Qualitative and semiquantitative assessment of thyroid hormone binding proteins in greyhounds and other dog breeds.

Total thyroxine (T4) concentrations are lower in healthy greyhounds compared to most other non-sighthound breeds. In humans, variations in the structure or concentration of the major thyroid hormone binding proteins are responsible for most reported differences between total T4 concentrations in healthy individuals from different ethnic groups or other subpopulations. The aim of this study was to determine if such variations are also responsible for the lower total T4 concentrations in greyhounds. The predicted protein sequences of thyroxine-binding globulin (TBG), transthyretin and albumin were determined in liver tissue from a euthyroid greyhound with decreased T4 concentration and a Jack Russell terrier using reverse-transcriptase PCR. Sequences were compared to each other and online reference sequences. Serum proteins from 21 greyhounds and 21 non-sighthound dogs were separated by denaturing electrophoresis and immunoblots probed with polyclonal antibodies to human TBG and transthyretin. Reactive bands were quantified by densitrometry, expressed relative to the mean of reference samples included in each gel. Serum albumin concentrations were measured using a commercially-available assay. Several SNPs were identified but none was thought likely to explain the lower total T4 concentrations in greyhounds. There was no significant difference between the quantity of any of the binding proteins in serum from greyhounds and non-sighthound dogs. However, total T4 and transthyretin concentrations were highly correlated in the greyhound group (r = 0.73, P = 0.0002). Variation in the sequence of thyroid hormone binding proteins is not responsible for low greyhound total T4 concentrations. Further evaluation of the role of transthyretin is warranted.

Association between hyperinsulinaemia and laminitis severity at the time of pituitary pars intermedia dysfunction diagnosis.

BACKGROUND: Hyperinsulinaemia is the suspected component of insulin dysregulation having the strongest association with laminitis and occurs variably in equids with pituitary pars intermedia dysfunction (PPID). OBJECTIVES: We hypothesised that magnitude of hyperinsulinaemia correlates with laminitis severity in PPID-affected equids. Furthermore, we hypothesised that owners can be unaware of chronic endocrinopathic laminitis. STUDY DESIGN: Cross-sectional study. METHODS: Serum insulin concentrations, owner-reported laminitis history and radiographic evidence of laminitis were determined in 38 client-owned horses and ponies with confirmed PPID. Laminitis severity was classified into four categories (normal [nonlaminitic], mild, moderate or severe laminitis) based on degree of distal phalangeal rotation. Animals were also categorised as normoinsulinaemic (<20 µU/ml), mildly hyperinsulinaemic (20-50 µU/ml) and severely hyperinsulinaemic (>50 µU/ml). One-way ANOVA, t tests and Fisher's exact tests were performed. RESULTS: While owners reported laminitis in 37% of animals, 76% were laminitic based on study criteria (P = 0.01). Owners reported laminitis more frequently in hyperinsulinaemic vs. normoinsulinaemic animals; recognition increased with severity of hyperinsulinaemia (P = 0.03). Mean insulin concentrations were higher in equids with moderate to severe radiographic laminitis (geometric mean 74.1, 95% confidence interval (CI) 38.4-143.1 uU/ml) vs. those classified radiographically as normal to mild (31.9, 95% CI 21.1-48.1 uU/ml P = 0.03). MAIN LIMITATIONS: Dynamic insulin testing was not performed; some normoinsulinaemic animals might have had subtle insulin dysregulation. CONCLUSIONS: Although radiographic abnormalities were present in most animals at the time of PPID diagnosis, chronic laminitis remained unrecognised by many owners. Owner awareness of laminitis increased with severity of hyperinsulinaemia and higher insulin concentrations were detected in association with more severe radiographic changes. The Summary is available in Chinese - See Supporting Information.

Effects of Levothyroxine Administration and Withdrawal on the Hypothalamic-Pituitary-Thyroid Axis in Euthyroid Dogs.

