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Background Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA. Objective Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism. Animals Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled. Methods cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA. Results cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01-0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0-2.1; median 1.3 μg/dL) compared to those with normal cTSH (T4 range 0.5-3.4, median 1.4 μg/dL; P=0.69) and controls (T4 range 0.3-3.8, median 1.8 μg/dL; P=0.35). After starting treatment, cTSH normalized after 2-4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation. Conclusions and Clinical Relevance Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH. [ABSTRACT FROM AUTHOR]

Background Effects and duration of commonly used protocols for cobalamin (Cbl) supplementation on cellular Cbl deficiency have not been determined in hypocobalaminemic cats. Hypothesis/Objectives To evaluate effect of Cbl supplementation on clinical signs, serum and urine methylmalonic acid (MMA) concentrations over 16 weeks. Animals Twenty client-owned hypocobalaminemic cats with enteropathy. Methods Prospective study. Serum Cbl and serum and urine MMA concentrations were determined prospectively in cats at enrollment (t0), immediately before (t6), and 4 (t10) and 10 weeks (t16) after 6th Cbl injection (250 μg, IM q 7 days). Clinical signs severity (activity, appetite, vomiting, diarrhea, body weight) graded at each time point and expressed as clinical disease activity score. Results Clinical disease activity score decreased during supplementation and increased after treatment discontinuation. Median serum Cbl concentration increased significantly from t0 (111 pmol/L, range 111-212) to t6 (2,332.5 pmol/L, range 123-22,730) ( P < 0.01). Values at t10 were 610.5 pmol/L (range, 111-2,527) and 180.5 pmol/L (range, 111-2,262) at t16 ( P < 0.01). Median baseline serum MMA concentration (372 μmol/L, range 0.39-147,000) decreased significantly to 1.62 μmol/L (range, 0.18-806) at t6 ( P < 0.01) and gradually increased to 5.34 μmol/L (range, 0.13-1,730) at t10 and 189 μmol/L (range, 0.4-983) at t16. Similar, nonsignificant, pattern observed for urine MMA concentration. Serum and urine MMA concentrations had not normalized in 12 and 6 cats, respectively, at t6. Conclusion and Clinical Importance The Cbl supplementation protocol used here did not lead to complete normalization of cellular Cbl deficiency in all examined cats, and biochemical improvements were transient. [ABSTRACT FROM AUTHOR]

Background Feline pancreas-specific lipase (Spec fPL) is considered a useful test for the antemortem diagnosis of pancreatitis in cats. A recent study found good agreement between the results of the Spec fPL and catalytic 1,2- o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester ( DGGR) lipase assay. Prospective studies evaluating their sensitivity and specificity are lacking. Objectives To compare the results of the Spec fPL and the DGGR assays with a standardized histologic assessment of the pancreas. Animals Sixty client-owned cats presented for necropsy. Methods Prospective study: Spec fPL concentrations and serum DGGR lipase activity were measured from the same blood sample. The pancreas was removed within 3 hours after euthanasia; serial transverse sections were made every 0.5 cm throughout the entire pancreas and reviewed using a histologic grading scheme. Sensitivity and specificity for the Spec fPL and DGGR assay results were determined. Results The sensitivity and specificity for the Spec fPL assay (cutoff value ≥5.4 μg/L) was 42.1 [95% confidence interval (95% CI), 29.4-55.9%] and 100% (95% CI, 31.0-100.0%). The sensitivity and specificity for the DGGR assay (cutoff value >26 U/L) was 36.8 (95% CI, 24.7-50.7%) and 100% (95% CI, 31.0-100.0%). When lymphocytic inflammation up to 10% of a section was considered normal, the sensitivity and specificity for Spec fPL assay (cutoff value ≥5.4 μg/L) was 61.1 (95% CI, 36.1-81.7%) and 69.0% (95% CI, 52.8-81.9%) and the sensitivity and specificity for the DGGR assay (cutoff value >26 U/L) was 66.7 (95% CI, 41.2-85.6%) and 78.6% (95% CI, 62.8-89.2%). Conclusions and Clinical Importance Both lipase assays performed similarly well, but their agreement with histologic pancreatic inflammation was limited. [ABSTRACT FROM AUTHOR]

