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Background: Knowledge about primary hypoadrenocorticism coexisting with immune-mediated thyroiditis (Schmidt's syndrome) in dogs is limited., Objective: To evaluate thyroid function in dogs with naturally occurring hypoadrenocorticism before and during treatment., Animals: Sixty-six client-owned dogs., Methods: Measurement of canine thyroid stimulating hormone (cTSH), total thyroxine (T4), free thyroxine, and autoantibodies against thyroglobulin, T4, and total triiodothyronine., Results: Thirty-eight dogs were assessed before and 28 during treatment. Follow-up data were available for 24/38 and 17/28 dogs, with median follow-up duration of 3.8 years (range, <1.0-8.8 years) and 4 years (range, 1.1 weeks to 10.5 years), respectively. Canine thyroid stimulating hormone was above the reference range at the time of diagnosis of hypoadrenocorticism in 10 of 38 dogs but decreased into the reference range in 7 for which follow-up data was available. Hypothyroidism was confirmed in 5 dogs at a median age of 11 years (range, 7-15 years). In 4 dogs, the condition was diagnosed after a median treatment duration of 5.75 years (range, 2.6-10 years), while in 1 dog, the diagnosis was made concurrently. One dog had detectable thyroid autoantibodies., Conclusions and Clinical Relevance: Hypothyroidism occurs as a rare concurrent condition in dogs with hypoadrenocorticism, potentially at any phase of treatment. Close monitoring of cTSH levels in these dogs could be beneficial, as early changes might indicate the onset of hypothyroidism. The low prevalence of detectable thyroid autoantibodies suggests that nonimmune mechanisms might contribute to thyroid dysfunction., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Primary hypoadrenocorticism (PH) is rare in cats and knowledge about treatment is sparse., Objective: To describe cats with PH with a focus on long-term treatment., Animals: Eleven cats with naturally occurring PH., Methods: Descriptive case series with data on signalment, clinicopathological findings, adrenal width, and doses of desoxycorticosterone pivalate (DOCP) and prednisolone during a follow-up period of >12 months., Results: Cats ranged from 2 to 10 years (median 6.5); 6 cats were British Shorthair. Most common signs were reduced general condition and lethargy, anorexia, dehydration, obstipation, weakness, weight loss, and hypothermia. Adrenal glands on ultrasonography were judged small in 6. Eight cats could be followed for 14 to 70 months (median: 28). Two were started on DOCP doses ≥2.2 mg/kg (2.2; 2.5) and 6 < 2.2 mg/kg (1.5-2.0 mg/kg, median 1.8) q28 days. Both high-dose cats and 4 low-dose cats needed a dose increase. Desoxycorticosterone pivalate and prednisolone doses at the end of the follow-up period were 1.3 to 3.0 mg/kg (median: 2.3) and 0.08 to 0.5 mg/kg/day (median: 0.3), respectively., Conclusions and Clinical Importance: Desoxycorticosterone pivalate and prednisolone requirements in cats were higher than what is currently used in dogs; thus, a DOCP starting dose of 2.2 mg/kg q28 days and a prednisolone maintenance dose of 0.3 mg/kg/day titrated to the individual need seems warranted. Small adrenal glands (width < 2.7 mm) on ultrasonography in a cat suspected of hypoadrenocorticism can be suggestive of the disease. The apparent predilection of British Shorthaired cats for PH should be further evaluated., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

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., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To investigate kidney function by determining serum symmetric dimethylarginine (sSDMA) and serum creatinine (sCr) concentrations in dogs with primary hypoadrenocorticism (PH) receiving long-term mineralocorticoid replacement therapy., Methods: Dogs with PH receiving a minimum of 12 months of either desoxycorticosterone pivalate or fludrocortisone acetate were included in the study provided that banked frozen serum samples were available for sSDMA analysis. sCr concentrations were retrieved from the medical records. In dogs still alive and presented for regular re-evaluations and in newly diagnosed patients, blood was prospectively collected for sSDMA and sCr determination., Results: Thirty-two dogs met the inclusion criteria. The treatment time ranged from 12 to 146 months after initial diagnosis (median, 55.5 months). The majority of dogs had normal sSDMA and sCr concentrations throughout the hormone replacement treatment. Both sSDMA and sCr concentrations were persistently elevated in three of 32 dogs. Further workup confirmed chronic kidney disease (CKD) in all three dogs., Conclusions: Based on these data, the prevalence of CKD could be higher in dogs with PH receiving long-term mineralocorticoid replacement treatment than in the general dog population. However, additional studies with a larger number of dogs are needed to confirm it., (© 2021 British Veterinary Association.)

