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  • Author or Editor: Raymond Nachreiner x
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Abstract

Objective—To establish a sensitive test for the detection of autoantibodies against thyroid peroxidase (TPO) in canine serum samples.

Sample Population—365 serum samples from dogs with hypothyroidism as determined on the basis of serum concentrations of total and free triiodothyronine (T3), total and free thyroxine (T4), and thyroidstimulating hormone, of which 195 (53%) had positive results for at least 1 of 3 thyroid autoantibodies (against thyroglobulin [Tg], T4, or T3) and serum samples from 28 healthy dogs (control samples).

Procedure—TPO was purified from canine thyroid glands by extraction with detergents, ultracentrifugation, and precipitation with ammonium sulfate. Screening for anti-TPO autoantibodies in canine sera was performed by use of an immunoblot assay. Thyroid extract containing TPO was separated electrophoretically, blotted, and probed with canine sera. Alkaline phosphatase–conjugated rabbit anti-dog IgG was used for detection of bound antibodies.

Results—TPO bands were observed at 110, 100, and 40 kd. Anti-TPO autoantibodies against the 40-kd fragment were detected in 33 (17%) sera of dogs with positive results for anti-Tg, anti-T4, or anti-T3 autoantibodies but not in sera of hypothyroid dogs without these autoantibodies or in sera of healthy dogs.

Conclusions and Clinical Relevance—The immunoblot assay was a sensitive and specific method for the detection of autoantibodies because it also provided information about the antigen. Anti-TPO autoantibodies were clearly detected in a fraction of hypothyroid dogs. The value of anti-TPO autoantibodies for use in early diagnosis of animals with thyroid gland diseases should be evaluated in additional studies.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine prevalence of thyroid hormone autoantibodies (THAA) in serum of dogs with clinical signs of hypothyroidism.

Design—Cohort study.

Sample Population—287,948 serum samples from dogs with clinical signs consistent with hypothyroidism.

Procedure—Serum THAA were detected by use of a radiometric assay. Correlation and X 2 analyses were used to determine whether prevalence varied with breed, age, sex, or body weight. Only breeds for which ≥ 50 samples had been submitted were used for analysis of breed prevalence.

Results—Thyroid hormone autoantibodies were detected in 18,135 (6.3%) samples. The 10 breeds with the highest prevalence of THAA were the Pointer, English Setter, English Pointer, Skye Terrier, German Wirehaired Pointer, Old English Sheepdog, Boxer, Maltese, Kuvasz, and Petit Basset Griffon Vendeen. Prevalence was significantly correlated with body weight and was highest in dogs between 2 and 4 years old. Females were significantly more likely to have THAA than were males.

Conclusions and Clinical Relevance—Thyroid hormone autoantibodies may falsely increase measured triiodothyronine (T3) and thyroxine (T4) concentrations in dogs; results suggest that T3 concentration may be falsely increased in approximately 57 of 1,000 dogs with hypothyroidism and that T4 concentration may be falsely increased in approximately 17 of 1,000 dogs with hypothyroidism. Results also suggested that dogs of certain breeds were significantly more or less likely to have THAA than were dogs in general. (J Am Vet Med Assoc 2002;220:466–471)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To assess associations between epidemiologic and laboratory variables and calciotropic hormones in cats with odontoclastic resorptive lesions (ORLs).

Animals—182 client-owned cats older than 1 year of age with oral disease.

Procedure—Information on medical history, behavior, living environment, and feeding management was assessed by use of a questionnaire. After induction of general anesthesia, oral examination was performed following standardized protocols and included dental probing and full-mouth radiography. Laboratory analyses included evaluation of FeLV-FIV status, serum biochemical analyses, CBC, urinalysis, and serum concentrations of intact parathyroid hormone (iPTH), parathyroid hormone-related peptide (PTHrP), 25-hydroxyvitamin D (25-OHD), free thyroxine (fT4), and ionized calcium (iCa).

