How high is too high????

What would you do when someone presents with an elevation in serum cortisol. The diagram beside shows some of the clinical features they may demonstrate...

• mood / sleep alterations
• acne
• moon faces
• dorsal fat pad
• cardiac hypertrophy / HTN
• central obesity
• abdominal striae
• osteoporosis
• muscle wasting / weakness
• easy bruising
• thin skin
• ulcerations and poor healing

CONFIRMING THE DIAGNOSIS

Thanks to the facilitator we discussed the limitations of isolated serum cortisol measurements including the diurnal variation of the hormone. We discussed the work-up for ? Cushing syndrome including available tests.

Urine 24 hour free cortisol: 85% + sensitive with false positives including over-collection, increased urine output and some drugs (carbemazepine and fenofibrinate). False negatives include incomplete collection or subclinical disease.

Dexamethasone 1mg supression test: 95% sensitive. False negatives of this test include estrogen treatment, drugs affecting dex metabolism (barbituates, dilantin, tegretol, rifampin) and acute or chronic illness.

Late Night Salivary Cortisol: 93% sensitive and 100% specific but not well studied

CONFIRMING THE ORIGIN (ACTH mediated?)

Once the diagnosis has been confirmed...the next step is to look at tests which help to determine the etiology of the excess cortisol state. In a broad sense (and ignoring exogenous sources) this differential includes:

ACTH excess (pituitary, ectopic ACTH and ectopic CRH) - THE MAJORITY approx80%)

ACTH suppressed (adrenal adenoma, adrenal hyperplasia, adrenal carcinoma)

This next step is easily determined by measuring the serum ACTH.

AND NOW WHAT.....

If the ACTH is suppressed - easy...look at the adrenals (CT scan)

If the ACTH is elevated you then must go on to decide whether this is pituitary-derived ACTH, ectopic ACTH or ectopic CRH production. Classically the test described for this differentiation is the High Dose (8mg) Dexamethasone Suppresion Test. This is said to be helpful because 'only' pituitary ACTH will have a positive suppression test (i.e. measured am cortisol is low after 8mg dexamethasone given the night before). The reality is that only 60-80% of pituitary ACTH excess will have a positive suppression test (cortisol suppressed) and 30% of ectopic ACTH producing states will have a positive suppression test....so you see far from perfect.

Other tests to add to your repertoire include:

• CRH stimulation test
• Vasopressin stimulation test
• Petrosal Venous Sinus Sampling
• Imaging (MRI brain and CT other....)

For complete details see "Evaluation and treatment of Cushing's syndrome" The American Journal of Medicine Vol: 118, Issue: 12, December, 2005 article. Direct LINK:

http://scholarsportal.info/cgi-bin/sciserv.pl?collection=journals&journal=00029343&issue=v118i0012&article=1340_eatocs