THE RADIOGRAPHIC APPEARANCE OF CANINE CONGENITAL HYPOTHYROIDISM: SKELETAL CHANGES WITH DELAYED TREATMENT

Congenital hypothyroidism was diagnosed in five Boxer dogs presented to the Veterinary Hospital of the University of Pennsylvania between 1978 and 1979. The dogs ranged in age from 5–19 months, and were from two unrelated litters. Congenital hypothyroidism was confirmed by serum T3 and T4 radioimmunoassay and TSH stimulation test. Serial radiographs made before and after L-thyroxine oral supplementation were studied retrospectively to evaluate the resolution of skeletal abnormalities and to compare skeletal with chronological age. On initial presentation, all five dogs had the following skeletal manifestations of congenital hypothyroidism: short broad skulls, shortened vertebral bodies, and epiphyseal dysgenesis and delayed maturation. Epiphyseal dysgenesis was most common in the humeral (n = 3) and femoral condyles (n = 4), and proximal tibia (n = 4). Accelerated epiphyseal ossification occurred during thyroid hormone supplementation. Three dogs developed osteochondrosistype lesions. Bowing of the radius and disproportionate radius and ulna length resulted in humeroradial joint widening (n = 4) and humeroulnar joint subluxation (n = 1). Degenerative joint changes in the elbows (n = 4), stifles (n = 1), and shoulder (n = 1) were more common in the older dogs.     

Congenital hypothyroidism of dogs and cats: a review

Congenital hypothyroidism is a rare and underdiagnosed congenital endocrine disorder in dogs and cats and the true incidence is unknown. The disorder may cause a range of clinical signs depending on the primary defect, which affect production of thyroid hormones; some cases present when adult. Hallmark clinical signs of congenital hypothyroidism are mental impairment and skeletal developmental abnormalities, resulting in disproportionate dwarfism; goitre may or may not be present. Documented causes of congenital hypothyroidism in dogs include deficiency of, or unresponsiveness to, thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH), thyroid dysgenesis, dyshormonogenesis and iodine deficiency. In cats, TSH unresponsiveness, thyroid dysgenesis, dyshormonogenesis and iodine deficiency have been confirmed. Adequate replacement therapy results in a successful outcome in the majority of cases, especially when started early in life, as permanent developmental abnormalities can be prevented. This review describes reported cases in dogs and cats, diagnostic investigation, and recommendations for treatment.     

Evaluation of thyroid function in dogs suffering from recurrent flank alopecia

Thyroid function was assessed in euthyroid dogs (n = 20), dogs suffering from canine recurrent flank alopecia (CRFA, n = 18), and hypothyroid dogs (n = 21). Blood samples obtained from all dogs in each group were assayed for total thyroxine (TT4), thyrotropin (TSH), and thyroglobulin autoantibody (TgAA) serum concentrations. Total T4 and TSH serum concentrations were significantly decreased and increased, respectively, in the hypothyroid group compared with the other 2 groups. No significant differences in TT4 and TSH serum values were found between the euthyroid and CRFA groups. Thyroglobulin autoantibodies were detected in 10, 11.1, and 61.9% of euthyroid dogs, dogs with CRFA, and hypothyroid dogs, respectively. In conclusion, dogs suffering from CRFA have a normal thyroid function, and the determination of TT4 and TSH serum concentrations allows differentiation of these dogs from dogs with hypothyroidism, in most cases. Occasionally, the 2 diseases can be concomitant.     

Congenital hypothyroidism in a boxer dog

Congenital central hypothyroidism was diagnosed in a one-year-old boxer dog. The dog was presented for investigation of lameness, lethargy and obesity. Survey skeletal radiographs revealed delayed bone maturation and epiphyseal dysgenesis. A diagnosis of hypothyroidism was confirmed on the basis of a low basal serum thyroxine (T₄) concentration that failed to increase following bovine thyroid stimulating hormone (TSH) administration. However, repeated administration of TSH resulted in reactivation of the thyroid gland suggesting a central rather than a primary problem. Consistently low basal plasma Cortisol concentrations were suggestive of a concurrent secondary or tertiary hypoadrenocorticism. Surprisingly, plasma growth hormone concentrations were elevated before treatment but decreased once thyroid replacement therapy had commenced.     

