Laboratory indicators of hypothyroidism and TgAA-positivity in the Eurasian dog breed.

BACKGROUND: Hereditary hypothyroidism represents a concern for dog breeders; thus, surveillance programs have been established for several dog breeds. METHODS: Thyroid profiles (total thyroxine (TT4), thyrotropin (thyroid stimulating hormone (TSH)), and thyroglobulin autoantibodies (TgAA)) collected as part of a breed surveillance program in Eurasians (2009-2017) were retrospectively analyzed. The study included data from 1,501 Eurasians from a German breeding club. Classification was exclusively based on laboratory data. Hypothyroidism was defined as a combined decrease in TT4 and increase in TSH in serum and was classified as TgAA-positive and TgAA-negative hypothyroidism. Thyroglobulin autoantibodies (TgAA) independent of the concentrations of TT4 and TSH were determined. The overall prevalence of hypothyroidism, TgAA-positive hypothyroidism, TgAA-negative hypothyroidism and TgAA-positivity was assessed when the dogs entered the program. Follow-up laboratory data was available for 324 dogs without hypothyroidism on initial examination. RESULTS: The initial screening was performed at a median age of 18 months (interquartile range (IQR): 15-29). The overall prevalence of hypothyroidism was 3.9% (n = 58; 95% CI: 2.9-4.8%) and the prevalence of a positive TgAA status was 7.9% (n = 118; 95% CI: 6.6-9.3%). The prevalence of TgAA-positive and TgAA-negative hypothyroidism was 1.7% (n = 26; 95% CI: 1.1-2.4%) and 2.1% (n = 32; 95% CI: 1.4-2.9%), respectively. 22.0% of dogs with positive TgAA status (26/118) were already hypothyroid on initial examination. Overall, 42.5% (17/40) of TgAA-positive dogs on initial examination developed hypothyroidism on follow-up. CONCLUSION: The results of this study demonstrate that the Eurasian dog breed exhibits a relevant risk for hypothyroidism and presence of TgAA. The predictive value of TgAA for hypothyroidism or developing hypothyroidism was high in this breed. Further investigations with longitudinal studies in individual dogs are warranted.

Wellbeing, quality of life, presence of concurrent diseases, and survival times in untreated and treated German Shepherd dogs with dwarfism.

BACKGROUND: Pituitary dwarfism (PD) in German Shepherd dogs (GSD) is a rare endocrinopathy. Cause and inheritance of the disease are well characterized, but the overall survival time, presence of concurrent diseases, quality of life (QoL) and influence of different treatment options on those parameters is still not well investigated. The aim of this study was to obtain data regarding the disease pattern of GSD with PD and to investigate the impact of treatment. METHODS: 47 dogs with dwarfism (presumably PD) and 94 unaffected GSD serving as controls were enrolled. Data were collected via a standardized questionnaire, which every owner of a participating dog had completed. Dogs with PD were grouped based on three categories of treatment: Group 1 (untreated), group 2 (treated with levothyroxine), group 3 (treated with thyroxine and progestogens or with growth hormone (GH)). Groups were compared using One-Way-Anova, Kruskal-Wallis test or Wilcoxon-rank-sum test. Categorical analysis was performed using Two-Sample-Chi-Squared-test. RESULTS: Dogs treated with thyroxine and gestagen or GH were significantly taller and heavier compared to all other dogs with PD. Quality of life was best in dogs with PD treated with thyroxine and similar to unaffected GSD. Treatment increased survival time in dogs with PD independent of the treatment strategy. Dogs receiving thyroxine and progestogens or GH did not develop chronic kidney disease (CKD). CONCLUSION: GSD with PD should be treated at least for their secondary hypothyroidism to increase survival time. Additional treatment with progestogens or GH improves body size and seems to protect against the occurrence of CKD.

Antibody Response to Canine Parvovirus Vaccination in Dogs with Hypothyroidism Treated with Levothyroxine.

