Assessment of criteria used by veterinary practitioners to diagnose hypothyroidism in sighthounds and investigation of serum thyroid hormone concentrations in healthy Salukis.

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 (T(4)), free T(4), total triiodothyronine (T(3)), free T(3), 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 T(4), free T(4), total T(3), free T(3), 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.

Etiopathologic findings of canine hypothyroidism.

The causes of canine hypothyroidism are varied, but most cases result from irreversible acquired thyroid pathologic changes and only a small proportion arise from congenital anomalies of the thyroid gland or pituitary. Of primary thyroid failure, at least half is the result of immune-mediated thyroiditis. Recent research has focused on the genetics and immunology of canine thyroid disease, adding to what is known from experimental and human studies. Epidemiologic and diagnostic laboratory studies continue to provide information on contributing factors and raise questions for future research directions. Serum antibodies against thyroid components are common in thyroid pathologic conditions and dysfunction, and understanding their properties and frequency is important in the interpretation of thyroid diagnostic test results.

Detection of autoantibodies against thyroid peroxidase in serum samples of hypothyroid dogs.

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 thyroid-stimulating 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.

Evaluation of calciotropic hormones in cats with odontoclastic resorptive lesions.

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.

Thyroid to salivary ratios determined by technetium-99m pertechnetate imaging in thirty-two euthyroid cats.

Thyroid to salivary (TS) ratio is the most commonly used scintigraphic parameter for differentiating euthyroid and hyperthyroid cats. Studies to determine the normal TS ratio have been performed in small cat populations. In this study, the TS ratio was determined in 32 cats between 8 and 13 years of age. The study population was documented to be euthyroid based on normal initial and 6-week follow-up serum thyroid concentrations and normal T3 suppression tests. All images were obtained with a low-energy all-purpose collimator between 20 and 40 min after the injection of approximately 111 MBq (3.0 mCi) pertechnetate. Manual regions of interest (ROI) were made of the thyroid and salivary glands of the ventral image A 95% prediction interval based on the natural log of the TS ratio was computed to provide a normal range of 0.48-1.66. This range is similar to previous studies, but suggests a slightly higher upper limit than previously reported.

Detection of parathyroid hormone-related protein in cats with humoral hypercalcemia of malignancy.

BACKGROUND: Increased serum parathyroid hormone-related peptide (PTHrP) concentration is used to diagnose humoral hypercalcemia of malignancy (HHM) in humans and animals. A commercially available assay for human PTHrP has diagnostic utility in the dog, but has not been assessed in cats. OBJECTIVE: The goals of this study were to determine serum or plasma levels of PTHrP in a population of hypercalcemic cats and to determine whether increased PTHrP concentration was associated with malignancy. In addition, we validated immunoradiometric assays (IRMAs) for intact parathormone (iPTH) and PTHrP for use with feline samples. METHODS: A retrospective analysis of iPTH and PTHrP results from 322 hypercalcemic cats (ionized calcium concentration > 1.4 mmol/L) was performed. Immunoassays for human iPTH and PTHrP (residues 1-84) were validated using standard methods, and reference intervals were calculated using values from 31 healthy adult cats. Hypercalcemic cats were classified as parathyroid-independent (iPTH < 2.3 pmol/L), equivocal (iPTH 2.3-4.6 pmol/L), or parathyroid-dependent (iPTH > 4.6 pmol/L). Seven cats with detectable or increased PTHrP concentrations were evaluated further for underlying disease. Formalin-fixed neoplastic tissues were immunohistochemically stained using rabbit antibody to human midregion PTHrP. RESULTS: Assays for iPTH and PTHrP showed acceptable precision for feline samples. The reference interval for iPTH was 0.8-4.6 pmol/L and for PTHrP was < 1.5 pmol/L. The majority of hypercalcemic cats (263/322, 81.7%) were parathyroid-independent, with fewer cats in the equivocal (32/322, 9.9%) and parathyroid-dependent (27/322, 8.4%) groups. In 31 (9.6%) cats, PTHrP concentration was > 1.5 pmol/L (range 1.5-26.6 pmol/L). All 7 cats for which follow-up information was available had HHM; 6 had carcinomas (4 lung carcinomas, 1 undifferentiated carcinoma, 1 thyroid carcinoma) and 1 had lymphoma. All tumors had mild to moderate positive staining for PTHrP; however, lung carcinomas from normocalcemic cats also stained positive. CONCLUSIONS: Human IRMA for PTHrP (1-84) can be used to measure PTHrP in cats. Malignancies, particularly carcinomas, appear to secrete PTHrP and induce HHM in this species. Immunohistochemistry alone cannot predict the occurrence of HHM in cats.

Prevalence of serum thyroid hormone autoantibodies in dogs with clinical signs of hypothyroidism.

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 chi2 analyses were used to determine whether prevalence varied with breed, age, sex, or body weight. Only breeds for which > or = 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.