Autoantibodies against thyroid hormones and their influence on thyroxine determination with chemiluminescence immunoassay in dogs

Autoantibodies against thyroxin (T4AA) and triiodothyronine (T3AA) are present in dogs with autoimmune thyroiditis and have been reported to interfere with immunoassays. The objectives of this study were to determine the frequency of autoantibodies and to determine whether interference occurs by T4AA, using a non-immunological method (high performance liquid chromatography, HPLC) for thyroxin (T4) measurement. Based on clinical symptoms, T4 and thyroid stimulating hormone (TSH) concentration, 1,339 dogs were divided into six groups: Group 1: hypothyroid (n = 149); Group 2: subclinical thyroiditis (n = 110); Group 3: suspicious for non thyroidal illness (n = 691); Group 4: biochemical euthyroid (n = 138); Group 5: hypothyroid dogs under substitution therapy (n = 141); Group 6: healthy dogs (n = 110). The incidence of T4AA and T3AA, determined using radiometric assay, was low (0.5% and 3.8%) and higher in hypothyroid dogs compared to dogs suspicious for hypothyroidism (Group 2-4) (p<0.05). T4AA was not detected in dogs with normal T4 and elevated TSH. T4 concentrations of T4AA positive samples determined using HPLC were comparable to results obtained by chemiluminescence immunoassay. These findings indicate that the probability of interference of T4AA leading to falsely elevated T4 concentration in the T4 assay seems to be low.     

Assessment of thyroid function in dogs with low plasma thyroxine concentration

BACKGROUND: Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. HYPOTHESIS: The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. ANIMALS: In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. METHODS: The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. RESULTS: Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.     

Evaluation of recombinant human thyroid-stimulating hormone to test thyroid function in dogs suspected of having hypothyroidism

OBJECTIVE: To evaluate the use of recombinant human (rh) thyroid-stimulating hormone (TSH) in dogs with suspected hypothyroidism. ANIMALS: 64 dogs with clinical signs of hypothyroidism. PROCEDURES: Dogs received rhTSH (75 microg/dog, IV) at a dose independent of their body weight. Blood samples were taken before and 6 hours after rhTSH administration for determination of total serum thyroxine (T(4)) concentration. Dogs were placed into 1 of 3 groups as follows: those with normal (ie, poststimulation values indicative of euthyroidism), unchanged (ie, poststimulation values indicative of hypothyroidism; no thyroid gland stimulation), or intermediate (ie, poststimulation values between unchanged and normal values) post-TSH T(4) concentrations. Serum canine TSH (cTSH) concentration was determined in prestimulation serum (ie, before TSH administration). RESULTS: 14, 35, and 15 dogs had unchanged, normal, and intermediate post-TSH T(4) concentrations, respectively. Basal T(4) and post-TSH T(4) concentrations were significantly different among groups. On the basis of basal serum T(4) and cTSH concentrations alone, 1 euthyroid (normal post-TSH T(4), low basal T(4), and high cTSH concentrations) and 1 hypothyroid dog (unchanged post-TSH T(4) concentration and low to with-in reference range T(4) and cTSH concentrations) would have been misinterpreted as hypothyroid and euthyroid, respectively. Nine of the 15 dogs with intermediate post-TSHT(4) concentrations had received medication known to affect thyroid function prior to the test, and 2 of them had severe nonthyroidal disease. CONCLUSIONS AND CLINICAL RELEVANCE: The TSH-stimulation test with rhTSH is a valuable diagnostic tool to assess thyroid function in selected dogs in which a diagnosis of hypothyroidism cannot be based on basal T(4) and cTSH concentrations alone.     