BACKGROUND: Chronic supplementation can suppress the hypothalamic-pituitary-thyroid axis (HPTA) and make it difficult to assess thyroid function after withdrawal of levothyroxine. OBJECTIVES: To determine whether the HPTA is suppressed after levothyroxine administration in euthyroid dogs and the time required for resolution of any suppression. ANIMALS: Twenty-eight healthy euthyroid dogs. METHODS: A prospective, randomized study administering levothyroxine to euthyroid dogs for 8 weeks (group 1) or 16 weeks (group 2). Serum concentrations of total thyroxine (T4 ), free thyroxine (fT4 ) by equilibrium dialysis, thyroid stimulating hormone; thyrotropin (TSH), and 3,5,3'-triiodothyronine (T3 ) were measured every 4 weeks during supplementation and for 16 weeks after levothyroxine was discontinued. RESULTS: Mean serum concentrations of T4 and fT4 were significantly higher (P < .0001) and TSH was lower (P < .0001) in all dogs during levothyroxine administration compared to baseline. Mean serum concentrations of T4 , fT4, and TSH in both groups, beginning 1 week after levothyroxine was discontinued, were significantly different (P < .01) compared to values during levothyroxine administration but not compared to baseline values (P > .3). CONCLUSIONS AND CLINICAL IMPORTANCE: Assessing thyroid function tests 1 week after cessation of levothyroxine at 26 µg/kg once a day for up to 16 weeks will provide an accurate assessment of thyroid function in healthy euthyroid dogs.

Evaluation of Basal Serum or Plasma Cortisol Concentrations for the Diagnosis of Hypoadrenocorticism in Dogs.

BACKGROUND: Previous studies that included limited numbers of affected dogs have suggested basal cortisol concentrations ≤55 nmol/L (2 µg/dL) are sensitive, but nonspecific, for a diagnosis of hypoadrenocorticism. A detailed assessment of the diagnostic utility of basal cortisol concentrations is warranted. HYPOTHESIS/OBJECTIVES: To evaluate the utility of basal cortisol concentrations for the diagnosis of hypoadrenocorticism in a large number of dogs, including those with and without serum electrolyte abnormalities. ANIMALS: Five hundred and twenty-two dogs, including 163 dogs with hypoadrenocorticism, 351 dogs with nonadrenal gland illness, and 8 dogs with equivocal results. METHODS: Retrospective study. Basal and post-ACTH cortisol concentrations and sodium and potassium concentrations were collected from medical records. A receiver operating characteristic (ROC) curve was constructed for basal cortisol concentrations by standard methodologies. Sensitivity, specificity, and predictive values were determined for various cut-points. RESULTS: The area under the ROC curve was 0.988 and was similarly excellent regardless of serum electrolyte concentrations. At the most discriminatory cut-point of 22 nmol/L (0.8 µg/dL), sensitivity and specificity were 96.9 and 95.7%, respectively. A basal cortisol concentration of ≤55 nmol/L (2 µg/dL) resulted in a sensitivity of 99.4%. Conversely, a basal cortisol concentration of ≤5.5 nmol/L (0.19 µg/dL) resulted in a specificity of 99.1%. CONCLUSIONS AND CLINICAL IMPORTANCE: Similar to findings in previous studies, basal cortisol concentrations >55 nmol/L (2 µg/dL) are useful in excluding a diagnosis of hypoadrenocorticism. Interestingly, excellent specificities and positive predictive values were observed at lower cut-point cortisol concentrations.

Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus.

A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs.

Serum concentrations of gastrin after famotidine and omeprazole administration to dogs.

BACKGROUND: The duration of antacid-induced hypergastrinemia after cessation of administration of omeprazole and famotidine apparently has not been determined in dogs. HYPOTHESIS: That serum gastrin will return to basal concentrations by 7 days after cessation of famotidine or omeprazole administration. ANIMALS: Nine healthy, adult, male, research colony dogs. METHODS: Randomized, cross-over design. Serum gastrin was determined daily for 7 days to establish baseline concentrations. Famotidine (1.0 mg/kg q24h) or omeprazole (1.0 mg/kg q24h) was administered PO for 7 days followed by a 14-day washout. Serum concentrations of gastrin were determined daily during 7 days of administration and daily for 7 days after cessation of administration. Each drug was evaluated in 8 of the 9 dogs. RESULTS: Omeprazole caused a significant increase in serum gastrin concentration (37.2 ± 7.3 to 71.3 ± 19.0 ng/L; P = .006). Famotidine induced a transient increase in serum gastrin (37.2 ± 7.3 to 65.5 ± 38.5 ng/L; P = .02) that peaked at administration day 3 and declined thereafter. By day 7 after cessation of both drugs, there was no difference in serum gastrin concentrations compared to those before administration (famotidine P = .99; omeprazole P = .99). During or after administration, gastrin concentrations above 3 times the upper reference range were rare (12 of 224 samples). CONCLUSIONS AND CLINICAL IMPORTANCE: A 7-day withdrawal from short-term administration of famotidine or omeprazole is sufficient for serum gastrin to return to baseline concentrations. Withholding famotidine or omeprazole for longer before investigating pathologic causes of hypergastrinemia is unnecessary.

