Velagliflozin, a once-daily, liquid, oral SGLT2 inhibitor, is effective as a stand-alone therapy for feline diabetes mellitus: the SENSATION study.

OBJECTIVE: To investigate safety and effectiveness of velagliflozin oral solution as sole therapy in naïve and previously insulin-treated diabetic cats. ANIMALS: 252 client-owned cats receiving ≥ 2 doses of velagliflozin; 214 (85%) naïve diabetics and 38 (15%) insulin-treated diabetics. PROCEDURES: Prospective, baseline-controlled, open-label clinical field trial. Cats received velagliflozin orally, once daily. Physical examinations and blood collections were performed days 0, 3, 7, 30, 60, 120, and 180. RESULTS: Data are median (range). Screening blood glucose (BG) was 436 mg/dL (272 to 676 mg/dL). On days 30, 60, 120, and 180, single BG after receiving velagliflozin was 153 mg/dL (62 to 480 mg/dL), 134 mg/dL (64 to 414 mg/dL), 128 mg/dL (55 to 461 mg/dL), and 125 mg/dL (77 to 384 mg/dL), respectively. Screening fructosamine was 538 µmol/L (375 to 794 µmol/L). On the same recheck days, fructosamine was 310 µmol/L (204 to 609 µmol/L), 286 µmol/L (175 to 531 µmol/L), 269 µmol/L (189 to 575 µmol/L), and 263 µmol/L (203 to 620 µmol/L). At day 180, 81% of 158 cats remaining had BG and/or fructosamine within reference ranges; 88.6% (124 of 140) and 87.7% (121 of 138) showed improvement in polyuria and polydipsia, respectively. Ketonuria developed in 35 cats (13.9%), including 18 (7.1%) that had ketoacidosis. Ketoacidosis was less common in naïve diabetic cats (11 of 214 [5.1%]) compared to insulin-treated diabetic cats (7 of 38 [18.4%]). At ketoacidosis diagnosis, 14 of 18 cats (77.8%) were euglycemic (ie, BG < 250 mg/dL). Most episodes of ketosis or ketoacidosis (30 of 35 [85.7%]) occurred within the first 14 days of treatment. Insulin-treated diabetic cats were less likely to complete the trial. No clinical hypoglycemia occurred. CLINICAL RELEVANCE: Velagliflozin improved glycemic parameters and clinical signs in diabetic cats. Velagliflozin provides an alternative to insulin as a stand-alone treatment of diabetic cats.

2016 AAFP Guidelines for the Management of Feline Hyperthyroidism.

CLINICAL CONTEXT: Since 1979 and 1980 when the first reports of clinical feline hyperthyroidism (FHT) appeared in the literature, our understanding of the disease has evolved tremendously. Initially, FHT was a disease that only referral clinicians treated. Now it is a disease that primary clinicians routinely manage. Inclusion of the measurement of total thyroxine concentration in senior wellness panels, as well as in diagnostic work-ups for sick cats, now enables diagnosis of the condition long before the cat becomes the classic scrawny, unkempt, agitated patient with a bulge in its neck. However, earlier recognition of the problem has given rise to several related questions: how to recognize the health significance of the early presentations of the disease; how early to treat the disease; whether to treat FHT when comorbid conditions are present; and how to manage comorbid conditions such as chronic kidney disease and cardiac disease with treatment of FHT. The 2016 AAFP Guidelines for the Management of Feline Hyperthyroidism (hereafter referred to as the Guidelines) will shed light on these questions for the general practitioner and suggest when referral may benefit the cat. SCOPE: The Guidelines explain FHT as a primary disease process with compounding factors, and provide a concise explanation of what we know to be true about the etiology and pathogenesis of the disease.The Guidelines also:Distill the current research literature into simple recommendations for testing sequences that will avoid misdiagnosis and separate an FHT diagnosis into six clinical categories with associated management strategies.Emphasize the importance of treating all hyperthyroid cats, regardless of comorbidities, and outline the currently available treatments for the disease.Explain how to monitor the treated cat to help avoid exacerbating comorbid diseases.Dispel some of the myths surrounding certain aspects of FHT and replace them with an evidence-based narrative that veterinarians and their practice teams can apply to feline patients and communicate to their owners. EVIDENCE BASE: To help ensure better case outcomes, the Guidelines reflect currently available, evidenced-based knowledge. If research is lacking, or if a consensus does not exist, the expert panel of authors has made recommendations based on their extensive, cumulative clinical experience.