Ateliotic Dwarfism in the German Shepherd Dog: LOW SOMATOMEDIN ACTIVITY ASSOCIATED WITH APPARENTLY NORMAL PITUITARY FUNCTION (2 CASES) AND WITH PAN-ADENOPITUITARY DYSFUNCTION (1 CASE)

Two types of ateliotic dwarfism in 3 German Shepherd dog puppies are described. Low somatomedin levels in serum and impaired growth of skeletal tissues were found in all 3 cases.One dog (case 2) had a histologically undeveloped adenohypophysis, and the dwarfism was apparently due to a generalized lack of adenopituitary function.The 2 other dogs (cases 1A and IB) had histologically normal adenohypophyses, and their condition was probably due to a reduced response to endogenous growth hormone in peripheral tissues.     

Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in epileptic dogs treated with anticonvulsants.

OBJECTIVE: To determine whether administration of phenobarbital, potassium bromide, or both drugs concurrently was associated with abnormalities in baseline serum total thyroxine (T4), triiodothyronine (T3), free T4, or thyrotropin (thyroid-stimulating hormone; TSH) concentrations in epileptic dogs. DESIGN: Prospective case series. ANIMALS: 78 dogs with seizure disorders that did not have any evidence of a thyroid disorder (55 treated with phenobarbital alone, 15 treated with phenobarbital and bromide, and 8 treated with bromide alone) and 150 clinically normal dogs that were not receiving any medication. PROCEDURE: Serum total T4, total T3, free T4, and TSH concentrations, as well as serum concentrations of anticonvulsant drugs, were measured in the 78 dogs with seizure disorders. Reference ranges for hormone concentrations were established on the basis of results from the 150 clinically normal dogs. RESULTS: Total and free T4 concentrations were significantly lower in dogs receiving phenobarbital (alone or with bromide), compared with concentrations in clinically normal dogs. Administration of bromide alone was not associated with low total or free T4 concentration. Total T3 and TSH concentrations did not differ among groups of dogs. CLINICAL IMPLICATIONS: Results indicate that serum total and free T4 concentrations may be low (i.e., in the range typical for dogs with hypothyroidism) in dogs treated with phenobarbital. Serum total T3 and TSH concentrations were not changed significantly in association with phenobarbital administration. Bromide treatment was not associated with any significant change in these serum thyroid hormone concentrations.     

Serum total thyroxine and thyroid stimulating hormone concentrations in dogs with behavior problems

The aim of this case controlled study was to determine whether dogs with behavioral problems have evidence of abnormal thyroid function on routine screening tests for hypothyroidism. The hypothesis of the study was that thyroid function, as assessed by serum total thyroxine (TT4) and serum thyroid stimulating hormone (thyrotropin) (TSH) concentrations, is normal in most dogs with behavioral problems. Concentrations of TT4 and TSH in 39 dogs with behavior problems presenting to a veterinary behavior referral clinic (abnormal behavior group), were compared with TT4 and TSH concentrations in 39 healthy control dogs without behavior problems presenting to 5 community veterinary practices (control group). Dogs in the control group were matched for age and breed with the abnormal behavior group. Dogs with behavioral problems had higher TT4 concentrations than dogs without behavioral problems (t-test: t = 2.77, N = 39, P = 0.009), however none of the TT4 values were outside the reference range. There was no significant difference in TSH concentration between the 2 groups. Two dogs with behavior problems and 1 dog without behavior problems had results suggestive of hypothyroidism. All other dogs were considered to be euthyroid. There was no evidence to support a diagnosis of hypothyroidism in the majority of dogs with behavior problems in this study. The higher concentration of TT4 in dogs with behavior problems suggests, however, that alteration in thyroid hormone production or metabolism may occur in some dogs with behavior problems. Further studies that include additional indicators of thyroid status such as serum total triiodothyronine, serum, free thyroxine, and anti-thyroid antibody concentrations are necessary to further evaluate the significance of this finding.     

