Thyroid Diagnosis, Treatment Options Evolve
By Lori Luechtefeld
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Options for diagnosing and treating the most common thyroid conditions in dogs and cats are far from stagnant.
“I always tell our students that if we proportioned the hours of our teaching of endocrinology to be consistent with the likelihood of seeing a problem in practice, I estimate that we’d spend 70 to 80 percent of our time teaching about thyroid disease,” says Duncan Ferguson, VMD.
Dr. Ferguson, Ph.D., Dipl. ACVIM and ACVCP, is a professor of pharmacology and head of the department of veterinary biosciences at the University of Illinois at Urbana-Champaign.
In dogs and cats, two thyroid conditions are by far the most prevalent.
“In dogs, the most common thyroid condition is hypothyroidism, with 50 percent lymphocytic thyroiditis and 50 percent idiopathic atrophy,” says Julie Flood, DVM, who works in the internal medicine department at Advanced Critical Care & Internal Medicine in Tustin and Culver City, Calif.
“It is currently unknown if the idiopathic atrophy is the end result of lymphocytic thyroiditis.
“In cats, the most common thyroid condition is hyperthyroidism—with more than 95 percent secondary to functional thyroid adenomas,” she adds. “Thyroid carcinomas are rare.”
Both hypothyroidism and hyperthyroidism present veterinarians with unique challenges.
Hypothyroidism in dogs may be easy to treat, but it is difficult to diagnose, Dr. Flood says.
“Do not test a dog for hypothyroidism unless you have a strong clinical suspicion of the disease,” she says. “Hypothyroidism in dogs is one of the most overdiagnosed diseases in dogs.
“A common condition known as compensatory hypothyroidism, or sick euthyroid syndrome (SES), may account for many of the false diagnoses of hypothyroidism,” she adds. “Virtually any condition, trauma, stress, injury, illness or poor diet can affect thyroid hormone levels and cause SES.”
The difference between true hypothyroidism and SES is that, with SES, a patient’s thyroid gland retains the ability to return to normal function, Flood says.
“If a dog with SES is misdiagnosed and is supplemented with thyroid hormone, the body’s protective mechanism can be negated,” she says. “And because the underlying cause of SES is overlooked, another disease persists undiagnosed and untreated.”
Ferguson says the most important recent development in the diagnosis of thyroid conditions is the development of the thyrotropin assay, reported in 1997 for the dog. Thyrotropin is also known as thyroid stimulating hormone, or TSH.
“Before this, veterinarians were limited to using either baseline values of serum thyroxine (T4) or triiodothyronine (T3), or using bovine TSH to estimate the thyroid functional reserve,” Ferguson says.
“Following the mad-cow disease outbreak and the development of human recombinant TSH as a pharmaceutical, the commercial sources of bovine TSH have reduced considerably.
“Measurement of serum TSH is a mainstay screening test for thyroid hypofunction in man, and is a confirmatory test in the dog,” he adds.
“However, in human diagnostics, it has been recognized that interlaboratory variability can be considerable, and in canine hypothyroid patients with confirmed hypothyroidism, there are reports that 25 percent to 42 percent of dogs do not have an elevated TSH, leaving open the possibility that some forms of the hormone were not being detected,” Ferguson says.
In addition to this high false-negative rate, Flood reports that TSH levels appear to be heightened in 7 percent to 18 percent of dogs with normal thyroid function, contributing to a false-positive rate of about 10 percent to 20 percent with the canine TSH assay.
In addition to attempts to develop a more-sensitive canine TSH assay, thyroid ultrasonography shows promise for aiding in the diagnosis of hypothyroidism in dogs, Flood says.
“It may prove useful as diagnostic aid for differentiating between hypothyroidism and SES,” Flood says. “Reference ranges for each breed will have to be established before ultrasound can be used to confirm a decrease in thyroid lobe size and volume.”
Possible Link to Diet
The seemingly meteoric rise in hyperthyroidism in cats continues to baffle many in the veterinary community.
“It is interesting that the first case of feline hyperthyroidism was published about 25 years ago, and this disease is now one of the most common diseases we see in elderly cats,” says Ellen Behrend, VMD, Ph.D., Dipl. ACVIM, associate professor in the department of clinical sciences at Auburn University in Alabama.
“No one is sure why the prevalence has increased so much. Good studies have been done to determine if environmental factors are at play, and some possible ones have been identified.”
Some suggest that there might be compounds in canned foods that are associated with an increased incidence of hyperthyroidism, Ferguson says.
“We do not know if there are compounds in dry cat food that reduce the likelihood of the condition,” he says.
“It does seem feasible that because of the nature of the cat’s metabolism of foreign compounds, it is more likely than many species to retain compounds that might impact thyroid function. It is too soon to recommend for or against certain kinds of diets, as no prospective studies have been performed.