Background Exenatide extended release ( ER) is a glucagon-like peptide-1 analogue that increases insulin secretion, inhibits glucagon secretion and induces satiation in humans with type 2 diabetes mellitus. The use of exenatide ER is safe and stimulates insulin secretion in healthy cats. Objectives The objective of this study is to assess the safety of exenatide ER and its effect on body weight, remission and metabolic control in newly diagnosed diabetic cats receiving insulin and a low-carbohydrate diet. Animals Thirty client-owned cats. Methods Prospective placebo-controlled clinical trial. Cats were treated with exenatide ER or 0.9% saline, administered SC, once weekly. Both groups received insulin glargine and a low-carbohydrate diet. Exenatide ER was administered for 16 weeks, or in cats that achieved remission it was given for 4 weeks after discontinuing insulin treatment. Nonparametric tests were used for statistical analysis. Results Cats in the exenatide ER and placebo groups had transient adverse signs including decreased appetite (60% vs. 20%, respectively, P = .06) and vomiting (53% vs. 40%, respectively, P = .715). Body weight increased significantly in the placebo group ( P = .002), but not in cats receiving exenatide ER. Cats on exenatide ER achieved remission or good metabolic control in 40% or 89%, respectively, whereas in control cats percentages were 20% or 58% ( P = .427 and P = .178, respectively). Conclusion and clinical importance Exenatide ER is safe in diabetic cats and does not result in weight gain. Our pilot study suggests that, should there be an additional clinically relevant beneficial effect of exenatide ER in insulin-treated cats on rate of remission and good metabolic control, it would likely approximate 20% and 30%, respectively. [ABSTRACT FROM AUTHOR]

Background The ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice. Objectives The objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs. Animals Twenty-two healthy dogs, 10 dogs with suspected hypoadrenocorticism ( HA) and 15 dogs with suspected hyperadrenocorticism ( HC). Methods Prospective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 μg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation. Results Peak cortisol concentrations were reached after 2-4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 μg/dL in all healthy dogs and >5 μg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol-increase above the detection-limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours. Conclusions and Clinical Importance The depot formulation can be used in place of the short-acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA-suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time. [ABSTRACT FROM AUTHOR]

Background The adrenocorticotropic hormone ( ACTH) stimulation test is the gold standard for diagnosing hypoadrenocorticism ( HA) in dogs. However, problems with the availability of synthetic ACTH (tetracosactrin/cosyntropin) and increased costs have prompted the need for alternative methods. Objectives To prospectively evaluate the cortisol-to- ACTH ratio ( CAR) as a screening test for diagnosing canine HA. Animals Twenty three dogs with newly diagnosed HA; 79 dogs with diseases mimicking HA; 30 healthy dogs. Methods Plasma ACTH and baseline cortisol concentrations were measured before IV administration of 5 μg/kg ACTH in all dogs. CAR was calculated and the diagnostic performance of ACTH, baseline cortisol, CAR and sodium-to-potassium ratios ( SPRs) was assessed based on receiver operating characteristics ( ROC) curves calculating the area under the ROC curve. Results The CAR was significantly lower in dogs with HA compared to that in healthy dogs and in those with diseases mimicking HA ( P < .0001). There was an overlap between HA dogs and those with HA mimicking diseases, but CAR still was the best parameter for diagnosing HA ( ROC AUC 0.998), followed by the ACTH concentration ( ROC AUC 0.97), baseline cortisol concentration ( ROC AUC 0.96), and SPR ( ROC AUC 0.86). With a CAR of >0.01 the diagnostic sensitivity and specificity were 100% and 99%, respectively. Conclusion and Clinical Importance Calculation of the CAR is a useful screening test for diagnosing primary HA. As a consequence of the observed overlap between the groups, however, misdiagnosis cannot be completely excluded. Moreover, additional studies are needed to evaluate the diagnostic reliability of CAR in more dogs with secondary HA. [ABSTRACT FROM AUTHOR]

Background Gastric acid suppressants frequently are used in cats with acid-related gastric disorders. However, it is not known if these drugs effectively increase intragastric pH in cats. Objectives To examine the effects of PO administered ranitidine and omeprazole on intragastric pH in cats and to compare the efficacy of once-daily versus twice-daily dosage regimens for omeprazole. Animals Eight domestic shorthair cats. Methods Using a randomized 4-way cross-over design, cats were given enteric-coated omeprazole granules (1.1-1.3 mg/kg q24h and q12h), ranitidine (1.5-2.3 mg/kg q12h), and placebo. Intragastric pH was monitored continuously for 96 hours using the Bravo™ system[Bravo™ pH ], starting on day 4 of treatment, followed by a median washout period of 12 days. Mean percentage of time pH was ≥3 and ≥4 was compared among groups using repeated measures ANOVA. Results Mean ± SD percentage of time intragastric pH was ≥3 and ≥4 was 67.0 ± 24.0% and 54.6 ± 26.4% for twice-daily omeprazole, 24.4 ± 22.8% and 16.8 ± 19.3% for once-daily omeprazole, 16.5 ± 9.0% and 9.6 ± 5.9% for ranitidine, and 9.4 ± 8.0% and 7.0 ± 6.6% for placebo administration. Twice-daily omeprazole treatment significantly increased intragastric pH, whereas pH after once-daily omeprazole and ranitidine treatments did not differ from that of placebo-treated cats. Conclusion and Clinical Importance Only twice-daily PO administered omeprazole significantly suppressed gastric acidity in healthy cats, whereas once-daily omeprazole and standard dosages of ranitidine were not effective acid suppressants in cats. [ABSTRACT FROM AUTHOR]