Relationship among serum creatinine, serum gastrin, calcium-phosphorus product, and uremic gastropathy in cats with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) in cats is associated with gastrointestinal signs commonly attributed to uremic gastropathy. Consequently, patients often are treated with antacids and gastrointestinal protectants. This therapeutic regimen is based on documented gastric lesions in uremic humans and dogs, but the nature and incidence of uremic gastropathy in cats are unknown. HYPOTHESIS/OBJECTIVES: Evaluate uremic gastropathy in CKD cats to facilitate refinement of medical management for gastrointestinal signs. ANIMALS: Thirty-seven CKD cats; 12 nonazotemic cats METHODS: Stomachs were evaluated for the presence of classic uremic gastropathy lesions. Histopathologic lesions were compared with serum creatinine concentrations, calcium-phosphorus product (CPP), and serum gastrin concentrations. RESULTS: Gastric ulceration, edema, and vascular fibrinoid change were not observed. The most important gastric lesions in CKD cats were fibrosis and mineralization. Sixteen CKD cats (43%) had evidence of gastric fibrosis of varying severity and 14 CKD cats (38%) had gastric mineralization. CKD cats were more likely to have gastric fibrosis and mineralization than nonazotemic controls (P = .005 and P = .021, respectively). Only cats with moderate and severe azotemia had gastric mineralization. CPP was correlated with disease severity; severely azotemic CKD cats had significantly higher CPP when compared with nonazotemic controls, and to mildly and moderately azotemic cats (P < .05). Gastrin concentrations were significantly higher in CKD cats when compared with nonazotemic controls (P = .003), but increased concentrations were not associated with gastric ulceration. CONCLUSIONS AND CLINICAL IMPORTANCE: Uremic gastropathy in CKD cats differs from that described in other species and this difference should be considered when devising medical management.

Nonthyroidal illness syndrome in adult horses.

BACKGROUND: This study was performed to determine whether sick horses have thyroid hormone (TH) alterations similar to those observed in nonthyroidal illness syndrome in other species. HYPOTHESIS: Horses suffering from systemic diseases have decreased THs and inappropriately low thyroid-stimulating hormone (TSH). ANIMALS: Seventy-one clinically normal horses; 380 hospitalized horses. METHODS: Total thyroxine (TT4), free thyroxine by equilibrium dialysis (fT4D), total triiodothyronine (TT3), free triiodothyronine (fT3), and TSH were measured in normal and hospitalized horses. Disease severity was categorized as mild, moderate, or severe by both subjective and objective criteria. RESULTS: Negative correlations existed between all THs, except TSH, and objective illness severity scores. These scores also increased with each subjective disease severity category. TT3 and fT3 were decreased with mild disease. TT3 progressively decreased more with moderate and severe disease. TT4 and fT4D remained normal with mild disease, but decreased progressively with disease severity. TSH increased with mild disease, but remained normal with moderate or severe disease. Horses that died or were euthanized had lower concentrations of all THs, except TSH, when compared with those that lived. In horses that received >3 doses of NSAIDs, corticosteroids, or heparin compared to 0-3 doses, TT3 and TT4 were decreased, whereas fT4D and TSH remained normal. There were minimal TH changes in horses that were not eating. CONCLUSIONS AND CLINICAL IMPORTANCE: Thyroid hormones decrease in horses with systemic disease. TT3 decreases first, followed by TT4 and fT4D. TSH fails to increase proportionally to the changes in THs, indicating hypothalamic-pituitary axis dysregulation. NSAIDs, corticosteroids, heparin, and fasting have less effect on THs compared with disease severity.

Influence of isoflurane general anesthesia or anesthesia and surgery on thyroid function tests in dogs.

