serum that has been spiked with a particular steroid with the same sample that has not been spiked. 

As demonstrated in the table, treatment of patients with dexamethasone, fludrocortisone or hydrocortisone will not significantly affect cortisol measurements. 

Specimen requirement is one lavender top tube for each time period.

References

Husni H et al. Cortiso values during the standard-dose cosyntropin stimulation test: personal experience with Elecsys cortisol II assay. Front Endocrinol.2022;13:978238.

Ospina NS et al. ACTH stimulation test for the diagnosis of adrenal insufficiency: systematic review and meta-analysis. J Clin Endocrinol Metab.2016;10(12):427-434.