Cortisol production rates in subjects with suspected Cushing's syndrome: Assessment by stable isotope dilution methodology and comparison to other diagnostic methods

It can be difficult to establish the diagnosis of Gushing's Syndrome (CS) i n patients with mild or nonspecific clinical and biochemical findings, beca use available diagnostic tests have limited predictive values. We hypothesi zed that measurement of 24-h cortisol produc tion rates (CPRs) might be a m ore sensitive indicator of CS in such patients. We measured CPRs in 28 pati ents with suspected CS (but equivocal biochemical findings) and in 22 healt hy control subjects, by infusing tracer amounts of deuterated cortisol, wit h simultaneous measurements of 24-h urine free cortisol (UFC) levels; and w e frequently sampled serum cortisol levels. CPRs were calculated from the r atio of isotopic enrichment to isotopic dilution of cortisol measured by ga s chromatography-negative ion chemical ionization mass spectrometry. Nine o f the patients proved to have CS by surgery (CS-Yes), whereas 19 patients w ere determined not to have CS by biochemical testing (GS-No). Mean 24-h UFC s, nocturnal serum cortisol levels, and CPRs were higher in CS-Yes, compare d with CS-No and normal subjects. However, one CS-Yes patient had a normal 24-h UFC, two had normal nocturnal serum cortisol levels, and two had norma l 24-h CPRs. There was extensive overlap in all of the biochemical paramete rs between the CS-Yes and the CS-No groups. Thus, measurement of CPR does n ot seem to offer any diagnostic advantage over available tests for the diag nosis of CS. Patients with proven CS can have normal UFC levels, normal CPR s, or normal nocturnal cortisol levels, whereas patients not thought to hav e CS may have elevated levels of any one or more these parameters.