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Background: The use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned. Objectives: To evaluate and compare 12 methods with which to monitor efficacy of trilostane treatment in dogs with HC. Animals: Forty-five client-owned dogs with HC treated with trilostane q12h. Methods: Prospective cross-sectional observational study. The dogs were categorized as well-controlled, undercontrolled, and unwell through a clinical score obtained from an owner questionnaire. The ability to correctly identify trilostane-treatment control of dogs with HC with the following variables was evaluated: before trilostane serum cortisol (prepill), before-ACTH serum cortisol, post-ACTH serum cortisol, plasma endogenous ACTH concentrations, prepill/eACTH ratio, serum haptoglobin (Hp) concentration, serum alanine aminotransferase (ALT), gamma-glutamyl transferase (γGT) and alkaline phosphatase activity, urine specific gravity, and urinary cortisol:creatinine ratio. Results: Ninety-four re-evaluations of 44 dogs were included; 5 re-evaluations of 5 unwell dogs were excluded. Haptoglobin was significantly associated with the clinical score (P

The objective of this study was to evaluate the safety and efficacy of insulin glargine in dogs with diabetes mellitus (DM). Twelve client-owned dogs with DM were included. All dogs received insulin glargine every 12 hours for at least six months, re-evaluations were performed after one, two, four, eight, 12 and 24 weeks and included clinical signs, blood glucose curves (BGCs) and measurement of serum fructosamine concentrations. Mean blood glucose concentrations were significantly lower after two weeks of treatment and remained significantly lower for the duration of the study. By week 24, polyuria/polydipsia had improved in 91 per cent of the dogs. No clinical signs that could have been caused by hypoglycaemia were observed. Based on BGCs and remission of the clinical signs for judging the success of the treatment, 58, 33 and 8 per cent of the dogs attained good, moderate and poor glycaemic control by week 24 of the study, respectively. Insulin glargine administered subcutaneously twice daily is a possible and safe method of treatment for dogs with naturally occurring DM. Although only a few studies are available on the use of other types of insulin in dogs, their success rate is somewhat greater than that with insulin glargine.

Background Hypercortisolism affects calcium and phosphate metabolism in dogs; however, the exact mechanisms are not completely understood. Objectives To evaluate circulating concentrations of whole parathormone (wPTH), 25‐hydroxyvitamin D (25‐(OH)D), calcitriol, and fibroblast growth factor‐23 (FGF‐23) in dogs with naturally occurring hypercortisolism (NOHC) and healthy dogs, and their association with calcium and phosphate homeostasis. Animals Twenty‐three client‐owned dogs with NOHC, and 12 client or staff‐owned healthy dogs. Methods Prospective cross‐sectional study. The circulating concentrations of total calcium, ionized calcium (iCa), phosphate, wPTH, 25‐(OH)D, calcitriol and FGF‐23, and the urinary fractional excretion of phosphate (FEP) and calcium (FECa) were compared between dogs with NOHC before treatment and healthy dogs. Results Dogs with NOHC had higher mean serum phosphate concentrations (4.81 mg/dL, SD ± 0.71 vs 3.86 mg/dL, SD ± 0.60; P

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.

Retroperitoneal paragangliomas are rare tumors of the neuroendocrine system. Only a few canine case reports are available with rare descriptions of their imaging features. The objectives of this multi-center, retrospective case series study were to describe the diagnostic imaging features of confirmed retroperitoneal paragangliomas and specify their location. Medical records and imaging studies of 10 affected dogs with cytological or histopathologic results concordant with retroperitoneal paragangliomas were evaluated. Dogs had a median age of 9 years. Four of them had clinical signs and laboratory reports compatible with excessive production of catecholamines. Six ultrasound, four CT, four radiographic, and one MRI studies were included. The paragangliomas did not have a specific location along the aorta. They were of various sizes (median 33mm, range: 9–85mm of length). Masses had heterogeneous parenchyma in six of 10 dogs, regardless of the imaging modality. Strong contrast enhancement was found in all CT studies. Encircling of at least one vessel was detected in six of 10 masses, clear invasion of a vessel was identified in one of 10 masses. In five of 10 cases, the masses were initially misconstrued as lymph nodes by the on-site radiologist. Retroperitoneal paragangliomas appear along the abdominal aorta, often presenting heterogeneous parenchyma, possibly affecting the local vasculature, and displaying strong contrast enhancement on CT. Clinical signs can be secondary to mass effects or excessive catecholamine production. Underdiagnosis and misdiagnosis of this tumor are suspected as they can be silent, of small size, or confused with other structures.

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.

Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as diagnostic (presence of PDH or csACT) and/or prognostic (disease recurrence, histological grade) non-invasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10−4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of

Background A factory-calibrated flash glucose monitoring system (FGMS; FreeStyle Libre) recently was evaluated in dogs with uncomplicated diabetes mellitus. It is not known if this system is reliable during diabetic ketoacidosis (DKA). Objectives To assess the performance of the FGMS in dogs with DKA and to determine the effect of severity of ketosis and acidosis, lactate concentration, body condition score (BCS), and time wearing the sensor on the accuracy of the device. Animals Fourteen client-owned dogs with DKA. Methods The interstitial glucose (IG) measurements were compared with blood glucose (BG) measurements obtained using a validated portable glucometer. The influence of changes in metabolic variables (β-hydroxybutyrate, pH, bicarbonate, and lactate) and the effect of BCS and time wearing on sensor performance were evaluated. Accuracy was determined by fulfillment of ISO15197:2013 criteria. Results Metabolic variables, BCS, and time wearing were not associated with the accuracy of the sensor. Good agreement between IG measurements and BG was obtained both before and after DKA resolution (r = .88 and r = .93, respectively). Analytical accuracy was not achieved, whereas clinical accuracy was demonstrated with 100% and 99.6% of results in zones A + B of the Parkes consensus error grid analysis before and after DKA resolution, respectively. Conclusions and clinical importance Changes in metabolic variables, BCS, and time wearing do not seem to affect agreement between IG and BG. Despite not fulfilling the ISO requirements, the FGMS provides clinically accurate estimates of BG in dogs with DKA.

Background Improvement in cardiac function has been demonstrated after thyroxine treatment in humans with hypothyroidism using the myocardial performance index (MPI). Cardiac changes after thyroxine supplementation are poorly documented in dogs with spontaneous hypothyroidism and comparison with clinically healthy dogs is lacking. Objectives To evaluate the electrical activity and mechanical function of the heart in dogs with primary hypothyroidism at baseline (T0) and after thyroxine supplementation (T60). Animals Forty client‐owned dogs with hypothyroidism and 20 clinically healthy dogs. Methods Prospective cohort study. Selected electrocardiographic and echocardiographic variables, including the MPI, were measured in all dogs at T0 and in 30 hypothyroid dogs at T60. Results Hypothyroid dogs had significantly decreased median or mean heart rate (HR), P wave amplitude, and R wave amplitude (P = .04, P = .002, and P = .003, respectively) and E‐point‐to‐septal separation normalized to body weight (EPSSn) and trans‐mitral E wave velocity (E max; P

Background: Hyperthyroidism is a common endocrinopathy of middle-aged and elderly cats. Dietary treatment has been proposed as an alternative to traditional therapies. Aim: The aim of this prospective study was to compare the efficacy of iodine-restricted food versus pharmacological therapy with methimazole in client-owned cats with hyperthyroidism. Methods: Indoor cats with newly diagnosed hyperthyroidism (consistent clinical signs and serum total thyroxine concentration greater than 50 nmol/l) were assigned to one of three groups: (A) received an iodine-restricted food as a single therapy; (B) received transdermal methimazole in pluronic lecithin organogel; and (C) received oral methimazole. In all groups, clinical parameters, biochemistry, and serum total thyroxine were evaluated at baseline and 10, 30, 60, and 90 days after treatment began. Results: Thirty-four cats were enrolled in the study (group A: n = 14; group B: n = 11; group C: n = 9). No significant differences were found between groups at diagnosis for signalment, clinical and laboratory findings, including serum total thyroxine concentrations. In all the groups, serum total thyroxine concentration decreased significantly following the baseline measurement. After 90 days of treatment, serum creatinine increased significantly only in the methimazoletreated groups. Liver enzyme activities decreased significantly only in group B, while no significant decreases were detected in groups A and C at any time. Conclusion: These results suggest that iodine-restricted food is effective at reducing the total thyroxine concentration in the serum of hyperthyroid cats. Moreover, the iodine-restricted food did not cause any increase in serum creatinine concentrations and failed to improve liver enzymes abnormalities. These findings could indicate a persistent hyperthyroid state in cats treated with iodine-restricted food despite normalization of serum total thyroxine concentrations. Keywords: Iodine-restricted food, Liver enzymes, Methimazole, Pluronic lecithin organogel, Thyroxine.

This study aims to gather knowledge about the use of deoxycorticosterone pivalate (DOCP) by Western European Veterinarians (WEV) in dogs with typical hypoadrenocorticism. An observational cross-sectional study was conducted using an online survey, translated into four languages and disseminated to veterinary affiliates and mailing lists in six countries of Western Continental Europe. Respondents were tasked to share their therapeutic approach to hypoadrenocorticism, whether they preferred DOCP or fludrocortisone and the specific practical use of DOCP. One-hundred and eighty-four responses were included. Of these, 79.9% indicated that they preferred prescribing DOCP over fludrocortisone as a first-line treatment for mineralocorticoid supplementation. A total of 154 respondents had used DOCP at least once. Eighty percent of those who reported their initial dosage prescribed 2.2 mg/kg. After starting DOCP, 68.2% of the respondents assess electrolytes 10 and 25 days after administration following manufacturer instructions. In stable dogs, electrolytes are monitored quarterly, monthly, semi-annually, and annually by 44.2%, 34.4%, 16.9%, and 4.6% of respondents respectively. When treatment adjustment is required, 53% prefer to reduce dosage while 47% increase the interval between doses. Overall, DOCP is the preferred mineralocorticoid supplementation among WEV. Reported variability underlies the need to investigate the best strategies for DOCP use and therapeutic adjustments.