Results—ORLs were identified in 72.5% of cats. Mandibular third premolars were the most commonly affected teeth. Cats with ORLs were significantly older (mean, 9.2 years) than cats without ORLs (mean, 6.6 years). Multivariate logistic regression analysis revealed that 25-OHD, urine specific gravity, jaw-opening reflex on probing, and missing teeth were significant variables, even after accounting for age. Cats with ORLs had significantly higher mean serum concentration of 25-OHD (112.4 nmol/L) and significantly lower mean urine specific gravity (1.0263), compared with cats without ORLs (89.8 nmol/L and 1.0366, respectively).

Conclusions and Clinical Relevance—Results did not indicate associations between iPTH, PTHrP, or fT4 and development of ORLs. In affected cats, the importance of high serum 25-OHD and low urine specific gravity has not been determined. (Am J Vet Res 2005;66:1446–1452)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess use of serum thyroid hormone concentrations by veterinarians to diagnose hypothyroidism in sighthounds and to evaluate serum thyroid hormone concentrations in healthy Salukis.

Design—Retrospective case series and cross-sectional study.

Animals—398 sighthounds of various breeds with a diagnosis of hypothyroidism and 283 healthy Salukis.

Procedures—Pretreatment thyroid hormone assay results from sighthounds subsequently classified as hypothyroid by practitioners were retrieved from a laboratory database. In healthy Salukis, serum concentrations of total thyroxine (T4), free T4, total triiodothyronine (T3), free T3, and thyroid-stimulating hormone (TSH) and antibodies against thyroglobulin and thyroid hormones were assayed.

Results—Records indicated hypothyroidism had been diagnosed in 303 (76.1%) sight-hounds on the basis of low serum thyroid hormone concentrations alone and in 30 (7.5%) others despite all thyroid hormone indices being within reference limits. Only 65 (16.3%) dogs had a high TSH concentration or positive thyroglobulin autoantibody result to support the diagnosis. In healthy Salukis, median (reference limits) serum concentrations of total T4, free T4, total T3, free T3, and TSH were 13.0 nmol/L (2.8 to 40.0 nmol/L), 12.0 pmol/L (2.0 to 30.3 pmol/L), 1.0 nmol/L (0.4 to 2.1 nmol/L), 4.0 pmol/L (1.6 to 7.7 pmol/L), and 0.18 ng/mL (0 to 0.86 ng/mL), respectively.

Conclusions and Clinical Relevance—Diagnosis of hypothyroidism by practitioners was most often made without adequate supportive laboratory evidence. Thyroid hormone values in healthy Salukis differed markedly from standard reference limits for some, but not all, thyroid hormone indices. Breed-specific reference limits should be used when interpreting thyroid hormone profiles of sighthounds.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective

To determine whether the urine cortisol-to-creatinine ratio (UCCR) could replace the ACTH stimulation test in monitoring effectiveness of mitotane induction treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH).

Animals

15 dogs with PDH.

Procedure

All 15 dogs were given an induction dose of mitotane (o, p'-DDD: 35 to 50 mg/kg of body weight/d) for 3 to 14 days. During the induction period, free-catch morning urine samples were collected for determination of UCCR, followed by ACTH stimulation testing, every other day. Treatment response was divided into 3 categories: well-controlled PDH (post-ACTH serum cortisol concentration ≥ 28 nmol/L but ≤ 138 nmol/L), deficient cortisol secretion (post-ACTH serum cortisol concentration < 28 nmol/L), and excess cortisol secretion (post-ACTH serum cortisol concentration > 138 nmol/L).

Results

The linear relation between UCCR and post-ACTH serum cortisol concentration was significant (P < 0.001); however, the prediction intervals surrounding the line were too broad to be clinically useful. The UCCR overlapped among the 3 categories of treatment response. Nevertheless, dogs with PDH receiving mitotane induction treatment and with UCCR > 79 × 10−6 were always classified as having excess cortisol secretion.

Conclusion and Clinical Relevance

The UCCR failed to predict post-ACTH cortisol concentration during mitotane induction treatment sufficiently close to be a clinically reliable indicator of treatment control. Seemingly, however, UCCR > 79 × 10−6 obtained from a dog with PDH during mitotane induction would indicate inadequate adrenal cortex destruction and the need for continued mitotane induction; UCCR ≤ 79 × 10−6 would be inconclusive. (Am J Vet Res 1998;59:258–261)

Free access
in American Journal of Veterinary Research

Summary

Administration of triiodothyronine (liothyronine, 15 μg, q 8 h, for 6 treatments) caused marked decrease in serum concentration of thyroxine (T4) and estimates of free T4 (fT4) concentration in clinically normal cats. A prospective clinical study was done to evaluate the use of this suppression test for diagnosis of hyperthyroidism in cats with clinical signs suggestive of the disease, but lacking high serum concentration of iodothyronines.

