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Thyroid disease is common in cats, but little is known about the biologic variability of serum thyroid hormone concentrations and its impact on diagnostic utility in either healthy cats or cats with thyroid disease. The purpose of this study was to determine the biological variation, index of individuality, and reference change values for thyroid hormones and thyroid-stimulating hormone (TSH) in clinically healthy cats. Serum samples for analysis of total thyroxine (T4), triiodothyronine (T3), free T4 by dialysis, and TSH were obtained weekly for 6 wk from 10 healthy cats, then frozen until single-batch analyzed. Data were evaluated for outliers, and we determined the CV within individual cats (CVI) and between individual cats (CVG) for each hormone and the variation between duplicates or analytical variation (CVA). The index of individuality and reference change values for each hormone were then calculated. Serum concentrations of total T4, free T4, T3, and TSH all showed greater variation between cats (CVG) than within cats (CVI). Total and free T4 had an intermediate index of individuality (1.1 and 1.2, respectively), suggesting that these hormones would be best evaluated by a combination of their population-based reference intervals and reference change values. Serum TSH concentrations had high index of individuality (1.8), suggesting this hormone would be best evaluated with reference change values rather than the population-based reference interval. Total T3 also had a high calculated index of individuality (1.8); however, T3 had high ratio of analytical variation (CVA) to within cat variation (CVI), so RCV could not be accurately calculated. This study demonstrates that clinically normal cats show considerable interindividual biological variation in serum thyroid hormone and TSH concentrations, whereas the intraindividual variability in hormone concentrations is much narrower. This suggests that for all serum thyroid hormones, but especially serum TSH and T3 concentrations, comparing individual cat's hormone results to a population-based reference interval may be misleading, especially in those with early or subclinical thyroid disease. Clinicians might improve the diagnosis of feline thyroid disease by establishing baseline concentrations of T4, free T4, T3, and TSH for individual cats (ideally when healthy) and applying reference change values to subsequent measurements.

Objective To determine if concentrations of free thyroxine (FT4) measured by semi-automated chemiluminescent immunoassay (CLIA) correspond to FT4 determined by equilibrium dialysis (ED) in hypothyroid dogs positive for thyroglobulin antibody (TGA). Animals Thirteen TGA-positive dogs classified as hypothyroid based on subnormal FT4 concentrations by ED. Methods Qualitative assessment of canine TGA was performed using an enzyme-linked immunosorbent assay. Serum total thyroxine and total triiodothyronine concentrations were measured by radioimmunoassay. Serum FT4 concentration was determined by ED, and also by semi-automated CLIA for human FT4 (FT4h) and veterinary FT4 (FT4v). Canine thyroid stimulating hormone concentration was measured by semi-automated CLIA. Results Each dog's comprehensive thyroid profile supported a diagnosis of hypothyroidism. For detection of hypothyroidism, sensitivities of CLIA for FT4h and FT4v were 62% (95% CI, 32–85%) and 75% (95% CI, 36–96%), respectively, compared to FT4 by ED. Five of 13 (38%) dogs had FT4h and 2 of 8 (25%) dogs had FT4v concentrations by CLIA that were increased or within the reference range. Percentage of false-negative test results for FT4 by CLIA compared to ED was significantly (P

Background: Determination of adrenocorticotropic hormone (ACTH) concentration is a commonly used test in the evaluation of endocrine causes of equine laminitis, but the concentration in healthy horses can be high at certain times of year, which alters the specificity of the ACTH test. Objective: To determine if circulating concentrations of ACTH, cortisol, glucose, insulin, and thyroxine vary month to month in healthy horses and in horses with equine metabolic syndrome (EMS). Animals: Nine healthy adult horses were studied on their farm/stable over the course of 1 year. After the diagnosis of EMS, 10 laminitic horses residing at the same farm/stable were also studied. Methods: Prospective study of healthy and laminitic horses. Plasma/serum samples were analyzed for concentrations of hormones and glucose. Results: ACTH was the only analyte to show a discrete seasonal pattern, with concentrations in healthy and EMS horses frequently outside of the reference range (9–35 pg/mL) in August through October. Insulin was elevated (>40 μIU/mL) in EMS horses during most months and median serum glucose was generally higher in EMS horses (100 mg/dL, range, 76–163 mg/ dL) than in controls (94 mg/dL, range, 56–110 mg/dL), but no seasonal patterns for insulin or glucose were found. Conclusions and Clinical Importance: An increased ACTH concentration in horses in late summer or autumn should be interpreted with caution. In contrast, insulin concentration is maintained within the reference range throughout the year in healthy horses, thus an increased insulin concentration at any time of year should raise suspicions of EMS, ECD, or both.