Background: Measurement of serum concentrations of insulin-like growth factor (IGF)-1 is used to diagnose acromegaly in cats., Hypothesis: Changes of body weight do not affect serum concentrations of IGF-1 in cats., Animals: Ten healthy purpose-bred cats., Methods: Prospective study. In lean cats, food availability was stepwise increased during the first week and given ad libitum for a total of 40 weeks to increase their body weight. From week 41 to week 60, food access was limited to reach a weight loss of 1% to 2% each week. Measurement of IGF-1 was performed at week 0, 16, 40, and 60. Insulin-like growth factor-1 was measured by radioimmunoassay. Body weight and IGF-1 were compared among the 4 time points., Results: Body weight increased by 44% from week 0 (4.5 ± 0.4 kg) to week 40 (6.5 ± 1.2 kg) (P < .001) and decreased by 25% from week 40 to week 60 (4.9 ± 0.7 kg) (P < .001). Serum IGF-1 concentrations did not differ during the study period (week 0, 16, 40, 60: 500 ± 188, 479 ± 247, 470 ± 184, 435 ± 154 ng/mL, respectively; P = .38). Correlations with body weight were not observed., Conclusions and Clinical Importance: Insulin-like growth factor-1 might not be influenced by changes of body weight in healthy cats, possibly suggesting that the latter is unimportant when interpreting IGF-1 results in this species., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objectives: The aims of this study were to validate a commercially available chemiluminescent assay for measurement of feline plasma adrenocorticotropic hormone concentration (ACTH), to determine the normal reference interval (RI) of plasma ACTH in healthy cats, to assess plasma ACTH in cats with naturally occurring hypercortisolism (HC), primary hypoadrenocorticism (PH) and other diseases (OD), and to evaluate the effect of aprotinin on plasma ACTH degradation., Methods: Forty healthy cats, 10 with HC, 11 with PH and 30 with OD, were included. The chemiluminescent enzyme immunometric assay was evaluated by measurement of intra-assay precision, interassay precision and linearity. The RI for plasma ACTH in healthy cats was established using robust methods. Plasma ACTH of samples collected with and without aprotinin, stored at 4°C and assayed over a 6-day period, was measured., Results: The intra-assay coefficients of variance (CVs) ranged from 2.7% to 4.3% and interassay CVs from 3.3% to 10.7%. Dilution studies showed excellent accuracy (R 2 >0.99). The RI for plasma ACTH in healthy cats was 32-370 pg/ml. Plasma ACTH was not significantly different between healthy cats and the OD group. Cats with pituitary-dependent hypercortisolism (PDH) and PH had significantly higher plasma ACTH than the other groups. Plasma ACTH did not show significant differences when samples collected with and without aprotinin were compared., Conclusions and Relevance: The Immulite chemiluminescent assay is a valid technique for measuring plasma ACTH in cats and the RI of plasma ACTH is quite wide. Owing to the low overlap between healthy or OD cats and cats with HC or PH, the measurement of plasma ACTH appears to be useful and should be included in the diagnostic work-up when HC or PH are suspected. Furthermore, the measurement of plasma ACTH may be an accurate test for differentiating PDH from adrenal-dependent hypercortisolism.

Hepatic fat fraction (HFF) can be non-invasively estimated with magnetic resonance imaging (MRI) multiple echo gradient recalled echo (GRE) sequence. The aim of this study was to test different methods of sampling strategies to quantify the HFF in healthy cats during body weight gain. Twelve healthy adult male cats were examined in a 3 Tesla MRI unit. Sequences included morphological images, and multiple echo GRE sequence. Cats were scanned at the beginning of the study and twice, each 20 weeks apart during body weight gain. HFF was calculated with 5 different methods of sampling on the multiple echo GRE sequence with different number, size and position of regions of interest (ROIs) and by 2 operators. Results indicated that HFF increased with increasing body weight, and the increase was appreciated with all the 5 methods. There was overall excellent agreement (interclass correlation coefficient = 0.820 (95% confidence interval:0.775-0.856)) between the 2 operators. HFF in the left lateral hepatic lobe was lower than in the other analyzed lobes. HFF measured on large free-hand drawn ROIs was higher than HFF measured with smaller ROIs size. This study proves that different sampling methods for quantification of HFF on multiple echo GRE sequence have overall excellent repeatability and ability to appreciate increased HFF., Competing Interests: The authors have declared that no competing interests exist.

Background: Glycemic variability (GV) is an indicator of glycemic control and can be evaluated by calculating the SD of blood glucose measurements. In humans with diabetes mellitus (DM), adding a glucagon-like peptide-1 (GLP-1) analogue to conventional therapy reduces GV. In diabetic cats, the influence of GLP-1 analogues on GV is unknown., Objective: To evaluate GV in diabetic cats receiving the GLP-1 analogue exenatide extended release (EER) and insulin., Animals: Thirty client-owned cats with newly diagnosed spontaneous DM., Methods: Retrospective study. Blood glucose curves from a recent prospective placebo-controlled clinical trial generated 1, 3, 6, 10, and 16 weeks after starting therapy were retrospectively evaluated for GV. Cats received either EER (200 μg/kg) or 0.9% saline SC once weekly, insulin glargine and a low-carbohydrate diet. Mean blood glucose concentrations were calculated and GV was assessed by SD. Data were analyzed using nonparametric tests., Results: In the EER group, GV (mean SD [95% confidence interval]) was lower at weeks 6 (1.69 mmol/L [0.9-2.48]; P = .02), 10 (1.14 mmol/L [0.66-1.62]; P = .002) and 16 (1.66 mmol/L [1.09-2.23]; P = .02) compared to week 1 (4.21 mmol/L [2.48-5.93]) and lower compared to placebo at week 6 (3.29 mmol/L [1.95-4.63]; P = .04) and week 10 (4.34 mmol/L [2.43-6.24]; P < .000). Cats achieving remission (1.21 mmol/L [0.23-2.19]) had lower GV compared to those without remission (2.96 mmol/L [1.97-3.96]; P = .01) at week 6., Conclusions and Clinical Importance: The combination of EER, insulin, and a low-carbohydrate diet might be advantageous in the treatment of newly diagnosed diabetic cats., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To determine the change in mean hepatic apparent diffusion coefficient (ADC) and hepatic fat fraction (HFF) during body weight gain in cats by use of MRI., Animals: 12 purpose-bred adult neutered male cats., Procedures: The cats underwent general health and MRI examination at time 0 (before dietary intervention) and time 1 (after 40 weeks of being fed high-energy food ad libitum). Sequences included multiple-echo gradient-recalled echo MRI and diffusion-weighted MRI with 3 b values (0, 400, and 800 s/mm 2 ). Variables (body weight and the HFF and ADC in selected regions of interest in the liver parenchyma) were compared between time points by Wilcoxon paired-sample tests. Relationships among variables were assessed with generalized mixed-effects models., Results: Median body weight was 4.5 and 6.5 kg, mean ± SD HFF was 3.39 ± 0.89% and 5.37 ± 1.92%, and mean ± SD hepatic ADC was 1.21 ± 0.08 × 10 -3 mm 2 /s and 1.01 ± 0.2 × 10 -3 mm 2 /s at times 0 and 1, respectively. Significant differences between time points were found for body weight, HFF, and ADC. The HFF was positively associated with body weight and ADC was negatively associated with HFF., Conclusions and Clinical Relevance: Similar to findings in people, cats had decreasing hepatic ADC as HFF increased. Protons associated with fat tissue in the liver may reduce diffusivity, resulting in a lower ADC than in liver with lower HFF. Longer studies and evaluation of cats with different nutritional states are necessary to further investigate these findings.