(1) Background: No information is available on how dogs with hypothyroidism (HypoT) respond to vaccination. This study measured pre- and post-vaccination anti-canine parvovirus (CPV) antibodies in dogs with HypoT treated with levothyroxine and compared the results to those of healthy dogs. (2) Methods: Six dogs with HypoT and healthy age-matched control dogs (n = 23) were vaccinated against CPV with a modified-live vaccine. Hemagglutination inhibition was used to measure antibodies on days 0, 7, and 28. The comparison of the vaccination response of dogs with HypoT and healthy dogs were performed with univariate analysis. (3) Results: Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HypoT (6/6; 95% CI: 55.7-100) and in 100% of healthy dogs (23/23; 95% CI: 83.1-100.0). A ≥4-fold titer increase was observed in none of the dogs with HypoT and in 4.3% of the healthy dogs (1/23; CI95%: <0.01-22.7). Mild vaccine-associated adverse events (VAAEs) were detected in 33.3% of the dogs with HypoT (2/6; 95% CI: 9.3-70.4) and in 43.5% (10/23; 95% CI: 25.6-63.2) of the healthy dogs. (4) Conclusions: There was neither a significant difference in the dogs' pre-vaccination antibodies (p = 1.000), or vaccination response (p = 0.735), nor in the occurrence of post-vaccination VAAEs (p = 0.798). The vaccination response in dogs with levothyroxine-treated HypoT seems to be similar to that of healthy dogs.

Antibody Response to Canine Parvovirus Vaccination in Dogs with Hyperadrenocorticism Treated with Trilostane.

It is unknown how dogs with hyperadrenocorticism (HAC) respond to vaccination. This study measured antibodies against canine parvovirus (CPV) in dogs with HAC treated with trilostane before and after CPV vaccination, and compared the immune response to that from healthy dogs. Eleven dogs with HAC, and healthy age-matched control dogs (n = 31) received a modified-live CPV vaccine. Antibodies were determined on days 0, 7, and 28 by hemagglutination inhibition. Univariate analysis was used to compare the immune response of dogs with HAC and healthy dogs. Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HAC (11/11; 95% CI: 70.0-100) and in 93.5% of healthy dogs (29/31; 95% CI: 78.3-99.2). No ≥4-fold increase in antibody titer was observed in dogs with HAC while in 22.6% of healthy dogs, a ≥4-fold titer increase was observed (7/31; 95% CI: 11.1-40.1). Mild vaccine-associated adverse events (VAAEs) were detected in 54.5% of dogs with HAC (6/11; 95% CI: 28.0-78.8) and in 29.0% of healthy dogs (9/31; 95% CI: 15.9-46.8). There was neither a significant difference in presence of pre-vaccination antibodies (p = 1.000), or response to vaccination (p = 0.161), nor in the occurrence of VAAEs (p = 0.158). Immune function of dogs with HAC treated with trilostane seems comparable to that of healthy dogs.

Prevalence and characterization of hypoadrenocorticism in dogs with signs of chronic gastrointestinal disease: A multicenter study.

BACKGROUND: Dogs with hypoadrenocorticism (HA) frequently show signs of gastrointestinal disease (SGD). The prevalence of dogs presented for chronic SGD with HA is unknown. OBJECTIVES: The aims of this study were to determine the prevalence of HA in dogs with chronic SGD and to identify clinical and laboratory variables for HA in this population. ANIMALS: One hundred fifty-one dogs with chronic SGD. METHODS: In this multicentered prevalence study a standardized workup was performed in prospectively enrolled dogs with SGD > 3 weeks duration. Basal serum cortisol concentration was measured in every dog with ACTH stimulation test (ACTHST) if basal serum cortisol concentration was <3 µg/dL. RESULTS: Basal serum cortisol concentration was <3 µg/dL in 80/151 (53%) dogs, <2 µg/dL in 42/151 (28%) dogs, and < 1 µg/dL in 9/151 (6%) dogs. In 6/151 dogs HA was diagnosed based on ACTHST (stimulated serum cortisol concentration < 2 µg/dL), a prevalence of 4%. There was no difference in history, physical examination, and laboratory variables between dogs with HA and those with other causes of chronic SGD. In 4/6 dogs with HA, there was melena or hematochezia indicating gastrointestinal blood loss. Hyperkalemia, hyponatremia, or both was not observed in any dog. CONCLUSION AND CLINICAL IMPORTANCE: The prevalence of HA among dogs with chronic SGD is higher than in the general population. Based on these results, testing adrenal function should be performed as a standard screening test in dogs with chronic SGD to differentiate between HA and chronic enteropathies.

Suspected bilateral adrenal gland tumour causing primary Addison's disease in a dog.

