Cushings Syndrome
Cushings syndrome is characterised by increased cortisol production.

Investigation is carried out in 3 stages

1.Exclude exogenous glucocorticoid exposure
2.Confirm increased cortisol production
3.Establish the aetiology

Initial testing

Perform either

24 hr urine free cortisol (UFC) on at least 2 collections (in plain bottles)

(Samples analysed at Leeds using highly specific LC-MS/MS method, adult 10-147 nmol/24 hrs)

Overnight 1mg dexamethasone suppression test (DST).

NB Need to stop any oestrogen containing drugs 6/52 prior to testing as oestrogen increases CBG.

Recommended diagnostic threshold is 50 nmol/L (sensitivity > 95%) - failure to suppress suggests Cushings.

Confirm with

48 hr, 2mg/day (low dose) DST.

NB results of DST may be influenced by variable absorption and metabolism of dexamethasone.

Note increased clearance of dexamethasone medicated through induction of CYP3A4 by phenytoin, phenobarbitone, carbamazapine, rifampicin and alcohol.

Dexamethasone may be measured to ensure adequate amounts in the plasma  (>5.6 nmol/L).



References

Nieman et al. J Clin Endocrinol Metab, 2008, 93(5), 1526-1540. The Diagnosis of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline.