Richard W. Nelson, DVM, DACVIM
The diagnosis of hyperthyroidism is based on identification of appropriate clinical signs, palpation of a thyroid nodule, and documentation of an increased serum T4 concentration. Hyperthyroidism typically occurs in cats older than 8 years, with a range of 4 to 20 years. The classic clinical signs include weight loss, polyphagia, and hyperactivity. Additional clinical signs include haircoat changes, polyuria, polydipsia, vomiting, diarrhea and aggressive behavior. In some cats, lethargy, weakness, and anorexia are the dominant clinical features, in addition to weight loss. A discrete thyroid mass is palpable in approximately 90% of cats with hyperthyroidism. However, palpation of a cervical mass, by itself, does not confirm and failure to palpate a thyroid mass does not rule out hyperthyroidism. The thyroid mass is commonly palpated in the region of the thoracic inlet and may descend into the anterior mediastinum.
Measurement of baseline serum thyroxine (T4) concentrations is extremely reliable in differentiating hyperthyroid cats from those without thyroid disease. An abnormally high serum T4 concentration strongly supports the diagnosis of hyperthyroidism, especially if appropriate clinical signs are present, and a low serum T4 concentration rules out hyperthyroidism, except in extremely uncommon situations where severe life-threatening nonthyroidal illness is present. Serum T4 concentrations that fall within the upper half of the normal range create a diagnostic dilemma, especially if clinical signs are suggestive of hyperthyroidism and a nodule is palpable in the ventral region of the neck. Cats with mild or occult hyperthyroidism and hyperthyroid cats with significant nonthyroidal illness can have "normal" serum T4 concentrations. The diagnosis of hyperthyroidism should not be excluded on the basis of one "normal" test result, especially in a cat with appropriate clinical signs and a palpable mass in the neck. If the serum T4 test result is not definitive, the recommendation is to measure serum T4 and free T4 (fT4) in 1 to 2 weeks and to rule out non-thyroidal illness. If the diagnosis is still not established, the veterinarian should consider repeating the serum T4 and fT4 tests in 4 to 8 weeks, obtaining a radionuclide thyroid scan, or completing a T3 suppression test. If available, a radionuclide thyroid scan is preferable over the T3 suppression test for diagnosing hyperthyroidism in cats with nondiagnostic serum T4and fT4concentrations. The T3 suppression test should only be considered in cats with persistently nondiagnostic serum T4 and fT4 concentrations and no access to radionuclide scanning facilities. It is important to remember that the thyroid nodule may also be nonfunctional and the clinical signs may be the result of another disease.
Measurement of baseline serum fT4 concentration using the modified equilibrium dialysis technique is a more reliable means of assessing thyroid gland function than measurement of the serum total T4 concentration, in part, because non-thyroidal illness has more of a suppressive effect on serum total T4 than fT4 and serum fT4 is increased in many cats with occult hyperthyroidism and "normal" T4 test results. Because of cost, measurement of fT4 concentration by MED is often reserved for cats with suspected hyperthyroidism where T4 values are borderline. Occasionally concurrent illness causes an increase in serum fT4 concentration in cats; an increase which can exceed the reference range. For this reason, serum fT4 concentration should always be interpreted in conjunction with total T4 concentration measured from the same blood sample. An increased serum fT4 concentration in conjunction with high-normal or increased serum T4 concentration is supportive of hyperthyroidism. An increased serum fT4 concentration in conjunction with a low-normal or low serum T4 concentration is supportive of euthyroid sick syndrome.
Hyperthyroidism in cats can be managed by thyroidectomy, oral antithyroid medications, and radioactive iodine. All three modes of therapy are effective. Surgery and radioactive iodine treatments are used in the hope of providing a permanent cure for the disease; oral antithyroid drugs only "control" the hyperthyroidism and must be given daily to achieve and maintain their effect. We initially treat hyperthyroid cats with the oral antithyroid drug methimazole to reverse the hyperthyroid-induced metabolic and cardiac derangements, decrease the anesthetic risk associated with thyroidectomy, and assess the impact of treatment on renal function. Because it is not easy to determine what impact the hyperthyroid state is having on renal function, we prefer to treat cats with reversible therapy (i.e., methimazole) until the impact of hyperthyroidism on renal function can be determined. If renal parameters remain static or improve following resolution of hyperthyroidism, a more permanent treatment can be recommended. If significant azotemia or clinical signs of renal insufficiency develop during methimazole therapy, the treatment protocol for the antithyroid drug should be modified to attain the best possible control of both disorders and treatment for renal insufficiency instituted. Maintaining a mild hyperthyroid state may be necessary to improve renal perfusion and GFR and avoid the uremia of renal failure.
