Feline Hyperthyroidism: Diagnosis & Therapeutic Modalities

David Bruyette, DVM, Diplomate ACVIM

Hyperthyroidism is recognized as the most common endocrinopathy of older cats. Traditional therapeutic measures include thyroidectomy, radioactive iodine therapy, and antithyroid medications. A new therapeutic option—a limited-iodine diet that helps normalize thyroid hormone concentrations and alleviate clinical signs—is now available.

Hyperthyroidism is recognized as the most common endocrinopathy of older cats. Despite worldwide occurrence, though, its pathogenesis remains unclear.

Traditional therapeutic measures for managing feline hyperthyroidism include:

• Thyroidectomy
• Antithyroid medications
• Radioactive iodine.

Recent studies have documented another therapeutic option for hyperthyroid cats—a limited-iodine diet, which helps normalize thyroid hormone concentrations and alleviate clinical signs.

All therapeutic options are effective, with their own pros and cons.

• Surgery and radioactive iodine provide permanent treatment for feline hyperthyroidism.
• Oral antithyroid drugs and nutritional management must be administered daily to control hyperthyroidism if a permanent solution is not chosen.

DIAGNOSIS

Diagnosis of feline hyperthyroidism is based on:

• Presence of one or more clinical signs (see Clinical Signs of Feline Hyperthyroidism)
• Increased serum total thyroxine (T₄) concentration.

However, up to 10% of all hyperthyroid cats and 40% of those with mild disease have serum T₄ values within the reference range.^1,2

• Hyperthyroidism should not be excluded based on a single, normal serum T4 value, especially in a cat with typical clinical signs, a palpable thyroid nodule, and serum T₄ in the upper half of the reference range.³
• In these cases, serum free T₄, measured by equilibrium dialysis (fT₄ED), may provide an alternative approach to diagnosis. Studies document that up to 20% of sick euthyroid cats can have increased fT₄ concentrations.⁴
• Therefore, it is appropriate and reliable to interpret the 2 values together:
  • Mid to high serum total T₄ and increased fT₄ concentration is consistent with hyperthyroidism.
  • Low serum total T₄ and normal or increased fT₄ values are usually associated with nonthyroidal illness.

MANAGEMENT OPTIONS

Methods of managing feline hyperthyroidism include:

• THYROIDECTOMY provides a permanent solution.
• RADIOACTIVE IODINE is considered the gold standard for treatment.
• ANTITHYROID MEDICATIONS are often oral and needed daily to achieve and maintain their effect.
• LIMITED-IODINE DIETS normalize thyroid hormone concentrations and alleviate clinical signs of hyperthyroidism.

All management options can be > 90% effective for controlling hyperthyroidism when used appropriately. The selected management option will differ for each cat based on several considerations (Table).

Radioactive iodine therapy is considered the gold standard for treatment of hyperthyroidism; however, most pet owners currently chose medical management with oral or transdermal antithyroid drugs. An additional option—nutritional management using a limited-iodine food—is now available for cats with hyperthyroidism.

RADIOACTIVE IODINE

Radioactive iodine therapy is often considered the best option for many hyperthyroid cats because:

• A single treatment has the potential to eliminate a benign thyroid tumor or abnormal thyroid tissue.
• Extra-thyroidal thyroid tissue, which may occur in 10% to 20% of hyperthyroid cats, is treated.
• No general anesthesia is required
• Reported side effects are minimal.

The goal of treatment is to restore euthyroidism with the smallest possible single dose of radioactive iodine, while avoiding development of hypothyroidism.⁶ Controversy exists as to the best method of calculating the optimum dose for individual cats.^5,6

Cats should be in stable condition prior to radioiodine therapy; those with clinically significant cardiovascular, renal, gastrointestinal (GI), or endocrine (eg, diabetes mellitus) disease may not be good candidates, especially due to the required boarding time after treatment.⁵

Mechanism of Action

After administration, radioactive iodine is actively concentrated by the thyroid gland, with a half-life of 8 days.

• It emits both beta-particles and gamma-radiation; the beta-particles are responsible for the majority of tissue destruction, but are only locally destructive, traveling a maximum of 2 mm.
• Therefore, no significant damage to adjacent parathyroid tissue, atrophic thyroid tissue, or other cervical structures is expected.

