Clinical signs and concurrent diseases of hypothyroidism in dogs and cats.

Canine hypothyroidism may present with a wide range of clinical signs. The most common clinical signs are those of a decreased metabolic rate and dermatologic manifestations; however, many other clinical signs have been associated with hypothyroidism. There is strong evidence for a causal relation between hypothyroidism and a variety of neurologic abnormalities; however, the association between hypothyroidism and other manifestations, such as reproductive dysfunction, clinical heart disease, and behavioral abnormalities, is less compelling. Further studies are necessary to determine the full spectrum of disorders caused by hypothyroidism.     

Is it possible to diagnose canine hypothyroidism?

A definitive diagnosis of hypothyroidism can be difficult because of the many clinical abnormalities associated with thyroid hormone deficiency, and the lack of readily available diagnostic tests with high sensitivity and specificity. Thyroid function tests should be performed only in dogs with clinical findings consistent with hypothyroidism. Measurement of serum total thyroxine (T4) concentration is a useful initial screening test since most hypothyroid dogs have values below the reference range. Serum free T4 concentration measured by equilibrium dialysis is a more sensitive and specific test of thyroid function than total T4 and is particularly useful in dogs with non-thyroidal illness or atypical clinical signs. Measurement of serum endogenous thyroid-stimulating hormone concentration is also helpful, but many hypothyroid dogs have normal results. The gold standard for diagnosis of hypothyroidism remains the thyroid-stimulating hormone response test. It should be used to confirm hypothyroidism when other tests do not agree with the clinical impression or if atypical signs or non-thyroidal illness exist or there has been administration of drugs known to alter thyroid function tests. Ultimately, a positive response to treatment is expected in hypothyroid dogs treated appropriately with levothyroxine.     

Blood–brain‐barrier disruption in chronic canine hypothyroidism

Background: Central nervous system (CNS) manifestations of hypothyroidism have been associated with cerebrovascular complications. Reports of cerebrospinal fluid (CSF) abnormalities are rare in hypothyroid dogs. Objective: The aim of this study was to determine if chronic hypothyroidism causes blood–brain‐barrier (BBB) abnormalities that are detectable using indirect CSF biomarkers. Methods: The study included 18 normal, euthyroid, female mixed‐breed dogs. Hypothyroidism was induced by ¹³¹iodine administration in 9 dogs; 9 served as untreated controls. Evaluations included physical and neurologic examination, complete CSF analysis, serum and CSF protein electrophoresis, measurement of plasma vascular endothelial growth factor (VEGF) and serum S‐100B concentrations, and calculation of CSF albumin quota (AQ) and were conducted at baseline and 6, 12, and 18 months after induction of hypothyroidism. Data were analyzed using repeated measures ANOVA. Results: At baseline, differences between groups were not detected for any variable. Throughout the study, controls dogs remained free of neurologic disease and had test variables that remained within reference intervals. Two hypothyroid dogs developed CNS signs during the study, and evidence of cerebrovascular disease was found at necropsy. At 12 and 18 months, the CSF total protein, VEGF, S‐100B, and fractional albumin concentrations, and AQ were significantly higher (P<.04) in hypothyroid dogs than controls. Among test variables assayed in serum or plasma, the only significant difference was a higher S‐100B concentration in hypothyroid dogs (P=.003) at 18 months. Conclusions: BBB integrity is disrupted in chronic hypothyroidism. Significant increases in CSF concentrations of VEGF and S100‐B in hypothyroid dogs indicate dysfunction in both endothelial and glial elements of the BBB.     

Epidemiological, clinical, haematological and biochemical characteristics of canine hypothyroidism

Hypothyroidism was diagnosed in 50 dogs and excluded in 86 dogs suspected of hypothyroidism, on the basis of the results of bovine thyrotropin response tests. Breed, pedigree, sex or neutering status did not significantly influence the likelihood of the dogs being hypothyroid. The hypothyroid dogs were significantly older than the non-hypothyroid dogs referred to the University of Glasgow during the same period. However, when dogs under two years of age were excluded from the statistical analyses there was no significant difference in age between the two groups. The most common clinical characteristics associated with hypothyroidism were metabolic signs (84 per cent of cases), particularly lethargy (76 per cent), obesity or weight gain (44 per cent), and exercise intolerance (24 per cent); and dermatological abnormalities (80 per cent), including alopecia (56 per cent), poor coat quality (30 per cent) and hyperpigmentation (20 per cent). When compared with the laboratory reference limits the most common biochemical and haematological abnormalities were increased concentrations of triglycerides (88 per cent), cholesterol (78 per cent), glucose (49 per cent), and fructosamine (43 per cent), and increased activities of creatine kinase (35 per cent), and decreased concentrations of inorganic phosphate (63 per cent), and a low red blood cell count (40 per cent). When compared with reference limits derived from the euthyroid dogs the most common abnormalities were increased concentrations of gamma-glutamyltransferase (21 per cent), cholesterol (18 per cent), and aspartate aminotransferase (15 per cent) and a decreased red blood cell count (29 per cent), and decreased neutrophils (18 per cent) and decreased activity of creatine kinase (15 per cent). Assessment of cholesterol, creatine kinase, aspartate aminotransferase, gamma-glutamyltransferase, and red blood cell and neutrophil counts may be particularly useful in distinguishing hypothyroid dogs from euthyroid animals with similar clinical signs.     

