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corticotropin-releasing hormone (CRH) stimulation test
Indications:
1) reserved for differentiating difficult cases of Cushing's disease & ectopic ACTH-secreting tumors
2) used in conjunction with high-dose dexamethasone suppression test
Specimen:
-> plasma (heparin) for ACTH*
2) serum or plasma for cortisol*
Procedure:
1) measure baseline plasma ACTH & cortisol 15 & 1 minute prior to administration of CRH
2) administer 1 ug/kg of ovine CRH IV at 0900-1200 hours
3) measure plasma ACTH & cortisol 5, 15, 30, 60 & 120 minutes after administration of CRH
4) specimens may also be drawn from inferior petrosal sinus (IPS) at 2, 5, 10 & 15 minutes after CRH administration & compared with values obtained from peripheral blood
5) procedure may be performed on an outpatient basis
* sensitivity drops & specificity increases when only cortisol response is considered
Reference interval:
1) 2-4 fold increase in mean baseline ACTH or cortisol
2) ratio of IPS/peripheral blood ACTH of > 3/1
Clinical significance:
1) pituitary Cushing's disease
a) normal or exaggerated response to CRH
b) IPS/peripheral blood ratio of > 3/1
2) ectopic ACTH-producing tumor
a) no response to CRH
b) IPS/peripheral blood ratio of < 3/1
Positive response to CRH stimulation or high dose dexamethasone suppression has 97% specificity for Cushing's disease.
A lack of response to BOTH CRH stimulation & high dose dexamethasone suppression has 100% specificity for ectopic ACTH secretion, whereas either test alone has only 64-78% negative predictive value.
ACTH concentrations peak 10-15 minutes after CRH injection. Peak values are higher in the morning than in the evening.
Serum cortisol levels peak 30-60 minutes after ACTH injection. Peak values are NOT dependent upon time of day.
Differential diagnosis:
- Cushing's disease
Related
adrenocorticotropic hormone; corticotropin; adrenocorticotropin (ACTH)
corticotropin-releasing factor; corticoliberin; CRF; corticotropin-releasing hormone (CRH)
cortisol; hydrocortisone (Cortef, Solu-Cortef, Alphaderm, Cetacort, Cortenema, Nutracort)
Cushing's syndrome; hypercortisolism; hyperadrenocorticism; pluriglandular syndrome
General
provocative clinical test
References
Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed.,
W.B. Saunders, 1995