Effect of dexamethasone or synthetic ACTH administration on endogenous ACTH concentrations in healthy dogs.

OBJECTIVE: To determine the effects of dexamethasone or synthetic ACTH administration on endogenous ACTH concentrations in healthy dogs. ANIMALS: 10 healthy neutered dogs. PROCEDURES: Each dog received dexamethasone (0.01 mg/kg), synthetic ACTH (5 µg/kg), or saline (0.9% NaCl) solution (0.5 mL) IV at intervals of ≥ 30 days. Plasma endogenous ACTH concentrations were measured before (baseline; time 0) and 1, 8, 12, and 24 hours after drug administration; serum cortisol concentrations were measured before and 1 hour after synthetic ACTH and saline solution administration and 8 hours after dexamethasone administration. RESULTS: Analysis of serum cortisol concentrations confirmed effects of drug administration. Dexamethasone significantly decreased the endogenous ACTH concentration from the baseline value at both 8 and 12 hours. Synthetic ACTH administration significantly decreased the endogenous ACTH concentration from the baseline value at 8 hours. Saline solution administration had no significant effect on endogenous ACTH concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Dexamethasone and synthetic ACTH administered IV at doses used routinely during testing for hyperadrenocorticism caused significant but transient reductions of endogenous ACTH concentrations in healthy dogs. Thus, a 2-hour washout period following ACTH stimulation testing before collection of samples for measurement of the endogenous ACTH concentration may be insufficient. Although this effect has not been verified in dogs with hyperadrenocorticism, these data suggested that samples for measurement of endogenous ACTH concentrations should be obtained before or > 8 hours after initiation of an ACTH stimulation test or before or > 12 hours after the start of a low-dose dexamethasone suppression test.

Evaluation of activation of G proteins in response to thyroid stimulating hormone in thyroid gland cells from euthyroid and hyperthyroid cats.

OBJECTIVE: To evaluate alterations in ligand-stimulated activity of G proteins in thyroid gland cells of hyperthyroid cats. SAMPLE POPULATION: Membranes of thyroid gland cells isolated from 5 hyperthyroid cats and 3 age-matched euthyroid (control) cats immediately after the cats were euthanatized. PROCEDURES: Isolated thyroid cell membranes were treated with thyroid-stimulating hormone (TSH), and activation of G protein was quantified by measurement of the binding of guanosine triphosphate gamma labeled with sulfur 35 (GTPgamma(35)S). The separate effects of G-protein inhibitory (G(i)) and G-protein stimulatory (G(s)) proteins were determined by the use of pertussis toxin and cholera toxin, respectively. RESULTS: Thyroid cell membranes from hyperthyroid cats had higher basal GTPgamma(35)S binding than did thyroid cell membranes from euthyroid cats. Thyroid cell membranes from hyperthyroid and euthyroid cats had a concentration-dependent increase in TSH-stimulated GTPgamma(35)S binding over the TSH range of 0 to 100 mU/mL, with maximal activity at 1 to 100 mU/mL for both. The percentage increase in GTPgamma(35)S binding stimulated by TSH was similar in magnitude between the membranes from hyperthyroid and euthyroid cats. The TSH-stimulated activation of G(s) and G(i) was not different between euthyroid and hyperthyroid cats. CONCLUSIONS AND CLINICAL RELEVANCE: Ligand-stimulated activation of G proteins was the same in thyroid cell membranes obtained from hyperthyroid and euthyroid cats. Therefore, alterations in inherent G(s) or G(i) activities did not appear to be part of the pathogenesis of hyperthyroidism in cats.

Feline thyroid storm: rapid recognition to improve patient survival.

In human medicine, thyroid storm is a well-recognized condition of acute thyrotoxicosis in which the patient's metabolic, thermoregulatory, and cardiovascular mechanisms are overwhelmed by excessive circulating levels of thyroid hormone. The etiology is unknown, but multiple precipitating factors have been proposed. Hyperthyroid cats presenting in thyrotoxic crisis have clinical signs similar to those of human thyroid storm patients; however, thyroid storm has not yet been fully characterized in veterinary medicine. Early recognition and prompt, appropriate treatment of this life-threatening condition are essential to obtaining a favorable outcome.

Flexible endoscopy in small animals.

Flexible endoscopy is a valuable tool for the diagnosis of many small animal digestive tract diseases. This article provides a basic introduction to small animal gastrointestinal endoscopy including its diagnostic advantages as well as its limitations and complications. Although proficiency in endoscopic techniques can only be obtained through many hours of practice, this article should also encourage and stimulate the novice endoscopist.