Resistance of the Peripheral Nervous System to the Effects of Chronic Canine Hypothyroidism

Background: Hypothyroidism has been implicated in the development of multiple peripheral mono‐ and polyneuropathies in dogs. The objectives of this study were to evaluate the clinical and electrophysiologic effects of experimentally induced hypothyroidism on the peripheral nervous system of dogs. Hypothesis: Chronic hypothyroidism will induce peripheral nerve sensorimotor dysfunction. Animals: Eighteen purpose‐bred, female dogs. Methods: Prospective, longitudinal study: Hypothyroidism was induced by radioactive iodine administration in 9 dogs, and the remaining 9 served as untreated controls. Neurological examinations were performed monthly. Electrophysiologic testing consisting of electromyography (EMG); motor nerve conduction studies of the sciatic‐tibial, radial, ulnar, and recurrent laryngeal nerves; sciatic‐tibial and ulnar F‐wave studies; sensory nerve conduction studies of the tibial, ulnar, and radial nerves; and evaluation of blink reflex and facial responses were performed before and 6, 12, and 18 months after induction of hypothyroidism and compared with controls. Results: Clinical evidence of peripheral nervous dysfunction did not occur in any dog. At 6 month and subsequent evaluations, all hypothyroid dogs had EMG and histologic evidence of hypothyroid myopathy. Hypothyroid dogs had significant (P≤ .04) decreases in ulnar and sciatic‐tibial compound muscle action potentials over time, which were attributed to the concurrent myopathy. No significant differences between control and hypothyroid dogs were detected in electrophysiologic tests of motor (P≥ .1) or sensory nerve conduction velocity (P≥ .24) or nerve roots (P≥ .16) throughout the study period, with values remaining within reference ranges in all dogs. Conclusion: Chronic hypothyroidism induced by thyroid irradiation does not result in clinical or electrophysiologic evidence of peripheral neuropathy, but does cause subclinical myopathy.     

Canine hypothyroidism: a review of aetiology and diagnosis

Hypothyroidism is recognised as an important endocrine disorder of dogs, and a frequent differential for numerous presenting complaints. Its diagnosis has never been straight forward as results suggestive of hypothyroidism can occur for a variety of reasons in dogs with normal thyroid function (euthyroid). As a consequence, the accurate investigation of hypothyroidism has been hindered by the potential inclusion of a number of cases not truly hypothyroid. In recent years, the development of newer diagnostic tests, e.g. free thyroxine, canine thyroid stimulating hormone, thyroglobulin autoantibodies, has significantly improved our ability to reliably differentiate hypothyroidism from other clinically similar disorders. This has led to a marked increase in our knowledge of the phenotypic, genotypic and aetiological aspects of this disorder in dogs.     

Calcium homeostasis in thyroid disease in dogs and cats.

Hyperthyroidism is the most common endocrine disorder of cats, and hypothyroidism is the most common endocrine disorder of dogs. Little is known regarding the effects of hyperthyroidism, hypothyroidism, or treatment of these disorders on calcium metabolism in the dog or cat, however, especially any potential effects on bone. With better diagnostic tools, better treatments, and increased longevity of pets, the clinical impact of thyroid disorders on calcium metabolism and bone may be uncovered.     

Fat absorption in dogs with diabetes mellitus or hypothyroidism

Quantitative fat absorption was studied in normal dogs and in dogs with hypothyroidism and diabetes mellitus. The serum triglyceride concentrations of diabetic and hypothyroid dogs were significantly higher at each sampling time than those of normal dogs. The fat absorption curve of hypothyroid dogs peaked at 180 minutes and though significantly raised was parallel to that of normal dogs whereas the fat absorption curve of diabetic dogs continued to rise up to 240 minutes. These results provide evidence for impaired plasma clearance of triglyceride in canine diabetes mellitus and hypothyroidism.     