Background Diagnosis of pheochromocytoma ( PC) is based on a combination of clinical suspicion, finding an adrenal mass, increased plasma, and urine concentrations of catecholamine metabolites and is finally confirmed with histopathology. In human medicine, it is controversial whether biochemically testing plasma is superior to testing urine. Objectives To measure urinary and plasma catecholamines and metanephrines in healthy dogs, dogs with PC, hypercortisolism (HC), and nonadrenal diseases (NAD) and to determine the test with the best diagnostic performance for dogs with PC. Animals Seven PC dogs, 10 dogs with HC, 14 dogs with NAD, 10 healthy dogs. Methods Prospective diagnostic clinical study. Urine and heparin plasma samples were collected and stored at −80°C before analysis using high-pressure liquid chromatography ( HPLC) coupled to electrochemical detection or tandem mass spectrometry were performed. Urinary variables were expressed as ratios to urinary creatinine concentration. Results Dogs with PC had significantly higher urinary normetanephrine and metanephrine : creatinine ratios and significantly higher plasma-total and free normetanephrine and plasma-free metanephrine concentrations compared to the 3 other groups. There were no overlapping results of urinary normetanephrine concentrations between PC and all other groups, and only one PC dog with a plasma normetanephrine concentration in the range of the dogs with HC and NAD disease. Performances of total and free plasma variables were similar. Overlap of epinephrine and norepinephrine results between the groups was large with both urine and plasma. Conclusion and clinical importance Measurement of normetanephrine is the preferred biochemical test for PC and urine was superior to plasma. [ABSTRACT FROM AUTHOR]

Background Cats with diabetes mellitus can have subclinical pancreatitis but prospective studies to confirm this are lacking. Metabolic control of diabetic cats with pancreatitis is difficult. Hypothesis Subclinical pancreatitis occurs in diabetic cats at the time diabetes is diagnosed or might develop during the follow-up period, hampering diabetic remission. Animals Thirty cats with newly diagnosed diabetes without clinical signs of pancreatitis on admission. Methods Prospective study. On admission and 2 and 6 months later, serum Spec fPL and DGGR-lipase were measured and the pancreas underwent ultrasonographic examination. Pancreatitis was suspected if serum markers were increased or ≥2 ultrasonographic abnormalities were detected. Cats were treated with insulin glargine and diabetic remission was defined as euglycemia ≥4 weeks after discontinuation of insulin. Nonparametric statistical tests were used for analysis. Results Subclinical pancreatitis at the time of diagnosis was suspected in 33, 50, and 31% of cats based on Spec fPL, DGGR-lipase and ultrasonography, respectively; and in 60% when diagnostic criteria were combined. During the follow-up period, suspected pancreatitis developed in additional 17-30% cats. Only 1 cat had transient clinical signs compatible with pancreatitis. Seventeen of the 30 cats (57%) achieved remission. Frequency of abnormal Spec fPL and DGGR-lipase and abnormal ultrasonographic findings did not differ in cats achieving remission and those who did not. Cats achieving remission had significantly lower Spec fPL at 2 months ( P < .001). Conclusions and Clinical Importance Based on laboratory and ultrasonographic measurements, many cats with diabetes might have pancreatitis, although without clinical signs. Cats with high Spec fPL might have a reduced chance of diabetic remission; however, this topic needs further studies in large cohorts of diabetic cats. [ABSTRACT FROM AUTHOR]

Background Remission occurs in 10-50% of cats with diabetes mellitus ( DM). It is assumed that intensive treatment improves β-cell function and increases remission rates. Hypothesis Initial intravenous infusion of insulin that achieves tight glycemic control decreases subsequent insulin requirements and increases remission rate in diabetic cats. Animals Thirty cats with newly diagnosed DM. Methods Prospective study. Cats were randomly assigned to one of 2 groups. Cats in group 1 (n = 15) received intravenous infusion of insulin with the goal of maintaining blood glucose concentrations at 90-180 mg/dL, for 6 days. Cats in group 2 (n = 15) received subcutaneous injections of insulin glargine (cats ≤4 kg: 0.5-1.0 IU, q12h; >4 kg 1.5-2.0 IU, q12h), for 6 days. Thereafter, all cats were treated with subcutaneous injections of insulin glargine and followed up for 6 months. Cats were considered in remission when euglycemia occurred for ≥4 weeks without the administration of insulin. Nonparametric tests were used for statistical analysis. Results In groups 1 and 2, remission was achieved in 10/15 and in 7/14 cats ( P = .46), and good metabolic control was achieved in 3/5 and in 1/7 cats ( P = .22), respectively. Overall, good metabolic control or remission occurred in 13/15 cats of group 1 and in 8/14 cats of group 2. In group 1, the median insulin dosage given during the 6-month follow-up was significantly lower than in group 2 (group 1: 0.32 IU/kg/day, group 2: 0.51 IU/kg/day; P = .013). Conclusions and Clinical Importance Initial intravenous infusion of insulin for tight glycemic control in cats with DM decreases insulin requirements during the subsequent 6 months. [ABSTRACT FROM AUTHOR]

