Canine Thyroid Function: A Clinical and Clinicopathological Investigation

This study evaluated commercially available tests of thyroid function in dogs. The diagnostic utility of these tests for hypothyroidism are reported, as are the epidemiological, clinical, biochemical and haematological features of the disease. The clinical and clinicopathological changes associated with treatment for hypothyroidism are reported and a strategy for therapeutic monitoring is provided. The value of thyroid function tests as prognostic markers in non-thyroidal illness (NTI) is evaluated. Commercial kit assays for total 3,5,3',5'-tetraiodothyronine (thyroxine, T4), free T4, total 3,5,3'-triiodothyronine (T3), endogenous canine thyrotropin (thyroid stimulating hormone, TSH) (cTSH) and thyroglobulin autoantibodies (TgAb) were successfully validated for use with canine serum and subsequently evaluated in 140 dogs with clinical signs suggestive of hypothyroidism. Hypothyroidism was confirmed (n=52) or excluded (n=88) based on the results of bovine TSH response tests. Median circulating total T4 (4.7 nmol/L), free T4 (3.22 pmol/L) and total T3 (1.32 nmol/L) concentrations were significantly decreased and cTSH (1.38 ng/ml) significantly increased in hypothyroid dogs compared to the corresponding values of 20.1 nmol/L, 13.84 pmol/L, 2.38 nmol/L and 0.27 ng/ml, respectively in euthyroid dogs with NTL Optimal diagnostic cut-off values for total T4, free T4, total T3 and cTSH for the confirmation of hypothyroidism were 14.8 nmol/L, 6.66 pmol/L, 1.77 nmol/L and 0.69 ng/ml, respectively. The corresponding test sensitivities and specificities for hypothyroidism were 0.96 and 0.70 (total T4), 0.81 and 0.93 (free T4), 0.76 and 0.80 (total T3), and 0.79 and 0.82 (cTSH), respectively. Transient increases in cTSH values in euthyroid dogs were usually due to recovery from NTI or the recent use of sulphonamide-containing drug therapy. Concurrent illness may reduce cTSH concentrations into the euthyroid range in hypothyroid dogs. No age, gender, neutering status or breed predilections for hypothyroidism were identified. Although hypothyroidism occurred in dogs of any age, it was rare in animals less than two years old. Evaluation of breed and pedigree status was hindered by inherent biases within the population studied. However, the most commonly affected breed-types were retrievers, spaniels, terriers, crossbreeds and doberman pinschers although these were also common amongst the dogs with NTI. No effect of pedigree status on the likelihood of developing hypothyroidism was identified. The most common clinical features associated with hypothyroidism were metabolic signs (85% cases), particularly lethargy (77%), weight gain (42%) or exercise intolerance (27%), and dermatological signs (79%), particularly hair thinning (56%), poor coat quality (29%), hyperpigmentation (19%) and superficial pyoderma (15%). Concurrent metabolic and dermatological signs occurred in 67% cases. The most common routine biochemical and haematological abnormalities compared with the laboratory reference range were increases in circulating triglyceride (88% cases), cholesterol (78%) and fructosamine (43%) concentrations and reduced red blood cell count (40%). However similar abnormalities frequently occurred in euthyroid dogs and the routine tests which most efficiently confirmed hypothyroidism were reduced red blood cell count and increased frictosamine values. Successful clinical resolution of hypothyroidism was achieved by once daily administration of synthetic L-thyroxine therapy. Metabolic signs usually improved within two weeks after starting therapy whereas dermatological improvements took longer. Mean body weight decreased by 10% in treated cases during the first three months of therapy. Most dogs were essentially clinically normal within 13 weeks of starting therapy. Six hour post-pill total T4 concentrations were a reliable method of objectively assessing therapeutic control. Corresponding mean values in well controlled cases were 55 nmol/L whereas values less than 35 nmol/L were usually associated with inadequate clinical improvement. Circulating cTSH estimation was of limited utility for therapeutic monitoring although increased concentrations usually predicted the need for an increase in therapy. Improvements in numerous biochemical and haematological parameters occurred during therapy and were consistent with metabolic normalisation. However, only creatinine estimation could be used to differentiate between dogs which were adequately or inadequately clinically controlled. This clinical, clinicopathological and epidemiological study has greatly increased the knowledge and understanding of canine thyroid function in hypothyroidism and NTI. The findings have improved the ability to diagnose, treat and prognosticate, and have opened the door for future research