Clinical,hematological, biochemical and endocrinological aspects of 32 dogs with hypothyroidism

During the years of 1996-2001, hypothyroidism was diagnosed at the clinic for small animal internal medicine, University of Zurich, in 32 dogs. Most of the dogs were large breeds. The most frequent clinical characteristics observed were exercise intolerance, obesity, dermatological, neurological and gastrointestinal signs. Predominant laboratory abnormalities were a low red blood cell count, increased concentration of cholesterol, triglycerides and fructosamin. 29 dogs had a T4 below the reference range (< 1.5 micrograms/dl), one dog had a T4 at the lower limit thereof (1.6 micrograms/dl). One dog had a T4 within the reference range (3.4 micrograms/dl), another had a very high T4 of 206.8 micrograms/dl; the results of the latter 2 dogs were interpreted as incorrectly increased T4 values due to in vitro interference with T4-autoantibodies. Diagnosis was confirmed in all of the dogs based on TSH-stimulation testing. Endogenous TSH (cTSH) measured parallelly, was elevated in only 60% of the dogs. In about 67% of the dogs, hypothyroidism was associated with thyroglobulin-autoantibodies. Canine hypothyroidism is a rather rare endocrine disorder in Switzerland. The TSH-stimulation test remains the gold standard in confirming the disease; a definitive diagnosis can be challenging for practitioners because bovine TSH, used for the TSH-stimulation test is not licensed for use in dogs. Since assessment of cTSH using current assays shows normal values in a high percentage of hypothyroid dogs, the diagnostic value is only limited. In most of the hypothyroid dogs T4 is decreased, with the presence of autoantibodies to T4, it can be normal or increased.     

Hypothyroid dogs treated with intravenous levothyroxine

The purpose of this retrospective study was to report clinical and clinicopathologic findings, response to treatment, and outcome of hypothyroid dogs treated with levothyroxine intravenously (IV). Seven levothyroxine IV treated hypothyroid dogs and 799 other hypothyroid dogs examined during the same period were included. Rottweiler dogs were overrepresented in the group of levothyroxine IV-treated hypothyroid dogs compared with other hypothyroid dogs (P < .0001). Common physical examination abnormalities were obese or overweight body condition (5 dogs), mental dullness (5 dogs), and nonpitting edema (4 dogs). Anemia (4 dogs) and hypercholesterolemia (5) were common, although 1 dog had neither. Concurrent disease (most commonly infection) was observed in 5 dogs. Glucocorticoids and nonsteroidal antiinflammatory drugs had been administered to 2 dogs before examination. Surgery was performed in 2 dogs before treatment with levothyroxine IV. Four of the 7 dogs received 4-5 microg/kg of levothyroxine IV. Subjective improvement in mentation or ambulation (6 of 7 dogs) and systolic hypotension (2 of 2 dogs) occurred within 30 hours of levothyroxine IV administration. Six of the 7 dogs responded well to therapy and were discharged from the hospital. It was concluded that physical examination and clinicopathologic findings of dogs with a hypothyroid crisis are nonspecific, although Rottweiler dogs may be at increased risk. Concurrent disorder, such as infection, concurrent administration of thyroid hormone-altering medication, and surgery, may be associated with development of a hypothyroid crisis. Resolution of abnormal mentation, ambulation, and systolic hypotension should be expected within 30 hours. Prognosis is good in most treated dogs.     

Serum insulin-like growth factor type 1 concentrations in healthy dogs and dogs with spontaneous primary hypothyroidism

Circulating insulin-like growth factor type 1 (IGF-1) concentrations in dogs have been correlated with standard breed bodyweight (SBBW or breed size). Thyroid and somatotropic functions, which have common effects and regulatory mechanisms, were investigated in hypothyroid dogs. IGF-1 was measured in 495 adult healthy dogs (N) and in 220 primary hypothyroid dogs (HOT) with clinical and biological signs of primary hypothyroidism. IGF-1 was determined as a function of SBBW (kg): ≤15 (group A); 1540 (group D). In HOT dogs, median fT4 and c-TSH values were 9pmol/L and 1.5ng/mL, respectively. A significant correlation between bodyweight (BW) and IGF-1 was observed in both HOT and N dogs. The median IGF-1 value (ng/mL) was significantly higher (P<0.01) in HOT dogs compared to N in groups B, C and D (230 vs. 182; 316 vs. 230; 606 vs. 306 respectively). In conclusion, IGF-1 concentration should be interpreted in the context of SBBW in dogs and increases in spontaneous primary hypothyroidism. However, it remains unclear if this association is directly due to hypothyroidism or is the result of the weight gain accompanying hypothyroidism.     