The aim of this retrospective single-center study was to evaluate which factors, including expression of P-glycoprotein (P-gp), a membrane-bound protein involved in multiple drug resistance, could predict the response to treatment in canine immunosuppressant-responsive enteropathy (IRE). Dogs with IRE or non-responsive enteropathy (NRE) that were examined from 2005 to 2014 were included and were divided into two groups (IRE vs. NRE). Signalment, history, and clinical and laboratory findings were collected. P-glycoprotein immunohistochemistry was carried out on duodenal biopsies of both groups stored in our biobank, and immunophenotyping and molecular clonality were performed on the NRE samples. Ninety-two dogs were enrolled, 73 IRE (79.3%) and 19 NRE (20.7%), with a prevalence of pure breed (78.3% vs. 21.7%) and male dogs (p &lt, 0.001). Factors associated with a worse prognosis were previous treatment with steroids (p = 0.033) and lower serum total protein concentration (p = 0.005). Clonality testing on the NRE duodenal biopsies showed 5/16 clonal responses, assuming a latent undiagnosed lymphoma as a possible cause of the NRE.

1,2-O-dilauryl-rac-glycero glutaric acid-(6′-methylresorufin) ester (DGGR) lipase activity has been proposed as a faster and less expensive test used in the diagnosis of acute pancreatitis (AP) compared to canine pancreatic lipase immunoreactivity (cPLI), which is considered the most sensitive and specific serum test available for dogs. Elevations in lipase activity have been observed in dogs with naturally occurring hypercortisolism (HC) and in those treated with exogenous steroids, which complicates the diagnosis of AP in dogs with HC. We compared lipase activity measured by DGGR and 1,2-diglyceride (1,2-DiG) assays in 22 dogs with HC, 22 with AP, and 22 healthy dogs. The dogs with HC had no clinical signs or ultrasonographic findings consistent with AP. DGGR lipase activity was elevated in 64% and 73% of the dogs with HC and AP, respectively, and in 18% of healthy dogs. 1,2-DiG lipase activity was high in 23% and 36% of the dogs with HC and AP, respectively, and in 5% of the healthy dogs. Both DGGR and 1,2-DiG lipase activities were significantly different between the healthy dogs and the other 2 groups, whereas no differences were detected between the dogs with HC and those with AP. Our results support a lack of specificity for both DGGR and 1,2-DiG lipase activity assays in aiding the diagnosis of AP in dogs with HC.

Background The FreeStyle Libre (Abbott Laboratories) is a flash glucose monitoring system (FGMS) that measures interstitial glucose concentration (IG). The system is factory-calibrated, easy to use, inexpensive, and could be useful for monitoring diabetic cats. Objectives To evaluate the analytical and clinical accuracy of the FGMS in cats and establish the lag-time between IG and blood glucose concentration (BG). Animals Twenty client-owned diabetic cats and 7 purpose-bred healthy cats. Methods Prospective study. Blood glucose concentration was measured using a portable glucose meter validated for use in cats that served as a reference method for IG, as measured by FGMS. In diabetic cats, data were collected for sensor wearing time with different methods of application and accuracy across glycemic ranges. Accuracy was determined by fulfillment of ISO15197:2013 criteria. In healthy cats, lag-time between IG and BG was established after IV administration of exogenous glucose. Results Good agreement between IG and BG was obtained (r = .93). Analytical accuracy was not achieved, whereas clinical accuracy was demonstrated with 100% of the results in zones A + B of the Parkes consensus error grid analysis. In the immediate 30 minutes after an IV bolus of glucose, when BG was increasing rapidly (approximately 2%/min), IG increased slowly, resulting in a difference of as much as 579 mg/dL, and no positive correlation between BG and IG was found. Conclusions and clinical importance The FGMS did not fulfill ISO requirements but is sufficiently accurate for glucose monitoring in cats, while considering the lag between IG and BG during periods of rapid changes in BG.

Background Successful treatment of cats with hypersomatotropism by transsphenoidal hypophysectomy is described in small numbers of cats. Objectives To describe the endocrine profile, survival, and remission rates of hypersomatotropism and diabetes mellitus in a cohort of cats with hypersomatotropism that underwent hypophysectomy between 2008 and 2020. Animals Twenty-five client-owned cats with spontaneous hypersomatotropism. Methods Retrospective study. Diagnosis of hypersomatotropism was based on clinical signs, plasma insulin-like growth factor-1 (IGF-1) concentration, and imaging of the pituitary gland. Growth hormone (GH) and IGF-1 concentrations were measured repeatedly after surgery. Survival times were calculated based on follow-up information from owners and referring veterinarians. Results Median postoperative hospital stay was 7 days (range, 3-18 days). One cat died within 4 weeks of surgery. Median plasma GH concentration decreased significantly from 51.0 ng/mL (range, 5.0-101.0 ng/mL) before surgery to 3.8 ng/mL (range, 0.6-13.0 ng/mL) at 5 hours after surgery. Remission of hypersomatotropism, defined as normalization of plasma IGF-1 concentration, occurred in 23/24 cats (median, 34 ng/mL; range, 14-240 ng/mL) and 22/24 cats entered diabetic remission. Median survival time was 1347 days (95% confidence interval, 900-1794 days; range, 11-3180 days) and the overall 1-, 2-, and 3-year all-cause survival rates were 76%, 76%, and 52%, respectively. Conclusions and clinical importance This study shows the beneficial outcome of hypophysectomy in cats with hypersomatotropism, marked by low death rate and a high percentage of diabetic remission and definitive cure.

