The hypothalamus secretes corticotrophin releasing hormone (CRF), which stimulates the pituitary to secrete ACTH. ACTH then stimulates the adrenal gland to produce cortisol. Cortisol exerts negative feedback effects both at the pituitary and the hypothalamic levels. ACTH also contributes to skin pigmentation.
The following test algorithm may be useful in diagnosing adrenal insufficiency. Testing begins with the rapid ACTH test. If it is abnormal, adrenal insufficiency is diagnosed.
The rapid ACTH stimulation test is performed in the following manner. After obtaining a basal cortisol level, 250 ug of cosyntropin (ACTH 1 - 24) is given IM or IV. Plasma samples are then drawn at 30 and 60 minutes. In normal subjects, baseline 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.
Steriod |
% Crossreactivity |
Corticosterone |
2.8 |
Cortisone |
7.4 |
Dexamethasone |
0.2 |
Fludrocortisone |
1.2 |
Hydrocortisone |
0.5 |
Methylprednisolone |
20.9 |
Prednisolone |
27.0 |
Prednisone |
6.6 |
As demonstrated in the table, treatment of patients with dexamethasone, fludrocortisone or hydrocortisone will not significantly affect cortisol measurements.
Specimen requirement is one red top tube for each time period.