Canine hypothyroidism (Proceedings)

Hypothyroidism is the most commonly diagnosed endocrinopathy in dogs, and is usually the result of lymphocytic thyroiditis or idiopathic atrophy. Secondary hypothyroidism, caused by inadequate production of TSH from the pituitary gland, accounts for fewer than 5% of hypothyroid cases. Primary hypothyroidism is most prominent in middle-aged dogs (2-6 years old). Golden retrievers, Dobermans, Great Danes, Shelties, and other breeds predisposed to hypothyroidism tend to develop the disease earlier (2-3 yrs old) than other breeds.

Clinical signs

The most common clinical signs reported in hypothyroid dogs include dermatologic abnormalities, decreased activity level, weight gain, and cold intolerance. Dermatologic manifestations occur in about 70% of hypothyroid dogs and include a symmetrical endocrine alopecia, thinning hair coat, hyperpigmentation, seborrhea, and "rat tail." Because of the insidious onset of disease, owners often attribute lethargy and weight gain to an increase in the dog's age, without recognizing it as abnormal. On the other hand, obesity is very common in the canine population, but the vast majority of obese dogs are not hypothyroid.

Less common clinical manifestations of hypothyroidism include neuromuscular abnormalities such as weakness, facial nerve paralysis, and vestibular disease. Seizures may occur secondary to severe hyperlipidemia. Megaesophagus and laryngeal paralysis have also been reported to occur in hypothyroid patients, although a causal relationship has not been proven. Cardiac abnormalities may include sinus bradycardia and decreased contractility. Concurrent dilated cardiomyopathy and hypothyroidism, with significant improvement in cardiac function following thyroid supplementation, has been reported in two Great Danes. Myxedema coma, in which patients present with severe lethargy, depression, and edema, is very rarely seen in dogs. Reproductive dysfunction in male and female dogs has also been associated with hypothyroidism.

Diagnosis

Diagnosis is based on consistent history, clinical signs, physical exam, minimum database (CBC/Chem/UA), and specific endocrine testing. Clinicopathologic changes include a normocytic, normochromic (non-regenerative) anemia, hypertriglyceridemia, and hypercholesterolemia. The utility of assessing the minimum database is two-fold. For one, more than 75% of hypothyroid dogs are hypercholesterolemic; thus, hypothyroidism is less likely in a patient with a normal cholesterol value. Additionally, the minimum data base helps the clinician identify other causes for the dog's clinical signs. Since thyroid testing is complicated by concurrent disease, misinterpretation (and misdiagnosis with hypothyroidism) is significantly more likely to occur with undiagnosed extra-thyroidal pathology.

Diagnostics used to assess thyroid function specifically include static measurement of a dog's total T4 (tT4), free T4 (fT4), thyroid-stimulating hormone (TSH), and antibodies against thyroglobulin, T4, and T3. Provocative testing includes TRH- and TSH-stimulation testing. However, availability and expense of these provocative tests significantly limit their use. tT3 concentrations are often measured as part of a thyroid panel, but due to fluctuations throughout the day, are generally not helpful in the diagnosis of hypothyroidism.

Euthyroid sick syndrome occurs when illness stimulates a physiologic (not pathologic) decrease in thyroid hormone concentrations. This phenomenon complicates the diagnosis of hypothyroidism because concurrent illness may result in a thyroid hormone concentration below the reference range in a dog with a normally-functioning thyroid gland. The mechanism for euthyroid sick syndrome is unclear. Certain drugs, such as steroids (exogenous or from secondary hyperadrenocorticism), phenobarbital, TMS, and some NSAIDS, may also alter results of thyroid testing.

tT4

The most useful screening test for hypothyroidism is the tT4 because its sensitivity is high (~90%). However, its specificity is lower. What this means practically is that a dog with a tT4 in the middle of the reference range is extremely unlikely to have hypothyroidism. However, a low tT4 does not, by itself, confirm the diagnosis of hypothyroidism. Euthyroid sick syndrome may cause decreased tT4 values in patients with extra-thyroidal illness. Even in normal dogs, T4 levels fluctuate throughout the day and in response to physiologic conditions. About half of all NORMAL (euthyroid) dogs have a tT4 below the reference range at some point in the day. In a healthy, euthyroid dog, re-measuring the tT4 at a different time on a different day may be all that is required to demonstrate a tT4 within reference range and rule-out hypothyroidism. A normal tT4 is very useful for ruling-out hypothyroidism, but additional testing is required to confirm hypothyroidism in a patient with a low T4.

fT4

Since the non-protein-bound (free) portion of thyroid hormone is biologically active, measurement of fT4 would theoretically be more useful than tT4 for the diagnosis of hypothyroidism. However, the most commonly used methods for measurement of fT4 (RIA) do not appear to be any more useful than the tT4. Measurement of fT4 by equilibrium dialysis (ED) significantly increases the test's usefulness, in addition to its expense. Like tT4, the sensitivity of a low fT4 measured by ED for hypothyroidism is high. The main benefit in measuring fT4 by ED is that its specificity is higher than the tT4, thus less likely to be decreased in a dog with normal thyroid function. Unfortunately, euthyroid sick syndrome may decrease the fT4 by ED, as well, but not as frequently.

TSH

Because of lack of feedback inhibition from thyroid hormones, TSH should (theoretically) be increased in hypothyroid dogs. Its clinical utility lies in its specificity: The concurrent measurement of a LOW T4 with a HIGH TSH is very specific (~98%) for the diagnosis of hypothyroidism. Thus, the measurement of low T4 and high TSH can be used to confirm hypothyroidism. However, the sensitivity of concurrent increased TSH and low tT4is less spectacular (~70%). This means that TSH will be normal in 30% of hypothyroid dogs. The reason for this is unclear. So a high TSH with concurrent low T4 is very useful for confirming the diagnosis of hypothyroidism, but a normal TSH does NOT completely rule-out hypothyroidism in a dog.

Anti-thyroglobulin (ATT), anti-T3, and anti-T4 antibodies

A result of thyroiditis, the prevalence of ATT, anti-T3, and anti-T3 antibodies in hypothyroid dogs is approximately 50%, 30%, and 15%, respectively, providing additional data for confirmation of hypothyroidism. Anti-T4 antibodies can interfere with hormone assays, potentially causing a spuriously increased tT4 and fT4 by RIA, but NOT ft4 by ED. Thus, anti-T4 antibodies could mask hypothyroidism by bumping measured T4 up into the reference range, when the dog's actual tT4 is below reference range. Measurement of fT4 by ED and measurement of antibodies is recommended for patients in which clinical suspicion is high, but tT4 measurement is at the low end of the reference range.

ATT antibodies CAN be present in patients without thyroid disease (<5%). A recent study suggests that up to 20% of euthyroid dogs with ATT antibodies developed signs of hypothyroidism within one year.

Treatment

Treatment consists of supplementation with a name-brand synthetic thyroid hormone. Twice daily dosing is preferred over once daily initially. If the patient responds to therapy, a trial of once-daily medication may be implemented.

A recheck of the patient's T4 should be repeated about a month after initiation of therapy and after each dose change, and every six months thereafter. Timing of therapeutic monitoring is controversial, so the reader may find different recommendations elsewhere. Ideally, two blood samples should be taken—one just prior to the dog's morning dose (trough) and at peak concentration (4-6 hours post-pill). Trough concentrations should be within reference range, and peak concentrations should be at the high end of the range, or even slightly above it. If only one sample can be drawn, in most cases, the post-pill concentration is preferable.