A 13-year old miniature poodle presented with a 3-day episode of vomiting, anorexia, and lethargy. Lack of micturition had been noted for 2 days. Clinical examination indicated dehydration and a tense, painful abdomen. Laboratory parameters (severe azotaemia, hyperkalaemia, severe hyponatraemia, hypochloraemia, and hyperphosphataemia with glucosuria and proteinuria) were consistent with anuric acute kidney injury (AKI). Abdominal ultrasound revealed bilateral adrenal masses. ACTH stimulation test was diagnostic for Addison's disease. Computed tomography confirmed bilateral adrenal masses and indicated multifocal liver nodules. Additionally, infiltration of the caudal vena cava with partial luminal occlusion was demonstrated. Surgical removal of the adrenal masses with venous plasty intervention and stenting of the vessels deemed unrewarding in this patient in respect to progressed tumour growth with assumed metastatic spread. The dog was treated for Addison's disease and discharged with good overall condition. Eight weeks later, the dog was euthanized due to progressive caudal vena cava occlusion. Whilst hypoadrenocoticism typically affects young to middle aged dogs, in old dogs primary Addison's disease might be caused by neoplastic bilateral adrenal gland destruction. This is the first case report of hypovolaemia leading to AKI secondary to bilateral adrenal masses causing Addison's disease in a dog.

Relationship between total thyroxine, thyroid palpation and a clinical index in hyperthyroid and healthy cats and cats with other diseases.

OBJECTIVES: Present-day diagnosis of hyperthyroidism is often established in the early stages where clinical signs and physical examination findings typically associated with the disease may not yet be present. The purpose of this study was to investigate thyroid palpation score (TPS), total thyroxine (T4), body weight, body condition score and a clinical scoring index, which assesses severity of illness and quality of life, in untreated hyperthyroid cats, healthy cats and cats with non-thyroidal illness. METHODS: Fifty-five cats with hyperthyroidism, 45 healthy cats and 327 euthyroid cats with non-thyroidal disease were prospectively enrolled. A Kruskal-Wallis test was used to determine any differences between metric data. A χ2 test was applied to compare nominal data between the three subgroups. Correlation between two variables was analysed using Spearman's correlation coefficient. RESULTS: Almost 80% of the hyperthyroid cats and up to 20% of the healthy cats and cats with non-thyroidal illness had a palpable thyroid gland. Median TPS in hyperthyroid cats was 2, which was significantly higher compared with the other groups. Although there was a significant correlation between TPS and T4 when evaluating all cats, this could not be demonstrated in the three subgroups. Hyperthyroid cats with larger thyroid glands (TPS >3) did not have higher T4 levels. Hyperthyroid cats with lower clinical scores had significantly higher T4 levels compared with hyperthyroid cats with higher scores. Hyperthyroid cats were older and had lower body weights and body condition scores than other cats. CONCLUSIONS AND RELEVANCE: Hyperthyroid cats were commonly found to have palpable thyroid glands, but they were smaller than previously reported.

[Diagnostic approach and management of hypercalcaemia in dogs exemplary of primary hyperparathyroidism]. / Diagnostische Aufarbeitung und Management der Hyperkalzämie des Hundes am Beispiel des primären Hyperparathyreoidismus.

Hypercalcaemia can be caused by many different diseases. This article summarizes the causes, pathophysiologic mechanisms and diagnostic procedures as well as treatment recommendations. The main focus is on hypercalcaemia in primary hyperparathyroidism (PH), complemented by a case report. An elevated total calcium level should generally be investigated and verified by measurement of ionized calcium concentration. The further diagnostic approach depends on the phosphate level. Tumour screening, measurement of parathormone and parathromone-related protein and sonography of parathyroid glands may be necessary. If the calcium-phosphate-product exceeds 60 mg/dl, there is a risk of tissue mineralisation and a rapid treatment of hypercalcaemia is required. For acute therapy, sodium chloride infusion, furosemide and glucocorticoids can be used. Glucocorticoids should only be given after strict indication and after a definite diagnosis. For long-term management, bisphosphates, particularly alendronate, are increasingly used successfully. Causal therapy of PH can be performed by parathyreoidectomy, heat ablation or ethanol ablation. Thereafter, particularly in cases of severe preoperative hypercalcaemia, hypocalcaemia can occur. Treatment is performed using vitamin D3 (calcitriol), which may also be given preoperatively in cases of severe hypercalcaemia. A concomitant oral calcium supplementation using calcium carbonate as medication of choice is contentious. Due to a potential relapse after successful excision of the affected parathyroid gland in PH, the serum calcium level should be monitored periodically.

Evaluation of an automated enzyme-linked fluorescent assay for thyroxine measurement in cat and dog sera.