Background Many diabetic dogs and cats require small doses of insulin that must be administered accurately. Objectives To compare the accuracy and precision of insulin syringes and pen‐injectors. Animals None. Methods To determine how accurately and precisely insulin doses are delivered, 0.5, 1, 2, 4, 8, and 16 U doses were dispensed 25 times from 5 SoloSTARs, 5 FlexPens, 5 KwikPens, 5 JuniorSTARs, 5 VetPens 0.5‐8 U, 5 VetPens 1‐16 U, and by 5 veterinarians using 30 U/0.3 mL and 40 U/mL insulin syringes. Each dose was weighed, using a precision balance, and the intended and delivered doses were compared. Results All pen‐injectors delivered less insulin than the intended dose, underdosage being inversely proportional to insulin dose. The differences between the intended and the delivered dose were not significant using JuniorSTAR and VetPen 0.5‐8 U at insulin doses of 0.5, 1, 2, and 4 U, using the 30 U/0.3 mL insulin syringe at the 4 U dose and using the 40 U/mL insulin syringe at the 4, 8, and 16 U doses. With all the devices, precision increased with increasing doses of insulin. The coefficient of variation was

Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for Severe Acute Respiratory Syndrome - Coronavirus – 2 (SARS-CoV-2). It has been identified in the human gastrointestinal tract (GIT), and SARS-CoV-2 has been isolated in human and animal fecal samples. The aim of the present study was to investigate the expression of ACE2 in the gastrointestinal tract of domestic (cat) and wild (tiger) felines. Samples of the pylorus, duodenum and distal colon were collected from six cats and one tiger. The tissues were processed for immunofluorescence assay with an anti-human ACE2 antibody. Angiotensin-converting enzyme 2 was widely expressed in the gastrointestinal mucosa of the cats and the tiger. In both the species, ACE2-immunoreactivity (ACE2-IR) was expressed by the mucosal epithelial cells of the GIT and by the enteric neurons. In the cats, ACE2-IR was also expressed by the smooth muscle cells of the blood vessels and the tunica muscularis. Angiotensin-converting enzyme 2 was widely expressed in the gastrointestinal mucosa of the cats and the tiger. The expression of the ACE2 receptor in enteric neurons may support the potential neurotropic properties of SARS-CoV-2. Although the evidence of ACE2-IR in the feline GIT does not necessarily indicate the possibility of viral replication and SARS-CoV-2 spread with stool, the findings in the present study could serve as an anatomical basis for additional studies considering the risk of the SARS-CoV-2 fecal-oral transmission between cats/felids, and between cats/felids and humans.

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.

OBJECTIVE To evaluate the performance of 2 assays for measurement of serum fructosamine (SF) and glycated hemoglobin (HbA1c) values in dogs and to compare the usefulness of the 2 glycated proteins for assessment of glycemic control in dogs with diabetes mellitus (DM). SAMPLE Blood samples from 40 healthy dogs, 13 diabetic dogs, and 23 anemic normoglycemic nondiabetic dogs and results of 200 assessments of glycemic control in 46 diabetic dogs. PROCEDURES Colorimetric and immunoturbidimetric methods were used for measurement of SF and HbA1c values, respectively. Linearity and precision were determined. The usefulness of SF and HbA1c values for assessment of glycemic control was evaluated with a clinical scoring method used as the reference standard. Cutoff values obtained from receiver operating characteristic curves were used to identify the percentage of dogs correctly categorized by means of SF and HbA1c values. RESULTS Mean intra-assay and interassay coefficients of variation were 3.8% and 2.5%, respectively, for the SF assay, and 1.2% and 1.8%, respectively, for the HbA1c assay. Excellent linearity (R2 > 0.99) was obtained for both assays. Values for SF and HbA1c were inversely correlated (r = −0.40 and −0.33, respectively) with clinical score and correctly indicated glycemic control in 99 of 200 (50%) and 88 of 200 (44%) assessments, respectively. CONCLUSIONS AND CLINICAL RELEVANCE The SF and HbA1c assays were precise, had good linearity, and appeared to be suitable for routine use in veterinary medicine. However, they performed poorly for classifying glycemic control in diabetic dogs.