There is limited information regarding the value of constitutive components of the ACTH stimulation test (ACTHST) and low-dose dexamethasone suppression test (LDDST) including serum baseline cortisol (BC), difference between post-ACTH stimulation cortisol (PC) and BC (ΔACTHC), cortisol concentration 4h after dexamethasone administration (4HC), difference between 4HC and BC (Δ4C), and the difference between cortisol concentration 8h after dexamethasone administration and 4HC (Δ8C). Therefore, the objective of this study was to determine if these components can predict hyperadrenocorticism, pituitary-dependent hyperadrenocorticism (PDH), or functional adrenocortical tumor (FAT) in dogs. Cortisol concentrations were normalized, as fold change (FC), to the PC reference interval upper limit. A total of 1267 dogs were included, with hyperadrenocorticism diagnosed in 537 (PDH, n=356; FAT, n=28; undetermined, n=153) and excluded in 730. The area under the receiver operating curves for BC, ΔACTHC, 4HC, Δ4C, and Δ8C to predict hyperadrenocorticism were 0.76 (95% confidence interval (CI), 0.73-0.79), 0.91 (95% CI, 0.89-0.93), 0.83 (95% CI, 0.80-0.87), 0.55 (95% CI, 0.50-0.60), and 0.67 (95% CI, 0.62-0.72), respectively. A diagnostic limit of ≥0.78 FC for ΔACTHC had excellent sensitivity (1.00; 95% CI, 0.74-1.00), but poor specificity (0.67; 95% CI, 0.64-0.71), to predict FAT in dogs with a positive ACTHST. A diagnostic limit of ≥-0.26 FC for Δ4C had excellent sensitivity (1.00; 95% CI, 0.79-1.00), but poor specificity (0.21; 95% CI, 0.18-0.26), to predict FAT in dogs with a positive LDDST. In hyperadrenocorticoid dogs that have positive ACTHST or LDDST results, ΔACTHC or Δ4C, respectively, could be used to exclude FAT., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Erythrocytes of diabetic cats have decreased superoxide dismutase activity, possibly indicative of oxidative stress., Hypothesis: Erythrocytes of diabetic cats undergo oxidative stress, which is caused by hyperglycemia and hyperlipidemia, and improves with treatment., Animals: Twenty-seven client-owned cats with diabetes mellitus, 11 matched healthy cats, and 21 purpose-bred healthy cats., Methods: Prospective study. Advanced oxidized protein products, carbonyls (protein oxidation by-products), and thiols (antioxidants) were quantified in erythrocyte membrane, thiobarbituric acid reactive substances (TBAR, lipid peroxidation by-products), and thiols in erythrocyte cytoplasm of all cats. Comparison were performed between diabetic and matched healthy cats, between diabetic cats achieving remission or not, and among purpose-bred cats after 10 days of hyperglycemia (n = 5) or hyperlipidemia (n = 6) versus controls treated with saline (n = 5) or untreated (n = 5)., Results: Compared with controls, erythrocytes of diabetic cats initially had higher median membrane carbonyls (4.6 nmol/mg total protein [range: 0.1-37.7] versus 0.7 [0.1-4.7], P < .001) and lower cytoplasmic TBAR (1.9 nmol/mg [0.5-2.4] versus 2.4 [1.4-3.5] P < .001), and thiols (419 nmol/mg [165-621] versus 633 [353-824], P < 0.001). After 12-16 weeks of treatment in diabetic cats, carbonyls decreased by 13% (P < .001), but remained higher (P < .001) and TBAR and thiols lower (P = .02, P < .001) than those in controls. No differences were observed between diabetic cats achieving remission or not, and among purpose-bred cats., Conclusions and Clinical Importance: Diabetes mellitus is associated with increased protein oxidation and reduced antioxidant defenses, which persist during treatment and remission, although mild improvement in protein oxidation occurs. Short-term hyperglycemia or hyperlipidemia does not cause oxidative stress. The reason for decreased TBAR remains unknown., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Lowering the dose of desoxycorticosterone pivalate (DOCP) for the treatment of dogs with primary hypoadrenocorticism (PH) decreases costs and could lead to increased owner motivation to treat their affected dogs., Objective: To evaluate the efficacy of a low-dose DOCP treatment protocol in dogs with PH., Animals: Prospective study, 17 client-owned dogs with naturally occurring PH (12 newly diagnosed, 5 previously treated with fludrocortisone acetate [FC])., Methods: Dogs with newly diagnosed PH were started on 1.5 mg/kg DOCP SC; dogs previously treated with FC were started on 1.0-1.8 mg/kg DOCP SC. Reevaluations took place at regular intervals for a minimum of 3 months and included clinical examination and determination of serum sodium and potassium concentrations. The DOCP dosage was adjusted to obtain an injection interval of 28-30 days and to keep serum electrolyte concentrations within the reference interval., Results: Median (range) follow-up was 16.2 months (4.5-32.3 months). The starting dosage was sufficient in all but 2 dogs and had to be significantly decreased after 2-3 months to a median dosage (range) of 1.1 mg/kg (0.7-1.8). Dogs 3 years of age or younger needed significantly higher dosages compared to older dogs. None of them, however, needed the 2.2 mg/kg DOCP dosage, recommended by the manufacturer., Conclusions and Clinical Importance: A starting dosage of 1.5 mg/kg DOCP is effective in controlling clinical signs and serum electrolyte concentrations in the majority of dogs with PH. An additional dose reduction often is needed to maintain an injection interval of 28-30 days. Young and growing animals seem to need higher dosages., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