Measurement of total thyroxine (T4) is the first testing step in the work-up of thyroid disease in small animals. We evaluated an enzyme-linked fluorescent assay (ELFA) as an in-house method to measure T4 in cats and dogs. We compared the T4 concentration in sera of 122 cats and 176 dogs measured by the ELFA with an enzyme immunoassay (EIA) to assess the concordance of the 2 methods. Bias of the ELFA in cats was -11.4% and in dogs 1.4%. Using Bland-Altman plots, limits of agreement were -81.5 to 58.7% in cats and -71.4 to 74.4% in dogs. Imprecision was calculated for both methods. Intra- and interassay coefficients of variation (CVs) of the ELFA in feline sera were 0.7 and 3.4% and of the EIA 7.6 and 15.7%, respectively. Intra- and interassay CVs of both ELFA and EIA in canine sera were <9.5%. Reference intervals for the ELFA method were established and were 13.3-49.5 nmol/L for cats and 10.1-42.9 nmol/L for dogs. Accuracy of the EIA and ELFA was scored by assessing if the measured T4 value would identify the expected T4 range (low, normal, or elevated) of patients, based on history, clinical presentation, other diagnostic means, and response to therapy. This was possible for 75 cats and 50 dogs. Both methods yielded acceptable results, but the EIA was more accurate compared to the ELFA (percentage of true-positives in cats and dogs: EIA: 97% and 100%; ELFA: 92% and 94%).

Prevalence of and risk factors for feline hyperthyroidism among a clinic population in Southern Germany. / Prävalenz und Risikofaktoren der felinen Hyperthyreose in einer Klinikpopulation in Süddeutschland.

OBJECTIVES: Feline hyperthyroidism is a common endocrine disorder in older cats. Previous studies have identified nutritional imbalances, thyroid-disrupting compounds, increasing age and being non-purebred as risk factors but the final trigger remains unknown. The purpose of this prospective study was a) to determine the hospital prevalence of hyperthyroidism in a client-owned cat population in Southern Germany, b) to exploit how frequently hyperthyroidism was diagnosed after the initial clinical suspicion and c) to determine putative intrinsic and extrinsic risk factors from the cats' signalment and a questionnaire analysis, respectively. METHODS: Total thyroxine (T4) was measured in sera of 495 cats ≥ 8 years. Prevalence was calculated with a 95% confidence interval (95% CI) Association between signalment and hyperthyroidism was analysed by Student's unpaired-t-test, chi-square test and Mann-Whitney U-test. Level of significance was set at 0.05. Multivariate logistic regression model was used to determine extrinsic risk factors. RESULTS: Sixty-one cats were diagnosed with hyperthyroidism leading to a prevalence of 12.3% (95% CI: 9.7-15.5). Older (p < 0.001) female cats (p = 0.019; odds ratio 1.9) were significantly more often affected. Domestic shorthair and domestic longhair cats were more likely hyperthyroid than purebred cats (p = 0.016). In 164 cats hyperthyroidism was considered a differential diagnosis and was verified in 20.1% (33/164). In 2.4% (12/495) cases the elevated T4 was an incidental finding. Hyperthyroid cats were more likely to be fed with moist cat food from aluminum tins (p < 0.013) compared to non-hyperthyroid cats. CONCLUSION AND CLINICAL RELEVANCE: Older, female non-purebred cats are predisposed to hyperthyroidism which is frequently diagnosed after the initial clinical suspicion leading to a prevalence of 12.3% among the study population. Components of the aluminum tins or the moist food itself or both may play a role in the etiopathogenesis.

Differential expression of circulating microRNAs in diabetic and healthy lean cats.

MicroRNAs (miRNAs) regulate gene expression and play a role in the pathogenesis of human type 2 diabetes mellitus. This study investigated whether miRNA expression profiles differ between healthy and diabetic cats. Total RNA was extracted from sera of healthy lean cats, newly diagnosed diabetic cats and cats in diabetic remission. Microarrays representing 1079 mouse miRNA targets were used to measure miRNA expression in serum samples from eight healthy lean and seven newly diagnosed diabetic cats; 227 distinct miRNAs could be detected. Nineteen miRNAs were differentially expressed in newly diagnosed diabetic cats compared to healthy lean cats, with a false discovery rate of 10%. Hierarchical cluster analysis of these 19 miRNAs grouped healthy lean and newly diagnosed diabetic cats into separate clusters. After correction for multiple testing, only miR-122 and miR-193b reached statistical significance (P<0.05), with a false discovery rate of 1%. Specific quantitative real-time PCR assays for three target miRNAs (miR-122, miR-193b and miR-483(*)) were applied to four samples from each of the three groups. miR-122 expression was >40-fold higher in newly diagnosed diabetic cats compared to healthy lean cats and cats in diabetic remission, whereas miR-193b showed >14-fold higher expression. MiR-483(*) was expressed sixfold higher in newly diagnosed diabetic cats compared to both other groups.

