Measurement of the urinary cortisol/creatinine ratio (UCCR) is based on the principle that if renal function is normal, the excretion of urinary creatinine remains fairly constant. Therefore, the cortisol/creatinine ratio eliminates the bias that the urine volume would have if the amount of cortisol in the urine were to be considered as an absolute value. In addition, regardless of the urine concentration or dilution, the ratio reflects the blood cortisol levels in the 8 hours prior to collection without the rapid fluctuations that typically occur in the blood due to the pulsatile release of this hormone.
To confirm the presence of high cortisol levels in the blood, two urine samples taken in the morning must be analysed for two consecutive days. The urine sample must be collected from the stream of urine and in the absence of stress. For this reason the urine sample must be collected by the pet’s owner at home. The sensitivity of the test varies from 75% to 100%. The difference between these values is mainly due to the different methods used to measure urinary cortisol and creatinine, to the urine sampling technique and to the time of sampling. The UCCR in a healthy dog is normally between 0.4-4.8x10-6, however the upper cut-off limit, which is set at 10x10-6, can vary from one laboratory to another. The specificity of the test differs widely, depending on the studies used, and values from 20-25% to 77% and 85% have been reported. The UCCR is considered a good screening test in view of its high sensitivity, the short time required to perform it and its ease of execution.
Should an additional dynamic test be considered necessary, on day 2, after collecting the urine sample, dexamethasone should be administered orally by the owner at a dose of 0.1 mg/kg every 8 hours. On the morning of day 3 an additional urine sample is taken. This is the high-dose dexamethasone suppression test (urinary HDDST), which can detect changes in cortisol concentrations in the urine rather than in the blood. Dexamethasone is a potent synthetic corticosteroid, used in this test because it does not cross-react with the methodology used for the measurement of blood cortisol. This part of the test enables ACTH-dependent hypercortisolism to be distinguished from the ACTH-independent form. If the value of the UCCR of the third sample is less than 50% of the mean values of the two samples taken in the two previous days, the animal either suffers from pituitary-dependent hyperadrenocorticism or is not suffering from hypercortisolism; in this latter case the high concentrations of urinary cortisol may be related to stress or other diseases. In contrast, if the third value is not suppressed by more than 50% of the average of the previous two values, the result is indicative of non-suppressible high blood cortisol levels, with a 50% chance of the animal having pituitary-dependent hyperadrenocorticism and a 50% chance of it having a cortisol-secreting adrenal tumour.