Objective – To determine if horses before undergoing anesthesia for surgical correction of colic would have lower plasma arginine vasopressin (AVP) concentrations than healthy horses undergoing anesthesia for arthroscopic surgery, and would not increase their plasma AVP concentrations in response to anesthesia and surgery. Design – Prospective clinical study. Setting – University teaching hospital. Animals – Fourteen horses with colic and 8 healthy horses. Interventions – Horses with colic underwent anesthesia and surgery for alleviation of colic, and healthy horses underwent anesthesia and surgery for arthroscopy. Measurements and Main Results – Plasma AVP was measured perioperatively in horses with colic and in healthy horses. Before anesthesia, and 30 and 60 minutes after induction, horses with colic had greater median plasma AVP concentrations than control horses (P≤0.001); thereafter during anesthesia differences in AVP concentrations between the 2 groups were not significant. In the control group, plasma AVP concentration increased during 120 minutes of anesthesia; no such increase occurred in colic horses. Conclusions – Compared with healthy horses, horses with colic had higher preanesthesia plasma AVP concentrations that did not increase further in response to anesthesia and surgery. Exogenous AVP is associated with decreased splanchnic perfusion in a variety of animal species and, therefore, could be detrimental to horses with colic. Thus, it may be inappropriate to use exogenous AVP in support of blood pressure in anesthetized horses with colic. Further studies are warranted to define appropriate indications for the use of AVP in horses with colic.

This study aimed to investigate endocrinologic test values and the response to treatment of two commonly encountered causes of endocrinopathic laminitis, equine Cushing's disease (ECD) and equine metabolic syndrome (EMS), in a veterinary practice setting. In particular, the study aimed to determine whether insulin concentration correlated to the severity of clinical laminitis in horses with EMS or ECD. Twenty-five horses were included in the study and assigned to one of three groups: ECD (n = 6), EMS (n = 10), and controls (n = 9). Blood samples were collected at an initial visit and then at regular intervals for the next 12 months. Plasma concentrations of adrenocorticotropin (ACTH), cortisol, and insulin and serum concentrations of glucose and total thyroxine (T4) were obtained. Horses with ECD had significantly higher plasma ACTH concentrations than EMS horses or controls. Horses with EMS and ECD both had significantly higher plasma insulin concentrations than control horses, which was correlated with the Obel grade of laminitis (r = 0.63). After treatment, there was a trend for a reduction in plasma ACTH concentration in horses with ECD. A program of diet and exercise for horses with EMS resulted in reductions in both plasma insulin concentrations and bodyweight, which was variable, depending on the individual. There was a significant correlation between the change in plasma insulin concentration and Obel grade of laminitis (r = 0.69). This study has highlighted the importance of baseline plasma insulin concentration as a potential indicator of the susceptibility of horses to laminitis and the response to a program of diet and exercise.

Background: Little information exists on the hypothalamic-pituitary-adrenal axis in septic foals. Hypothesis: The plasma concentrations of adrenocorticotropin (ACTH) and cortisol are expected to be higher in septic foals as compared to normal foals. The concentrations of hormones in septic foals also are expected to differ further depending upon survival. Animals: Twenty-eight control foals and 46 septic foals < 14 days of age were included in this study. Methods: Blood was collected in EDTA once from 28 normal foals born in the University of Georgia or Cornell University equine research herds and from 46 septic foals within 12 hours after admission to 1 of the 3 tertiary care referral centers involved in the study. Septic foal selection was based on a sepsis score of >11 or a positive blood culture. The control foals were age matched to the septic foals in the study. ACTH and cortisol concentrations were measured by a chemiluminescent immunoassay system. Results: Cortisol concentrations in control foals did not vary with age. Septic foals had significantly higher mean ACTH, cortisol, and ACTH/cortisol ratios than did normal foals. Within the septic foal group, 28 foals survived to discharge, and 18 were euthanized or died. The mean age was not significantly different between the septic surviving and nonsurviving foals. The mean ACTH/cortisol ratio was significantly higher in the septic nonsurviving foals as compared to the septic surviving foals. Conclusions and Clinical Importance: Septic foals had higher hormone concentrations as compared to normal foals, which is an expected endocrine response to critical illness. The increased ACTH/cortisol ratio in nonsurviving septic foals in comparison to surviving septic foals could indicate hypothalamic-pituitary-adrenal axis dysfunction at the level of the adrenal gland in critically ill septic foals.