Dermoid cysts presenting as enlarged thyroid glands in a cat.

A 5-year-old spayed female cat was evaluated for hyperthyroidism based on an elevated free thyroxine (T(4)) measurement and bilaterally enlarged symmetric subcutaneous masses in the area of the thyroid glands. Physical examination revealed bilateral subcutaneous masses on either side of the cervical trachea. Blood was obtained for serum biochemical profile and thyroid function analysis. Mild hyperalbuminemia, mild hypercalcemia, and mildly increased alanine aminotransferase activity were identified. Serum concentrations of total and free thyroxine were within the reference interval. Cytologic analysis of fine-needle aspirates from one of the masses was suspicious for neoplasia. Nuclear scintigraphy revealed no abnormalities. Surgically obtained excisional biopsies of both masses were submitted for histopathology and diagnosed as bilateral dermoid cysts. After excisional biopsy, the patient recovered without incident. The histopathologic diagnosis of completely excised bilateral dermoid cysts indicated that no further medical or surgical intervention was required. This is the first report of a cat presenting with bilateral dermoid cysts in the area of the thyroid glands. Histopathologic examination was necessary to make a definitive diagnosis. Practitioners should include cysts in their list of differential diagnoses for ventral neck masses in cats.

Elevated PBDE levels in pet cats: sentinels for humans?

Co-incident with the introduction of polybrominated diphenyl ethers (PBDEs) into household materials nearly 30 years ago, feline hyperthyroidism (FH) has increased dramatically. Risk of developing FH is associated with indoor living and consumption of canned catfood. We hypothesized that increases in FH were, in part, related to increased PBDE exposure, with key routes of exposure being diet and ingestion of house dust. This study was designed to determine whether body burdens of PBDEs in hyperthyroid (HT) cats were greater than that of young or sick non-HT cats. Serum samples and clinical information were collected from 23 cats. Serum and dry and canned cat food were analyzed for PBDEs. A spectrum of BDE congeners was detected in all cats, with BDE-47, 99, 207, and 209 predominating. Mean +/- standard error (and median) cumulative sigma PBDE serum concentrations of young, old non-HT, and HT cats were 4.3 +/- 1.5 (3.5), 10.5 +/- 3.5 (5.9), and 12.7 +/- 3.9 (6.2) ng/mL, respectively. Due to high variability within each group, no association was detected between HT cats and sigma PBDE levels. Indicative of age- or disease-dependent changes in PBDE metabolism, BDE-47/99 ratios were inversely correlated with age, and 47/99 and 100/ 99 ratios in HT cats were significantly lower than those in the other cats. Overall, sigma PBDE levels in cats were 20- to 100-fold greater than median levels in U.S. adults. Our results support the hypothesis that cats are highly exposed to PBDEs; hence, pet cats may serve as sentinels to better assess human exposure and adverse health outcomes related to low-level but chronic PBDE exposure.

Etiopathologic findings of hyperthyroidism in cats.

None of the studies to date have isolated a single dominant factor that could be incriminated in the development of hyperthyroidism in cats. Rather, most of the studies provide further evidence of the widely held view that hyperthyroidism is a multifactorial disease in this species. At this time, the most likely candidates include one or more of the goitrogenic chemicals that have been shown to be present in cat food or the cat's environment. In addition, mutations of the thyroid stimulating hormone receptor gene or mutations of its associated G proteins seem to play an important role in the pathogenesis of this disease.

Feline thyroid storm.

Thyroid storm is a syndrome described in human medicine to define a multisystemic disorder resulting from organ exposure to excessive levels of thyroid hormone. This form of acute thyrotoxicosis, although uncommon, can be life threatening and is a significant cause of mortality in human emergency rooms. Although thyroid storm is a well-recognized clinical entity in human medicine, it has not been described in veterinary medicine. This article discusses the human syndrome and defines a similar syndrome in hyperthyroid veterinary patients. The clinical signs of and treatment modalities for feline thyroid storm are also presented.

Liver function in cats with hyperthyroidism before and after 131I therapy.