Vitamin D intoxication caused by ingestion of commercial cat food in three kittens.

Two siblings, a 6-month-old sexually intact male weighing 2.5 kg (cat 1) and a sexually intact female (cat 2) British Shorthair cat weighing 2.3 kg, were examined because of a 3-week history of polyuria, lethargy and laboured breathing. One year previously, another sibling (cat 3) had been presented because of similar, yet more severe, clinical signs at the age of 5 months. Physical examination revealed lethargy, dehydration and polypnoea with slightly increased inspiratory effort. Diagnostic investigation revealed severe hypercalcaemia (cats 1-3), renal azotaemia (cats 1 and 3) and a radiologically generalised miliary interstitial pattern of the lungs (cats 1-3) attributable to hypervitaminosis D caused by ingestion of commercial cat food. Cat 3 was euthanased. Cats 1 and 2 were treated with isotonic saline solution (180 ml/kg IV daily), sucralfate (30 mg/kg PO q12h), terbutaline (only cat 1: 0.1 mg/kg SC q4h), furosemide (1.5 mg/kg IV q8h) and tapering doses of prednisolone. Cat 2 was normal on day 14. Cat 1 had stable renal disease and was followed up to day 672. The radiological generalised military interstitial pattern of the lungs had improved markedly. Excessive cholecalciferol-containing commercially available cat food poses a great hazard to cats. Supportive treatment may result in long-term survival and improvement of radiological pulmonary abnormalities.

Adrenal function in cats with hyperthyroidism.

Adrenal function may be altered in animals with hyperthyroidism. The aim of the study was to assess adrenal function of hyperthyroid cats (n = 17) compared to healthy cats (n = 18) and cats with chronic diseases (n = 18). Adrenal function was evaluated by adrenocorticotropic hormone (ACTH) stimulation test and the urinary cortisol to creatinine ratio (UCCR) was determined. Length and width of both adrenal glands were measured via ultrasound. Hyperthyroid cats had significantly higher cortisol levels before and after stimulation with ACTH than the other groups. However, the UCCR was not elevated in hyperthyroid cats. The size of the adrenal glands of hyperthyroid cats was not significantly different from the size of those of healthy cats. The results indicate that cats with hyperthyroidism have a higher cortisol secretory capacity in a hospital setting. The normal size of the adrenal glands suggests that cortisol levels may not be increased permanently.

Diagnosis and treatment of blastomycosis affecting the nose and nasopharynx of a dog.

CASE DESCRIPTION: A 2-year-old 38.9-kg (85.58-lb) sexually intact male German Shepherd Dog was examined because of a 4-month history of severe nasal swelling and nasal mucosa congestion. The signs were slowly progressive. CLINICAL FINDINGS: Physical examination revealed that the dorsal aspect of the dog's nose was swollen and hard. Mucous membranes in both nostrils were hyperemic and edematous. Diagnostic investigation revealed severe nasal osteolysis and pyogranulomatous rhinitis and nasopharyngitis attributable to blastomycosis. TREATMENT AND OUTCOME: Oral administration of itraconazole was initiated (5 mg/kg [2.27 mg/lb], q 12 h for 5 days and then q 24 h). After a treatment period of 3 months, the nose had regained its normal appearance. After 5 months of treatment, the Blastomyces infection was eliminated as confirmed by results of rhinoscopy and biopsy specimen examination. No relapse was evident within 1 year after discontinuation of treatment. CLINICAL RELEVANCE: In dogs, nasal and nasopharyngeal blastomycosis can result in severe osteolysis of the nasal bone. Resolution of disease can be achieved with oral administration of itraconazole for a period of at least 5 months.

Utility of serum cystatin C as a clinical measure of renal function in dogs.

A human kit for cystatin C determination was evaluated for use with canine sera. A reference range was also established. The association between cystatin C and glomerular filtration rate (GFR) was evaluated in 60 dogs with various diseases, by using exogenous creatinine plasma clearance (ECPC) as a measure of GFR. The correlation between cystatin C and ECPC (correlation coefficient [r] = -0.630; P<0.001) was stronger than the correlation between serum creatinine and ECPC (r = -0.572; P<0.001). Nonrenal diseases (e.g., neoplasia, infection) did not influence serum cystatin C concentration. Test sensitivity was significantly better (P<0.001) for cystatin C (76%) than for creatinine (65%). Specificities for the two tests were 87% and 91%, respectively.