Induction of estrus with deslorelin implants was followed by abortions in bitches that conceived during the induced estrus. Lowering the deslorelin dose and choosing a better implantation site prevented the abortions. This study investigated the hypothesis that induction of estrus with deslorelin is followed by reduced serum progesterone concentrations (SPC) during the ensuing diestrus. Assuming that reduced luteal function resulted from reduced LH secretion due to hypophyseal down-regulation of GnRH receptors, the effect of human chorionic gonadotropin (hCG) treatment on the SPC of diestrous bitches was also investigated. In Experiment 1, 10 spontaneously cycling bitches served as controls, whereas estrus was induced with deslorelin implants in 24 others. In Experiment 2, six diestrous bitches were treated with a single dose of hCG between Days 39 and 45 of diestrus. The SPC was lower in deslorelin-induced bitches from Days 35 to 56 of diestrus and hCG increased SPC during the first 24 h after treatment, followed by a dramatic decline thereafter. Although SPC recovered in pregnant bitches, it remained much lower (< or = 1 ng/mL) than in untreated, non-pregnant bitches. The suppression of progesterone secretion after hCG treatment suggested that decreased luteal activity in deslorelin-induced bitches may not be a simple consequence of down-regulation of hypophyseal GnRH receptors.

The purpose of this study was to evaluate the variation in plasma adrenocorticotropic hormone (ACTH) concentration and dexamethasone suppression test (DST) results with season, age, and sex in healthy, pony mares (n = 15)and pony stallions (n = 14) living under semiferal conditions and horse mares (n = 10) living at pasture. Plasma ACTH concentrations were measured in September 2002, and in January, May, and September 2003. DSTs were performed in January and September 2003. Plasma ACTH concentrations in September 2002 and September 2003 were similar and were significantly greater than in January and May (P .05). Seasonal changes in plasma ACTH concentration and DST results should be considered when interpreting endocrine test results.

Objective: To determine endogenous serum insulin concentration in dogs with diabetic ketoacidosis (DKA), and to compare it to endogenous serum insulin concentration in diabetic dogs with ketonuria but no acidosis (KDM), diabetic dogs with uncomplicated diabetes mellitus (DM) that did not have ketonuria or acidosis, and dogs with non-pancreatic disease (NP). Design: Prospective study. Setting: Veterinary Hospital of the University of Pennsylvania. Animals: Forty-four client-owned dogs; 20 dogs with newly diagnosed diabetes mellitus (7 dogs with DKA, 6 dogs with KDM, and 7 dogs with DM) and 24 dogs with non-pancreatic disease. Interventions: Blood and urine samples were obtained at the time of admission to the hospital. Measurements and main results: Signalment, clinical signs, physical examination findings, and concurrent disease were recorded for all dogs. Blood glucose concentration, venous blood pH, venous blood HCO3− concentration, urinalysis, and endogenous serum insulin concentration were determined in all dogs. Dogs with DKA have significantly decreased endogenous serum insulin concentrations compared to dogs with DM (P = 0.03) and dogs with non-pancreatic disease (P = 0.0002), but not compared to dogs with KDM (P = 0.2). Five of 7 dogs with DKA had detectable endogenous serum insulin concentrations, and 2 of these dogs had endogenous serum insulin concentration within the normal range. Conclusions: Diabetic dogs with ketoacidosis have significantly decreased endogenous serum insulin concentration compared to dogs with uncomplicated diabetes mellitus. However, most dogs with DKA have detectable endogenous serum insulin concentrations, and some dogs with DKA have endogenous serum insulin concentrations within the normal range.