8658860258318000Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D ( SDHB and SDHD ) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL; together PPGL), suggesting dogs might be an interesting comparative model for the study of human PPGL. To study whether canine PPGL resembled human PPGL, we investigated a series of 50 canine PPGLs by immunohistochemistry to determine the expression of synaptophysin (SYP), tyrosine hydroxylase (TH) and succinate dehydrogenase subunit A (SDHA) and B (SDHB). In parallel, 25 canine PPGLs were screened for mutations in SDHB and SDHD by Sanger sequencing. To detect large chromosomal alterations, single nucleotide polymorphism (SNP) arrays were performed for 11 PPGLs, including cases for which fresh frozen tissue was available. The immunohistochemical markers stained positive in the majority of canine PPGLs. Genetic screening of the canine tumors revealed the previously described variants in four cases; SDHB p.Arg38Gln ( n = 1) and SDHD p.Lys122Arg ( n = 3). Furthermore, the SNP arrays revealed large chromosomal alterations of which the loss of chromosome 5, partly homologous to human chromosome 1p and chromosome 11, was the most frequent finding (100% of the six cases with chromosomal alterations). In conclusion, canine and human PPGLs show similar genomic alterations, suggestive of common interspecies PPGL-related pathways., Competing Interests: The authors declare no conflict of interest

Obesity and inactivity are major risk factors of feline diabetes mellitus (FDM) and human type II diabetes mellitus (T2DM). In recent years, changes in the gut microbiota have been suggested as a contributing factor to T2DM. Whether the gut microbiota (GM) composition plays a role in FDM remains unknown. The aim of the current study was firstly a cross-sectional comparison of the GM of diabetic cats, to that of lean, and of obese/overweight non-diabetic cats of a similar age. Specifically, fecal samples from 82 privately-owned cats from Denmark and Switzerland were sequenced using 16S rRNA gene amplicon metabarcoding. Secondly dietary intervention data was generated, by obtaining additional samples from a subset of cats after placing them on a high-protein diet for four weeks. The GM diversity of diabetic cats was lower than that of lean cats in the cross-sectional study, and lower compared to lean and to overweight/obese cats after diet intervention. Diabetic cats also exhibited fewer Anaerotruncus, Dialister, and unknown Ruminococcaceae than lean cats. Serum fructosamine levels correlated negatively with Prevotellaceae abundance and positively with Enterobacteriaceae abundance. In summary the intestinal microbiota of diabetic cats was characterized by decreased GM diversity and loss of butyrate producing bacterial genera.

OBJECTIVE To describe perfusion and diffusion characteristics of the liver, spleen, and kidneys of healthy adult male cats as determined by morphological, perfusion-weighted, and diffusion-weighted MRI. ANIMALS 12 healthy adult male cats. PROCEDURES Each cat was anesthetized. Morphological, perfusion-weighted, and diffusion-weighted MRI of the cranial aspect of the abdomen was performed. A region of interest (ROI) was established on MRI images for each of the following structures: liver, spleen, cortex and medulla of both kidneys, and skeletal muscle. Signal intensity was determined, and a time-intensity curve was generated for each ROI. The apparent diffusion coefficient (ADC) was calculated for the hepatic and splenic parenchyma and kidneys on diffusion-weighted MRI images. The normalized ADC for the liver was calculated as the ratio of the ADC for the hepatic parenchyma to the ADC for the splenic parenchyma. RESULTS Perfusion-weighted MRI variables differed among the 5 ROIs. Median ADC of the hepatic parenchyma was 1.38 × 10 -3 mm 2 /s, and mean ± SD normalized ADC for the liver was 1.86 ± 0.18. Median ADC of the renal cortex and renal medulla was 1.65 × 10 -3 mm 2 /s and 1.93 × 10 -3 mm 2 /s, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results provided preliminary baseline information about the diffusion and perfusion characteristics of structures in the cranial aspect of the abdomen of healthy adult male cats. Additional studies of cats of different sex and age groups as well as with and without cranial abdominal pathological conditions are necessary to validate and refine these findings.

OBJECTIVE To evaluate the effects of storage conditions and duration on cobalamin concentration in serum samples from dogs and cats. DESIGN Experiment. SAMPLE Serum samples from 9 client-owned cats and 9 client-owned dogs. PROCEDURES Serum harvested from freshly obtained blood samples was separated into 11 aliquots/animal. One aliquot (baseline sample) was routinely transported in light-protected tubes to the laboratory for cobalamin assay; each of the remaining aliquots was stored in a refrigerator (6°C; n = 5) or at room temperature (20°C) with exposure to daylight (5) for 24, 48, 72, 96, or 120 hours. Aliquots were subsequently wrapped in aluminum foil, frozen (-20°C), and then transported to the laboratory for measurement of cobalamin concentration, all in the same run. Percentage decrease in cobalamin concentration from baseline was analyzed by means of linear mixed modeling. RESULTS No differences in cobalamin values were identified between cats and dogs; therefore, data for both species were analyzed together. Median baseline serum cobalamin concentration was 424 ng/L (range, 178 to 1,880 ng/L). Values for serum samples stored with daylight exposure at room temperature were significantly lower over time than were values for refrigerated samples. Although values for refrigerated samples did not decrease significantly from baseline values over time, values for the other storage condition did; however, the mean percentage decrease for serum samples stored at room temperature was small (0.14%/h; 95% confidence interval, 0.07% to 0.21%/h). CONCLUSIONS AND CLINICAL RELEVANCE Overall, serum cobalamin concentration appeared stable for 5 days when feline and canine serum samples were refrigerated at 6°C. The effect of light and room temperature on serum cobalamin concentration, although significant, was quite small for samples stored with these exposures for the same 5-day period.