Endogenous TSH in the diagnosis of hypothyroidism in dogs

To determine whether measurement of canine thyrotropin (cTSH) would aid in the diagnosis of hypothyroidism, serum samples of 65 dogs with clinical signs suggestive of hypothyroidism were evaluated. Diagnosis was confirmed in 26 dogs and excluded in 39 dogs based on TSH-stimulation testing. Total thyroxine (T4) was significantly lower and cTSH significantly higher in hypothyroid dogs compared to euthyroid dogs. Canine TSH was above (> 0.6 ng/ml) in 15 (57.7%) and below the upper limit of the reference range in 11 (42.3%) of the hypothyroid dogs. All of the euthyroid dogs had a cTSH < 0.6 ng/ml. In all dogs with a cTSH above the upper limit of the reference range hypothyroidism could be confirmed. Therefore, our results show that measurement of cTSH has an excellent specificity (100%) and is a valuable tool in confirming canine hypothyroidism. However, due to the low sensitivity of cTSH assays (60%), it can not be recommended to exclude the disease.     

Assessment of the value of quantitative thyroid scintigraphy for determination of thyroid function in dogs

Objective : To assess the value of thyroid scintigraphy to determine thyroid status in dogs with hypothyroidism and various non‐thyroidal illnesses. Methods : Thyroid hormone concentrations were measured and quantitative thyroid scintigraphy performed in 21 dogs with clinical and/or clinicopathological features consistent with hypothyroidism. Results : In 14 dogs with technetium thyroidal uptake values consistent with euthyroidism, further investigations supported non‐thyroidal illness. In five dogs with technetium thyroidal uptake values within the hypothyroid range, primary hypothyroidism was confirmed as the only disease in four. The remaining dog had pituitary‐dependent hyperadrenocorticism. Two dogs had technetium thyroidal uptake values in the non‐diagnostic range. One dog had iodothyronine concentrations indicative of euthyroidism. In the other, a dog receiving glucocorticoid therapy, all iodothyronine concentrations were decreased. Markedly asymmetric technetium thyroidal uptake was present in two dogs. All iodothyronine concentrations were within reference interval but canine thyroid stimulating hormone concentration was elevated in one. Non‐thyroidal illness was identified in both cases. Clinical Significance : In dogs, technetium thyroidal uptake is a useful test to determine thyroid function. However, values may be non‐diagnostic, asymmetric uptake can occur and excess glucocorticoids may variably suppress technetium thyroidal uptake and/or thyroid hormone concentrations. Further studies are necessary to evaluate quantitative thyroid scintigraphy as a gold standard method for determining canine thyroid function.     

Thyroid-Stimulating Hormone Stimulation Tests in Cardiomyopathic Doberman Pinschers: A Retrospective Study

Thyroid-stimulating hormone (TSH) response tests were performed in 152 Doberman Pinschers. Seventy-nine dogs had cardiomyopathy (46 were in congestive heart failure [CHF] and 33 were not in CHF). Seventy-three dogs were presented for noncardiac problems (15 with skin disease, 21 with neurologic disease, 20 with internal medicine disorders, and 17 with other problems), although some may have had cardiomyopathy. The TSH response test results in the cardiomyopathic group were interpreted as normal or euthyroid-sick in 45 (57%) dogs, abnormal in 23 (29%) dogs, and equivocal in 11 (14%) dogs. The prevalence of hypothyroidism in the CHF and non-CHF cardiomyopathy groups was not different. Among the dogs presented for noncardiac problems, 27 (37%) were assessed as normal or euthyroid-sick, 29 (40%) as hypothyroid, and 17 (23%) as equivocal. No significant differences were found in the prevalence of hypothyroid test results among the subgroups of these dogs. The prevalence of hypothyroidism was not higher in the cardiomyopathic group compared to the other group, and 63 and 49% of cardiomyopathic dogs with or without CHF, respectively, tested as either euthyroid or euthyroid-sick.     