Decreased serum apolipoprotein A1 (Apo-A1) concentration is associated with mortality in human sepsis. The diagnostic and prognostic role of serum Apo-A1 concentrations in canine sepsis was evaluated. Serum samples from septic dogs (n = 91) and healthy controls (n = 15) were retrospectively analyzed. According to the sepsis origin, four categories were identified: parvoviral enteritis (n = 26), pyometra (n = 20), septic peritonitis (n = 19), and miscellanea (n = 26). The canine acute patient physiologic and laboratory evaluation fast score (APPLEfast), serum C-reactive protein (CRP) and albumin concentrations were reviewed in all enrolled dogs. Increased CRP (252.6 ± 119.2 mg/L; Reference Interval: 0–8.5 mg/L) and significant lower serum albumin and Apo-A1 concentrations were documented in dogs with sepsis (22.8 ± 5.3 g/L and 1.17 ± 0.27 g/L, respectively) compared to healthy ones (33.1 ± 2.5 g/L and 1.32 ± 0.05 g/L, respectively) (P < 0.0001). According to the origin of sepsis, only the subgroup of dogs with septic peritonitis had significantly lower Apo-A1 (1.03 ± 0.26 g/L) concentrations compared to healthy dogs (P < 0.001). No significant differences were found in serum albumin and CRP concentrations, and in APPLEfast score values among the different subgroups of sepsis. Diagnosis of septic peritonitis was associated with a higher frequency of death (P = 0.006). In septic dogs, significant lower Apo-A1 concentrations were detected in non-survivors (1.02 ± 0.28 g/L; n = 27) compared to survivors (1.23 ± 0.24 g/L; n = 64; P = 0.0007). Moreover, significant higher values of the APPLEfast score were calculated in non-survivors (26 ± 4; n = 19) compared to survivors (23 ± 4; n = 51) (P = 0.0114). According to the area under the ROC curve analysis, Apo-A1

Background Flash glucose monitoring system (FGMS; FreeStyle Libre) was recently validated for use in diabetic dogs (DD). It is not known if this system is clinically useful in monitoring DD. Objective To compare the clinical utility of FGMS against blood glucose curves (BGCs) obtained with a portable blood glucose meter (PBGM) in monitoring DD. Animals Twenty dogs with diabetes mellitus. Methods Prospective study. Dogs with diabetes mellitus on insulin treatment for at least 1 month were included. Comparisons of insulin dose recommendations based on the in-hospital GCs acquired using FGMS and a PBGM, consecutive-day interstitial GCs (IGCs) acquired at home using the FGMS, and consecutive-day, home vs hospital IGCs acquired using the FGMS were made using concordance analysis. Results There was good concordance between insulin dose recommendations based on FGMS and PBGM generated GCs and IGCs obtained in the 2 different environments on 2 consecutive days, but almost absent concordance between IGCs obtained on 2 consecutive days at home. Glucose nadirs were detected in 34/43 (79%) of Ambulatory Glucose Profile (AGP) reports of the FGMS. In comparison, concordant glucose nadirs were identified in 14/34 (41%) BGCs using PBGM. The individual FGMS scans and PBGM identified 60% and 9% of low IG/hypoglycemic episodes, respectively. Conclusions and clinical importance Insulin dose adjustments based on BGCs can be suboptimal. The FGMS allows a more accurate identification of the glucose nadirs and hypoglycemic episodes compared to the use of a PBGM and assessment of day-to-day variations in glycemic control.

Background A novel flash glucose monitoring system (FGMS) (FreeStyle Libre, Abbott, UK) was recently developed for humans. It continuously measures the interstitial glucose (IG) concentrations for 14 days. Objectives To assess the clinical and analytical accuracy of the FGMS in diabetic dogs. Animals Ten client-owned diabetic dogs on insulin treatment. Methods Prospective and observational study. The FGMS was placed on the neck for up to 14 days. During the 1st–2nd, 6–7th, and 13–14th days from application, the IG measurements were compared with the plasma (EDTA) glucose (PG) concentrations analyzed by a reference hexokinase based method. Results The application and the use of the FGMS were apparently painless, easy, and well tolerated by all dogs. Mild erythema at the site of the application was found in 5/10 dogs at the end of the wearing period. A good correlation between IG and PG concentrations (rho = 0.94; P < .001) was found. The FGMS was 93, 99, and 99% accurate at low, normal, and high blood glucose concentrations. Mean ± standard deviation difference from the reference method was 2.3 ± 46.8 mg/dL. Conclusion and clinical importance The FGMS is easy to use and is accurate for IG glucose measurement in diabetic dogs.

