Feline hyperthyroidism is easily treated using radioactive iodine (I131). Radioiodine therapy is curative for the majority of cats and has few direct contraindications. However, the overall success of I-131 for treatment of feline hyperthyroidism depends heavily on proper patient selection and pre-treatment preparation.
Patient selection is important. Candidate cats for I-131 therapy should have stable, well-defined hyperthyroidism and should be free of conditions that could interfere with the efficacy of I-131 therapy, such as cardiac, renal, or other concurrent illness. After therapy, cats must remain healthy enough to survive the mandatory hospitalization (decontamination) period that follows I-131 therapy.
Fortunately, although hyperthyroidism most often occurs in older cats (greater than 8 years), a many hyperthyroid cats are free of concurrent disease and are excellent candidates for I-131 therapy. In this group of cats, the efficacy of I-131 therapy will correlate better to the cat's general health rather than to any specific factor, like age. The overall morbidity of I-131 therapy will be further reduced if the cat's cardiac status and true renal function (i.e., renal function without the influence of excessive thyroid hormones) are ascertained prior to I-131 therapy. Thus, the ideal cat for I-131 therapy has clinical and laboratory consistent with hyperthyroidism, lacks significant cardiac thyrotoxicosis, has good general health, and will require only minimal additional therapy during the I-131 treatment and isolation period.
Problems that must be considered before I131 treatment. Of course, not all cats are ideal candidates for I-131 therapy. Up to 20% of cats may have a reaction to methimazole; overall, about 5% of cats will have a reaction to methimazole that is severe enough to warrant stop methimazole therapy before euthyroidism is achieved. Other cats may have laboratory evidence of hyperthyroidism but clinical symptoms that are incompatible with the diagnosis; I-131 may fail to provide symptomatic relief in these cases. Furthermore, predicting the long-term prognosis for cats with concurrent illnesses or clinically significant cardiac or renal disease can be challenging.
Methimazole reactions. A methimazole trial is appropriate for most cats that will eventually be treated with I-131. A proper methimazole trail can reduce symptoms in the interval between diagnosis and definitive (I-131) therapy. Importantly, the methimazole trial can provide the clinician with information about the cat's renal function that might influence subsequent management. Hyperthyroidism in most cats will be controlled with 5-15 mg methimazole given twice daily. Unfortunately, there is a fairly high incidence of adverse effects from the drug. The most common side effect is gastric upset and vomiting, which is observed in up to 20% of treated cats. Referring veterinarians often withdraw the drug when the owner reports vomiting. However, this is a self-limiting effect of the drug in many cats and vomiting will often spontaneously resolve. In other cats, simple dose reduction will be sufficient to eliminate gastric irritation. More serious adverse effects of methimazole include facial excoriations, hepatopathy, and, less commonly, cytopenias. Administration of the drug should be stopped immediately if any of these complications are observed; under these circumstances, methimazole therapy should probably never be re-instituted. Facial pruritis, leading to self-mutilation and excoriation is probably the most commonly reported serious adverse effect of methimazole. It will resolve once the drug is withdrawn. Methimazole-induced hepatopathy can be difficult to distinguish from changes in hepatic enzymes commonly observed in hyperthyroid cats. Almost all hyperthyroid cats will have persistent elevations of serum alanine transferase (ALT); the elevation can be marked in some cats and may not return to normal immediately despite establishment of euthyroidism. Elevations in serum alkaline phosphatase (ALP) and aspartate transferase (AST) are also common.
A small number of cats have mild increases in serum total bilirubin as a result of hyperthyroidism. When evaluating a cat for the possibility of methimazole-induced hepatopathy, I examine trends in the serum liver enzymes. Once anti-thyroid treatment is begun and T4 begins to fall, liver enzymes may decrease or remain static but rarely continue to rise. If bilirubin elevation is present initially, it generally resolves. Sudden increases in serum liver enzyme concentrations or bilirubin, with or without clinical signs related to liver disease, in a cat receiving methimazole should prompt consideration of drug hepatopathy. Methimazole administration should be stopped immediately and supportive care provided. The hepatopathy is considered to be reversible once drug is withdrawn.
Clinical signs are incompatible with hyperthyroidism. Occasionally, cats with laboratory evidence of hyperthyroidism are presented with signs that are inconsistent with clinical hyperthyroidism. In some cases, it is difficult to determine whether I-131 therapy will benefit the cat (that is, will resolve the observed signs). The distinction can be especially problematic when the reported signs are GI related. For example, vomiting, diarrhea, and weight loss in combination are commonly reported with hyperthyroidism and inflammatory bowel disease (IBD). Primary hepatic disease (e.g., cholangiohepatitis and related disorders) can mimic laboratory findings of hyperthyroidism, but may have subtle differences in clinical presentation. Unfortunately, there is no method to sort out these various presentations that will be useful in all cases. Careful history taking and physical exam are needed to help decide the next course of action. However, although there are exceptions, I adhere to the rule that most cats with run-of-the mill hyperthyroidism will not appear to be very ill. Clients usually report that the cat maintains its activity level, appetite, and water intake. Thus, I am always suspicious that hyperthyroidism is not the principal problem when a cat with complaints of lethargy, inappetence, or dehydration is presented as a possible candidate for I-131 therapy. Such cases not only require stabilization before I-131 is considered, they also require a diagnostic work-up to look for other possible causes of the clinical signs. A methimazole trial can be helpful in some instances to clarify the contribution of hyperthyroidism to the cat's clinical presentation.