BACKGROUND: Anesthesia and surgery affect thyroid function tests in humans but have not been studied in dogs. HYPOTHESIS: Anesthesia and anesthesia with surgery will affect thyroid function tests in dogs. ANIMALS: Fifteen euthyroid dogs. METHODS: Prospective, controlled, interventional study. Dogs were assigned to one of 3 groups: control, general anesthesia, and general anesthesia plus abdominal exploratory surgery. Dogs in the anesthesia and surgery groups were premedicated with acepromazine and morphine, induced with propofol, and maintained on isoflurane. Samples for measurement of serum thyroxine (T4), free T4 (fT4) by equilibrium dialysis, triiodothyronine (T3), reverse T3 (rT3), and thyroid-stimulating hormone concentrations were collected from each dog immediately before premedication, at multiple times during anesthesia, surgery, 4, 8, 12, 24, 36, and 48 hours after anesthesia, once daily for an additional 5 days, and once 14 days after anesthesia. Sampling was performed at identical times in the control group. RESULTS: Serum T4 decreased significantly from baseline in the surgery and anesthesia groups compared with the control group at 0.33 (P= 0.043) and 1 hour (P= 0.018), and 2 (P= 0.031) and 4 hours (P= 0.037), respectively, then increased significantly in the surgery group compared with the control group at 24 hours (P= 0.005). Serum T3 decreased significantly from baseline in the anesthesia group compared with the control group at 1 hour (P= 0.034). Serum rT3 increased significantly from baseline in the surgery group compared with the control and anesthesia groups at 8 (P= 0.026) and 24 hours (P= 0.0001) and anesthesia group at 8, 12, 24, and 36 hours (P= 0.004, P= 0.016, P= 0.004, and P= 0.014, respectively). Serum fT4 increased significantly from baseline in the surgery group compared to the control at 24 hours (P= 0.006) and at day 7 (P= 0.037) and anesthesia group at 48 hours (P= 0.023). CONCLUSIONS AND CLINICAL IMPORTANCE: Surgery and anesthesia have a significant effect on thyroid function tests in dogs.

An investigation of the action of Neutral Protamine Hagedorn human analogue insulin in dogs with naturally occurring diabetes mellitus.

BACKGROUND: Neutral Protamine Hagedorn human analogue insulin (Humulin N) is commonly used for treatment of canine diabetes mellitus (DM). However, blood glucose and serum insulin concentrations in Humulin N-treated dogs with naturally occurring DM have not been reported. OBJECTIVE: To investigate blood glucose and serum insulin concentrations in the clinical setting of client-owned Humulin N-treated dogs with naturally occurring, well-regulated DM. ANIMALS: Ten client-owned dogs with naturally occurring, well-regulated DM. METHODS: In this clinical study, blood glucose and serum insulin concentrations were measured when dogs received food and insulin (T(0)), at approximately every half hour for the next 2 hours, and then approximately every 2 hours for an additional 8 hours. Insulin duration of action was defined as the number of hours from T(0) to the lowest blood glucose concentration and until blood glucose concentration returned to an interpolated value of 70% of basal blood glucose concentration (Glucose(b)). RESULTS: Mean percent of insulin-induced blood glucose suppression was 49.9 +/- 17.1% (median, 46%; range, 29-78%). Insulin duration of action ranged from 4 to 10 hours. Blood glucose concentration increased initially and returned to Glucose(b) within 0.6-2.2 hours after T(0) in 5 dogs. This initial blood glucose surge then was followed by blood glucose suppression in all 5 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that Humulin N administered SC twice daily is an effective mode of treatment for dogs with naturally occurring DM. Postprandial hyperglycemia is present in some well-regulated diabetic dogs treated with Humulin N.

Thyroid hormone responses to endurance exercise.

REASONS FOR PERFORMING STUDY: Limited information exists about changes in circulating thyroid hormone concentrations during prolonged endurance exercise in horses. OBJECTIVE: To examine the effects of prolonged exercise on serum iodothyronine concentrations in horses performing endurance exercise of varying distances. METHODS: Serum concentrations of iodothyronines were measured in horses before and after completion of 40, 56, 80 and 160 km endurance rides (Study 1); daily during a 5 day, 424 km endurance ride (Study 2); and before and for 72 h after completion of a treadmill exercise test simulating a 60 km endurance ride (Study 3). RESULTS: In Study 1, 40 and 56 km of endurance exercise had little effect on serum iodothyronine concentrations with the exception of a 10% decrease (P<0.05) in free thyroxine (FT4) concentration after the 56 km ride. In contrast, total thyroxine (T4), total triiodothyronine (T3), FT4 and free triiodothyronine (FT3) concentrations all decreased (P<0.05) after successful completion of 80 and 160 km rides, with decreases ranging from 13-31% and 47-54% for distances of 80 and 160 km, respectively. Further, pre-ride T4 concentration was lower (P<0.05) and FT3 concentration was higher (P<0.05) in horses competing 160 km as compared to horses competing over shorter distances. In Study 2, serum concentrations of T4, T3 and reverse triiodothyronine (rT3) progressively decreased (P<0.05) over the course of the multi-day ride. In Study 3, the greatest decrease (P<0.05) in all iodothyronines was observed at 12 h of recovery, ranging from 25% for FT4 to 53% for FT3, but all thyroid hormone concentrations had returned to the pre-exercise values by 24 h of recovery. CONCLUSION: Endurance exercise results in transient decreases in serum iodothyronine concentrations. POTENTIAL RELEVANCE: These data are important to consider when thyroid gland function is assessed by measurement of serum iodothyronine concentrations in endurance horses.