The epidemiological characteristics of spontaneous hypercortisolism (HC) were derived from 21,281 client-owned dogs selected from four private veterinary clinics and one university reference center for endocrinology. The odds ratio (OR) method was employed to investigate the risk of developing HC related to breed, gender, and sexual status. The estimated prevalence of HC in the four private clinics was 0.20% [95% confidence interval (CI), 0.13–0.27] and was significantly different compared to the university reference center (1.46%; 95% CI, 1.12–1.80). Sex, breed, and age resulted in risk factors for HC. Mean (± SD) age for dogs with HC was 9.8 (± 2.5) yr. Females had higher risk for HC compared to males (OR 1.85; 95% CI, 1.24–2.75); all neutered dogs (both males and females) had higher risk than intact dogs (OR 2.54; 95% CI, 1.72–3.73); and neutered females had higher risk compared to intact females (OR 2.61; 95% CI, 1.54–4.42). Using the mixed breed dogs as a control population (OR = 1), the risk of developing HC was significantly higher in the Standard Schnauzer (OR 58.1; p < 0.0001) and Fox Terrier (OR 20.33; p < 0.0001). With regard to HC, this study identified an overall prevalence of 0.20%. The data support the existence of sex predisposition, with the highest risk for neutered females.Keywords: Cortisol, Hyperadrenocorticism, Hypercortisolism, PDH

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.

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 Percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) of adrenal gland lesions is controversial in veterinary medicine. Objective To evaluate the frequency and radiologists' perception of the risk of the procedure as well as determining the incidence of complications. Methods Retrospective study. A first survey was submitted by e-mail to all board-certified radiologists of the American College of Veterinary Radiology (ACVR) and European College of Veterinary Diagnostic Imaging (ECVDI). A second survey was sent to radiologists who declared having performed the procedure at least once in their career (observational cross-sectional case study). Results The first survey was sent to 977 diplomates and answered by 138. Of 138 diplomates, 40 currently performed the procedure and 98 did not; 44 of the 98 gave the hypertensive crisis risk in pheochromocytoma as a reason. To the second survey, 12 of 65 responded positively; 50 dogs with 58 lesions were recruited, including 23 pheochromocytomas. Complications were reported in 4 of 50 dogs; 3 hemorrhages (1 mild and 1 moderate) and 1 death from acute respiratory distress syndrome (possibly related to laryngeal paralysis). No hypertensive crisis was reported. There was no relationship between the method of FNA/type of needle used and occurrence of complications. Based on the recollection of these 65 radiologists, who performed approximately 200 FNA of adrenal lesions, a death rate of approximately 1% was estimated. Conclusions and Clinical Importance Percutaneous US-guided FNA of adrenal lesions can be considered a minimally risky procedure, despite the negative perception by radiologists.

Acromegaly results from the overproduction of growth hormone in adulthood and is characterised by overgrowth of soft tissue and/or bone as well as insulin resistance. There are few data indicating the risk factors associated with this disease in dogs or its clinicopathological features and sequelae. The objective of this retrospective study was to catalogue and assess these aspects of the disease in German shepherd dogs (GSDs) which were found to be over-represented among acromegalic dogs attending two veterinary referral clinics over a period of 7 years. Each acromegalic dog (AD) was compared with two breed/age/sex matched controls. Clinical signs of acromegaly included panting, polyuria/polydipsia, widened interdental spaces, weakness, inspiratory stridor, macroglossia, weight gain, redundant skin folds, thick coat, exophthalmos and mammary masses. Serum alkaline phosphatase, creatine-kinase, glucose, triglyceride, phosphate ion, and ‘calcium per phosphate product’ concentrations were significantly higher in acromegalic animals while haemoglobin concentration, blood urea nitrogen, sodium and chloride ion concentrations, and urinary specific gravity, osmolality and fractional excretion of phosphate were significantly lower. Although, in the majority of cases clinicopathological abnormalities resolved following ovariohysterectomy, in one dog, acromegalic signs abated and insulin-like growth factor-1 concentrations normalised only following the surgical excision of mammary tumours carried out 2 months after ovariohysterectomy. The findings of this study indicate that GSDs are predisposed to the development of acromegaly with a suspected inherited susceptibility.

Background Diabetes mellitus (DM) is one of the most common endocrine disorders in dogs, but prognostic factors are still largely unknown. The aim of this retrospective, single-centre, case series study was to determine overall survival time and identify the prognostic value of several clinical and clinicopathological variables in dogs with newly diagnosed DM. Methods Cases of DM were identified within the electronic medical records of one referral centre. Sixty-eight dogs with DM were included. Cox proportional hazards models were used to analyse variables associated with survival. Results The median survival time was 964 days (range 22–3140). In multivariable model analysis, length of survival was significantly shorter for dogs with higher haematocrit value (hazard ratio (HR) 1.06, 95 per cent confidence interval (CI) 1.00 to 1.13) and higher serum phosphate concentrations (HR 1.83, 95 per cent CI 1.13 to 2.97). Serum phosphate concentrations were above the reference interval in 24 of 65 (37 per cent) dogs. Conclusion Diabetic dogs have a good life expectancy. Hyperphosphataemia is a relatively common finding in dogs with newly diagnosed DM and represents a negative prognostic factor. The presence of pancreatitis might not be associated with an unfavourable outcome.