With the aim to improve current therapeutic and monitoring options for diabetic cats, the present study compared pharmacodynamic parameters of protamine zinc insulin (PZI) and insulin degludec and validated the continuous glucose monitoring system (CGMS) iPro2 with Sof-sensor and Enlite-sensor focusing on the low glycemic range. Three doses (0.1, 0.2 and 0.3IU/kg) of the two insulin preparations and the CGMS iPro2 with two different sensors were tested in six healthy cats. After each insulin administration, onset of action, time to glucose nadir and duration of action were calculated by measuring glucose concentrations with a portable blood glucose meter (PBGM). After sensor placement, paired PBGM and sensor glucose measurements were done and analytical and clinical accuracy were calculated according to the ISO 15197:2013 criteria. Onset of action, time to glucose nadir and glucose nadir were similar for both insulin formulations. Duration of action of insulin degludec was significantly longer than those of PZI at 0.1IU/kg (P=0.043) and 0.2IU/kg (P=0.043). Overall, 166/191 (87%) Sof-sensor measurements and 106/121 (88%) Enlite-sensor measurements met ISO criteria for analytical accuracy, and all sensor measurements fulfilled ISO criteria for clinical accuracy. Insulin degludec was well tolerated in healthy cats and showed longer duration of action than PZI. Further studies on the use of insulin degludec in diabetic cats might be recommended. Both sensors had good clinical accuracy, when used with the CGMS iPro2, but the analytical accuracy was below the minimum set by ISO 15197:2013., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Little information is available about posthypoglycemic hyperglycemia (PHH) in diabetic cats, and a causal link between hypoglycemia and subsequent hyperglycemia is not clear. Fluctuations in blood glucose concentrations might only represent high glycemic variability., Hypothesis: Insulin induces PHH in healthy cats, and PHH is associated with poorly regulated diabetes and increased glycemic variability in diabetic cats., Animals: Six healthy cats, 133 diabetic cats., Methods: Insulin (protamine-zinc and degludec; 0.1-0.3 IU/kg) administered to healthy cats. Blood glucose curves were generated with portable glucose meter to determine the percentage of curves with PHH. Data from insulin-treated diabetic cats with blood glucose curves showing hypoglycemia included data of cats with and without PHH. Post-hypoglycemic hyperglycemia was defined as blood glucose concentrations <4 mmol/L followed by blood glucose concentrations >15 mmol/L within 12 hours. Glycemic variability was calculated as the standard deviation of the blood glucose concentrations., Results: In healthy cats, all insulin doses caused hypoglycemia but PHH was not observed; glycemic variability did not differ between insulin preparations. Among diabetic cats with hypoglycemia, 33 (25%) had PHH. Compared with cats without PHH, their daily insulin dose was higher (1.09 ± 0.55 versus 0.65 ± 0.56 IU/kg; P < .001), serum fructosamine concentration was higher (565 ± 113 versus 430 ± 112 µmol/L; P < .001), remission was less frequent (10% versus 56%; P < .001), and glycemic variability was larger (8.1 ± 2.4 mmol/L versus 2.9 ± 2.2 mmol/L; P < .001)., Conclusions and Clinical Importance: Insulin-induced hypoglycemia did not cause PHH in healthy cats but it occurred in 25% of diabetic cats with hypoglycemia, particularly when diabetes was poorly controlled. Glycemic variability was increased in cats with PHH., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Prospective studies on maintenance treatment for Beagles with hereditary selective cobalamin (Cbl) malabsorption (Imerslund-Gräsbeck syndrome, IGS) are lacking. In our experience, measurement of methylmalonic acid (MMA), a Cbl-dependent metabolite, seems more helpful to monitor Cbl status as compared with serum Cbl concentrations., Objectives: To evaluate a standardized Cbl supplementation scheme in Beagles with IGS. We hypothesized that a single parenteral dose of 1 mg hydroxocobalamin (OH-Cbl) would maintain clinical and metabolic remission for up to 2 months., Animals: Six client-owned juvenile Beagles with genetically confirmed IGS and 28 healthy control dogs., Methods: Prospective study. Monthly IM OH-Cbl (1 mg) supplementation was done over a median of 9 months (range, 6-13) in 6 dogs, followed by bimonthly (every 2 months) injections in 5 dogs over a median of 6 months (range, 3-10). Health status was assessed by routine clinical examinations at injection time points and owner observations. Voided urine samples were collected immediately before OH-Cbl injections for measurement of MMA-to-creatinine concentrations using a gas-liquid chromatography-tandem mass spectrometry (GC-MS) method., Results: All dogs were clinically healthy while receiving monthly and bimonthly OH-Cbl supplementation. Urinary MMA results in healthy dogs ranged from 1.3 to 76.5 mmol/mol creatinine (median, 2.9). Median urinary MMA concentrations did not differ between dogs with IGS receiving monthly (n = 49; 5.3 mmol/mol creatinine; range, 2.3-50.4) and bimonthly (n = 31; 5.3 mmol/mol creatinine; range, 1.6-50) injections., Conclusions and Clinical Importance: A maintenance parenteral dose of 1 mg OH-Cbl monthly or bimonthly appears adequate in Beagles with IGS monitored by metabolic testing., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Multiple endocrine neoplasia (MEN) is a well-known syndrome in human medicine, whereas only a few cases of concurrent endocrine neoplasias have been reported in dogs and cats. The aim of this study was to evaluate the prevalence of concurrent endocrine neoplasias in dogs and cats at our clinic, identify possible breed and sex predispositions and investigate similarities with MEN syndromes in humans. Postmortem reports of 951 dogs and 1155 cats that died or were euthanased at the Clinic for Small Animal Internal Medicine, University of Zurich, between 2004 and 2014 were reviewed, and animals with at least two concurrent endocrine neoplasias and/or hyperplasias were included. Twenty dogs and 15 cats met the inclusion criteria. In dogs, the adrenal glands were most commonly affected. Multiple tumours affecting the adrenal glands and the association of these tumours with pituitary adenomas were the most common tumour combinations. Only one dog had a combination resembling human MEN type 1 syndrome (pituitary adenoma and insulinoma). In cats, the thyroid glands were most commonly affected and there were no similarities to human MEN syndromes. The prevalence of concurrent endocrine neoplasia was 2.1 per cent in dogs and 1.3 per cent in cats and MEN-like syndromes are very rare in these species., Competing Interests: Competing interests: None declared., (© British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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 80ml 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 48h. 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objectives The aim of the study was to evaluate circulating insulin-like growth factor-1 (IGF-1), feline pancreas-specific lipase (fPLI) and total thyroxine (TT4) concentrations and urinary corticoid-to-creatinine ratio (UCCR) as indicators for the prevalence of acromegaly, pancreatitis, hyperthyroidism and hypercortisolism in cats with diabetes mellitus. Methods Blood and urine samples were collected from diabetic cats treated in primary care clinics in Switzerland and the Netherlands. Standardised questionnaires and physical examination forms provided clinical information from owners and veterinarians. Laboratory testing included serum biochemistry profile analysis and measurement of circulating fructosamine, IGF-1, fPLI, and TT4 concentrations and UCCR. CT of the pituitary gland was performed using a multidetector computed tomography scanner. Results Blood samples were available from 215 cats and urine samples were collected at home from 117 cats. Age ranged from 2-18 years (median 12 years) and body weight from 2.7-12.3 kg (median 5.5 kg). Sixty-five percent of the cats were castrated male and 35% were female (33% spayed); 82% were domestic shorthair cats. Eighty percent of cats received a porcine insulin zinc suspension, 19.5% insulin glargine and 0.5% a human neutral protamine hagedorn insulin. Thirty-six of 202 (17.8%) cats had IGF-1 concentrations >1000 ng/ml. Serum fPLI, and TT4 concentrations and UCCR were increased in 86/196 (43.9%), 9/201 (4.5%) and 18/117 cats (15.3%), respectively. Prevalence did not differ between countries. Conclusions Hyperthyroidism is rare, whereas increased fPLI concentration, possibly reflecting pancreatitis, is common in diabetic cats. The high UCCR may reflect activation of the hypothalamus-pituitary-adrenal axis, which also occurs in diabetic humans. The percentage of cats with increased IGF-1 was high but lower than reported in recent studies.