Twenty-three cats were confirmed as hyperthyroid on the basis of histologic changes in the thyroid gland or clinical improvement in response to administration of methimazole. Mean ± sd serum concentration of T4 (34.3 ± 12.7 to 31.3 ± 11.5 nmol/L) and estimate of fT4 concentration (26.6 ± 6.4 to 25.6 ± 6.9 pmol/L) did not change after administration of liothyronine to these cats. Twenty-three cats were classified as nonhyperthyroid by histologic confirmation of other disease, abnormal results of other diagnostic tests that strongly supported primary disease other than hyperthyroidism, or spontaneous remission of weight loss without treatment. Mean ± sd serum concentration of T4 (27.9 ± 10.3 to 11.7 ± 6.4 nmol/L) and estimate of fT4 concentration (21.7 ± 5.4 to 10.4 ± 4.4 pmol/L) decreased significantly (P < 0.001) in response to administration of liothyronine.

Discriminant analysis was used to identify variables from iodothyronine assays (eg, absolute concentration of T4 or absolute estimate of fT4 concentration, or changes of T4 or fT4 concentration) that provided the best diagnostic sensitivity and specificity. The endocrine end points that best differentiated hyperthyroid vs nonhyperthyroid cats were the concentration of T4 or estimate of fT4 concentration in serum obtained after liothyronine administration and predictive values ues calculated from postliothyronine serum concentration of T4 or fT4 and percentage decrease of T4 concentration. Difference in diagnostic sensitivity among endocrine end points compared was not apparent. Use of postliothyronine estimate of fT4 concentration alone or as part of a predictive value improved diagnostic specificity for differentiation of hyperthyroid vs non-hyperthyroid cats (P ≤ 0.081).

Results of this study further confirm existence of hyperthyroidism in cats that do not have high serum concentration of iodothyronines. We concluded that the triiodothyronine suppression test is a safe and accurate test for diagnosis of hyperthyroidism in cats with suggestive clinical signs of the disease, but lacking high serum concentration of iodothyronines.

Free access
in Journal of the American Veterinary Medical Association

SUMMARY

The effects of treatment with l-thyroxine (1 mg/m2 of body surface/d, po, for 8 weeks) on the thyroxine (T4) and triiodothyronine (T3) responses to thyrotropin (tsh) and thyrotropin-releasing hormone (trh) administration were determined in 10 euthyroid Beagles; 4 other dogs acted as controls. The tsh response test was performed before treatment and at weeks 2, 4, and 8 of treatment in all dogs and at 2 and 4 weeks after cessation of treatment in 6 dogs. The trh response test was performed before treatment and at week 6 of treatment in all dogs and at 5 weeks after cessation of treatment in 6 dogs.

Suppression of the T3 response to tsh was evident at treatment week 2, whereas the T4 response was suppressed at week 4 and remained suppressed for the duration of the study. Four weeks after l-thyroxine treatment was stopped, T3 response to tsh had returned to pretreatment values. Four weeks after stopping treatment, T4 and T3 responses to tsh in 2 dogs were within the hypothyroid range. The T4 response to trh was completely suppressed after 6 weeks of thyroxine treatment, but returned to pretreatment values by 5 weeks after cessation of treatment. Suppression of thyroid and pituitary function is evident after administration of a replacement dose of l-thyroxine to euthyroid dogs.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether pamidronate disodium can reduce cholecalciferol-induced toxicosis in a dose-related manner.

Animals—20 clinically normal, 8- to 12-month-old male Beagles.

Procedure—All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were randomly assigned to 4 groups of 5 dogs each. Dogs were treated with IV administration of 0.9% NaCl solution (SC group), 0.65 mg of pamidronate/kg in 0.9% NaCl solution (LP group), 1.3 mg of pamidronate/kg in 0.9% NaCl solution (MP group), or 2.0 mg of pamidronate/kg in 0.9% NaCl solution (HP group) on days 1 and 4 after administration of CCF. Dogs were observed for 14 days, and serial blood samples were collected for serum biochemical, electrolyte, and 25-hydroxyvitamin D3 analyses. Urine samples were collected for determination of specific gravity. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Histologic examination of renal tissue was performed.