Posttreatment Hypothyroidism

Based on the majority of reported cases, posttreatment hypothyroidism is transient and generally uncommon (2%–7% of cases); even fewer cats have clinical signs or appear to require thyroid hormone replacement.^7-11 However, in 1 study, up to 30% (50/165 cats) were hypothyroid 3 months after radioiodine therapy; of these:

• 56% (19/34 hypothyroid cats with available information) had clinical signs of hypothyroidism.
• 52% (23/44 cats) were given thyroid hormone supplementation.¹²

Since hypothyroidism has been associated with azotemia and decreased survival time in previously hyperthyroid cats, thyroid hormone replacement may be needed in some cats, especially those with concurrent kidney disease.¹³ Owners should be advised of this possibility, particularly if their motivation for this particular treatment is to avoid long-term medical therapy.

Limitations

The main limitation to widespread use of radioactive iodine is the requirement for special licensing and isolation of the cat after treatment, which can range from several days to several weeks depending on state or local radiation regulations and the dose administered.⁶

ANTITHYROID DRUGS

Antithyroid drugs are commonly used for treatment of hyperthyroidism in cats.^14-21 They are widely recommended to stabilize hyperthyroid cats prior to surgery and are the only drugs that can be used chronically for management of hyperthyroidism.⁶ Almost all cats are potential candidates unless thyroid carcinoma is suspected.

Mechanism of Action

If administered appropriately, antithyroid drugs reliably inhibit the synthesis of thyroid hormones and, thereby, lower serum thyroid hormone concentrations. These drugs do not affect the thyroid gland’s ability to trap inorganic iodide or release preformed hormones.

Administration

The antithyroid drugs used most often in cats are methimazole and carbimazole; both can be given orally or formulated for transdermal application.

• Custom formulation of transdermal products may increase expense of therapy and there is no guarantee of product stability.
• However, results of a recent prospective study showed that once daily treatment for 12 weeks with transdermal methimazole in a novel lipophilic vehicle was as effective as twice-daily carbimazole administered orally.¹⁴

Side Effects

While many cats are successfully managed long-term with antithyroid drugs, it is important to monitor for side effects associated with their use.^15,18,19,21

• In the study with the largest number of cats, 18% had side effects associated with methimazole; a more recent study revealed that 44% of 39 cats had side effects.^15,19
• In 44 cats receiving carbimazole for 1 year, 44% had associated side effects, with GI signs (decreased appetite, vomiting, diarrhea) being most common.
• In another study, 13% of 39 cats treated with carbimazole experienced side effects.¹⁸

Determining what percentage of side effects are caused by the drug versus another factor, such as concurrent disease, is difficult.²¹

Most adverse reactions occur within the first few weeks to months after beginning therapy and include depression, inappetence, vomiting, and self-induced excoriations of the head and neck (facial pruritus).

• GI signs are less common with transdermal administration of methimazole.¹⁶
• Mild to serious hematologic complications, including agranulocytosis and thrombocytopenia either alone or concurrently and, more rarely, immune-mediated hemolytic anemia, may also occur.
• Hepatic toxicity with marked increases in bilirubin concentration and hepatic enzyme activity has been described in less than 2% of cats treated with methimazole.
• Serum antinuclear antibodies develop in approximately 50% of cats treated with methimazole for longer than 6 months, usually in cats on high-dose therapy (> 15 mg/day). Although clinical signs of a lupus-like syndrome have not been reported, decreasing the daily dosage is recommended.⁶

Cessation of therapy is required if serious hematologic or hepatic reactions develop.

NUTRITIONAL MANAGEMENT

A limited-iodine therapeutic food containing < 0.3 ppm on a dry matter basis (DMB) is now available as an option for managing cats with hyperthyroidism (Prescription Diet y/d Feline, hillsvet.com).

Mechanism of Action

Production of thyroid hormone requires sufficient dietary iodine. The only known function for ingested iodine is for thyroid hormone synthesis.⁵ This observation led to the hypothesis that limiting dietary iodine intake could be used to control thyroid hormone production and potentially manage hyperthyroidism in cats.

Research Studies

Multiple feeding trials to determine the safety and effectiveness of limited dietary iodine in the management of feline hyperthyroidism were conducted in a research colony (over 100 cats) with naturally occurring hyperthyroidism.