BACKGROUND: The clinical significance of high serum concentration or activity of markers of liver damage in cats with hyperthyroidism is unknown. OBJECTIVE: To evaluate serum markers of liver function and damage, and ultrasonographic changes in cats with hyperthyroidism and with high liver enzymes, and to determine if abnormalities resolve after treatment with 131I. ANIMALS: Nineteen cats with hyperthyroidism (15 with high serum activities of liver enzymes) and 4 age-matched healthy control cats. METHODS: Serum bile acids, albumin, ammonia, cholesterol, and blood urea nitrogen concentrations, and activities of liver-derived enzymes, and blood glucose concentrations were measured before and after 131I therapy. These values were compared with those of cats that were euthyroid. In addition, gross liver parenchymal changes detected by abdominal ultrasonographic examination, before and after 131I therapy were evaluated. RESULTS: High serum liver enzyme activities were not associated with abnormalities in hepatic parenchyma and liver functional variables, regardless of the degree of increase. Serum liver enzyme activities return to normal after control of hyperthyroidism with 131I therapy. Cats with hyperthyroidism have a significantly higher serum fasting ammonia concentration than cats who were euthyroid (P = .019). Cats with hyperthyroidism also have significantly lower serum cholesterol (P = .005) and glucose (P = .002) concentrations before compared with after 131I therapy. Nine of 19 cats with hyperthyroidism had trace ketonuria. CONCLUSIONS AND CLINICAL IMPORTANCE: These results demonstrate that extensive examination for hepatobiliary disease in most cats with hyperthyroidism is unnecessary.

Expression of inhibitory G proteins in adenomatous thyroid glands obtained from hyperthyroid cats.

OBJECTIVE: To identify within guanosine triphosphate-binding proteins (G proteins) the subset of inhibitory G proteins (G) that have decreased expression in adenomatous thyroid glands obtained from hyperthyroid cats. SAMPLE POPULATION: Adenomatous thyroid glands obtained from 5 hyperthyroid cats and normal thyroid glands obtained from 3 age-matched euthyroid cats. PROCEDURE: Expression of G(i1), G(i2), and G(i3) in enriched membrane preparations from thyroid glands was quantified by use of immunoblotting with G(i) subtype-specific antibodies. RESULTS: Expression of G(i2) was significantly decreased in tissues of hyperthyroid glands, compared with expression in normal thyroid tissue. Expression of G(i1) and G(i3) was not significantly different between normal thyroid tissues and tissues from hyperthyroid glands. CONCLUSIONS AND CLINICAL RELEVANCE: A decrease in G(i2) expression decreases inhibition of adenylyl cyclase and allows a relative increase in stimulatory G protein expression. This results in increased amounts of cAMP and subsequent unregulated mitogenesis and hormone production in hyperthyroid cells. Decreased G(i2) expression may explain excessive growth and function of the thyroid gland in cats with hyperthyroidism.

Thyrotropin-stimulated DNA synthesis and thyroglobulin expression in normal and hyperthyroid feline thyrocytes in monolayer culture.

Feline hyperthyroidism is a common, spontaneous disease in older cats that is similar clinically and histopathologically to human toxic multinodular goiter (TNG). In this study, the functional response of feline normal thyroid (NT) and hyperthyroid (HT) cells grown in monolayer culture to thyrotropin (TSH) was determined. Basal levels of DNA synthesis were similar in NT and HT cells. TSH stimulated concentration-dependent DNA synthesis in NT and HT cells, with maximal stimulation seen at 1 and 10 mU/mL TSH in NT and HT cells, respectively. HT cells had higher basal levels of thyroglobulin (Tg) expression. TSH stimulated Tg expression in NT and HT cells in a concentration-dependent fashion, with maximal activity at 0.5 and 5 mU/mL TSH, respectively. These results demonstrate that NT and HT cells in monolayer culture exhibit growth and functional responses to TSH. HT cells have higher basal Tg expression than NT cells and require higher TSH concentrations to stimulate DNA synthesis and Tg expression, two measures of thyroid cell activation. These data support the idea that feline hyperthyroidism is caused by cell abnormalities, resulting in dysregulated growth and hormone synthesis, and emphasize its importance as an animal model for TNG.

Familial insulin-dependent diabetes mellitus in Samoyed dogs.

Five adult Samoyed dogs from two unrelated litters were diagnosed with diabetes mellitus. Two full-sibling male dogs (Family A) were raised in the same household. The other three dogs, two female and one male, were also full siblings (Family B) raised in different households. All five dogs developed polyuria and polydipsia and demonstrated fasting hyperglycemia and glucosuria. Diabetes mellitus was diagnosed in all five dogs and responded to appropriate therapy with insulin. The occurrence of insulin-dependent diabetes mellitus in multiple, closely related Samoyed dogs suggests a familial predisposition in this breed.