Background Although gastroesophageal reflux ( GER) often is assumed to be causative for upper gastrointestinal and respiratory signs in dogs, no attempts have been made to verify this assumption. Objectives To monitor esophageal pH with the Bravo pH system in healthy dogs and client-owned dogs displaying signs commonly attributed to GER. Animals Seven healthy and 22 client-owned dogs. Methods After routine esophagogastroduodenoscopy, radiotelemetric pH capsules were placed in distal esophagus for continuous pH recording. Reflux was defined as single pH measurement <4. At discharge, owners were instructed to press individually predefined clinical sign-buttons on the receiver whenever indicated. Results between groups were compared using Mann-Whitney U-test. Results The median (range) number of refluxes in client-owned and healthy dogs, respectively, was 17 (1-205) and 10 (1-65), the number of refluxes >5 minutes in duration was 1 (0-14), and 1 (0-4), duration of longest reflux (min) was 10 (0-65) and 8 (0-27), and fractional time pH <4 (%) was 0.76% (0.01-6.28), and 0.3% (0-3.1). No differences were found between groups. The median of 7 (1-35) clinical sign-button pushes were recorded in 21 dogs. Median of 12.5% (2.8% [1/35]-50% [2/4]) reflux-positive clinical sign-button pushes was found in 10 dogs with reflux-positive pushes. Five (22.7%) dogs had increased esophageal acid exposure, and mild esophagitis was noted in 1 dog. Conclusion and Clinical Importance Despite evidence of increased GER in some dogs, the clinical sign-reflux association remained poor. Future investigation should focus on dogs with esophagitis. [ABSTRACT FROM AUTHOR]

Background Determination of the urinary corticoid-to-creatinine ratio ( UCCR) is an important screening test in the diagnosis of hypercortisolism ( HC). However, urinary cortisol metabolites interfere with cortisol measurement in immunoassays, leading to decreased specificity. Gas chromatography-mass spectrometry ( GC- MS) is considered the gold standard for steroid hormone analysis, because it provides a high level of selectivity and accuracy. Objectives To prospectively compare the UCCR of healthy dogs and dogs with HC determined by 5 different immunoassays and by GC- MS and to evaluate the influence of veterinary care on UCCR. Animals Twenty healthy dogs; 18 dogs with HC. Methods Urine was collected in the hospital and again after 6 days at home. Three chemiluminescence immunoassays (Access 2, Beckmann; Immulite 2000, DPC Siemens, with and without trichloromethane extraction) and 2 RIAs (Utrecht in house; Access Beckmann) were used. GC- MS analyses were performed with Agilent 6890N/5973N. Urinary corticoid concentrations were related to urinary creatinine concentrations. Results Immunoassay results were significantly higher compared to GC- MS results. Evaluation of bias plots and clinical assessment made on the basis of the assay results of each dog indicated substantial disagreement among the assays. Sensitivity varied from 37.5 to 75% and with selected assays was lower in samples from day 6 compared to day 0. GC- MS was not superior to the immunoassays in discriminating healthy from HC dogs. Conclusions and Clinical Importance Considerable variation must be anticipated comparing different urinary cortisol assays. Establishing an assay- and laboratory-specific reference range is critical when using UCCR. [ABSTRACT FROM AUTHOR]

Background Measurement of plasma renin activity ( PRA) is the gold standard for monitoring mineralocorticoid treatment in humans with primary hypoadrenocorticism ( PH). Objectives To compare PRA in dogs with newly diagnosed PH, dogs with diseases mimicking PH, and healthy dogs, and evaluate measurement of PRA to monitor therapeutic effects in dogs with PH treated with different mineralocorticoids. Animals Eleven dogs with newly diagnosed PH (group 1), 10 dogs with diseases mimicking PH (group 2), 21 healthy dogs (group 3), 17 dogs with treated PH (group 4). Methods In group 1, PRA was measured before treatment and at different times after initiating treatment. In groups 2 and 3, PRA was measured at initial presentation only. In group 4, no baseline PRA was obtained but PRA was measured once or every 1-6 months during treatment. Mineralocorticoid treatment consisted of fludrocortisone acetate ( FC) or desoxycorticosterone pivalate ( DOCP). Results Plasma renin activity before treatment was increased in dogs with PH compared to normal dogs and dogs with diseases mimicking PH with median activity of 27, 0.8, and 1.0 ng/mL/h, respectively. In dogs with PH, PRA decreased and normalized with mineralocorticoid treatment using DOCP but not with FC. In dogs treated with DOCP, PRA was lower than in dogs treated with FC. Plasma sodium concentrations were higher and potassium concentrations were lower with DOCP treatment compared to FC treatment. Conclusion and Clinical Importance Plasma renin activity is a reliable tool for monitoring mineralocorticoid treatment. DOCP treatment more effectively suppresses PRA compared to FC in dogs with PH. [ABSTRACT FROM AUTHOR]