Goiter with vascular anomalies in a litter of Polish Lowland sheepdogs

At approximately 4-5 mo of age, three Polish Lowland sheepdog puppies from a single litter of eight puppies presented to their respective primary veterinarians with bilateral subcutaneous masses in their ventral cervical regions. Evaluation, including thyroid function testing, surgical exploration with resection, computed tomography, and angiography, identified the masses as enlarged thyroid glands with severely dilated and abnormal vasculature in the regions of the glands. The dogs were also found to have serum concentrations of thyroid hormones that were below the reference ranges. None of the three dogs showed clinical signs of hypothyroidism, except for the presence of goiter. One dog also had a patent ductus arteriosus that was surgically repaired. All dogs were clinically normal at 2 yr of age. This is the first report of major vascular anomalies associated with goiter in any species. The mechanism is unknown.     

Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism before and during Treatment

Background

Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA.

Objective

Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism.

Animals

Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled.

Methods

cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA.

Results

cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01–0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0‐2.1; median 1.3 μg/dL) compared to those with normal cTSH (T4 range 0.5‐3.4, median 1.4 μg/dL; P=0.69) and controls (T4 range 0.3‐3.8, median 1.8 μg/dL; P=0.35). After starting treatment, cTSH normalized after 2–4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation.

Conclusions and Clinical Relevance

Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH.     

Thyroid sonography as an effective tool to discriminate between euthyroid sick and hypothyroid dogs

The diagnosis of canine hypothyroidism and its differentiation from euthyroid sick syndrome still is a major diagnostic challenge. In this study, ultrasonography was shown to be an effective tool for the investigation of thyroid gland diseases. Healthy control dogs (n = 87), dogs with euthyroid sick syndrome (n = 26), thyroglobulin autoantibody-positive (TgAA-positive, n = 30) hypothyroid dogs, and TgAA-negative (n = 23) hypothyroid dogs were examined by thyroid ultrasonography. Maximal cross sectional area (MCSA), thyroid volume, and echogenicity were measured. Statistical analysis identified highly significant (P < .001) differences between euthyroid and hypothyroid dogs both in thyroid volume and in MCSA, whereas no significant differences in thyroid size were detected between healthy euthyroid dogs and dogs with euthyroid sick syndrome. In euthyroid and euthyroid sick dogs, parenchymal echotexture was homogeneous and hyperechoic, whereas relative thyroid echogenicity of both TgAA-positive and TgAA-negative hypothyroid dogs was significantly lower (P < .001). When using arbitrarily chosen cutoff values for relative thyroid volume, MCSA, and echogenicity, thyroid volume especially was found to have highly specific predictive value for canine hypothyroidism. In summary, the data reveal that thyroid sonography is an effective ancillary diagnostic tool to differentiate between canine hypothyroidism and euthyroid sick syndrome.     

CNS hypomyelination in Rat Terrier dogs with congenital goiter and a mutation in the thyroid peroxidase gene

Arrested physical development and neurologic abnormalities were identified in 3 of 5 Rat Terrier puppies at 9 weeks of age. Bilaterally firm symmetrical masses were palpated in the region of the thyroid glands. Low serum total (T4) and free thyroxine (FT4, by equilibrium dialysis) and markedly elevated thyroid stimulating hormone (TSH) concentrations supported the diagnosis of hypothyroidism. At necropsy, the thyroid gland was grossly enlarged and histologically exhibited severe, diffuse hyperplasia of the follicular epithelium. Gross examination of the central nervous system revealed a myelin deficiency, most evident in the corpus callosum. Regional distribution of hypomyelination was confirmed histologically, affecting the corpus callosum and, to a lesser degree, the corona radiata, the longitudinal fibers of the pons, the pyramids, and the lateral funiculi of the spinal cord. Myelin reduction was paralleled by axon reduction, suggesting that hypomyelination was a consequence of reduced axonal formation. A homozygous nonsense mutation in the thyroid peroxidase gene was identified in the affected puppies. The dam and a clinically normal litter mate were heterozygous for this mutation, confirming simple autosomal recessive inheritance of the disease trait. The same mutation, causing congenital hypothyroidism with a goiter was previously described in the Toy Fox Terrier breed. Given the ongoing practice of introducing the Toy Fox Terrier genetic background into some Rat Terrier breeding programs to obtain a smaller stature and the apparent relative incidence of the disorder in the 2 breeds, it is likely that this mutation crossed into the Rat Terrier breed from Toy Fox Terriers fairly recently.     

