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Today's VeTerinary PracTice | January/February 2016 | tvpjournal.com canine PiTuiTary dePendenT HyPeradrenocorTicism series Peer reviewed 38 Urine Cortisol to Creatinine Ratio UCCR provides an integrated refection of cortisol production, adjusting for fuctuations in blood concentrations. Determination of basal UCCRs can be performed alone or in tandem with other endocrine testing. Indications. UCCR can be used as a screening test for hypercortisolemia, although a single positive result should not be overinterpreted. Adding oral dexamethasone suppression to UCCR testing has the advantage of potentially demonstrating both increased cortisol production and decreased sensitivity to glucocorticoid feedback. Sensitivity/Specifcity. When a single, random urine sample is collected in veterinary hospitals, reported sensitivity and specifcity of UCCR for diagnosis of HAC ranges from 75% to 100% and 20% to 25%, respectively. 20,21 In some dogs, there is considerable day-to-day variation in UCCR results. 22 However, in dogs with physical and biochemical changes consistent with HAC, when 2 basal UCCRs were above the cut-off level: 22 • Sensitivity was 99%; 95% confidence interval (94%–100%) • Specificity was 77%; 95% confidence interval (64%–87%). DIFFERENTIATING PDH FROM ADH: LABORATORy ANALySIS Given that PDH and adrenal dependent hyperadrenocorticism (ADH) are the most common forms of HAC, and that their treatment options and prognoses differ, it is important to recommend additional testing to determine the exact etiology of HAC. Several diagnostic modalities are commonly used to differentiate between PDH and ADH (Table 4): • Endogenous ACTH • Dexamethasone suppression • Dexamethasone suppression with UCCR. Endogenous ACTH Canine ACTH is secreted from the pituitary gland in an episodic, pulsatile fashion in both healthy dogs and those with PDH. 1 A circadian rhythm has not been convincingly demonstrated, although one study reported higher plasma concentrations of canine ACTH (cACTH) in late afternoon than in the morning. 23 Indications. Concentrations of cACTH do not differ between healthy dogs and those with PDH, and its measurement is not useful to screen for HAC. However, measurement of cACTH is the most accurate stand-alone biochemical test for differentiating PDH from an adrenocortical tumor (AT), but the sensitivity of the assay differs with methodology. Normal or elevated concentrations of cACTH are consistent with PDH, while suppressed values are consistent with ADH. Sensitivity/Specifcity. The most common problem with the cACTH assay is poor sensitivity. The largest study of cACTH in dogs with HAC used a 2-site solid-phase chemiluminescent immunometric assay (Immulite 2000 Immunoassay System for ACTH; healthcare.siemens.com) and showed excellent discrimination between PDH and AT. The likelihood of falsely low ACTH values in dogs with PDH is increased by: • Intra-assay and interassay variability (increased at lower cACTH concentrations) • Pulsatile ACTH secretion • Inappropriate sample handling allowing ACTH degradation. 23-28 Dexamethasone Suppression Dexamethasone administration in: • Normal dogs: Causes rapid and prolonged suppression of cortisol secretion • Patients with an AT: At any dosage does not suppress cortisol secretion • Dogs with PDH: 2,29 Synthetic polypeptides, such as Cortrosyn (cosyntropin) or Synacthen (tetracosactrin), contain the biologically active frst 24 amino acids of ACTH; however, their potencies have not been compared. In several studies, after administration of cosyntropin (5 mcg/kg or 250 mcg/dog IV or IM), peak cortisol concentrations occurred at 60 to 90 minutes. After administration of 5 mcg/kg IV, no difference was detected between 60- and 90-minute cortisol concentrations. 13-16 Cosyntropin can be reconstituted, divided into aliquots in plastic syringes, and frozen at -20°C for 6 months. 19 Whether tetracosactrin can be frozen has not been investigated; according to the manufacturer, store it at temperatures from 2°C to 8°C. Compounded ACTH products have been evaluated in healthy dogs. Sixty minutes after administration, cortisol concentrations were similar among 4 compounded products (2.2 U/kg IM) and cosyntropin (5 mcg/kg IV). However, at later times, cortisol concentrations varied considerably with the compounded products. 13 Synthetic Versus Compounded ACTH