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tvpjournal.com | January/February 2016 | Today's VeTerinary PracTice canine PiTuiTary dePendenT HyPeradrenocorTicism series Peer reviewed 37 Several endocrine screening tests are available to arrive at a diagnosis of HAC, including: • Low-dose dexamethasone suppression (LDDS) • ACTH stimulation • Urine cortisol to creatinine ratio (UCCR). Additional tests may be required to differentiate PDH from other causes of hypercortisolemia, such as endogenous ACTH measurement and advanced imaging. INITIAL ENDOCRINE SCREENING Low-Dose Dexamethasone Suppression LDDS demonstrates decreased pituitary sensitivity to negative feedback from glucocorticoids, via mechanisms discussed in the frst article in this series. Indications. Most consider LDDS the screening test of choice for HAC unless the patient history suggests iatrogenic HAC, in which case ACTH stimulation is preferred. Sensitivity/Specifcity. In veterinary medicine, the reported sensitivity and specifcity of the LDDS test range from 85% to 100% and from 44% to 73%, respectively. 2-10 Test Results. Blood samples are obtained (1 ) before, (2) 4 hours after, and (3) 8 hours after dexamethasone administration (0.01 mg/kg IV). Diagnosis of HAC is based on lack of suppression of cortisol concentration 8 hours after dexamethasone administration. ACTH Stimulation ACTH stimulation assesses adrenocortical reserve. Due to greater purity and quality control, use of synthetic ACTH is recommended. Use of compounded ACTH is discouraged, especially when monitoring patients on adrenolytic agents or adrenal enzyme blockers (see Synthetic Versus Compounded ACTH, page 38). Indications. ACTH stimulation is the gold standard for diagnosis of iatrogenic HAC and spontaneous Addison's disease (hypoadrenocorticism). Diagnosis of HAC is based on fnding an elevated cortisol concentration (post ACTH administration) based on the reference range established by the laboratory. Sensitivity/Specifcity. Sensitivity of ACTH stimulation for all forms of spontaneous canine HAC ranges from 57% to 95%. In dogs with PDH, sensitivity is 80% to 83%. Specifcity ranges from 59% to 93%. 11-18 Due to its low sensitivity, it is inferior to LDDS as a screening test for spontaneous HAC. However, many clinicians still use ACTH stimulation because of its convenient study duration of 60 minutes and relative effectiveness in the clinical setting, especially when combined with abdominal ultrasound evaluation and interpreted in light of the history and physical examination. Table 3. Diagnostic Tests to Evaluate Patients with Suspected PDH TEST COMPONENTS PROCEDURES Low-Dose Dexamethasone Suppression (LDDS) Dexamethasone sodium phosphate or polyethylene glycol: 0.01–0.015 mg/kg IV a Obtain blood samples: 1. Before administration 2. 4 H after administration 3. 8 H after administration ACTH Stimulation Cosyntropin or tetracosactrin: 5 mcg/kg IV or IM Obtain blood samples: 1. Before administration 2. 60 min after administration Urine Cortisol to Creatinine Ratio (UCCR) Urine collected from dog in the morning b Have owner collect urine at home for at least 2 to 3 consecutive mornings; submit aliquot of the pooled samples to diagnostic laboratory a. Calculate dose using parent compound. b. Urine collected by the owner is less likely to be infuenced by stress; in addition, morning urine is preferred because it usually represents several hours of urine production. Notes: • Consult with your reference laboratory for specifc reference ranges. • The effect of feeding on LDDS or ACTH stimulation test results is unknown; however, feeding during these tests is not recommended. Fasting before testing is not necessary unless lipemia affects the cortisol assay results (check with your laboratory for specifc details). • In veterinary medicine, the ability of glucocorticoids, progestagens, and ketoconazole to suppress cortisol secretion is known. However, no effect on LDDS, ACTH stimulation, or UCCR has been documented in dogs treated with phenobarbital. 1,2 References 1. Foster SF, Church DB, Watson ADJ. Effect of phenobarbitone on the low-dose dexamethasone suppression test and the urinary corticoid:creatinine ratio in dogs. Aust Vet J 2000; 78:19-23. 2. Muller PB, Wolfsheimer KJ, Taboada J, et al. Effects of long-term phenobarbital treatment on the thyroid and adrenal axis and adrenal function tests in dogs. J Vet Intern Med 2000; 14:157-164. if a patient has a concurrent serious illness, postpone testing until the illness or injury has resolved or been controlled to minimize false positive test results.