Advanced Care

Feline Radioactive Thyroid (I-131) Treatment

Hyperthyroidism is the most common endocrine disease in the cat and affects about 10% of senior and geriatric cats. The majority of hyperthyroid cats (~95%) have benign thyroid adenomatous hyperplasia (or adenoma) involving one or both thyroid lobes at the time of diagnosis. Thyroid carcinoma (cancer) occurs in about 2-5% of the newly diagnosed cases. However, the incidence of thyroid carcinoma in cats treated with methimazole that are referred for I-131 therapy because of refractoriness to higher doses of methimazole, has dramatically increased.

Unfortunately, the excess of thyroid hormones leads to several changes in the body, which include heart disease (hypertrophic cardiomyopathy), systemic hypertension, cardiac arrhythmias, kidney disease, weight loss despite a ravenous appetite (rarely decreased appetite), increases in liver enzymes, unkempt hair coat, as well as gastrointestinal signs (e.g. vomiting and diarrhea). Therefore, it is imperative that treatment be implemented as soon as possible.

Differentiating between benign or malignant thyroid tumors:
Thyroid scintigraphy has been recommended as the gold standard test for the diagnosis of hyperthyroidism. There is some controversy, but it is thought that normal cats undergoing methimazole therapy may appear hyperthyroid on thyroid scintigraphy. Besides the benefit of hyperthyroidism diagnosis, thyroid scintigraphy also provides further information regarding the number of thyroid glands affected, ectopic thyroid tissue, the potential for metastatic thyroid carcinoma (malignant cancer), and evidence of metastasis (spread) carcinoma if present. It is important to know however, that the only definitive way to confirm a diagnosis of thyroid carcinoma is by histopathologic examination.

Even though thyroid scintigraphy is not a sensitive method in diagnosing thyroid carcinoma, it remains a valuable and essential tool in evaluating cats with suspect thyroid carcinoma. Thyroid imaging is the best way to assess tumor functionality and determine the size of the thyroid which will help planning the treatment. This is especially important because conventional doses I-131 treatment is not effective for thyroid carcinomas. Thyroid carcinomas can be treated via I-131, but much higher doses and longer hospitalization are required. 

If your cat is coming to our hospital for I-131 therapy, a scintigraphy will be recommended to confirm diagnosis and evaluate for features of thyroid cancer. 

Hyperthyroidism and chronic kidney disease:
Hyperthyroidism will "artificially" increase the blood flow to the kidneys. When this happens in a hyperthyroid cat with underlying kidney disease, it can mask the chronic kidney disease. Additionally, blood concentration of BUN and creatinine may be normal despite mild to moderate chronic kidney disease. Treating the hyperthyroidism, will normalize (decrease) the blood flow to the kidneys and this can result in apparent worsening of the kidney values in the blood.
About 20-25% of all hyperthyroid cats with normal kidney values prior to hyperthyroidism treatment, will have increased kidney after therapy independently of the therapy method chosen (methimazole, surgical thyroidectomy or radioactive iodine). This poses a diagnostic dilemma for veterinarians as to treat the animal permanently with I-131 or perform a methimazole trial prior to a more definitive treatment in cats with concurrent CKD (chronic kidney disease).
In the past, methimazole trial has been recommended in order to differentiate between cats with pre-existing CKD or not. However, because untreated hyperthyroidism is also known to cause and worsen kidney function, the need for a trial in animals without pre-treatment azotemia is questionable since treatment for hyperthyroidism is advisable regardless of the outcome. This is supported by one study showing that survival time for hyperthyroid cats is not affected by the degree of azotemia post-treatment.
Additionally, most cats that develop post-treatment azotemia, will not be clinically sick since they usually will not progress more than one IRIS stage after treatment. For animals with IRIS stage 3-4 chronic kidney disease prior to treatment, it is generally advised to try medical management prior to I-131 therapy.
In summary, a methimazole trial prior to definitive therapy is not needed in cats without obvious chronic kidney disease.
Hyperthyroidism and heart disease:
Other important considerations in a cat with hyperthyroidism includes addressing possible cardiac abnormalities (systemic hypertension, hypertrophic cardiomyopathy, tachycardia (fast heart rate), and cardiac arrhythmias). The minimal required tests we require to assess for possible heart conditions are blood pressure measurement and chest radiographs. We may recommend an evaluation by a cardiologist depending on these findings. This is especially important before considering I-131 treatment because the treatment requires isolation.  This is aimed at decreasing hospitalization risks. Even though the hypertrophic cardiomyopathy can be secondary to hyperthyroidism, it is important to know the severity of the cardiac disease and assess the risk of cardiac failure during hospitalization.