Adult-onset hair loss in Chesapeake Bay retrievers: a clinical and histological study.

Ten Chesapeake Bay retriever (CBRS) dogs with hair loss were recruited in collaboration with the American Chesapeake Club. All dogs had nonpruritic, noninflammatory, regionalized hair loss affecting the same areas of the body in male and female dogs. Hormonal investigations showed increased adrenal and sex steroid concentration in seven cases. Histopathology revealed follicular hyperkeratosis and plugging, follicular atrophy, and occasional melanin clumping with malformed hair shafts. This study suggests that hair loss in CBRS is a breed syndrome in which young adult dogs have hair loss characterized by unusual histological features and abnormal steroid production. A familial predisposition seems likely and selective breeding might reduce the occurrence of this condition.

Effects of propylthiouracil and bromocryptine on serum concentrations of thyrotrophin and thyroid hormones in normal female horses.

REASONS FOR PERFORMING STUDY: There exists a need for better diagnostic tests to characterise thyroid disease in horses. Currently available diagnostic tests fail to differentiate between thyroid gland disorders and thyroid abnormalities resulting from pituitary or hypothalamic problems. OBJECTIVES: To evaluate the effects of treatment with propylthiouracil (PTU) and bromocryptine (BROM) on serum concentrations of triiodothyronine (T3), thyroxine (T4), reverse T3 (rT3) and equine thyroid-stimulating hormone (e-TSH, thyrotrophin) in mature horses. METHODS: Healthy mature horses were treated using either PTU or BROM for 28 days. The effect of treatment on the thyroid axis was assessed by measuring T3, T4, rT3 and e-TSH before and at +14 and +28 days. The effect of PTU and BROM on the response of T3, T4, rT3 and e-TSH to thyrotrophin-release hormone (TRH) administration was also assessed before and at +14 and +28 days of treatment. RESULTS: Treatment with PTU led to a significant reduction in serum concentrations of T3, T4 and rT3 on Day 28 and increase of e-TSH on Day 28 (P < 0.05). Treatment with BROM did not cause any measurable effect on serum concentrations of T3, T4, rT3 or e-TSH. The percentage increment by which serum concentration of T4, T3 and e-TSH increased following stimulation with TRH was decreased by treatment with PTU for 28 days (P < 0.05) but were not affected by treatment with BROM for 28 days. CONCLUSIONS: These results suggest that 1) treatment with PTU may be used in horses as a model of primary hypothyroidism; 2) the use of BROM as a model of secondary hypothyroidism in horses is not supported; and 3) e-TSH assay deserves further investigation for the clinical diagnosis of thyroid axis dysfunction in horses. POTENTIAL RELEVANCE: Propylthiouracil effectively causes primary hypothyroidism. There is substantial variability between horses with respect to their sensitivity to this substance when administered orally. Further studies pertaining to the characterisation of equine thyroid disorders are warranted and the use of both PTU for the experimental induction of primary hypothyroidism and e-TSH for the diagnostic characterisation of thyroid disorders in horses should be considered.

Heparinised blood ionised calcium concentrations in horses with colic or diarrhoea compared to normal subjects.