Comparison of thyroid analytes in dogs aggressive to familiar people and in non-aggressive dogs

A cross-sectional study was performed in order to examine the association between canine aggression to familiar people and serum concentrations of total thyroxine (TT4), free thyroxine (fT4), thyroxine autoantibodies (T4AA), total triiodothyronine (TT3), free triiodothyronine (fT3), triiodothyronine autoantibodies (T3AA), thyroid stimulating hormone (TSH), and thyroglobulin autoantibodies (TgAA). The subjects were 31 dogs historically aggressive to familiar people and 31 dogs with no history of aggression. Behavioral evaluation and physical examination were completed for each dog in addition to a complete blood count, serum chemistry panel, TT4, fT4 by equilibrium dialysis, TT3, fT3, TgAA, T3AA, and T4AA. Significant differences were found between the two groups with respect to only T4AA, which was increased in the aggressive group, but the concentrations for both groups were within the normal reference range. There were no differences between the two groups in the thyroid analytes most commonly measured by veterinary practitioners evaluating thyroid function in dogs. The results of this study revealed no significant difference between aggressive and non-aggressive dogs in the thyroid concentrations most commonly used to diagnose canine hypothyroidism.     

Adenohypophyseal Function in Dogs with Primary Hypothyroidism and Nonthyroidal Illness

Background: A recent study of dogs with induced primary hypothyroidism (PH) demonstrated that thyroid hormone deficiency leads to loss of thyrotropin (TSH) hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with large vacuolated "thyroid deficiency" cells that double-stained for growth hormone (GH) and TSH, indicative of transdifferentiation of somatotropes to thyrosomatropes.
Hypothesis: Similar functional changes in adenohypophyseal function occur in dogs with spontaneous PH as do in dogs with induced PH, but not in dogs with nonthyroidal illness (NTI).
Animals: Fourteen dogs with spontaneous PH and 13 dogs with NTI.
Methods: Adenohypophyseal function was investigated by combined intravenous administration of 4 hypophysiotropic releasing hormones (4RH test), followed by measurement of plasma concentrations of ACTH, GH, luteinizing hormone (LH), prolactin (PRL), and TSH. In the PH dogs this test was repeated after 4 and 12 weeks of thyroxine treatment.
Results: In 6 PH dogs, the basal TSH concentration was within the reference range. In the PH dogs, the TSH concentrations did not increase with the 4RH test. However, TSH concentrations increased significantly in the NTI dogs. Basal and stimulated GH and PRL concentrations indicated reversible hypersomatotropism and hyperprolactinemia in the PH dogs, but not in the NTI dogs. Basal and stimulated LH and ACTH concentrations did not differ between groups.
Conclusions and Clinical Importance: Dogs with spontaneous PH hypersecrete GH but have little or no TSH hypersecretion. Development of hyperprolactinemia (and possible galactorrhea) in dogs with PH seems to occur only in sexually intact bitches. In this group of dogs with NTI, basal and stimulated plasma adenohypophyseal hormone concentrations were not altered.     

Canine serum thyroglobulin autoantibodies in health, hypothyroidism and non-thyroidal illness

Thyroglobulin autoantibody (TGAA) was measured in serum from dogs with hypothyroidism (n = 42), non-thyroidal illness (NTI) (n = 77) and clinically healthy dogs (n = 70) using a commercially available enzyme immunoassay kit. Precision studies were consistent with good intra-assay and inter-assay repeatability. TGAA positive results occurred in 15 of the 42 (36 per cent) hypothyroid and four healthy dogs of the remaining 147 animals resulting in a lower incidence of false positive results than obtained with previous TGAA assays. The presence of TGAA was not influenced by age, sex, neutering or pedigree status. Of the four apparently healthy TGAA -positive dogs, two had additional clinicopathological evidence of hypothyroidism. TGAA was positive in 43 per cent of hypothyroid dogs with unexpectedly normal serum c TSH concentrations and was particularly useful in the classification of these cases.     

