During his canine hypothyroidism session at CVC Kansas City—now Fetch a dvm360 conference—David Bruyette, DVM, DACVIM, queried the attendees about how they administered thyroid hormone replacement therapy and how they monitored dogs once they were receiving a thyroid supplement. After listening to responses from attendees, he quipped, “That’s a problem.”
So, how would Dr. Bruyette recommend that you treat and monitor a hypothyroid dog?
Once-a-day dosing … really?
For more than half a century, the recommended thyroid hormone replacement dosing regimen was 0.10 mg/10 lb (20 μg/kg) of levothyroxine, given twice a day. This dosage does not appear to be based on any particular scientific research. As Dr. Bruyette says, it just miraculously appeared in the first edition of Current Veterinary Therapy. Finally, years later, Dr. Duncan Ferguson decided to design a study that would determine whether this was, in fact, the best dose. The study confirmed that 0.10 mg/10 lb is the proper dose. However, the study also determined that the drug should be administered only once a day, rather than twice a day.
The half-life of levothyroxine in dogs is 10 to 16 hours. If this is the half-life, then why would this be a once-a-day drug? Dr. Bruyette explains: “When you give the drug orally, it is absorbed, it binds to the protein in the blood, and it is converted to free thyroxine (fT4). Then fT4 enters the cell and becomes free triiodothyronine (fT3), and then that goes into the nucleus and does its thing. That’s a 24-hour process. The serum half-life does not equate to the biologic half-life of the tablet. Biologically, it’s a once-a-day drug.” This has been studied and shown to be true whether you administer the levothyroxine orally as a solution, tablet or chewable. It also holds true with both name-brand and generic formulations.
A caveat while we’re on the subject: As mentioned, the half-life of thyroxine in dogs is 10 to 16 hours (compared with a 7-day half-life in people). This means canine dosages are much higher than human dosages. So remember this if clients choose to fill prescriptions for their dogs at pharmacies that do not routinely handle veterinary prescriptions. (You may have to do some educating of those pharmacy personnel.)
To monitor … or not?
Once canine hypothyroidism has been diagnosed, what are Dr. Bruyette’s recommendations for laboratory monitoring? He says that many veterinarians, including those attending this CVC session, were taught that they should draw blood for T4 testing from four to six hours after the thyroid hormone pill was administered. Dr. Bruyette says, “The percentage of T4 that is absorbed from the gut varies from 13% to 87% in a given dog from day to day. So, on Monday, the dog may absorb 13% of the dose; on Tuesday, it may absorb 87% of the dose. The post-pill test is severely affected by the intrinsic ‘weirdness’ of the T4 bioavailability. Therefore, the post-pill test is probably physiologically meaningless.”
So, is there a way to confirm a dog is euthyroid when it is receiving thyroid hormone supplementation? There are two options: thyroid-stimulating hormone (TSH) measurements or free T4 by equilibrium dialysis (fT4 by EqD). If the TSH is normal, the dog is euthyroid. If the TSH is high, it needs more thyroid hormone; if it’s low, the dog is getting too much of the hormone.
But if you read the companion article “Canine hypothyroidism: Shield your patients from overdiagnosis,” you may have already spotted the problem with this option. In that article, we stated that with the TSH assay, 25% of hypothyroid dogs have a normal TSH concentration to start with (because the assay does not work well). Therefore, to use TSH assays to monitor a dog on hormone replacement therapy, you must have had a pre-treatment TSH result that was high. Without that, you simply can’t interpret what the TSH concentration means now.
The other option is to measure fT4. After two weeks of thyroid hormone supplementation, fT4 concentrations over a 24-hour period are constant. With the fT4 by EqD test, it doesn’t matter what time of day or when in relation to the pill administration you collect the blood sample, because the concentrations don’t fluctuate.
So is there even a need to monitor a dog with lab tests? Dr. Bruyette says, “Probably not very often. Because if you have a dog that was hypothyroid and you put him on the appropriate dose and the clinical signs went away, you don’t really need to test his fT4, or anything. The dog is a euthyroid dog.”
You might want to test a dog if it is still showing clinical signs, even though it is receiving an appropriate dose of thyroid hormone. You need to know if the dog is not euthyroid. To establish that, submit blood for an fT4 by EqD test. If that test is normal, then whatever clinical signs are present are not due to thyroid disease.