Confusing laboratory abnormalities. The first order of business when evaluating a cat as a possible candidate for I-131 therapy is to ascertain that the cat is indeed hyperthyroid. This is straightforward diagnosis in cats with elevated total T4, elevated free T4, or both. The diagnosis becomes less straightforward when the total T4 is in the reference range, but is readily made by demonstrating substantial increases in the free T4. The diagnosis is problematic when the total T4 is in the reference range and the free T4 is just mildly elevated; this is of particular concern when the cat has minimal signs of hyperthyroidism, or when the abnormalities were discovered incidentally (e.g., during routine screening). In the latter situation, it is not necessarily the diagnosis, but the recommendation for I-131 therapy that must be carefully considered. In these circumstances, thyroid re-evaluation every several months is a reasonable recommendation, although it is likely that I-131 will be needed at some future time.
The typical changes in the complete blood count, biochemistry panel, and hormone profile of hyperthyroid cats have been well described. However, the laboratory assessment can become complicated when less common laboratory changes are detected. When atypical laboratory changes are detected, I consider whether the abnormality reflects a second disease process or is simply an unusual manifestation of hyperthyroidism, and also whether the abnormality, regardless of the cause, will impact I-131 therapy and post-treatment management. Some of the atypical laboratory changes that can cause concern are elevations in serum total bilirubin, calcium, sodium, and abnormalities of phosphorus. Elevations in bilirubin are almost always slight (<2.0 mg/dl) when due to hyperthyroidism, although I have seen a few cats with more substantial elevations. These changes should resolve once euthyroidism is achieved and persistent bilirubin elevation after I-131 therapy is an indication for further diagnostics. A mild serum sodium elevation is detected in many hyperthyroid cats and a modest elevation (~165 mEq/L) is seen in a few cats.
The hypernatremia could have any number of causes including interference with antidiuretic hormone action by T4, mild dehydration, hypermetabolism, or renal insufficiency. This degree of hypernatremia has not had any clinical impact on the success of subsequent I-131 therapy. Similarly, the modest hypercalcemia or hyperphosphatemia that is occasionally detected usually resolve with definitive therapy for hyperthyroidism. The most marked elevations in creatine kinase (CK), alkaline phosphatase, and phosphorous tend to occur in cats with severe hyperthyroidism, although this is not a consistent finding; these findings are also expected to resolve when euthyroidism is restored. Non-specific leukocytosis, neutrophilia, lymphocytosis, and, occasionally, eosinophilia are common in hyperthyroidism. These causes of these changes are uncertain and are usually clinically silent.
Assessment of renal function. Subclinical renal dysfunction can be difficult to assess in hyperthyroid cats. Physical examination and imaging (radiographs or ultrasound examination) may provide hints about whether renal disease is present but functional assessment of the kidneys can be challenging. Providing the cat can tolerate the drug, a methimazole trial is recommended for every cat that may have I-131 therapy. Renal function is assessed at the beginning of the trial and again when euthyroidism is achieved. The renal status at the end of the methimazole is taken to be roughly the level of renal function after I-131 therapy. Unfortunately, in rare cases, renal function after I-131 treatment is worse than that predicted by the methimazole trial. One reason for this is that the methimazole trial does not directly mimic the effects of I-131. In particular, methimazole, which gradually lowers T4 concentrations, may not reproduce the acute hypothyroidism caused by the relatively rapid destruction of thyroid tissue by I-131.
Assessment of cardiac function. Assessment of cardiac status is essential to avoid acute complications as a result of I-131 therapy. Hyperthyroid cats with unstable cardiac disease are not suitable candidates for treatment with I-131. Potential complications from untreated cardiac disease, including cardiac failure, arrhythmia, and sudden death, represent an unacceptable risk for I131 therapy in most situations. Routine examination and thoracic radiographs are sufficient in the most cases to make a reasonable assessment of cardiac status. Further evaluation (a cardiology referral is suggested) is indicated if there are physical signs of severe cardiac disease, radiographic indicators of cardiac failure, or an arrhythmia is detected.
In conclusion, I-131 is a safe, effective, and practical therapy for hyperthyroidism but the overall effectiveness of this treatment modality is greatly influenced by patient selection. The effectiveness of I-131 makes it the most useful therapy for hyperthyroidism and there are few contraindications for its use in most cats.