Background: Leptospirosis is a re-emerging bacterial zoonosis caused by spirochetes of the genus Leptospira. Severe disease has been reported in dogs in Europe despite vaccination with bivalent Leptospira vaccines. Recently, a tetravalent canine Leptospira vaccine (Nobivac® L4) was licenced in Europe. The goal of this study was to investigate clinical signs, microscopic agglutination test (MAT) titres, haematology, blood biochemistry, cardiac (c) Troponin I levels and echocardiography before and after vaccination with this tetravalent vaccine. Forty-eight healthy dogs were prospectively enrolled and vaccinated twice, 3-4 weeks apart (T0 and T1). Before vaccination (T0) and 16-31 days after the second vaccination (T2), MAT (n = 48), haematology (n = 48), blood biochemistry (n = 36) and cTroponin I measurements (n = 29) were performed, and MAT was repeated 347-413 days after the second vaccination (T3, n = 44). Echocardiography was performed before the first and second vaccination (T0 and T1, n = 24)., Results: Mild and transient clinical signs within 5 days following the first and second vaccination occurred in 23% and 10% of the dogs, respectively. Before the first vaccination (T0), all dogs showed negative MAT titres for the tested serovars except for Canicola (50% with titres 100-400). At T2, positive MAT titres to the serovars Canicola (100%), Australis (89%), Grippotyphosa (86%), Bratislava (60%), Autumnalis (58%), Copenhageni (42%), Pomona (12%), Pyrogenes (8%) and Icterohaemorrhagiae (2%) were found. Median to high titres (≥ 400) were most common to the serovar Canicola (92%) and less common to the serovars Australis (41%), Grippotyphosa (21%), Bratislava (12%), Autumnalis (4%), Pyrogenes (4%) and Pomona (2%). At T3, positive MAT titres (titre range: 100-400) were found in 2-18% of the dogs to serovars of the vaccine serogroups and in 2-18% of the dogs to the non-vaccine serovars Pomona, Autumnalis, Pyrogenes and Ballum. Haematology, blood biochemistry, cTroponin I levels and echocardiography results did not change significantly following vaccination., Conclusions: Clinical signs following vaccination with Nobivac® L4 were transient and mild in all cases. Seroconversion differed considerably among individual dogs and among the vaccine serogroups.

The aim of this study was to examine the safety and reliability of a research-grade implantable pump for controlled delivery of insulin glargine in cats. For this purpose, a small telemetrically controlled drug delivery pump with a refillable reservoir was implanted into the subcutaneous tissues of the dorsal neck in 10 clinically healthy cats. The reservoir was filled with insulin glargine, and the pump was programmed to deliver four boluses of 0.25 IU/kg, 2-3 weeks apart. As a control, insulin glargine (0.25 IU/kg) was injected SC. Blood glucose and plasma insulin glargine concentrations were measured before each bolus and SC injection and for 8 h afterward. Cats were monitored for signs of discomfort. Pumps were easily implanted and well tolerated by all cats. The experiment was completed in five of 10 cats. In four, the pump failed because of technical reasons; another cat developed severe hypoglycaemia attributable to insulin leakage. Overall, plasma insulin glargine increased after six of eight (75%) initial boluses and after one of 16 (6%) successive boluses. Glucose decreased after seven of eight (88%) initial boluses and after four of 16 (25%) successive boluses. Only the first bolus significantly increased plasma insulin glargine (P = 0.008) and decreased glucose (P = 0.008). Of 20 SC injections, 10 (50%) increased plasma insulin glargine (P <0.001) and 12 (60%) decreased glucose (P <0.001). The pump did not cause discomfort in cats, but life-threatening hypoglycaemia occurred in one. Frequent device problems suggest that the pump needs improvements. Because successive boluses did not increase plasma insulin glargine, this type of insulin may not be appropriate with the pump., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Trilostane therapy, the treatment of choice for pituitary- dependent hyperadrenocorticism (HAC) in dogs, is monitored by assessing resolution of clinical signs and measuring adrenocortical reserve capacity with an ACTH-stimulation test. The aim of this prospective study was to evaluate agreement between clinical signs reported by owners and cortisol or ACTH concentrations before and during trilostane therapy (starting dose 1-2 mg/kg once daily). A questionnaire on signs of HAC was used and a clinical score calculated as the sum of the 9 questions. Eighteen questionnaires at diagnosis and 97 during therapy were filled out by owners of 32 dogs. An ACTH-stimulation test was performed at each reevaluation. There were weak correlations between abdominal girth, appetite or weight gain and cortisol concentrations during therapy. However, the clinical score did not correlate with cortisol or cACTH values. In 50% of dogs, trilostane application had to be changed from once daily to twice daily during the study. Clinical signs reported by owners matched poorly with cortisol or cACTH concentrations at any time point. If low-dose trilostane is used, treatment frequency often has to be increased.