Background Spec cPL is the most sensitive and specific test for diagnosing pancreatitis in dogs. Its results have not been compared to those of the 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester ( DGGR) lipase assay or those of abdominal ultrasonography. Objectives To investigate agreement of Spec cPL with DGGR lipase activity and pancreatic ultrasonography in dogs with suspected pancreatitis. Animals One hundred and forty-two dogs. Methods DGGR lipase activity (reference range, 24-108 U/L) and Spec cPL were measured using the same sample. The time interval between ultrasonography and lipase determinations was <24 hours. The agreement of the 2 lipase assays at different cutoffs and the agreement between pancreatic ultrasonography and the 2 tests were assessed using Cohen's kappa coefficient (κ). Results DGGR lipase (>108, >216 U/L) and Spec cPL (>200 μg/L) had κ values of 0.79 (95% confidence interval [CI], 0.69-0.9) and 0.70 (CI, 0.58-0.82). DGGR lipase (>108, >216 U/L) and Spec cPL (>400 μg/L) had κ values of 0.55 (CI, 0.43-0.67) and κ of 0.80 (CI, 0.71-0.9). An ultrasonographic diagnosis of pancreatitis and DGGR lipase (>108, >216 U/L) had κ values of 0.29 (CI, 0.14-0.44) and 0.35 (CI, 0.18-0.52). Ultrasonographically diagnosed pancreatitis and Spec cPL (>200, >400 μg/L) had κ values of 0.25 (CI, 0.08-0.41) and 0.27 (CI, 0.09-0.45). Conclusions and Clinical Importance Although both lipase assays showed high agreement, agreement between ultrasonography and lipase assays results was only fair. Because lipase results are deemed more accurate, ultrasonography results should be interpreted carefully. [ABSTRACT FROM AUTHOR]

Background Some dogs with primary hypoadrenocorticism ( HA) have normal sodium and potassium concentrations, a phenomenon called atypical Addison's disease. The assumption that the zona glomerulosa and aldosterone secretion in these dogs are normal seems widely accepted; however, aldosterone measurements are missing in most published cases. Objectives To measure aldosterone in dogs with HA with and without electrolyte abnormalities and to determine the time point of aldosterone peak concentrations during ACTH stimulation. Animals Seventy dogs with HA, 22 dogs with diseases mimicking HA, and 19 healthy dogs. Methods Prospective study. Blood samples were taken before and 60 minutes after injection of 250 μg ACTH in all dogs. Additional blood samples were taken 15, 30, and 45 minutes after ACTH in 7 dogs with HA and in 22 with diseases mimicking HA. Results Baseline and ACTH-stimulated aldosterone was significantly lower in dogs with HA than in the other groups. Aldosterone was low or undetectable in 67/70 dogs with HA independently of sodium and potassium levels. In 3 dogs, sodium/potassium concentrations were normal; in 1 dog, sodium was normal and potassium decreased. In all 4, ACTH-stimulated aldosterone concentrations were below the detection limit of the assay. Aldosterone concentrations were not different at 30, 45, or 60 minutes after ACTH administration. Conclusion and Clinical Importance Cortisol and aldosterone secretion is compromised in dogs with HA with and without electrolyte abnormalities. The term atypical Addison's disease, used for dogs with primary HA and normal electrolytes, must be reconsidered; other mechanisms allowing normal electrolyte balance without aldosterone should be evaluated in these dogs. [ABSTRACT FROM AUTHOR]

This report offers a consensus opinion on the diagnosis of spontaneous canine hyperadrenocorticism. The possibility that a patient has hyperadrenocorticism is based on the history and physical examination. Endocrine tests should be performed only when clinical signs consistent with HAC are present. None of the biochemical screening or differentiating tests for hyperadrenocorticism are perfect. Imaging can also play a role. Awareness of hyperadrenocorticism has heightened over time. Thus, case presentation is more subtle. Due to the changes in manifestations as well as test technology the Panel believes that references ranges should be reestablished. The role of cortisol precursors and sex hormones in causing a syndrome of occult hyperadrenocorticism remains unclear. [ABSTRACT FROM AUTHOR]

Background Serum lipase activities measured by catalytic assays are claimed to be of limited utility for diagnosing pancreatitis in cats. The Spec fPL assay currently is believed the most sensitive test; however, studies comparing different lipase assays are lacking. 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester (DGGR) assay for the determination of lipase activity has been evaluated in dogs, but no information is available in cats. Objectives To investigate the agreement of DGGR-lipase activity and Spec fPL concentration in cats with clinical signs consistent with pancreatitis. Animals Two hundred fifty-one client-owned cats. Methods DGGR-lipase activity and Spec fPL concentration measured from the same blood sample in cats undergoing investigation for pancreatitis. The agreement between DGGR-lipase and Spec fPL at different cutoffs was assessed using Cohen's kappa coefficient (κ). Sensitivity and specificity were calculated for 31 cases where pancreatic histopathology was available. Results DGGR-lipase (cutoff, 26 U/L) and Spec fPL (cutoff, >5.3 μg/L) had a κ of 0.68 (standard error [SE] 0.046). DGGR-lipase (cutoff, 26 U/L) and Spec fPL (cutoff, >3.5 μg/L) had a κ of 0.60 (SE, 0.05). The maximum κ at a Spec fPL cutoff >5.3 μg/L was found when the DGGR-lipase cutoff was set >34 U/L and calculated as 0.755 (SE, 0.042). Sensitivity and specificity were 48% and 63% for DGGR-lipase (cut-off, 26 U/L) and 57% and 63% for Spec fPL (>5.3 μg/L), respectively. Conclusions and Clinical Importance Both lipase assays agreed substantially. DGGR assay seems a useful and cost-efficient method compared to the Spec fPL test. [ABSTRACT FROM AUTHOR]