• Study results showed that a therapeutic food with dietary iodine < 0.3 ppm iodine (DMB) provided a safe and effective management option for cats with naturally occurring hyperthyroidism.
• Serum total thyroxine concentrations returned to a normal range within 4 to 12 weeks of initiating nutritional management and 90% of the hyperthyroid cats maintained on the limited-iodine food as the sole source of nutrition became euthyroid.

Three studies were designed to determine the:

• Magnitude of iodine control necessary to return newly diagnosed cats to a euthyroid state²²
• Maximum level of dietary iodine that maintains cats in a euthyroid state²³
• Effectiveness of a therapeutic food formulated (based on the previous studies) to control naturally occurring hyperthyroidism in cats.²⁴

In summary, results of these studies demonstrated that a food with 0.17 or 0.32 ppm iodine (DMB) maintained normal thyroid hormone concentrations in hyperthyroid cats, helping to further define the amount of iodine that effectively manages hyperthyroidism.

A prospective study, which should be completed in 2013, is evaluating the efficacy of a limited-iodine diet in managing feline hyperthyroidism relative to pre- and posttreatment:

• Monitoring of thyroid function (T₄, fT₄ED, TSH)
• Clinical signs
• Body weight
• Renal function
• Blood pressure.

To date, over 150 cats with naturally occurring hyperthyroidism have been managed successfully by feeding a limited-iodine food, most for 2 to 3 years and some cats for as long as 6 years.

Administration

If the limited-iodine food is selected as the management option for a client’s hyperthyroid cat, gradual transition to the food over a minimum of 7 days is recommended. It is very important for owners to understand that success of nutritional management depends on maintaining this food as the sole source of nutrition for their cats.

Follow-Up

The first recheck evaluation should:

• Take place once the cat has been eating the new food exclusively for 4 weeks
• Include, at minimum, a physical examination and measurement of T₄, blood urea nitrogen, serum creatinine, and urine specific gravity.

All cats should have T₄ concentrations compared with previous baseline results; many will have returned to normal by the 4-week evaluation. Clinical improvements, such as weight gain, improved hair coat, and decreased tachycardia/cardiac murmur, may also be noted.

The second recheck evaluation should take place at 8 weeks.

• Clinical signs should show continued improvement by this evaluation.
• Most cats will also be euthyroid at this point; however, some cats require additional time.
• 90% of cats should have normal T₄ concentrations if the limited-iodine food is their sole source of nutrition.

If euthyroidism is not achieved within 4 to 12 weeks, a thorough history is indicated to confirm that only the limited-iodine food is being fed.

Long-Term Monitoring

Once a euthyroid state is achieved, it is appropriate to continue patient monitoring indefinitely.

• For stable patients without concurrent disease, evaluations (including T₄) can take place every 6 months during the recommended wellness examination.
• However, clinicians may schedule more frequent monitoring based on clinical judgment of individual patients/owners.
• Hyperthyroid cats with concurrent diseases generally should be evaluated at least every 3 to 4 months.

IN SUMMARY

Hyperthyroidism is the most common endocrine disease of older cats worldwide. While pathogenesis is unclear, several effective management options are available, including thyroidectomy, radioactive iodine therapy, and antithyroid medications. In addition, feeding a limited-iodine food is now an available option for management of hyperthyroid patients. All options should be discussed with pet owners to allow the best option to be selected for individual patients and their owners.

CKD = chronic kidney disease; DMB = dry matter basis; free thyroxine by equilibrium dialysis = fT₄ED; GFR = glomerular filtration rate; GI = gastrointestinal; thyroxine = T₄; TSH = thyroid-stimulating hormone

References

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David Bruyette, DVM, Diplomate ACVIM, is the medical director at West Los Angeles Animal Hospital and a clinical professor in the Department of Radiation Oncology at University of California—Los Angeles. Prior to his current positions, he was an assistant professor and head of internal medicine at Kansas State University and director of its Analytical Chemistry Laboratory. Dr. Bruyette received his DVM from University of Missouri and completed an internship at Purdue University and residency in internal medicine at University of California—Davis. He then became a staff internist at West Los Angeles Veterinary Medical Group and member of the Department of Comparative Medicine at Stanford University.