Critical illness can be associated with transient alterations in circulating thyroid hormone concentrations, indicating the presence of non-thyroidal illness (NTI). NTI is well described in humans, but there are few reports on its occurrence and prognostic significance in dogs. This retrospective study assessed the occurrence of NTI in a population of dogs with systemic inflammatory response syndrome (SIRS) and investigated its association with disease severity (APPLEfast scores). A total of 41 SIRS dogs were included and were divided by SIRS origin (non-septic SIRS, n = 10; septic SIRS, n = 41) and final outcome (survivors, n = 37; non-survivors, n = 4). Healthy, age-matched dogs (n = 15) were included as controls. Serum thyroid hormone levels including total T3, free T3, total T4, and reverse T3 were measured upon admission. Compared to controls, there were significant changes in serum thyroid hormone concentrations in SIRS dogs, suggesting the presence of NTI. Septic SIRS dogs had higher APPLEfast scores and lower serum thyroid hormones concentrations than those in non-septic SIRS and control dogs. In conclusion, NTI was frequent in dogs with SIRS and may be associated with the presence of sepsis or high illness severity

Background The distinction between adrenocortical tumors and pheochromocytoma can be challenging using clinical findings, diagnostic imaging and laboratory tests. Cytology might be a simple, minimally invasive method to reach a correct diagnosis. Objectives The purpose of this study was to assess the accuracy of cytology in differentiating cortical from medullary tumors of the adrenal glands in dogs and cats. Methods Cytologic key features of adrenocortical tumors and pheochromocytoma were defined by one reference author. Cytologic specimens from primary adrenal tumors were submitted to 4 cytopathologists who were asked to classify the tumors based on the previously defined key features without knowledge of previous classification. Results Twenty specimens from histologically confirmed adrenal tumors (Group 1) and 4 specimens from adrenal tumors causing adrenal-dependent Cushing's syndrome (Group 2) were evaluated by the 4 cytopathologists. Accuracy in differentiating cortical from medullary origin ranged from 90% to 100%, with a Kappa coefficient of agreement between cytopathologists of 0.95. Conclusions The origin of an adrenal tumor can be easily determined by cytology alone in many cases. However, cytology was not reliable in distinguishing benign from malignant neoplasia. Additional studies are needed to assess possible risks and complications associated with fine-needle biopsy of adrenal tumors in dogs and cats.

Some comments have been done on an article describing a pilot trial evaluating the potential use of moxidectin contained in a spot-on formulation in the prevention of canine filarioses in a confined area where the three major canine filariae live in sympatry. We herein present our response to these comments.

Background Diagnosis of pituitary-dependent hyperadrenocorticism (PDH) in cats is challenging because there is no specific diagnostic test. Hypothesis/Objective The determination of plasma ACTH precursor (POMC and pro-ACTH) concentration might facilitate the diagnosis of PDH in cats. The aim of the study was to evaluate prospectively the plasma concentrations of ACTH precursors in a small cohort of cats with PDH and to estimate the value of this approach for diagnosis. Animals Four groups of cats were included: group 1 (cats with PDH), group 2 (cats with diabetes mellitus but not hyperadrenocorticism (HAC)), group 3 (cats with diabetes mellitus and confirmed acromegaly but not HAC), and group 4 (healthy cats). Methods PDH diagnosis was based on clinical data, low-dose dexamethasone suppression test (LDDST), and adrenal and pituitary gland computed tomography (CT) scan. For groups 2, 3, and 4, hyperadrenocorticism was excluded by LDDST or urine cortisol:creatinine ratio (UCCR). An immunoluminometric assay was used to determine plasma concentrations of ACTH precursors in the 4 groups of cats. Results Group 1 contained 9 cats (enlarged pituitary gland in 7/9). Plasma ACTH precursor concentrations ranged from 1010 pmol/L with 8/9 concentrations ≥229 pmol/L. Groups 2, 3, and 4 included 13, 7, and 13 cats, respectively. Plasma ACTH precursor concentrations ranged from 100 pmol/L) is highly suggestive of PDH.