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., 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., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: To assess the effects of 3 contrast medium injection techniques on attenuation values for canine adrenal glands during contrast-enhanced CT., Animals: 9 healthy Beagles., Procedures: 3 protocols were evaluated in a randomized cross-over design study: 700 mg of iodine/kg at a constant injection rate over 20 seconds (full-dose constant rate), the same dose at a rate following an exponential decay curve over 20 seconds (full-dose decelerated rate), and 350 mg of iodine/kg at a constant injection rate over 10 seconds (half-dose constant rate). Multislice CT images were obtained before and at predetermined time points after the start of contrast medium injection., Results: Median peak attenuation values were 129, 133, and 87 Hounsfield units with the full-dose constant rate, full-dose decelerated rate, and half-dose constant rate injection protocols, respectively. Peak attenuation differed significantly between the full-dose constant rate and half-dose constant rate injection protocols and between the full-dose decelerated rate and half-dose constant rate injection protocols. Median time to peak attenuation did not differ significantly among injection methods and was 30, 23, and 15 seconds for the full-dose constant rate, full-dose decelerated rate, and half-dose constant rate injections, respectively., Conclusions and Clinical Relevance: The dose of contrast medium and the timing of postinjection CT scanning were main determinants of peak attenuation for adrenal glands in healthy dogs; effects of the 3 injection protocols on attenuation were minor. The exponentially decelerated injection method was subjectively complex. A constant injection protocol delivering 700 mg of iodine/kg over 20 seconds, with scans obtained approximately 30 seconds after starting contrast medium injection, provided images with maximum adrenal gland attenuation values.

Gastrointestinal (GI) protein loss, due to lymphangiectasia or chronic inflammation, can be challenging to diagnose. This study evaluated the diagnostic accuracy of serum and fecal canine α1-proteinase inhibitor (cα1PI) concentrations to detect crypt abscesses and/or lacteal dilation in dogs. Serum and fecal cα1PI concentrations were measured in 120 dogs undergoing GI tissue biopsies, and were compared between dogs with and without crypt abscesses/lacteal dilation. Sensitivity and specificity were calculated for dichotomous outcomes. Serial serum cα1PI concentrations were also evaluated in 12 healthy corticosteroid-treated dogs. Serum cα1PI and albumin concentrations were significantly lower in dogs with crypt abscesses and/or lacteal dilation than in those without (both P <0.001), and more severe lesions were associated with lower serum cα1PI concentrations, higher 3 days-mean fecal cα1PI concentrations, and lower serum/fecal cα1PI ratios. Serum and fecal cα1PI, and their ratios, distinguished dogs with moderate or severe GI crypt abscesses/lacteal dilation from dogs with only mild or none such lesions with moderate sensitivity (56-92%) and specificity (67-81%). Serum cα1PI concentrations increased during corticosteroid administration. We conclude that serum and fecal α1PI concentrations reflect the severity of intestinal crypt abscesses/lacteal dilation in dogs. Due to its specificity for the GI tract, measurement of fecal cα1PI appears to be superior to serum cα1PI for diagnosing GI protein loss in dogs. In addition, the serum/fecal cα1PI ratio has an improved accuracy in hypoalbuminemic dogs, but serum cα1PI concentrations should be carefully interpreted in corticosteroid-treated dogs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Pancreatic amyloidosis and loss of α and β cells have been shown to occur in cats with diabetes mellitus, although the number of studies currently available is very limited. Furthermore, it is not known whether pancreatic islet inflammation is a common feature. The aims of the present study were to characterize islet lesions and to investigate whether diabetic cats have inflammation of the pancreatic islets. Samples of pancreas were collected postmortem from 37 diabetic and 20 control cats matched for age, sex, breed, and body weight. Histologic sections were stained with hematoxylin and eosin and Congo red; double labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/proliferating cell nuclear antigen, and glucagon/Ki67; and single labeled for amylin and Iba1. Mean insulin-positive cross-sectional area was approximately 65% lower in diabetic than control cats (P = .009), while that of amylin and glucagon was similar. Surprisingly, amyloid deposition was similar between groups (P = .408). Proliferation of insulin- and glucagon-positive cells and the number of neutrophils, macrophages, and T (CD3) and B (CD20) lymphocytes in the islets did not differ. The presence of T and B lymphocytes combined tended to be more frequent in diabetic cats (n = 8 of 37; 21.6%) than control cats (n = 1 of 20; 5.0%). The results confirm previous observations that loss of β cells but not α cells occurs in diabetic cats. Islet amyloidosis was present in diabetic cats but was not greater than in controls. A subset of diabetic cats had lymphocytic infiltration of the islets, which might be associated with β-cell loss., (© The Author(s) 2015.)

