Clinical features and long-term management of cats with primary hypoadrenocorticism using desoxycorticosterone pivalate and prednisolone.

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.

Evaluation of symmetric dimethylarginine and creatinine in dogs with primary hypoadrenocorticism receiving long-term mineralocorticoid replacement therapy.

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.

Serum insulin-like growth factor-1 concentrations in healthy cats before and after weight gain and weight loss.

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.

Feline plasma adrenocorticotropic hormone: validation of a chemiluminescent assay and concentrations in cats with hypercortisolism, primary hypoadrenocorticism and other diseases.

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 (R2 >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.

Sample strategies for quantification of hepatic fat fraction mean MRI in healthy cats during body weight gain.

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.

Glycemic variability in newly diagnosed diabetic cats treated with the glucagon-like peptide-1 analogue exenatide extended release.

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.

Evaluation of the changes in hepatic apparent diffusion coefficient and hepatic fat fraction in healthy cats during body weight gain.

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/mm2). 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 mm2/s and 1.01 ± 0.2 × 10-3 mm2/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.

Oxidative status of erythrocytes, hyperglycemia, and hyperlipidemia in diabetic cats.

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.

Diabetic remission in a cat treated with an implantable pump to deliver insulin.

A diabetic cat was referred because of poor metabolic control and difficulties the owner experienced injecting insulin. A pump, telemetrically controlled with a smartphone, was implanted subcutaneously to deliver insulin. Before implantation, the pump reservoir was filled with a rapid-acting human recombinant insulin. The insulin was administered through continuous infusion or periodic boluses over 2 weeks while the cat was hospitalized and over another 2 weeks after discharge from the hospital. Adjustments of insulin dosage were performed based on blood glucose concentrations measured with a continuous blood monitoring system (CGMS). The cat achieved diabetic remission that is still lasting after 1 year. The treatment protocol adopted in this cat contributed to achieving remission. The owner's unwillingness to inject insulin into an uncooperative cat was circumvented with the implantable pump. Key clinical message: The implantable subcutaneous pump, telemetrically controlled by a smartphone, easily allowed the clinician to modify the type of administration and the amount of insulin delivered; the concurrent use of a CGMS allowed detection of sudden changes in blood glucose while limiting stress to the cat.

Rémission du diabète chez un chat traité avec une pompe implantable pour administrer l'insuline.Un chat diabétique fut référé pour cause de pauvre contrôle métabolique et des difficultés rencontrées par le propriétaire pour injecter l'insuline. Une pompe, contrôlée par télémétrie avec un téléphone intelligent, fut implantée sous-cutané afin d'injecter l'insuline. Avant l'implantation, le réservoir de la pompe fut rempli avec une insuline humaine recombinante à action rapide. L'insuline était administrée par infusion continue ou des bolus périodiques pendant une période de 2 semaines alors que le chat était hospitalisé et pendant un 2 semaines supplémentaires après avoir obtenu son congé de l'hôpital. Des ajustements du dosage de l'insuline furent effectués sur la base des concentrations de glucose sanguin mesurées par un système continu de surveillance du sang (CGMS). Une rémission du diabète fut possible pour ce chat et persiste toujours après 1 an. Le protocole de traitement adopté chez ce chat a contribué à atteindre cette rémission. La réticence du propriétaire à injecter l'insuline chez un chat non-collaborateur fut contournée par une pompe implantable.Message clinique important :La pompe implantable sous-cutanée, contrôlée par télémétrie avec un téléphone intelligent, a facilement permis au clinicien de modifier le type d'administration et la quantité d'insuline donnée; l'utilisation concomitante d'un CGMS a permis la détection de changements soudains dans la glycémie tout en limitant le stress au chat.(Traduit par Dr Serge Messier).

Molecular Alterations in Dog Pheochromocytomas and Paragangliomas.

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.

Diabetic cats have decreased gut microbial diversity and a lack of butyrate producing bacteria.

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.

Evaluation of a low-dose desoxycorticosterone pivalate treatment protocol for long-term management of dogs with primary hypoadrenocorticism.

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.

Perfusion-weighted and diffusion-weighted magnetic resonance imaging of the liver, spleen, and kidneys of healthy adult male cats.

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 mm2/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 mm2/s and 1.93 × 10-3 mm2/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.

Effects of storage conditions and duration on cobalamin concentration in serum samples from cats and dogs.

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.

Glucose concentrations after insulin-induced hypoglycemia and glycemic variability in healthy and diabetic cats.

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.

Comparison of the pharmacodynamics of protamine zinc insulin and insulin degludec and validation of the continuous glucose monitoring system iPro2 in healthy cats.

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.

Concurrent endocrine neoplasias in dogs and cats: a retrospective study (2004-2014).

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.

Clinical, serological and echocardiographic examination of healthy field dogs before and after vaccination with a commercial tetravalent leptospirosis vaccine.

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.

Evaluation of insulin-like growth factor-1, total thyroxine, feline pancreas-specific lipase and urinary corticoid-to-creatinine ratio in cats with diabetes mellitus in Switzerland and the Netherlands.

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.

Effects of contrast medium injection technique on attenuation values of adrenal glands in healthy dogs during contrast-enhanced computed tomography.

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.