“And because of the long course of development of this condition, it would be a very expensive study.”
Feline-Specific TSH Studies
Although diagnosis of feline hyperthyroidism isn’t as problematic as that of hypothyroidism in dogs, diagnostic tools continue to evolve.
“Recognition that measurement of free T4 by dialysis is a great method for diagnosing hyperthyroid cats has made diagnosis much easier,” says Dr. Behrend. She notes that while the method isn’t new, it is the latest development in diagnosis of feline thyroid disease.
Ferguson says better tests for hyperthyroidism are still needed—such as a feline-specific TSH assay that has adequate sensitivity to reliably distinguish a normal value from a low one.
“Work in my laboratory has focused during the last decade upon the cloning and sequencing of canine and feline TSH,” Ferguson says. “This has allowed us to evaluate these recombinant hormones as standards for available immunoassays. ...
“We actually have done more work to understand feline TSH, and have identified that there is high similarity in subunit structure in cat TSH compared to canine TSH—95 percent—but that available immunological reagents do not yet have the sensitivity to detect the depression of feline TSH that hyperthyroidism would cause.
“Several studies have attempted to show that most hyperthyroid cats have undetectable TSH in the canine TSH assay, but a careful analysis of how many euthyroid cats have undetectable TSH has not been reported,” he adds.
The treatment of thyroid conditions in dogs and cats continues to evolve.
“The treatment of canine hypothyroidism has been a fairly standard procedure, and the main change in oral medication has been the recent availability of a liquid product, allowing more flexibility to dosing,” Ferguson says.
“One question that has not been studied, to my knowledge, is the effect of simultaneous food administration on the absorption of any L-thyroxine replacement product.
“In human patients, protein components of food inhibit gastrointestinal absorption. For optimal consistency and maximal absorption, to the extent possible, the prudent thing would be to administer all oral L-thyroxine products separately from food. ”
Drug delivery options for the treatment of hyperthyroidism in cats have also increased in recent years.
“For cats, the best development of late is the use of transdermal methimazole for treatment,” Behrend says. “Although I’m not a big fan of transdermal drugs in general for a number of reasons, transdermal methimazole can be effective.
“Some cats that couldn’t tolerate oral methimazole can now still be treated medically, which makes treatment available to more cats,” Behrend says. “One question that remains, however, is whether the formulation of the transdermal product makes a difference—meaning it is uncertain whether all transdermal methimazole products are equally efficacious.”
Another recent development is the use of percutaneous ultrasound-guided radiofrequency heat ablation, Flood says.
“This has been used in humans to ablate small masses in hepatic, breast and prostatic tissues and in dogs for treatment of hyperparathyroidism,” Flood says.
“Radiofrequency energy is converted to heat at the needle tip, which causes thermal necrosis of exposed tissue. It’s believed to result in fewer complications than with ethanol ablation, in part because of the greater control in application without leakage into surrounding tissues as can be observed with ethanol.
“The technique is known to be effective, at least short term. However, cats require multiple treatments, [and] complications include Horner’s syndrome and unilateral laryngeal paralysis. It requires great expertise, it is not readily available, and there is still very limited experience.
“But it may be promising in the future if the technique can be improved,” Flood says.
Regardless, Flood says the best mode of treatment for hyperthyroidism in cats is radioactive iodine, also called radioiodine.
“It’s a single safe injection, no anesthesia is required, and there’s no daily pilling of the cats,” she says.
Indeed, Rand Wachsstock, DVM, says the major change in the treatment of hyperthyroidism in cats over the past decade has been the increased availability of radioiodine therapy. Dr. Wachsstock is cofounder of Radiocat, a 16-clinic veterinary practice devoted exclusively to the treatment of feline hyperthyroidism.
“The prevalence of hyperthyroidism in cats has risen significantly,” Wachsstock says. “Veterinarians have recognized this and are testing cats earlier. Therefore, the condition is being diagnosed at a younger age, and cats are in better shape when they come to us for treatment.”
The treatment consists of one injection of radioiodine, which is absorbed into and destroys only the thyroid tumor in cats. By law, cats are required to stay in the clinic until they reach a safe and legal level of radiation release.
“Clients are becoming more accepting of leaving their cat in a hospital for a week—or two, depending on regulations—to allow radioactive iodine treatment for hyperthyroidism,” Flood says.
“It is being realized that medical management of a cat with hyperthyroidism for a couple of years costs about the same as radioactive iodine. The difference is that with oral medications, the cost is spread out. Since cats are living longer, the cost of medical management could be more expensive in the long run.”
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Thyroid Diagnosis, Treatment Options Evolve
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