The effects of thyroid hormones on the skin of beagle dogs

The effects of hypothyroidism on canine skin were determined by comparing morphologic, morphometric, and hair cycle differences in skin biopsy samples from 3 groups of age- and gender-matched Beagle dogs: (1) euthyroid dogs; (2) dogs made hypothyroid by administration of 131I; and (3) dogs made hypothyroid and maintained in a euthyroid state by treatment with synthetic thyroxine. After 10 months of observation, there was slower regrowth of hair 2 months after clipping in the untreated-hypothyroid dogs. Untreated-hypothyroid dogs had a greater number of follicles in telogen and fewer hair shafts (ie, a greater number of hairless telogen follicles) than did the control group. The control dogs had a greater number of telogen follicles but the same number of hair shafts as the treated-hypothyroid group. Treated-hypothyroid dogs had the greatest number of follicles in the growing stage of the hair cycle (anagen). This study suggests that, at least in Beagles, induced hypothyroidism does not affect the pelage as dramatically as has been described in naturally occurring disease. This is because normal Beagles retain hair shafts in follicles for long periods, and the alopecia of hypothyroidism appears to evolve slowly because of the prolongation of this haired telogen stage. The evaluation of thyroxine-treated hypothyroid dogs demonstrates that thyroid hormone supplementation of Beagle dogs with induced hypothyroidism stimulates hair growth.     

Thyroid-stimulating hormone and total thyroxine concentrations in euthyroid, sick euthyroid and hypothyroid dogs

Canine thyroid-stimulating hormone (cTSH) was measured in a variety of clinical cases (n= 72). The cases were classified as euthyroid, sick euthyroid, hypothyroid or hypothyroid on non-thyroidal therapy on the basis of their history, clinical signs, laboratory results (including total thyroxine concentrations and, where indicated, thyroid-releasing hormone [TRH] stimulation tests) and response to appropriate therapy. Additional samples were taken during some of the TRH stimulation tests to measure the response of cTSH concentrations following TRH administration. A reference range (0 to 0–41 ng/ml) was calculated from the basal concentrations of cTSH in a group of 41 euthyroid dogs. Six of nine cases of confirmed hypothyroidism had basal cTSH concentrations above the reference range, whereas the remainder were within the normal range. One of these three remaining cases was a pituitary dwarf and did not show a rise in cTSH concentration following TRH stimulation. In contrast, only one of a group of six hypothyroid dogs that had been on non-thyroidal treatment within the previous four weeks had increased concentrations of basal cTSH. This study also found that five of a group of 16 dogs with sick euthyroid syndrome had increased cTSH concentrations. It was concluded that cTSH measurements are a useful additional diagnostic test in cases of suspected hypothyroidism in dogs but that dynamic testing is still required to confirm the diagnosis of hypothyroidism.     

Effect of 131I-induced hypothyroidism on indices of reproductive function in adult male dogs

Hypothyroidism has been cited as a cause of infertility, abnormal semen quality, and poor libido in people and animals. The purpose of this study was to evaluate the effect of hypothyroidism on variables indicative of reproductive function in adult male dogs. Nine normal dogs were randomly assigned to 2 groups. Hypothyroidism was induced with 131I in 6 dogs. Three dogs remained untreated, normal, and euthyroid. Thyroid hormone concentrations, body weight, clinical signs, and reproductive function were determined for each dog every 3 months for 2 years. Reproductive function was assessed by determining daily sperm output, total scrotal width, spermatozoal motility and morphology, libido, and serum testosterone and luteinizing hormone concentration responses to exogenous gonadotropin-releasing hormone. The 131I-treated dogs developed clinical and laboratory signs of hypothyroidism. In the hypothyroid dogs, serum concentrations of thyroid hormones were consistently below the reference range and were significantly lower than that in the euthyroid dogs. There was no difference in reproductive function between the hypothyroid and euthyroid dogs. The results of this study show that 131I-induced hypothyroidism does not affect indices of reproductive function in adult male dogs.     

Prevalence of thyroglobulin autoantibodies detected by enzyme-linked immunosorbent assay of canine serum in hypothyroid, obese and healthy dogs in Japan

Thyroglobulin autoantibodies (TgAA) were detected in sera of hypothyroid (n=19), obese (n=28) and clinically healthy dogs (n=52) using a commercially available immunoassay kit. TgAA-positive results occurred in 10 of 19 hypothyroid, 1 of 28 obese and 1 of 52 clinically healthy dogs. The clinically healthy TgAA-positive dog had additional evidence of hypothyroidism supported by low total T(4), low free T(4) and high canine TSH. Among the breeds, Golden Retriever had the highest frequency of hypothyroid (9/19) and TgAA-positive hypothyroid dogs (6/10). This study was the first survey about the prevalence of canine TgAA in Japan and could be a useful reference for clinicians.     

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.