Objective: To test the hypothesis that low-volume resuscitation with hemoglobin glutamer-200 improves hemodynamic function and tissue oxygenation, whereas arginine vasopressin resuscitation improves blood pressures more than low-volume saline or hemoglobin glutamer infusion but compromises systemic and muscle blood flow and oxygenation. Design: Randomized laboratory investigation. Setting: University research facility. Subjects: Nineteen dogs. Interventions: Dogs were instrumented to determine heart rate; arterial, central venous, pulmonary arterial, and pulmonary arterial occlusion pressures; cardiac output; and quadriceps muscle blood flow and oxygen tension (P M o 2 ). Total and plasma hemoglobin, oxygen content, lactate, pH, standard base excess, and arginine vasopressin levels were determined, and systemic oxygen delivery (Do 2 I) and extraction ratio were calculated. Measurements were made before and 30 mins following hemorrhage. Dogs were resuscitated over 60 mins with saline (8.5 mL/kg), arginine vasopressin (0.4 lU/kg bolus plus 0.08 IU·kg -1 ·min -1 ), or 1:1 diluted hemoglobin glutamer-200. Recordings were then repeated. Subsequently, animals received 30 mL/kg shed blood (60 mL·kg -1 ·hr -1 ), and recordings were repeated immediately and 1 hr later. Measurements and Main Results: Hemorrhage (∼52 mL/kg) caused characteristic changes in hemodynamic, hematologic, systemic P M o 2 , and acid-base variables. Saline resuscitation increased both Do 2 I and muscle perfusion by 42% and 51%, while arginine vasopressin treatment reduced heart rate by 31% and increased mean arterial pressure by 22% but not cardiac output, Do 2 I, or muscle blood flow, resulting in a further decrease of P M o 2 by 68% and worse metabolic acidosis. Hemoglobin glutamer-200 infusion caused systemic and pulmonary vasoconstriction, however, without deterioration of cardiac output, Do 2 I, muscle blood flow, or P M o 2 despite lack of oxygen content increase. Blood transfusion restored most variables. Conclusions: Low-volume crystalloid or hemoglobin glutamer-200 resuscitation posthemorrhage may improve (but not restore) macro- and microvascular functions and tissue oxygenation, while arginine vasopressin infusion may only improve blood pressures and result in lower overall systemic perfusion compared with low-volume saline or hemoglobin glutamer-200 treatment and worsening of anaerobic conditions in skeletal muscle.

Plasma ACTH levels have been variable in horses with a positive clinical response for therapy for equine Cushing's Disease (ECD). Therefore, our purpose was to determine the value of monitoring plasma adrenocorticotropin (ACTH) levels during treatment of equine Cushing's disease (ECD) with either cyproheptadine (n = 32) or pergolide (n = 10). First, we validated the chemiluminescent ACTH assay (specificity, precision, accuracy, intra-assay and interassay variations) and tested methods of handling the whole blood from the time of collection to when the ACTH was assayed. The sensitivity and specificity of high plasma ACTH levels for detecting ECD was determined in a retrospective study on hospitalised horses (n = 68). Surveys were sent to veterinarians who submitted equine ACTH levels that were high initially and had at least 2 ACTH samples to determine the value of monitoring ACTH levels during therapy of ECD. The ACTH chemiluminescent assay was valid. The ACTH was stable when whole blood was collected and held in plastic tubes for 8 h before separating the plasma. The sensitivity and specificity of plasma ACTH levels for detecting ECD were 84% (n = 19,95% CI 60,97) and 78% (n = 49,95% CI 63,88), respectively. Treated horses generally showed a decrease in plasma ACTH. Plasma ACTH levels may be helpful when monitoring therapy of ECD, although improvement in clinical signs should be considered most important. There were no differences between cyproheptadine and pergolide in terms of improvements in any of the clinical signs.

The present study sought to determine the spectrum of diseases associated with subnormal concentrations of serum cobalamin in cats undergoing investigation of suspected gastrointestinal problems. The solid-phase boil radioassay (RA) for cobalamin employed in the present study was immunologically specific, precise, and accurate, with a sensitivity of 15 pg/mL. The RA yielded results that strongly correlated with those obtained by bioassay (Spearmann rho = .805; P < .0001), although the absolute values were lower for the RA. Forty-nine of 80 serum samples submitted during the period of January 1996-January 1998 had cobalamin concentrations below the reference range for healthy cats (range 900-2,800 pg/mL; mean +/- SD, 1,775 +/- 535 pg/mL; n = 33). Cats with subnormal cobalamin concentrations (mean +/- SD; 384 +/- 272 pg/mL, range 3-883 pg/mL) were middle-aged or older and were presented for weight loss. diarrhea, vomiting, anorexia, and thickened intestines. Definitive diagnoses in 22 cats included inflammatory bowel disease (IBD), intestinal lymphoma, cholangiohepatitis or cholangits, and pancreatic inflammation. Serum concentrations of cobalamin were particularly low in cats with intestinal lymphoma, three-fifths of whom also had subnormal serum concentrations of folate (< 9 ng/mL). The simultaneous presence of disease in the intestines, pancreas, or hepatobiliary system in many cats made it difficult to determine the cause of subnormal cobalamin concentrations. The circulating half-life of parenteral cyanocobalamin was shorter in 2 cats with IBD (5 days) than in 4 healthy cats (12.75 days). The presence of subnormal serum concentrations of cobalamin in 49 of 80 cats evaluated suggests that the measurement of serum cobalamin may be a useful indirect indicator of enteric or pancreatic disease in cats. The rapid depletion of circulating cobalamin in cats suggests that cats may be highly susceptible to cobalamin deficiency. However, the relationship of subnormal serum cobalamin concentrations to cobalamin deficiency and the effect of cobalamin deficiency on cats remain to be determined.