Diagnosing Canine Hypothyroidism and the Euthyroid Sick Syndrome
Hypothyroidism is a common endocrinopathy in dogs. Because of the variety of clinical signs and the limitations of thyroid tests, hypothyroidism is frequently misdiagnosed. Several factors like nonthyroidal diseases or medications can lower thyroid hormones (T4, FT4 and T3) concentrations in euthyroid dogs. In the other hand, some dogs with confirmed hypothyroidism may have one or more thyroid function test within reference ranges (TSH and occasionally T4). Therefore, the diagnosis of hypothyroidism in dogs should rely on a clinical diagnosis-including a careful history and physical exam, routine blood test, urinalysis, and exclusion of nonthyroidal illnesses and medications-and thyroid testing.
Canine hypothyroidism occurs as a consequence of an inadequate secretion of thyroid hormones. These hormones act on most organic tissue; therefore, clinical findings are multi systemic, variable and non-specific.
Signalment. Hypothyroidism usually occurs in medium to large size dogs. Breeds with known predisposition are Doberman, Golden Retriever, Irish Setter, Miniature Schnauzer, Dachshund, Cocker Spaniel, and Airedale Terrier. Most hypothyroid dogs are middle aged (4-10 years) and there is not strong sex predisposition.
History. Hypothyroidism is a slow progressing disease. Classical findings on history of these patients are lethargy, exercise intolerance, and weight gain. Some of these dogs may develop hypothermia and seek for heat spots.
Physical Exam. Many hypothyroid dogs present dermatological changes such us dull hair coat, excessive shedding, hyperpigmentation, hair thinning, alopecia or pyoderma. In advanced cases, facial myxedema may be present due to the accumulation of glycosaminoglycans in the dermis. These changes are responsible for a ''tragic'' facial expression in some hypothyroid dogs. Other findings on physical exam of dog with hypothyroidism include obesity, bradycardia, and lipid corneal deposits. Neurological signs like lower motor neuron signs, peripheral vestibular disease, laryngeal paralysis or megaesophagus may occur.
Routine Blood Test. Hemogram, biochemical and urinalysis findings associated with hypothyroidism are helpful to support a clinical suspicion of hypothyroidism but are also very helpful to rule out other diseases that may affect thyroid function testing. A third of hypothyroid dogs would present normocytic, normochromic, nonregenerative anemia. The most common serum biochemical abnormality is hypercholesterolemia, which occurs in about 75% of dogs with hypothyroidism. Other clinicopathologic abnormalities may include high serum triglyceride concentrations, high serum alkaline phosphatase activity, and high serum creatine kinase activity. Urinalysis is usually unremarkable.
There are a wide variety of thyroid function tests but none of them if 100% accurate. Therefore, the diagnosis of hypothyroidism can never be based solely on thyroid testing and this test should be reserved for confirmation of a clinical suspicion of hypothyroidism.
Total Serum Thyroxine (T4). Basal serum total T4 concentration is useful for the diagnosis of hypothyroidism. Mos hypothyroid dogs can be distinguished from normal dogs based on a low resting serum total T4 concentration. Normal concentrations of serum T4 are rarely found in the hypothyroid dog and values in the mid- to upper normal range rules out hypothyroidism. However, many nonthyroidal illnesses and administration of various drugs including glucocorticoids, sulfonamides, anticonvulsants or nonsteroidal anti-inflammatory agents may lower serum T4 concentrations in dogs. Even when historical and physical findings do not suggest other factors that would lower serum T4, the diagnosis of hypothyroidism should be confirmed with another test (endogenous TSH concentration).
Total Serum Triiodothyronine (T3). Serum T3 concentration remain normal in many hypothyroid dogs. Therefore, serum T3 concentrations are generally considered unreliable in the diagnosis of hypothyroidism and is not longer recommended.
TSH Stimulation Test. This test has been considered for years the gold standard for diagnosing canine hypothyroidism. However, the limited availability of TSH, high cost and potential anaphylactic reactions has prevented many veterinarian from using this test.
Free Serum Thyroxine (FT4). Free T4 is the fraction of the thyroid hormone T4 that circulates unbound to plasma proteins (normally 0.1% of total T4). Determination of free T4 is most accurately performed by methods that include a dialysis step (eg, equilibrium dialysis). Because FT4 reflects the hormone available for entry into cells, FT4 determinations provide a more consistent assessment of thyroid status at the tissue level than does measurement of total T4. Furthermore, the FT4 concentration is not as likely as total T4 determinations to be affected by nonthyroidal illness. Unfortunately, 17 to 43% dogs with moderate to severe disease will also present low FT4 concentration.
Endogenous serum thyroid stimulating hormone (TSH) concentrations. Most hypothyroid dogs will suffer from hypothyroidism of thyroidal origin (primary) and, therefore, we would expect this dogs to have a high TSH concentration as occur in human primary hypothyroidism. Unfortunately, serum TSH concentrations remain normal in 20 to 40% of dogs with hypothyroidism; although some of these dogs may have secondary hypothyroidism (ie, pituitary TSH deficiency), most certainly have primary hypothyroidism. Serum TSH concentration may be high in 10 to 20% of euthyroid sick dogs. Therefore, serum TSH determinations should never be evaluated alone, but always in conjunction with the dog's careful clinical diagnosis, and total or free T4 concentrations.
Combination of T4 and endogenous TSH. The combined T4 and TSH determination is the recommended approach to diagnosis of hypothyroidism since this combination will minimize false positive results. While 7 to 60% of euthyroid sick dogs will have a low T4 concentration, depending on the severity of the disease (the more severe the more likely to develop a low T4 concentration). Less than 3% of these euthyroid dogs will have both a low T4 and a high TSH concentration. We should not forget, however, that a normal TSH concentration does not rule out hypothyroidism since 1 every 3 or 4 hypothyroid dogs will remain with TSH concentration within the reference range.
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