Results—One dog in the SC group was euthanatized 3 days after administration of CCF because of severe clinical signs of toxicosis. Dogs in the HP group had significantly higher mean GFR (day 3), serum potassium concentrations (day 14), and urine specific gravity (days 7 and 14) and significantly lower mean serum creatinine concentrations and total calcium × phosphorus concentration product (days 4 and 7) than dogs in the SC group. Dogs in the HP group had no abnormal findings on histologic examination of renal tissue, dogs in the LP and MP groups had trace to mild mineralization of renal tissue, and dogs in the SC group had moderate mineralization and cellular necrosis of proximal renal tubules.

Conclusions and Clinical Relevance—Pamidronate disodium is a potentially useful drug to reduce CCFinduced toxicosis and other causes of hypercalcemia associated with increased bone resorption in dogs. (Am J Vet Res 2000;61:9–13)

Full access
in American Journal of Veterinary Research

Abstract

Objectives

To determine whether pamidronate di-sodium can reduce vitamin D3-induced hypercalcemia in dogs and whether combination treatment with calcitonin is more effective than treatment with pamidronate alone.

Animals

20 clinically normal male Beagles.

Procedure

All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were assigned randomly to 4 groups of 5 dogs each. Dogs were given 0.9% NaCl solution IV (group 1), calcitonin SC and 0.9% NaCl solution IV (group 2), pamidronate and 0.9% NaCl solution IV (group 3), or a combination of all 3 agents (group 4). Dogs were observed for 28 days, and serial blood and urine samples were collected for determination of serum biochemical, electrolyte, and 25(OH)D3 values, CBC, and urine mineral excretion. Samples of kidney, stomach, lung, aorta, liver, duodenum, and brain were evaluated by light microscopy and quantitative mineral analysis.

Results

Two dogs in group 1 were euthanatized 4 days after CCF administration because of severe clinical signs of disease. Dogs in group 3 lost less weight and had significantly lower serum phosphorus, total and ionized calcium, and urinary zinc concentrations, compared with dogs in group 1. On day 4, serum urea nitrogen concentration was significantly lower in dogs of groups 3 and 4, compared with dogs in group 1. Mild to moderate mineralization of kidneys and stomach were observed in the 2 group-1 dogs euthanatized on day 4.

Conclusions

Pamidronate administration effectively prevents CCF-induced hypercalcemia and mineralization of soft tissues.

Clinical Relevance

Pamidronate is a potentially useful antidote against CCF toxicosis in dogs. (Am J Vet Res 1999;60:1092-1097)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To document and determine changes in the mineral profiles of sera and mammary secretions from a population of periparturient mares.

Animals

18 clinically normal periparturient Arabian broodmares.

Procedure

Inductively coupled argon emission spectroscopy was used to measure Ca, Cu, Fe, K, Mg, Mn, Na, P, and Zn concentrations in sera and mammary secretions of periparturient mares. In addition, S was measured in mammary secretions.

Results

Serum concentrations of Ca, Cu, Fe, K, Mg, Na, P, and Zn remained constant throughout late pregnancy and the first 7 days of lactation. Compared with values on day 11 before foaling, mammary fluid concentrations of Ca, Cu, K, Mg, P, S, and Zn increased prior to parturition and all element concentrations, except Ca, decreased with the onset of lactation. In contrast, Na concentrations in mammary secretions decreased precipitously as parturition approached. Iron concentrations in mammary secretions remained relatively constant up to the time of parturition, decreased at parturition, and remained constant during lactation.

Conclusions and Clinical Relevance

Prior to foaling, increasing concentrations of Ca, Cu, K, Mg, P, S, or Zn in mammary secretions in concert with precipitous decreases in Na concentrations may provide a predictive index of impending parturition in the mare and a means of assessing fetal readiness for birth. (Am J Vet Res 1997;58:376–378)

Free access
in American Journal of Veterinary Research