Background The effectiveness of trilostane treatment is currently monitored by regular ACTH stimulation tests, which are time-consuming and expensive. Therefore, a monitoring system without a stimulation protocol and with less client expense would be preferable. Hypothesis/Objectives The aim of our study was to evaluate if baseline cortisol, endogenous ACTH ( ACTH) concentration or the baseline cortisol to ACTH ratio (cortisol/ ACTH ratio) could replace the ACTH stimulation test. Animals Forty trilostane-treated dogs with pituitary-dependent hypercortisolism ( PDH) were included in this prospective study. Methods A total of 148 ACTH stimulation tests and 77 ACTH concentrations and cortisol/ ACTH ratios were analyzed. Control of cortisol release was classified according to cortisol concentration after ACTH administration as excessive (<1.5 μg/dL; group 1), adequate (1.5-5.4 μg/dL; group 2), or inadequate (>5.4 μg/dL; group 3). Results Baseline cortisol concentrations had considerable overlap between excessively, adequately, and inadequately controlled dogs. Only baseline cortisol >4.4 μg/dL (in 12% of tests) was a reliable diagnosis of inadequate control. Endogenous ACTH concentrations did not differ between groups. The overlap of the cortisol/ ACTH ratio between groups was large. Correct classification was only possible if the cortisol/ ACTH ratio was >15, which occurred in 4% of tests. Conclusions and Clinical Importance To monitor trilostane treatment the ACTH stimulation test cannot be replaced by baseline cortisol, ACTH concentration, or the cortisol/ ACTH ratio. [ABSTRACT FROM AUTHOR]

Background Transdermal methimazole is an acceptable alternative to oral treatment for hyperthyroid cats. There are, however, no studies evaluating the duration of T4 suppression after transdermal methimazole application. Such information would be valuable for therapeutic monitoring. Objective To assess variation in serum T4 concentration in hyperthyroid cats after once- and twice-daily transdermal methimazole administration. Animals Twenty client-owned cats with newly diagnosed hyperthyroidism. Methods Methimazole was formulated in a pluronic lecithin organogel-based vehicle and applied to the pinna of the inner ear at a starting dose of 2.5 mg/cat q12h ( BID group, 10 cats) and 5 mg/cat q24h ( SID group, 10 cats). One and 3 weeks after starting treatment, T4 concentrations were measured immediately before and every 2 hours after gel application over a period of up to 10 hours. Results Significantly decreased T4 concentrations were observed in week 1 and 3 compared with pretreatment concentrations in both groups. All cats showed sustained suppression of T4 concentration during the 10-hour period, and T4 concentrations immediately before the next methimazole treatment were not significantly different compared with any time point after application, either in the BID or SID groups. Conclusions Because transdermal methimazole application led to prolonged T4 suppression in both the BID and SID groups, timing of blood sampling does not seem to be critical when assessing treatment response. [ABSTRACT FROM AUTHOR]

Background In human patients with interstitial cystitis, intravesical instillation of alkalinized lidocaine sometimes is associated with sustained amelioration of symptoms beyond the acute treatment phase. Interstitial cystitis shares many features in common with feline idiopathic cystitis. Objective To evaluate whether intravesical instillation of alkalinized lidocaine decreases recurrence of urethral obstruction and severity of clinical signs in cats with obstructive idiopathic LUTD. Animals Twenty-six cats with obstructive idiopathic LUTD. Twelve cats in case group (treatment with alkalinized lidocaine) and 14 control cats (treatment with placebo or standard treatment). Methods Cats were randomly assigned to treatment (2 or 4 mg/kg lidocaine and sodium bicarbonate) or placebo groups (0.2 mL/kg saline solution and sodium bicarbonate). The intravesical instillation was done once a day for 3 days. Some cats underwent standard treatment only (indwelling urinary catheter for 3 days without intravesical instillations). A 2-week, 1-month, and 2-month follow-up after treatment was made using a questionnaire. The recurrence rate and amelioration scores of clinical signs were assessed and compared. Results Recurrence of urethral obstruction was 58% (7/12) in the case group and 57% (8/14) in the control group. Amelioration scores were similar between the 2 groups. Conclusion and Clinical Importance Intravesical administration of lidocaine for up to 3 consecutive days had no apparent beneficial effect on decreasing recurrence rate and severity of clinical signs in cats with obstructive idiopathic LUTD. [ABSTRACT FROM AUTHOR]

