Cortisol free serum,Cortisol free urine (24-hour), or Salivary Cortisol?
Can the measurement of salivary cortisol replace the measurement of cortisol free serum in the assessment of free cortisol status in ambulatory pacientes?
I like the overnight dexamethasone suppression test for screening. It is simple and cheap, and good suppression will rule out Cushing's. However, to make the diagnosis more specific, I like the salivary cortisol. The key to diagnosis of Cushing's is demonstrating the absence of diurnal variation. Serum is fine, but trying to collect blood samples at midnight is tough to do as an outpatient. Salivary cortisol is a good surrogate when drawing blood is not feasible.
The gold standard is Cortisol free urine (24-hour). Salivary cortisol in ambulatory pacientes ?salivary cortisol is influenced by some factors that are difficult to standardize in ambulatory patients - such as smoking - you should not smoke before testing because nicotine suppresses the enzyme that converts active cortisol in idle kortizon.Ne need to eat before one study also do not brush their teeth ...
Robert Steed is absolutely right, diurnal variation can be "easasily" excluded by saliva sampling, no matter that no real normalization is possible on saliva samples
The best screening test is the measurement of urinary cortisol in a 24-hour urine sample. This should be performed on three different collection samples in order to correct for incomplete urinary samples. If the urinary cortisol is elevated, an overnight dexamethasone suppression test may be indicated (J. Int Fed. Clin Chem. 6 (1994) 154-158.).
Clinical or basic science... I prefer several days of salivary cort with samples at wake-up, then every few hours to develop a response profile. Then you have more than just dichotomous "Cushings yes or no". Plasma good for binding globulins, CRH, etc. Urine good for metabolites. Really depends on what you want to know about the patient.
The diagnosis of Cushing's syndrome can be difficult. In cushing's syndrome elevated cortisol is present without the usual controlling mechanisms. Therefore the investigation of Cushing's Syndrome would involve assessing both. 1. assess whether there is elevated cortisol - a) urine free cortisol is good, b) random cortisol can be misleading, c) 9 a.m. and midnight cortisol (showing lack of diurnal variation) can be informative, d) salivary cortisol (9 am and midnight) looks promising but not used much in the UK yet. 2. Assess lack of usual control a) midnight and 9 am to assess lack of control, b) dexamethasone suppression test - 2 mg overnight.
In summary i agree with Walter Golf 24h urine cortisol to see whether there is "excess" cortisol, and overnight dexamethasone suppression to see whether cortisol responds to suppression.
The best test for screening is overnight dexamethasone suppression test (however the reference range is still controversial: 2? 3? or 5 mcg/dl?). Elevated midnight cortisol and increased free cortisol in 24h urine confirm diagnosis. On the other hand I have several dozens of patients with adrenal tumors with subclinical hypercortisolaemia in which surgery brought improvement of clinical status, despite normal urine free cortisol at the diagnosis. They all had lack of post-dexamethasone suppression (at present we use border on 3 mcg/dl, formerly 2 mcg/dl) , slightly elevated midnight cortisol and low (suppressed) morning levels of ACTH.
All have limitations but depends on clinical context (clinical index of suspicion) and initial tests
CONFIRMATION OF DIAGNOSIS:
24h UFC -
Diffculty in accurate 24 h urine collections
False negatives in those with renal impairment.
Dexamethasone Suppression tests
Overnight (1mg or 2 mg) easy to perform or 48h LDDST (gold standard)
False positives: Drugs which increase Dex metabolism eg certain anti-convulsants; Non compliance; immunoassay interference; increased CBG eg OCP
Midnight Salivary Cortisol
If appropriately low excellent exclusion
Only MS methods really suitable
No EQA schemes
When obvious no diffculty but others may be required in equivocal cases
NB: New category of subclincal autonomous glucocorticoid hypersecretion (SAGH) - we find 24 h UFC usually high normal or borderline elevated and ACTH not always suppressed
An advantage of salivary cortisol is the ease of monitoring cortisol levels over an extended period and in 'at-home' normal everyday environments. Interpretation and diagnosis of longitudinal 'profiles' is complex, and ideally includes detailed information about sleep, diet, activity, and psycho-social stress.