Everything Old Is New Again: Examining Thyroxine

by | 06.20.2014 | 11:01am

Off-label use of thyroxine (sold as Thyro-L, Levoxine Powder, or Levo-Powder) has been popular among trainers since the 1970s, but recent revelations from leading Thoroughbred conditioners about blanket use of the product in their barns has veterinarians and regulators concerned.

When used according to label instructions, levothyroxine supplements are intended to correct hypothyroidism—a condition in which a horse's thyroid does not function adequately on its own. A normal thyroid produces both thyroxine, known as T4, and triiodothyronine, known as T3, which work with chemicals in the brain to maintain normal biological processes and control metabolism. Too little of either T3 or T4 will reduce metabolism, and causes hypothyroidism. Hypothyroidism in horses is characterized by a fatty, cresty neck, resistance to losing weight despite exercise, lethargy, a poor hair coat, and even decreased temperature or anemia in extreme cases.

The opposite can also occur—a horse can produce too much T3 or T4 in a condition known as hyperthyroidism. Hyperthyroidism is characterized by a difficulty putting on weight, increased appetite, increased heart rate, and hyperactivity.

Veterinarians say both conditions are relatively rare among horses.

“In our practice, I think if we had half a dozen horses a year that we put on thyroxine that's probably too many,” said Dr. Jeff Blea, a Southern California racetrack veterinarian who currently is president of the American Association of Equine Practitioners. “Hypothyroidism is a pretty rare metabolic disease in the horse.”

The few true cases of hypothyroidism in the horse population are usually among foals who develop the condition as a result of an iodine deficiency (iodine is used to produce T3 and T4).

In humans and small animals, the easiest way to determine whether a patient is suffering from hypothyroidism or another metabolic conditionis with a blood test. In horses, Blea said, a blood test is not always a helpful tool. Studies have shown that T4 levels naturally vary through the course of a day or week. Certain environmental factors like training schedule, diet, and the use of phenylbutazone, can falsely raise or lower T4 rates. A biopsy of the thyroid can also provide confirmation in small animals, but isn't much more reliable than the blood test in horses.

“A lot of the time it's used based on clinical signs,” said Blea. “When all this came about a year or two ago, people called me and I laughed and said, 'Why would they be doing that [giving thyroxine to horses without hypothyroidism]?'”

Good question.

“I made some phone calls to trainers. I think it's used almost as a nutritional supplement, which I don't particularly agree with. I don't use it that way,” said Blea. “If thyroid regulates metabolism, and you have a 1,200-pound Thoroughbred who's in race training, he's going to have an increased metabolism.”

That metabolism becomes even higher with the addition of thyroxine, which runs $24 or less per month depending on the size of the dose prescribed.

“As an athlete, as your metabolism increases, your fitness, muscle mass, strength, definition, and proportions also increase … Unfortunately, that's not how it should be used.”

The danger is that veterinarians still don't know what the artificial boost to a horse's thyroid could do—especially in the longterm. Blea said that it's difficult to know how much of the drug horses are getting, and whether the amounts trainers are giving can induce unseen symptoms of hyperthyroidism. In humans, hyperthyroidism is associated with increased heart rate, increased blood pressure, cardiac arrhythmia, and, according to one study published in the European Journal of Endrocrinology, a 20 percent higher risk of death.

Blea also can't be sure whether most Thoroughbreds get enough of the drug to produce the hyperactivity characteristic of hyperthyroidism, or whether that hyperactivity could serve as a performance enhancer. He suspects that if a trainer saw some of the outward symptoms that accompany hyperthyroidism, like poor coat and hair loss, they would likely back off on the drug—but this doesn't mean that its off-label use in moderate doses is risk-free, and many horsemen may not realize it.

“I think they think it's an innocuous supplement,” Blea said.

Dr. Rick Sams, laboratory director at LGC Sport and Specialized Analytical Services in Kentucky, said he has heard anecdotally of horses receiving “massive” doses of thyroxine on the track, but has no direct knowledge of how it is typically administered. The California Horse Racing Board's investigation into trainer Bob Baffert revealed that thyroxine was given in the horses' feed, which was often mixed by the grooms. Its administration was so routine that a prescription was accidentally written for a horse a week after its death.

Another wild card is speculation that thyroxine could be used to mitigate the effects of cobalt chloride, believed by some to act similarly to a blood doping agent in horses.

“I suspect that thyroxine is getting more attention today due to its association with cobalt administration and the use of thyroxine to protect against the adverse effects of cobalt on thyroid function,” said Sams. “I am unaware of any documented evidence that orally administered thyroxine is useful in preventing adverse effects of cobalt administration in the horse.”

Regulators in California have made moves to curb the widespread use of thyroxine, but successful post-race testing for unnecessary thyroxine administration is still in the development stages. The challenge is that T4 levels vary so much naturally, and biologically-produced T4 might slow to a trickle to compensate for a dose of artificial T4.

Blea said that thanks to historical records of necropsies on California tracks and other archived data, a better understanding of thyroxine and possible links to cobalt are  just around the corner.

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