Background Endoscopic ultrasound ( EUS)-guided fine needle aspiration ( EUS- FNA) has proven a useful and safe diagnostic tool for assessing pancreatic disease in human medicine. No information about pancreatic EUS- FNA is available in dogs. Objectives To assess the feasibility and safety of pancreatic EUS-FNA in healthy dogs. Animals Thirteen beagles with a median body weight of 13.4 kg. Methods Experimental study. An ultrasound endoscope (insertion tube outer diameter 11.8 mm) was used, and FNA was carried out with 19 G needles. The optimal puncture site was chosen with the aid of Doppler imaging. Complete clinicopathologic assessments including pain scoring and pancreas-specific lipase measurements were obtained before EUS as well as on day 1 and day 2 after EUS- FNA. Results The pancreatic body was identified in all dogs, the left lobe was clearly identified in 9/13 and appeared indistinctly marginated in 4/13 dogs, and the distal third of the right lobe could not be identified in 7/13 dogs. EUS- FNA was carried out in 12/13 dogs. Cellularity of smears was adequate for evaluation in 8/12 cases, in which samples were obtained transgastrically (n = 4) or transduodenally (n = 4). All dogs recovered uneventfully and no clinical and laboratory abnormalities occurred during the 48 hour monitoring period after the procedure. Conclusion and Clinical Importance Although the healthy canine pancreas is difficult to visualize in its entirety with EUS, pancreatic EUS- FNA with a 19 G needle is feasible in medium-sized dogs and can be considered a safe procedure. Its diagnostic usefulness should be evaluated in dogs with pancreatic disease. [ABSTRACT FROM AUTHOR]

Background: The continuous glucose monitoring system ( CGMS) Guardian REAL-Time® allows the generation of very detailed glucose profiles in cats. The performance of CGMS to generate short-term glucose profiles to evaluate treatment response has not been yet evaluated in diabetic cats. Hypothesis: Analysis of glucose profiles generated using the CGMS produces insulin dose recommendations that differ from those of profiles generated using the portable blood glucose meter ( PBGM) in diabetic cats. Animals: Thirteen client-owned diabetic cats. Methods: Prospective, observational study. Simultaneous glucose profiles were generated over an 8-10 hour period using the CGMS, blood glucose concentration was measured every 2 hours with the PBGM. Profiles were submitted to three internal medicine specialists who used them to determine the insulin dose. Differences between insulin doses deduced from paired profiles were compared. Percentages of nadirs recorded with the CGMS that were lower, higher, or equal to those derived with the PBGM were calculated. Results: Twenty-one paired glucose profiles were obtained. There was no difference of insulin doses based on CGMS and PBGM profiles (median 0 U; range: −1 to +0.5). Treatment decisions did not differ among investigators. Compared with the observed PBGM nadir, the CGMS nadir was lower, higher, or equal in 17, 2, and 2 of 21 cases, respectively. Conclusions and Clinical Importance: Adjustments in insulin dose based on glucose profiles generated with the CGMS are similar to those based on the PBGM. The common occurrence of lower nadirs recorded with the CGMS suggests that this device detects hypoglycemic periods that are not identified with the PBGM. [ABSTRACT FROM AUTHOR]

Cats with diabetes mellitus frequently achieve clinical remission, suggesting residual β-cell function. Responsiveness of β-cells to arginine persists the longest during diabetes progression, making the intravenous arginine stimulation test (IVAST) a useful tool to assess residual insulin and glucagon secretion. Diabetic cats with and without remission will have different arginine-induced insulin or glucagon response. Seventeen cats with diabetes, 7 healthy cats. Blood samples collected on admission and during subsequent IVAST. Glucose, insulin, and glucagon were measured. Response to IVAST was assessed by calculating the insulin and glucagon area under the curve (AUC) and the AUC glucagon-to-insulin ratio. Diabetic cats were treated with insulin and were followed for 18 weeks. Remission was defined as normoglycemia and disappearance of clinical signs of diabetes for ≥4 weeks, without requiring insulin. Seven diabetic cats (41%) achieved remission. On admission, blood glucose concentration was significantly lower in cats with remission (median, 389 mg/dL; range, 342-536 mg/dL) than in those without remission (median, 506 mg/dL; range, 266-738 mg/dL). After IVAST, diabetic cats with remission had higher AUC glucagon-to-insulin ratios (median, 61; range, 34-852) than did cats without remission (median, 26; range, 20-498); glucose, insulin, and glucagon AUCs were not different. Diabetic cats had lower insulin AUC than did healthy cats but comparable glucagon AUC. Diabetic cats with and without remission have similar arginine-stimulated insulin secretion on admission. Although cats with remission had lower blood glucose concentrations and higher AUC glucagon-to-insulin ratios, large overlap between groups prevents use of these parameters in clinical practice. [ABSTRACT FROM AUTHOR]

Examines the non-invasive measurement of the cardiovascular effects of chronic hypoxemia on dogs living at moderately high altitude. Arterial hypoxemia in altitude dogs; Lower arterial oxygen saturation; Lower derived systolic pulmonary arterial pressure.