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., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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 i.v. 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., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: To investigate the effects of insulin detemir in dogs with diabetes mellitus., Design: Prospective, uncontrolled clinical trial., Animals: 10 client-owned dogs with naturally occurring diabetes mellitus., Procedures: Dogs were treated with insulin detemir SC every 12 hours for 6 months. Follow-up evaluations were done at 1, 2, 4, 12, and 24 weeks and included evaluation of clinical signs and measurement of blood glucose concentration curves and serum fructosamine concentrations., Results: Insulin detemir administration resulted in a significant decrease in blood glucose and serum fructosamine concentrations at 6 months, compared with pretreatment values. Median insulin dosage at the end of the study was 0.12 U/kg (0.055 U/lb; range, 0.05 to 0.34 U/kg [0.023 to 0.155 U/lb], SC, q 12 h). Hypoglycemia was identified in 22% (10/45) of the blood glucose concentration curves, and 6 episodes of clinical hypoglycemia in 4 dogs were recorded. A subjective improvement in clinical signs was observed in all dogs during the 6-month study period. On the basis of clinical signs and blood glucose concentration curves, efficacy of insulin detemir at the end of the study was considered good in 5 dogs, moderate in 3, and poor in 2., Conclusions and Clinical Relevance: Results suggested that SC injection of insulin detemir every 12 hours may be a viable treatment for diabetes mellitus in dogs. Insulin detemir dosages were lower than reported dosages of other insulin types needed to maintain glycemic control, suggesting that insulin detemir should be used with caution, especially in small dogs.

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, 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., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.)

Incretin analogues and inhibitors of the breakdown of endogenous incretins are antidiabetic drugs that increase β-cell proliferation and glucose-stimulated insulin secretion in rodents and humans. Objectives were to test whether exenatide, exenatide extended-release, and sitagliptin can be safely used in cats, to identify the most effective drug, and to test the effects of prolonged exenatide extended-release administration. Three cats each were given exenatide (0.2-2 µg/kg, q12h, subcutaneously, 5 days), exenatide extended-release (40-400 µg/kg, subcutaneously, once), and sitagliptin (1-10 mg/kg, q24h, orally, 5 days). Before and after treatment, glucose, insulin and glucagon areas under the curve (AUC) were assessed by meal response tests (MRT). Exenatide increased insulin AUC by 224%, 258%, 331% and 93%, exenatide extended-release by 127%, 169%, 178% and 95%, and sitagliptin by 32%, 69%, 62%, and 43%, respectively. The tested drugs are safe to use in cats and enhance insulin secretion. Incretin-based therapy may be beneficial in cats with diabetes mellitus., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Practical Relevance: Diabetes mellitus (DM) is a common endocrinopathy in cats that appears to be increasing in prevalence. The prognosis for affected cats can be good when the disease is well managed, but clinical management presents challenges, both for the veterinary team and for the owner. These ISFM Guidelines have been developed by an independent, international expert panel of clinicians and academics to provide practical advice on the management of routine (uncomplicated) diabetic cats., Clinical Challenges: Although the diagnosis of diabetes is usually straightforward, optimal management can be challenging. Clinical goals should be to limit or eliminate clinical signs of the disease using a treatment regimen suitable for the owner, and to avoid insulin-induced hypoglycaemia or other complications. Optimising bodyweight, feeding an appropriate diet and using a longer acting insulin preparation (eg, protamine zinc insulin, insulin glargine or insulin detemir) are all factors that are likely to result in improved glycaemic control in the majority of cats. There is also some evidence that improved glycaemic control and reversal of glucose toxicity may promote the chances of diabetic remission. Owner considerations and owner involvement are an important aspect of management. Provided adequate support is given, and owners are able to take an active role in monitoring blood glucose concentrations in the home environment, glycaemic control may be improved. Monitoring of other parameters is also vitally important in assessing the response to insulin. Insulin adjustments should always be made cautiously and not too frequently--unless hypoglycaemia is encountered., Evidence Base: The Panel has produced these Guidelines after careful review of the existing literature and of the quality of the published studies. They represent a consensus view on practical management of cats with DM based on available clinical data and experience. However, in many areas, substantial data are lacking and there is a need for better studies in the future to help inform and refine recommendations for the clinical management of this common disease., (© ISFM and AAFP 2015.)

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., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Information on composition of uroliths collected between 2003 and 2009 from dogs in Switzerland and epidemiologic data of affected dogs are summarised in this paper. Of 490 stones analysed 44% were composed of calcium oxalate, 330% of struvite, 80% of silica, 7% of urate, 3% of cystine, 3% were mixed stones and 1% each were calcium phosphate and xanthine stones. Compared to other dogs, Norwich Terriers, Norfolk Terriers, Miniature Schnauzers, Miniature Pinscher and Yorkshire Terriers had a significantly increased risk to suffer from calcium oxalate stones, Dalmatians and Continental Bulldogs from urate stones and English Bulldogs from cystine stones. No breed had an increased risk of struvite or silica stones. Stones composed of silica were more prevalent in Switzerland compared to other countries and were more common in the eastern part than in the western part of Switzerland. This study shows that there are differences in occurrence and prevalence of uroliths between Switzerland and surveys of other countries.

In humans, diabetes mellitus (DM) is an important cause of renal damage, with glomerular lesions being predominant. In cats, although diabetes is a common endocrinopathy, it is yet unknown whether it leads to renal damage. The aim of the study was to compare renal histologic features and parameters of renal function in diabetic cats against a control population matched for age, gender, breed, and body weight. Thirty-two diabetic and 20 control cats were included. Kidney sections from paraffin-embedded kidney samples were stained and examined with optical microscopy to identify glomerular, tubulointerstitial, and vascular lesions and to assess their frequency and severity. Serum creatinine and urea concentrations were also compared. Glomerular lesions were observed in 29 cats overall, with mesangial matrix increase being more common (19 cats). Tubulointerstitial lesions were observed in 42 cats, including lymphocytic infiltration (29), fibrosis (22), or tubular necrosis (21). Vascular lesions were observed in 5 cases. The frequency and severity of histologic lesions did not differ between diabetic and control cats; however, among diabetics, those that survived longer after diagnosis had more glomerular and vascular lesions. Serum creatinine and urea concentrations were similar between groups; in diabetic cats median creatinine was 109 μmol/l (range, 51-1200) and urea was 12 mmol/l (range, 4-63), and in controls creatinine was 126 μmol/l (range, 50-875) and urea 11 mmol/l (range, 3-80). The results suggest that DM in cats does not lead to microscopically detectable kidney lesions or clinically relevant renal dysfunction. The authors hypothesize that the short life expectancy of diabetic cats may be the main reason for the difference from human diabetics., (© The Author(s) 2014.)

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., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)