Understanding and diagnosing canine hypothyroidism
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Canine hypothyroidism is a slowly progressive disorder resulting from the inability of the thyroid gland to secrete sufficient amounts of thyroid hormones to maintain normal organ functions. Although hypothyroidism is relatively common and thyroid hormone tests are readily available, diagnosis is difficult as clinical signs can be subtle and highly variable. Additionally, there are many causes of low thyroid hormone levels in euthyroid dogs. These factors can make it difficult to make a correct diagnosis of hypothyroidism.
Canine hypothyroidism usually results from a failure of the thyroid gland. This may be due to lymphocytic thyroiditis (destruction of the thyroid gland by inflammation) or idiopathic thyroid atrophy (degeneration of the thyroid gland in the absence of apparent inflammation). Insufficiency of the thyroid gland is called primary hypothyroidism and accounts for most cases of canine hypothyroidism. Less commonly, there is secondary hypothyroidism, in which the thyroid gland is healthy but the pituitary gland fails to secrete thyrotropin (TSH), resulting in secondary failure of the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3).
Primary hypothyroidism affects different races; mixed-breed dogs, golden retrievers, Doberman pinschers and Labrador retrievers are among the most affected. The age at which clinical signs appear varies, but the diagnosis between middle age and old age is typical. Because it is the most common, the diagnostic approach for primary hypothyroidism will be the focus of this article.
Since thyroid hormones affect virtually all organs, the clinical manifestations of the disease may be different for each patient. Dogs with hypothyroidism often have a reduced metabolic rate, resulting in lethargy, dullness, and weight gain without polyphagia. Dermatologic effects are the most common clinical sign of hypothyroidism, including alopecia, a dull, brittle coat, hyperpigmentation of the skin, and pyoderma. Neurological (peripheral neuropathy, vestibular disease, myopathy) and cardiovascular (bradyarrhythmia) effects are less frequent but occur. Rarely, dogs with severe untreated hypothyroidism may develop myxedema coma, characterized by life-threatening hypothermia, bradyarrhythmia, and deterioration in mental status. Myxedema coma is usually the result of untreated hypothyroidism in the face of additional serious illness.
Clinicopathologic changes in hypothyroid dogs are relatively few but characteristic. Hypercholesterolemia is observed in approximately 75% of hypothyroid dogs; some will also have hypertriglyceridemia. Hyperlipidemia can lead to the deposition of lipids in the eye, which can be recognized on physical examination. Mild, normocytic, normochromic, non-regenerative anemia is observed in approximately one-third of hypothyroid dogs.
Causes of diagnostic confusion: factors that decrease T4 in euthyroid dogs
It is extremely important to remember the factors that can influence thyroid hormone tests, and the following should be carefully considered before making a diagnosis of hypothyroidism.
Various drugs can influence several thyroid hormone tests, especially the total T4 test (TT4). Prednisone, nonsteroidal anti-inflammatory drugs, phenobarbital, and tricyclic antidepressants are among the most common offenders. If possible, patients should be withdrawn from treatment with these drugs before evaluation for hypothyroidism.
Eutyroid greyhounds are known to have TT4 levels below the reference range. Fortunately, these dogs are rarely affected by hypothyroidism.
The level of TT4 decreases with age and may fall below the reference range in very old dogs.
Sometimes euthyroid dogs with no other complicating factor may have a TT4 level that transiently drops below the reference interval. This should not be accompanied by clinical signs and repeated evaluation will likely show a TT4 level within the normal range.
Systemic illnesses, malnutrition, trauma, and surgery can all lead to low thyroid hormone levels. This is often referred to as euthyroid disease syndrome. Although the mechanism is not clear, the condition is believed to be a physiological adaptation to stress or illness. Most often the level of TT4 is decreased, but the level of free T4 (fT4) may also be affected.
Diagnostic approach: specific thyroid tests
The TT4 test includes both bound and unbound (free) T4. T4 is the most abundant hormone secreted by the thyroid gland. This test is used to rule out hypothyroidism. Very few truly hypothyroid dogs will have a normal TT4 level. As mentioned, there are many factors that can lead to low level of TT4 in euthyroid dogs. For this reason, a low level of TT4 alone should never be used to diagnose hypothyroidism. Additional thyroid diagnoses should be sought to support the diagnosis before starting treatment.
FT4 is the small fraction of total T4 that is biologically active. Since the fT4 level is less affected by non-thyroid disease (NTI) than TT4 levels, this test is frequently used as a follow-up to a low TT4 result if there is a clinical suspicion of hypothyroidism but the NTI is present.
Lack of negative feedback to the pituitary gland in primary hypothyroidism will lead to an increase in TSH. Hypothyroid dogs will have TSH levels above the reference range in about two-thirds of cases. The TSH test is used in conjunction with low TT4 and / or fT4 test results to support a diagnosis of hypothyroidism.
Tests for thyroiditis
Some laboratories offer assays for antithyroglobulin, anti-T3 and anti-T4 autoantibodies. About half of dogs with hypothyroidism will have anti-thyroglobulin antibodies. Anti-T3 and anti-T4 antibodies can also be detected but are less common. These tests can be added to the diagnostic workup of a dog with suspected hypothyroidism to increase confidence in the diagnosis if the combination of TT4 and / or fT4 and TSH levels is equivocal. It is important to note that the absence of these antibodies does not rule out hypothyroidism.
Diagnostic approach: put everything in place
Due to the many factors that complicate the diagnosis of the thyroid, a workup for hypothyroidism should always begin with a reasonable clinical suspicion based on the history, examination results, and clinicopathologic parameters. It is important to carefully examine and, if possible, rule out non-thyroid causes of low T4 levels before testing.
The definitive diagnosis of hypothyroidism requires several diagnoses of supporting thyroid hormones, the most specific combination of tests being TT4, fT4, and TSH. Since few non-thyroid factors affect TSH levels, a low TT4 and / or fT4 result associated with a high TSH level is strongly consistent with true hypothyroidism.
Since up to a third of hypothyroid dogs will have TSH levels within the baseline range, a normal TSH result cannot be used to rule out hypothyroidism. In these cases, a suspicious clinical presentation of hypothyroidism, exclusion of non-thyroid factors, a low TT4 and fT4 result, and a TSH level between the middle and the high end of the reference range are sufficient to diagnose hypothyroidism. . In case of equivocal laboratory results, testing for anti-pyroglobulin, T3, and T4 antibodies may help increase the suspicion of true hypothyroidism.
Laura R. Van Vertloo, DVM, MS, DACVIM, is Assistant Professor of Veterinary Clinical Sciences at Iowa State University, College of Veterinary Medicine in Ames, Iowa.