Diabetes mellitus is a common endocrinopathy in cats that is associated with pancreatic islets lesions. Research on isolated islets contributed to the understanding of the pathophysiology of human diabetes. Therefore, by improving the existing methods of isolation in cats, we aimed at increasing islet yield, purity and viability of feline isolated islets. Islet isolation was accomplished by pancreas perfusion with 80 ml of Collagenase type IV through the pancreatic duct at the site of the major papilla. The enzymatic digestion was combined with mechanical disruption and controlled by dithizone staining. Purification was performed by filtration and handpicking. Purified islets were plated on extracellular matrix pre-coated plates and cultured for 48 h. Feline islets with a high degree of viability and purity were isolated and cultured for the first time. Although the percentage of islet free from the acinar tissue relative to the total number of isolated islets was low compared to other species, the suggested protocol represents a promising progress in the procedure of islet isolation in cats. [ABSTRACT FROM AUTHOR]

Abstract: Diabetes mellitus is a common endocrinopathy in humans and in cats. The general prevalence of diabetes mellitus, and in particular of type 2 diabetes, has risen dramatically in recent years. This increase has often been linked to the rise in the obesity pandemic because obesity and the ensuing metabolic consequences constitute major risk factors for human type 2 and for feline diabetes. Feline diabetes shares many features of human type 2 diabetes in respect to its pathophysiology, underlying risk factors and treatment strategies. This review will briefly summarize major characteristics in the human and the feline disease and where available, point out the current knowledge on similarities and differences. [Copyright &y& Elsevier]

• Healthy and diabetic cats have similar serum tetra-hydroxylated bile acid (THBA) levels. • Retinoid-related orphan receptor γ (RORγ) and matrix metalloproteinase 3 (MMP3) are expressed in feline adipocytes. • Synthetic THBA is considered safe for use in cats. • Supplementation of THBA reduces mRNA expression of MMP3 and promotes the development of small feline subcutaneous adipocytes with reduced expression of IL6, and TNFα and increased expression of adiponectin. • Supplementation of THBA likely improves insulin sensitivity of feline subcutaneous adipocytes. Obesity leads to insulin resistance and is a major risk factor for the development of diabetes mellitus in cats. Prevention of obesity and obesity-induced insulin resistance is difficult, and reliable long-term strategies are currently lacking. Retinoid-related orphan receptor gamma (RORγ) was recently identified as an important transcription factor in the development of large insulin-resistant adipocytes in mice and humans. RORγ negatively affects adipocyte differentiation through expression of its target gene matrix metalloproteinase 3 (MMP3) and promotes the development of large insulin-resistant adipocytes. Preliminary studies in mice showed that RORγ can be inhibited by its ligand tetra-hydroxylated bile acid (THBA). In the present study, serum THBA levels were determined in healthy and diabetic cats. Moreover, potential side effects and the effects of THBA supplementation on adipocyte size, mRNA expression of RORγ, MMP3, interleukin 6, tumor necrosis factor α, adiponectin and leptin in feline subcutaneous adipocytes and insulin sensitivity were investigated in healthy normal weight cats. Thirteen healthy and 13 diabetic cats were used for determination of serum THBA level, and six healthy normal-weight cats were included in a feeding trial. Similar THBA levels were determined in serum of healthy and diabetic cats. Supplementation of 5 mg/kg THBA for 8 wk did not cause any negative effect on feeding behavior, general condition and blood parameters of tested cats. It significantly reduced adipocyte size and mRNA expression of MMP3, interleukin 6, and tumor necrosis factor α in adipocytes, while mRNA expression of adiponectin significantly increased and mRNA expression of RORγ and leptin remained unchanged. Administration of THBA did not influence fasting blood glucose levels or the response of cats to acute insulin administration. Based on these results, THBA is palatable and is considered safe for use in cats. It reduces expression of MMP3 and promotes the development of small adipocytes with increased expression of adiponectin and reduced expression of interleukin 6 and tumor necrosis factor α. Further studies are recommended to evaluate the effect of THBA on adipocyte size and insulin sensitivity in obese cats. [ABSTRACT FROM AUTHOR]

Abstract: It was investigated if IGF-1 levels in cats which experience diabetic remission (i.e. transient diabetes mellitus) differ from those in cats with permanent disease. Thirteen of 32 diabetic cats showed remission within 16 weeks after initiating insulin therapy, 19 cats continued to need insulin therapy. IGF-1 concentrations were measured before (t 0), 1–3 (t 1) and 4–8 (t 2) weeks after initiating insulin therapy. No difference in IGF-1 levels was found between cats with transient and permanent diabetes at any point in time. In both groups of cats IGF-1 concentrations were significantly lower compared to those of controls before insulin administration. After starting insulin therapy IGF-1 increased significantly in both groups. In cats with transient diabetes IGF-1 levels were not different from controls already at t 1, whereas in cats with permanent diabetes it took until t 2. Although IGF-1 levels seem to normalize faster in cats with transient diabetes mellitus, measurement is not helpful to predict the course of the disease. [Copyright &y& Elsevier]