The recommended initial dose of methimazole is 2.5 mg PO once a day for 2 weeks. Adverse reactions are less likely to occur when the dosage of methimazole is started low (typically at subtherapeutic dose initially) and gradually increased to effect. If adverse reactions are not observed by the owner, the physical examination reveals no new problems, results of a CBC and platelet count are within reference limits, and serum T4 concentration is greater than 26 nmol/l after 2 weeks of therapy, the dose is increased to 2.5 mg twice daily and the same parameters evaluated 2 weeks later. The dosage should continue to be increased every two weeks by 2.5-mg/day increments until the serum T4 concentration is between 13 and 26 nmol/l or adverse reactions develop. Serum T4 concentrations decline into the reference range within 1 to 2 weeks once the cat is receiving an effective dose of methimazole; clinical improvement is usually noted by owners within 2 to 4 weeks once good control of serum T4 concentration is achieved.
Adverse reactions to methimazole typically occur within the first 4 to 8 weeks of therapy. The cat should be examined and a CBC, platelet count, and assessment of kidney function performed every 2 weeks during the first 3 months of methimazole treatment and evaluated every 3 to 6 months thereafter. Using the dosing protocol described above, lethargy, vomiting, and anorexia occur in less than 10% of cats; mild hematologic changes (eosinophilia, lymphocytosis, transient leucopenia) occur in less than 10%; severe thrombocytopenia (platelet counts of less than 75,000/mm3), neutropenia (total white blood cell counts of less than 2000/mm3), and immune-mediated hemolytic anemia occur in less than 5%; and hepatic toxicity or injury occurs in less than 2% of cats receiving methimazole. Some cats test positively for antinuclear antibodies, but the importance of this finding is not known. If any of the serious complications develop, methimazole treatment should be discontinued and thyroidectomy or radioactive iodine recommended.
Thyroidectomy should be considered once euthyroidism has been established with methimazole treatment. Thyroidectomy should always be considered an elective procedure and postponed or not performed if the risk of anesthesia in the cat is unacceptable, its renal function is questionable, the likelihood of postoperative hypocalcemia is great, ectopic thyroid tissue is present in the thorax, or thyroid carcinoma with metastasis is suspected. If possible, an ultrasound examination of the ventral neck or a pertechnetate scan should be performed before surgery to identify the location of the abnormal thyroid tissue, differentiate unilateral from bilateral lobe involvement, and provide some insight into the probability of hypocalcemia developing postoperatively. Similar information can also be gained by direct visualization at the time of surgery. There is a direct correlation between the size of the thyroid lobes, the inability to visualize the external parathyroid glands, and the risk of hypocalcemia. Care must be taken to preserve at least one, but preferably both, external parathyroid glands and their associated blood supply. A "subcapsular" thyroidectomy affords the best chance of retaining functional parathyroid glands. Abnormal, adenomatous thyroid cells may remain adhered to the capsule after subcapsular thyroidectomy, and these "rest" cells may serve as the source for the redevelopment of hyperthyroidism 6 to 24 months later. If all four parathyroid glands are inadvertently removed, the two external parathyroid glands should be removed from their respective thyroid lobes, minced, and placed within the muscle belly of one of the sternohyoideus muscles by bluntly dissecting parallel to the muscle fibers. Hypoparathyroidism usually resolves within a month of surgery, if revascularization of the parathyroid autotransplant occurs.
Radioactive iodine (131I) is the radionuclide of choice for the treatment of functional thyroid tumors causing hyperthyroidism. 131I administered IV or SC is concentrated within the thyroid, and the emitted radiation destroys surrounding functioning follicular cells without causing radiation damage to contiguous structures. The cells killed are those that are functioning. Atrophied normal cells are spared, preventing long-term hypothyroidism in most cats. Depending on the dose administered, more than 80% of treated cats become euthyroid within 3 months, most within 1 week, and more than 95% of treated cats are euthyroid at 6 months. Clinical signs and laboratory data consistent with hypothyroidism develop in approximately 2% of 131I-treated cats, 2% to 4% require a second 131I treatment, and hyperthyroidism recurs in 2% within 1 to 6 years of treatment. The only recognized adverse reaction is hypothyroidism, which typically develops in cats with bilateral, large, diffusely affected thyroid lobes.