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With Thyroid Replacement, Consistency Matters

Educate your staff and clients about when quality and consistency count, such as with thyroid replacement therapy.

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Everyone is aware of the economic challenges facing veterinary practices today: Visits to the veterinarian are down, and clients are getting concerned about some pet care costs. Some are even selecting alternate resources, including online pharmacies, and requesting prescriptions to have medications filled at human pharmacies at a lower cost.

Practice managers or buyers might try to economize by going for the least expensive option when purchasing medications to stock for the clinic pharmacy, to help offset some of these concerns.

Medically speaking, if veterinarians are dispensing human generic products in certain categories, there may not be a big difference in the actual product, but this is not the case for every prescription. Educate your staff and clients about when quality and consistency count, such as with thyroid replacement therapy.

Overall, some aspects of hypothyroidism in dogs are fairly straightforward and simple. Most cases arise from irreversible acquired thyroid gland disease, due to either immune-mediated lymphoid thyroiditis (a heritable trait) or idiopathic follicular atrophy (normal thyroid tissue is replaced by connective and adipose tissue).

In the immune-mediated form, there is a chronic, progressive lymphocytic destruction of the thyroid gland with a slow onset. Auto antibodies against thyroglobulin can be present, and cross-reactivity to T3 and T4 has been reported.

Large-breed dogs have a predilection for this type of disease, including golden retrievers, Doberman pinschers and English setters, among others. Other breeds predisposed to hypothyroidism include Schnauzers, poodles, cocker spaniels and dachshunds, but they express the auto antibodies less frequently, grouped more into the idiopathic category. 

This tends to be a disease of middle-aged dogs (around 7 years), with common signs of lethargy, weight gain and hair loss, most of which are secondary to the decreased metabolism.

Up to 88 percent of dogs present with a bilateral, symmetrical non-pruritic truncal alopecia (notably in areas of increased wear), with some going on to develop pyoderma and otitis externa. Decreased fertility and neurological signs are seen in a few patients.

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Arriving at an accurate diagnosis is where things get more complex. While canine hypothyroidism may share some similarities with human cases, the differences are significant. Auto antibodies are present in both species, in dogs reactive against thyroglobulin but against the antigen thyroperoxidase (TPO) in humans.

The TSH stimulation test is the gold standard for people, but for dogs, there is a limited access to reagents and the cost is prohibitively high. And when it comes to therapy replacement, doses needed for treating dogs are substantially higher that humans, due to the short biologic half life of thyroxine in dogs.

In dogs, a combination of thyroid diagnostic testing is often needed to arrive at a diagnosis, and response to therapy often gives those results validation.

  • Subnormal T4 can be seen in healthy euthyroid dogs or sick euthryoid dogs
  • Total T3 can be normal in up to 74-90 percent of hypothyroid dogs, so it is the least helpful, and free T3 (fT3) contributes little information and can be decreased in euthyroid dogs, healthy or ill.
  • Elevated T3 and T4 levels may indicate the presence of autoantibodies that can falsely increase their concentrations
  • Serum free T4 (fT4) by equilibrium or direct dialysis is a sensitive and specific way to evaluate hypothyroidism
    • Low fT4 with low T4 and clinical signs are strong indicators of hypothyroid disease
    • Low fT4 can be found in hyperadrenocorticism (which should be treated first, if present)
  • High TSH levels in combination with low T4 or fT4 strongly indicates hypothyroidism
    • TSH is best used in conjunction with other tests
  • Thyroglobulin auto antibodies (TgAA) can be predictive of immune-mediated thyroiditis, but not all patients with TgAA progress to disease
  • Auto antibodies can be crossreactive to T3 and T4
    • Unlikely to have a medical impact
    • Can falsely elevate (rarely decrease) T3 and T4 assays

Once the diagnosis is made, selection of the appropriate medication, dose and dosing interval is initiated, another aspect of hypothyroidism that can be complicated. There can be great variability in the therapeutic equivalence and bioequivalence of different formulations of levothyroxine.

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For each patient, the extent of oral absorption may be quite variable, particularly if a patient is on any medication that could alter absorption of the drug, or concomitant administration of other medications. Some patients may be more consistent at the absorption and even with the elimination, as compared to other patients.

That makes the pharmacokinetics of even a consistent drug highly individualized among various patients.

Thyroid supplementation can make a dramatic impact in the clinical aspect of the patient, with activity and mental alertness improving in as little as one to two weeks. Dermatological abnormalities often take a bit longer, but some improvement should start to be evident within a month.

In fact, clinical response to medication will be used in conjunction with laboratory results to help determine the optimal dose for the individual dog.

A traditional starting point of 0.1mg/10lb/day may not be adequate for some dogs, so initial dosing should be calculated at 0.02 mg/kg orally every 12 hours, or 0.05mg/m2/day divided every 12 hours. Dosage based on body surface area may result in a relatively larger dose in small dogs and a lesser dose for large dogs, so each patient should be monitored closely.

Clinical response to therapy is an integral part of patient follow-up, and T4 levels should be followed. Peak serum T4 concentrations at four to eight hours after administration can be helpful, but in some patients, especially those on once-daily dosing, the trough levels just prior to a dose may provide more information.

If that level is too low, that patient may benefit from staying on twice-daily medication. However, the mean residence of time of T4 is very close to 24 hours, and this helps support the decision for once-daily therapy once the patient is stabilized.

If there is concurrent metabolic disease (hepative, renal, cardiac, endocrine), initiation of treatment should start more slowly, at 25 percent of the standard beginning dose, and gradually increase over a three-month period.

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In monitoring hypothyroidism in a canine patient, lack or decrease in clinical response and unfavorable serum T4 levels may indicate a need for increasing that patient’s dosage. Before considering an increase (or a decrease) in dose, first:

  • Make sure client is being compliant and accurate in dosing
  • Check gastrointestinal function and/or medications to make sure there are no barriers to absorption
  • Confirm that there has been no change in the brand of medication
  • Re-evaluate dosing based on any weight change (decrease)

The FDA has determined that some, but not all, human levothyroxine products are interchangeable. One can never assume they are all the same. If brands are ever switched, it is recommended that human patients have an additional TSH test in eight to 12 weeks.

In the veterinary field, some advocate avoiding generic forms of levothyroxine, as there can be a wide variability in the absorption and bioavailability of therapeutic drug.

The take-home message: In treating canine hypothyroidism, don’t cut corners. Be thorough on the beginning diagnostics, be comprehensive in the follow-up monitoring to appropriately adjust dosing, and don’t let economic factors result in the chance of using an inferior or inconsistent product, whether it is the owner’s action or the clinic purchasing the best sale item.

Dr. Heidi Lobprise, Dipl. AVDC, is senior technical manager for Virbac Corp.

This Education Series article was underwritten by Virbac Corp. of Fort Worth, Texas.

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