Our objectives were to 1) establish ionised calcium (ICa), C-terminal PTH and biologically active PTH (intact molecule) concentrations in blood from normal horses, 2) examine the stability of ionised calcium and acid-base values in stored equine heparinised blood and serum and 3) check the applicability of the formulas based on these parameters in certain disease states. Mean +/- s.d. % ionised calcium in heparinised blood of normal Warmbloods was 51 +/- 2.7 (n = 20) of total calcium, range 1.45-1.75 mmol/l (n = 15) at Michigan State University and 1.43-1.69 mmol/l (n = 20) at Utrecht University. Mean +/- s.d. EDTA plasma concentration for intact +/PTH in normal horses measured 0.6 +/- 0.3 pmol/l (n = 11). Both mean serum and the heparinised blood ionised calcium concentrations changed (not significantly) after 102 h storage at room temperature. Six cycles of freezing and thawing did not affect serum ionised calcium concentration significantly. Ionised calcium concentration and pH in heparinised blood of 20 normal Warmbloods were used to calculate the regression equation for the prediction of the adjusted ionised calcium concentration to a pH of 7.4. The linear regression equation found was: adjusted plasma ICa at pH 7.4 mmol/l = -6.4570 + 0.8739 x (measured pH) + 0.9944 x (measured ICa mmol/l). By means of this formula, mean adjusted ionised calcium concentration in heparinised blood calculated was 100% of the actual value given by the analyser in the normal horses. When using this formula in horses with colic or diarrhoea, mean adjusted ionised calcium concentration was underestimated by 0.2 and 0.3%, respectively. Furthermore, to adjust the measured ionised calcium concentration in heparinised blood to a pH of 7.4 in healthy as well as in 2 groups of diseased horses 2 formulas with a good prediction are now available.

Update on the diagnosis and treatment of disorders of calcium regulation.

The availability of PTH, iCa, PTHrP, and 25OHD assays for evaluation of calcium abnormalities in companion animals has been well received [table: see text] by clinicians and diagnosticians. Use of these assays has heightened awareness that some of these disorders are more common than originally thought. Also, there is added insight of alterations of calcium homeostasis as a consequence of other illness or environmental factors such as diet. Animal counterparts of other disorders of calcium metabolism in people are likely to be identified, and use of these assays should play a significant role. As already emphasized, the foundation of using [table: see text] these assays is first assessing whether the calcium abnormality is of a parathyroid-dependent or parathyroid-independent classification.

Lymphocytic thyroiditis.

Lymphocytic thyroiditis is a common canine condition that can lead to functional hypothyroidism. It is associated with more than 50% of cases of canine hypothyroidism. Evidence in human beings and experimental situations suggests that it is a disease of defective immunoregulation, but specific investigation of the molecular pathogenesis of the naturally occurring disease in dogs has not yet been carried out. The condition is heritable in those breeds that have been studied, and progression to hypothyroidism, if it occurs, can be slow. Factors that influence the progression from subclinical thyroiditis to hypothyroidism in dogs are still to be identified, but excessive iodine intake is an important factor in other species.

The postmortem diagnosis of cholecalciferol toxicosis: a novel approach and differentiation from ethylene glycol toxicosis.

The objectives of this study were to develop a novel approach to postmortem diagnosis of cholecalciferol (CCF) toxicosis in dogs using kidney, bile, and urine samples, and to differentiate CCF from ethylene glycol (EG) toxicosis. To achieve these objectives, specimens collected from 2 previous laboratory studies in which dogs were given a single oral toxic dose of CCF (8.0 mg/kg) were used. For EG toxicosis, historical data from the previous 13 years (1985-1998) were reviewed and confirmed cases of EG toxicosis were selected. The historical data were used to compare trace mineral concentrations, specifically of calcium and phosphorus to differentiate between intoxications caused by CCF from that caused by EG in dogs. Kidneys, bile, and urine from dogs that died of CCF toxicosis were analyzed for 25 monohydroxy vitamin D3 (25(OH)D3) and 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) and compared to known control unexposed dogs. Results of this study show that biliary and renal 25(OH)D3 concentrations and renal calcium to phosphorus ratio are of diagnostic value in dogs exposed to toxic concentrations of CCF. The renal calcium to phosphorus ratio was <0.1 in normal dogs, 0.4-0.9 in dogs that died of CCF toxicosis, and >2.5 in dogs that died of EG toxicosis.

Short-term influence of prednisone and phenobarbital on thyroid function in euthyroid dogs.

The short-term effects of prednisone and phenobarbital on serum total thyroxine (tT4), free thyroxine (fT4), and thyroid stimulating hormone (TSH) were evaluated in euthyroid dogs. Twenty-six beagles were randomly divided into 3 groups receiving, respectively, a placebo, prednisone (1.2 to 2 mg/kg body weight, per os, every 12 hours for 3 weeks), or phenobarbital (1.8 to 3 mg/kg body weight for 1 week, then 2.7 to 4.5 mg/kg body weight, per os, every 12 hours for 2 weeks). Blood samples taken over a 6-week period were assayed for serum tT4, fT4, and TSH. Phenobarbital therapy in our study did not affect serum tT4, fT4, or TSH concentrations. Prednisone therapy, however, significantly decreased serum tT4 and fT4, but did not affect serum TSH concentrations.