Methimazole or 131Iodine Therapy?
Methimazole (and other anti-thyroid medications) is among the most common chosen treatments for hyperthyroidism. It acts by blocking production of T4 and T3 in the thyroid, which improves clinical signs. However, it does not treat the tumor itself. Subsequently, the thyroid adenoma continues to grow larger or increases its secretion of thyroid hormone and some cats will eventually become completely resistant to methimazole.
There is increasing evidence that with time and as the disease progresses, benign thyroid adenomas presented in early feline hyperthyroidism transform into malignant thyroid carcinoma in some cats.
It has been shown that the prevalence of thyroid carcinoma is higher than 20% in hyperthyroid cats managed with methimazole longer than 4 years. This also increases the possibility of transformation from benign to malignant cancer. However, anti-thyroid drugs have been shown to be carcinogenic in rodents. Therefore, it is also possible that methimazole may be playing a role in the transformation of adenomas into carcinomas as well (unlikely). Based on this, treatment of hyperthyroidism with radioiodine (131Iodine) may be in the patient's best interest.
Additionally, methimazole can have deleterious side effects that need to be considered. Some cats can develop gastrointestinal signs (vomiting, diarrhea and decreased appetite), facial scratching, bone marrow toxicity [e.g. neutropenia (low white cell count), thrombocytopenia (low platelet count)], liver toxicity (increased liver enzymes), besides unmasking chronic kidney disease. In this case, it is very important to monitor blood work (CBC and chemistry panel), urine specific gravity, total T4 (thyroid hormone) every 3 weeks until thyroid hormone is controlled. Gastrointestinal signs are more common when methimazole is given orally and can be circumvented by the use of topical methimazole. However, the other side effects occur regardless of the route of administration, thus the importance of discontinuing methimazole if these side effects occur. It is important to remember that topical methimazole takes on average 2 weeks longer to achieve thyroid hormone control.
Systemic 131 Iodine Therapy:
Systemic 131 Iodine therapy is a widely accepted treatment modality for cats with hyperthyroidism.  Numerous reports in the veterinary literature advocate the use of radioiodine treatment for cats with thyroid adenoma and carcinoma.  Advantages of systemic iodine therapy over medical or surgical treatment for cats with hyperthyroidism are that this procedure is noninvasive (compared to surgery) and usually only 1 dose is enough to return the animal to a euthyroid state, compared to daily administration of conventional anti-thyroid drugs. It is expected that your cat will return to a euthyroid state (normal) between 1 and 4 months after being treated with 131 Iodine.
I-131 is considered a permanent and effective treatment in more than 95% of cases. A small percentage of cats will require a second treatment or develop hypothyroidism (require thyroid hormone supplementation for life). Therefore, several considerations should be made prior to seeking this therapy. These recommendations are aimed to maximize treatment efficacy and minimize risks.

Prior to I-131 treatment:
1. Documentation of hyperthyroidism and evaluation of your cat's health must be performed prior to 131 Iodine treatment.  These diagnostics may be conducted with your regular veterinarian or at VCA Arboretum View Animal Hospital.  Pre-treatment evaluation consists of (not included in treatment cost estimate):

Blood work (CBC, Chemical profile, T4 concentration)
Blood pressure
Thoracic radiographs

2. Occasionally ECG and echocardiogram might be required.

3. We recommend stopping methimazole prior to I-131 treatment. The number of days to stop metimazole is determined by how severely affected by hyperthyroidism your cat is. Please, consult your veterinarian or us before stopping methimazole. Not stopping methimazole prior to I-131 treatment may increase the likelihood of hypothyroidism post-treatment. Hyperthyroidism leads to atrophy of the normal thyroid glands because these glands respond to normal feedback mechanisms. Once hyperthyroidism is controlled via medical therapy, these glands go back to secreting thyroid hormone. Thus, they will also be affected (destroyed) if I-131 is given to cats that are normothyroid. Otherwise, atrophied glands are protected from I-131 therapy since I-131 has preferential uptake for thyroid secreting glands. Therefore, theoretically these cats are more predisposed to developing hypothyroidism after I-131. Recently, it has been shown that hypothyroidism is particularly detrimental if cats have concurrent chronic kidney disease. Cats with chronic kidney disease and post-treatment hypothyroidism live on average less than cats with chronic kidney disease that are euthyroid (normal thyroid function) post-treatment. The normal thyroid glands in hyperthyroid (uncontrolled hyperthyroidism) cats are atrophied, therefore will be less affected by I-131 treatment, thus it will be less likely for these cats to become hypothyroid after I-131treatment.  

4. Scheduling systemic 131 Iodine therapy and pretreatment evaluation: Due to limited available space and trained personnel, and to limit human exposure, the number of animals treated with systemic 131 Iodine therapy at the VCA Arboretum View Animal Hospital is limited to 4 per week.  Scheduling animals for 131 Iodine treatment should be made through the Internal Medicine Service (630) 963-0424.

5. Investment:
The cost of I-131 treatment does not include pre-treatment diagnostics that your cat may require.  I-131 treatment is estimated between $1850 (without thyroid scan/scintigraphy) or $2550 (including the thyroid scan/scintigraphy).  Treatment cost includes:
Consultation with the Internal Medicine Specialist, blood pressure evaluation and T4. 
Hospitalization with daily visual assessments and measured food intake (4-10 days)
99m TC-pertechnate thyroid scintigraphy (included with thyroid scan)
Sedation procedure and sedation drugs (included with thyroid scan)
Monitoring Equipment used during sedation (included with thyroid scan)
Radiologist interpretation of scintigraphy (included with thyroid scan)
Radioactive Isotope delivery, administration and disposal
131 Iodine treatment will be performed only if pre-treatment evaluation confirms hyperthyroidism and if the animal's health status is compatible with isolation.  Animals will not be treated if they are not considered to be safe candidates for treatment. 131 Iodine treatment will not be recommended if kidney function is not adequate unless the pet does not tolerate medical treatment with methimazole.  

Cristiane Otoni, MV, DACVIM (SAIM)
Joao Felipe de Brito Galvao, MV, MS, DACVIM (SAIM)