Evaluation of the thyroid status of Basenji dogs in Australia

Objective To determine the thyroid status of Basenji dogs in Australia. Methods Jugular or cephalic venipuncture blood samples were taken from 113 Basenji, comprising 47 males, 5 castrates, 48 entire and 13 spayed bitches, and sent on ice in plain and EDTA tubes to a single laboratory to determine haematocrit and serum concentrations of total thyroid hormone (thyroxine, TT4), thyroid‐stimulating hormone (TSH) and cholesterol. In a subgroup of 8 dogs with abnormal elevated TSH concentrations and subnormal TT4 concentrations, 5 were further examined by dynamic endocrine testing using recombinant human (rh) TSH (54 µg). Results Ages ranged from 1 to 14 years and weight range was 6.5 to 14.0 kg. TT4 concentrations (nmol/L) ranged from 2 to 27, with a median of 13 and a mean ± SD of 13.0 ± 5.7. Importantly, 85/113 (75%) of TT4 values were lower than the normal laboratory reference range (17–37). TSH concentrations (ng/mL) ranged from 0.05 to 5.37, with a median of 0.16 and a mean ± SD of 0.3 ± 0.6. Conclusions Basenji have a similar reference range for serum TSH, but a considerably lower reference range for TT4 (2–27 nmol/L) than most breeds and crossbreds, resembling the sight hounds in this respect. Given the difficulty of accurately measuring TT4 concentrations that are so low, concomitant serial TSH determinations are essential to properly asses thyroid function. Taken alone, TT4 determinations are only of use when the value is within the reference range, in which case a diagnosis of hypothyroidism is likely excluded.     

Dwarfism in Tibetan Terrier dogs with an LHX3 mutation

Canine pituitary dwarfism in German Shepherd and related dog breeds has been reported to be associated with a 7-bp deletion mutation in intron 5 of the LHX3 gene. This mutation is transmitted as an autosomal recessive trait that results in dwarf dogs with significantly smaller stature and abnormal haircoat, and potentially early death. Phenotypically, affected adult dogs are proportionally dwarfs. These dwarfs also have a soft, woolly puppy coat that fails to transition into the typical adult hair coat, and marked hair loss occurs in some dogs. We report a similar manifestation of dwarfism in Tibetan Terriers with the same LHX3 mutation. Dwarf Tibetan Terrier puppies were born physically normal but failed to gain weight or to grow at the same rate as their normal littermates. The 7-bp deletion mutation of the LHX3 gene was identified in both alleles of 3 Tibetan Terrier dwarfs from 3 litters, which were biologically related. All parents of these dogs are carriers, confirming transmission of dwarfism in an autosomal recessive manner. Recognition and detection of this mutation will help in guiding future breeding plans to eventually eliminate this trait from Tibetan Terriers.     

Changes in serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs receiving phenobarbital for one year

A multicentric prospective study was conducted to monitor the effect of phenobarbital on serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in epileptic dogs. Serum T4 concentrations were determined for 22 epileptic dogs prior to initiation of phenobarbital therapy (time 0), and 3 weeks, 6 months, and 12 months after the start of phenobarbital. Median T4 concentration was significantly lower at 3 weeks and 6 months compared to time 0. Thirty-two percent of dogs had T4 concentrations below the reference range at 6 and 12 months. Nineteen of the 22 dogs had serum TSH concentrations determined at all sampling times. A significant upward trend in median TSH concentration was found. No associations were found between T4 concentration, dose of phenobarbital, or serum phenobarbital concentration. No signs of overt hypothyroidism were evident in dogs with low T4, with one exception. TSH stimulation tests were performed on six of seven dogs with low T4 concentrations at 12 months, and all but one had normal responses. In conclusion, phenobarbital therapy decreased serum T4 concentration but did not appear to cause clinical signs of hypothyroidism. Serum TSH concentrations and TSH stimulation tests suggest that the hypothalamic-pituitary-thyroid axis is functioning appropriately.