Hypothyroidism has historically been cited as a possible cause of megaesophagus. However, a definitive association between hypothyroidism and megaesophagus has not been proved. A 7-year old entire female German Shepherd dog was presented with a ten day history of regurgitation a few minutes after feeding. It was also reported that the dog was weak and had nonpruritic dermatological abnormalities since months: poor and dull hair coat and hair loss. On the physical examination, the dog had a body condition score of 6/9 and a diffusely poor, dull and dry hair coat with bilaterally symmetric rarefaction in the truncal area, alopecia and hyperpigmentation in the friction areas and on the tail was evidenced. The remainder of the physical examination was unremarkable. The blood results showed a moderate non regenerative normochromic and normocytic anaemia and a mild increase in serum cholesterol concentration. On survey radiographies (figure 1) of the thorax, pre and post barium PO administration, a consistently diffuse megaesophagus was evident. Further diagnostic work-up included: measurement of serum canine thyroid stimulating hormone (cTSH), recombinant human thyroid stimulating hormone (rhTSH) stimulation test to investigate hypothyroidism, measurement of Acetylcholine (Ach) receptor antibodies to investigate MG and skin scraping to investigate demodicosis. There was a high concentration of cTSH associated with low basal total thyroxine (T4) which did not increase six hours post stimulation. These findings allowed to diagnose a primary hypothyroidism. The serology for Ach receptors antibodies was negative and, therefore, a focal MG was considered less likely. The final diagnosis was hypothyroidism associated with most likely secondary megaesophagus. Treatment was initiated with levothyroxine 20 μg/kg body weight q12h PO and specific feeding instructions for the megaesophagus were recommended. One week later the owner was telephonically contacted, he reported that the dog was much more active and not regurgitating anymore. Twenty five days after treatment the dog was in a good general condition, the haircoat was less dull, with new areas of hairgrowth. Follow up blood results and chest radiographies (figure 1) were within normal limits. Two years after the diagnosis, the dog is clinically well and no further dermatological signs or regurgitations are reported. The association between hypothyroidism and megaesophagus is controversial. In a retrospective study by Jaggy and others (1994) of 29 hypothyroid dogs, four had megaesophagus; one dog showed an improvement of the esophageal clinical signs after therapy but radiological evidence of megaesophagus persisted in all dogs. As previously reported, complete resolution of clinical and radiographic signs was achieved in our case. Although concurrent MG was unlikely, it was not possible to completely exclude spontaneous recovery from a focal MG at the same time of levothyroxine supplementation. Finally, only the suspension of levothyroxine therapy, with a recrudescence of the megaesophagus, could have proven irrefutably the connection between hypothyroidism and megaesophagus, however, such procedure was not performed for ethical reasons.

The aim of this study was to investigate albumin to creatinine ratio (U:A/C) in dogs with diabetes mellitus (DM) and hypercortisolism (HC). Furthermore, the relationship between U:A/C as well as protein to creatinine ratio (U:P/C) with systemic pressure was investigated. Two cohorts of dogs diagnosed with DM (n=20) or HC (n=14) were included. A further group of healthy dogs (n=21) was evaluated as control. Urinalysis was performed to rule out urinary tract infections. Results indicate that pathologic proteinuria is highly prevalent in either DM or HC dogs. Our data confirm that U:A/C is more sensitive in assessing proteinuria than U:P/C. 25% of DM dogs and 14% of HC dogs showed U:A/C above reference range and U:P/C within the reference range. Neither U:A/C nor U:P/C correlated significantly with systemic pressure.

Pituitary-dependent hypercortisolism (PDH) in dogs is frequently associated with high serum phosphate and parathormone concentrations which are in turn associated with prognosis and clinical presentation. The pathogenesis of such abnormalities remains unknown. The aim of the present study was to evaluate the serum and urinary concentrations and the urinary fractional excretion of phosphate and calcium in dogs with PDH. Medical records of newly diagnosed PDH dogs before treatment from one referral centre were retrospectively evaluated. One clinically normal and one sick dog for each dog with PDH were included as controls. One hundred and sixty-seven dogs with PDH were included. The serum phosphate concentration in PDH dogs was significantly (P

M. Pietra1*, F. Gentilini1, S. Pinna2, F. Fracassi1, A. Venturini2 and M. Cipone1 Department of Veterinary Clinical Science (1Section of Internal Medicine; 2Section of Surgery), Faculty of Veterinary Medicine, University of Bologna, 40064 Ozzano dell’Emilia (BO), Italy *Correspondence: Dipartimento Clinico Veterinario, Universita degli Studi di Bologna, V ia T olara di Sopra 50, 40064, Ozzano dell’Emilia (BO), Italy E-mail: mpietra@vet.unibo.it

Objective—To evaluate the pharmacokinetics and clinical efficacy of budesonide in dogs with inflammatory bowel disease (IBD). Animals—11 dogs (mean ± SD age, 5.7 ± 3.9 years; various breeds and body weights) with moderate or severe IBD. Procedures—Each dog received a controlled-release formulation of budesonide (3 mg/m2, PO, q 24 h) for 30 days (first day of administration was day 1). The concentration of budesonide and its metabolite (16-α-hydroxyprednisolone) was measured via liquid chromatography–tandem mass spectrometry in plasma and urine samples obtained on days 1 and 8 of treatment. On those days, plasma samples were obtained before the daily budesonide administration and 0.5, 1, 2, 4, and 7 hours after drug administration, whereas urine samples were obtained after collection of the last blood sample. A clinical evaluation was performed on the dogs before onset of drug administration and on days 20 and 30 after start of drug administration. Results—The highest plasma concentration of budesonide and 16-α-hydroxyprednisolone on day 1 was detected at 1 hour and at 2 hours after drug administration, respectively. After standardization on the basis of specific gravity, the ratio between urinary concentrations of budesonide and 16-α-hydroxyprednisolone was 0.006 and 0.012 on days 1 and 8, respectively. The clinical response was adequate in 8 of 11 dogs. Conclusions and Clinical Relevance—Budesonide was rapidly absorbed and metabolized in dogs with IBD. The drug gradually accumulated, and there was an adequate therapeutic response and no adverse effects.