IN-DEPTH: ENDOCRINOLOGY IN GERIATRICS Although uncommon, overt type 2 diabetes melli-
tus also occurs, particularly in horses with PPID. In these cases, pancreatic insulin output declines due to -cell exhaustion and glycemic control is lost. Hyperglycemia can be seen in conjunction with hy- perinsulinemia or normoinsulinemia. Factors such as stress, pain, diet, and drug administration can cause hyperglycemia and must be considered when interpreting test results.
Dynamic Tests of ID
Because ID is a multifactorial condition, hyperinsu- linemia and tissue insulin resistance can occur ei- ther independently or concurrently. Dynamic tests involving administration of an oral glucose chal- lenge incorporate evaluation of the enteroinsular axis, whereas intravenous glucose challenges and the intravenous insulin tolerance test evaluate pe- ripheral tissue insulin sensitivity. To obtain a com- prehensive picture of the animal’s endocrine status, both types of tests may be performed concurrently.
Oral Sugar Test
Following a 3–8-hour fast, baseline blood insulin and glucose samples are collected, and then corn syrup (Karo® Syrup Light) is administered at a dose of 0.15 mL/kg orally using a dosing syringe. Addi- tional blood samples are collected at 60 and 90 min- utes for measurement of insulin and glucose. An insulin response 45 U/mL supports the presence of ID, as it indicates increased -cell responsiveness to glucose or decreased insulin clearance. Detec- tion of hyperglycemia, particularly in the baseline sample, indicates diabetes mellitus. Fasting can be accomplished by providing the horse with a single hay flake the night prior to testing, with testing performed the following morning.
In-Feed Oral Glucose Test
After an overnight fast, baseline blood insulin and glucose samples are collected, and then dextrose powder is administered at a dose of either 0.5 or 1.0 g/kg in nonglycemic feed. Blood is then collected 2 hours later for measurement of insulin and glucose. An insulin response 68 U/mL for 0.5 g/kg or 85 U/mL for 1.0 g/kg is supportive of ID. Glucose concentration is measured to ensure that the meal was consumed and to detect diabetes mellitus.
Insulin Tolerance Test
Horses should not be fasted prior to testing. A baseline blood glucose sample is collected, followed by administration of 0.10 IU/kg regular (soluble) insulin intravenously. A blood sample is then col- lected 30 minutes later for measurement of glucose. Failure of glucose concentration to decrease to 50% or less of the baseline value is consistent with pe- ripheral insulin resistance and decreased tissue re- sponsiveness to the effects of insulin. This test carries a small risk of inducing hypoglycemia. If this occurs, 50% dextrose solution should immedi-
176 2018 Vol. 64 AAEP PROCEEDINGS
ately be administered intravenously at a dose of 0.1–0.2 mL/kg.
Combined Glucose-Insulin Tolerance Test
Baseline blood insulin and glucose samples are col- lected, followed by concurrent administration of 150 mg/kg of dextrose and 0.1 U/kg of regular (soluble) insulin intravenously. Another sample is collected 45 minutes later for measurement of insulin and glucose. Failure of glucose concentration to return to baseline by 45 minutes or an insulin concentra- tion over 100U/mL at 45 minutes are indicative of peripheral tissue insulin resistance. As with the insulin tolerance test, there is a small risk of induc- ing hypoglycemia.
Static Tests for PPID
Measurement of resting endogenous plasma ACTH concentration is frequently used to diagnose PPID, particularly in equids with more advanced disease. This hormone is prone to rapid degradation, so proper sample handling is important. Plasma should be collected in a plastic ethylenediaminetet- raacetic acid (EDTA)-coated tube, then spun and frozen within 4 hours. Samples can be collected at any time of day and
fasting is not necessary prior to testing. When performing this test, appropriate seasonal reference ranges must be used, as ACTH concentra- tions normally increase from mid-July to mid-No- vember as part of physiological processes that alter metabolism in preparation for winter. Horses with PPID retain this circannual fluctuation in ACTH concentration; in fact, the magnitude of the fall sea- sonal rise is more pronounced in PPID- affected animals, increasing the sensitivity of this test during the fall months. During non-fall sea- sons (mid-November to mid-July), resting plasma ACTH concentrations 30 pg/mL are considered normal, concentrations between 30–50 pg/mL are equivocal, and those 50 pg/mL support the pres- ence of PPID. During the fall, these values are50 pg/mL, 50–100 pg/mL, and 100 pg/mL, respec- tively. If normal or equivocal results are obtained, yet there remains a high clinical index of suspicion for PPID, dynamic testing is recommended. False positive results can occur with severe systemic ill- ness, stress, pain, exercise, and transportation.
Dynamic Tests for PPID
Thyrotropin-Releasing Hormone Stimulation Test Melanotropes of the pars intermedia express the thyrotropin-releasing hormone (TRH) receptor, and secretion of ACTH in response to TRH administra- tion is exaggerated in PPID-affected animals. This test is performed by collecting a baseline plasma ACTH sample, followed by administration of either 0.5 mg (horses 250 kg) or 1 mg (horses 250 kg) of TRH intravenously. A second plasma sample is collected exactly 10 minutes later for measurement
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