Cushing's syndrome laboratory findings
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When Cushing's syndrome is suspected, either a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH level) or a 24-hour urinary measurement for cortisol offer equal detection rates. Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, high cortisol would be indicative of Cushing's syndrome. A novel approach, recently cleared by the US FDA, is sampling cortisol in saliva over 24 hours, which may be equally sensitive, as late night levels of salivary cortisol are high in Cushingoid patients. Other pituitary hormone levels may need to be ascertained.
The laboratory findings associated with Cushing's syndrome are:
Diagnosis of hypercortisolism
Hypercortisolism can be established by any of the following tests:
- 24-hour urine cortisol
- Midnight salivary cortisol
- Low dose dexamethasone suppression test; high cortisol level after the dexamethasone test is suggestive of hypercortisolism.
Tests to establish the cause of hypercortisolism
- Measure Adrenocorticotrophic hormone (ACTH) levels.
- If ACTH is less than 5 pg/dl, perform an adrenal CT scan or MRI to search for possible adrenal causes.
- If ACTH is higher than 5 pg/dl Corticotrophic releasing hormone (CRH) test also called desmopressin test can be used to differentiate between Cushing disease and ectopic ACTH secretion.
Approach to the diagnosis of Cushing's syndrome
|24 hr urine cortisol or midnight salivary cortisol shows hypercortisolism|
|Measure serum ACTH|
|ACTH independent Cushing syndrome||Corticotrophic releasing hormone (CRH) (desmopressin) test||ACTH dependent Cushing syndrome|
|Adrenal CT/MRI||Evaluate as ACTH independent Cushing syndrome if NO ACTH response||Evaluate as ACTH dependent Cushing syndrome if there is an ACTH response||Corticotrophic releasing hormone (CRH) (desmopressin) AND high dose dexamethasone suppression test OR MRI brain|
|Adequate stimulation and suppression OR pituitarty mass >6mm||Mixed/negative response OR no pituitary mass OR mass < 6mm|
|Cushing disease||Inferior petrosal sinus sampling|
|Cushing disease if step-up in ACTH||Ectopic ACTH secretion if no step-up in ACTH|
Other Laboratory findings
- Raff H, Findling JW. A physiologic approach to the diagnosis of the Cushing's syndrome. Ann Intern Med 2003;138:980-91. PMID 12809455