Individualized radioiodine (I-131) therapy for your hyperthyroid cat
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. This makes this therapy highly desirable. The main disadvantage of I-131 is the precautions associated with radioactivity needed after treatment. Thyroid carcinoma (cancer) occurs in <1% of the newly diagnosed cases. However, approximately 20% of cats that have had hyperthyroidism for >4 years will develop suspected thyroid carcinoma. We suspect that this is because of a transformation from benign to malignant over time.
Diagnosis of hyperthyroidism:
Hyperthyroidism is typically not difficult to diagnose. Generally, a high blood T4 (thyroid hormone) in the presence of symptoms of hyperthyroidism (e.g. history of weight loss in the face of a good appetite, vomiting, unkempt haircoat, increased activity, among others) is sufficient to confidently diagnose hyperthyroidism.
Hyperthyroidism is typically not difficult to diagnose. Generally, a high blood T4 (thyroid hormone) in the presence of symptoms of hyperthyroidism (e.g. history of weight loss in the face of a good appetite, vomiting, unkempt haircoat, increased activity, among others) is sufficient to confidently diagnose hyperthyroidism.However, 6-12% of cats with non-thyroidal illnesses will have a high free-T4 (false-positive result). Treating these false-positive cats with I-131 would be a mistake and likely cause them to become hypothyroid after treatment.
Thyroid scintigraphy is considered the gold standard test to confirm hyperthyroidism. In this test, a short-acting radionuclide that accumulates in the thyroid tissue is administered. A special machine (gamma camera – see below) is used to visualize where radionuclide has accumulated. This procedure uses thyroid physiology to create an image, which is why it is so sensitive in detecting what is actually happening to the thyroid tissue. Unfortunately, because of the cost of the machine, special training, and licensing, most radioiodine treatment facilities elect not to offer thyroid imaging for their hyperthyroid patients. Nonetheless, the use of thyroid scintigraphy is very important in cases of mild hyperthyroidism to confirm the diagnosis. It is also an important tool in the individualized I-131 dose determination protocol, as well as in cases of thyroid carcinomas, which require a much higher I-131 dose (up to 10 times the dose of a benign hyperthyroidism case).
Individualized I-131 dose determination:
Each patient receives an individualized I-131 dose according to the characteristics of his or her hyperthyroidism. This method takes into consideration a number of patient-specific variables, including the degree of hyperthyroidism, the size of the thyroid tumor, and several specific physiologic parameters such as the biologic half-life and iodine uptake. The dose is calculated based on:
The fixed-dose approach, on the other hand, assumes that most hyperthyroid cats can be treated with a fixed dose no matter how large their thyroid tumor is, for instance. However, to attain, a moderate success rate, a large number of cats are either over or under-dosed with I-131.
This newer individualized dosing technique has shown to decrease the likelihood of hypothyroidism post-I-131 to approximately 21.2% (vs. up to 79% with fixed-dose of 3-5 mCi of I-131) where only 4.1% (vs. 18% with fixed-dose I-131) of cats have overt hypothyroidism while 17.1% (vs. 46% with fixed-dose I-131) have subclinical hypothyroidism.
Below are some examples of thyroid scintigraphy studies. It is intuitive to imagine that the more hyperactive tissue is affected, the more I-131 is required to effectively treat the patient. Unfortunately, there are many factors that play a role in feline hyperthyroidism, which include the variability of T4 secretion (T4 secretion can vary significantly throughout the day), the intensity of secretion of thyroid tissue, size of thyroid tumor, thyroid tumor’s ability to retain I-131, among others. Thus, the difficulty in finding one size fits all dosing scheme. Therefore, several parameters are now used to determine the ideal dose for each patient. The final dose is the average of the calculated dose for each parameter. This has significantly improved the success rate, especially in lowering the prevalence of hypothyroidism post-I-131 treatment.
*SHIM-RAD (severe elevations to T4, huge tumor size, intrathoracic nodules, multifocal disease, and refractory to treatment with antithyroid drugs)
Hypothyroidism post-treatment and chronic kidney disease:
Hypothyroidism is a possible consequence of I-131 therapy. Until the recent past, this was largely ignored. Previously, hypothyroidism was only treated if it was associated with clinical signs like excessive weight gain, lethargy, and skin problems. More recently, it was discovered that cats with chronic kidney disease and hypothyroidism post-I-131 had a shorter survival when compared to cats with chronic kidney disease that had a normal thyroid function. This has led to increased concern about making cats hypothyroid post-treatment.
Fixed I-131 dose is associated with the development of hypothyroidism in as much as almost 70% of cats where 18% have overt hypothyroidism and 48% with subclinical hypothyroidism. Fortunately, the individualized dosing technique has decreased the chances of post-I-131 hypothyroidism to approximately 20% where only 3.1% of cats have overt hypothyroidism while 16.9% have subclinical hypothyroidism. Decreasing the chances of hypothyroidism post-treatment is especially important in case there is underlying chronic kidney disease.
There is a suspicion that chronic kidney disease may lower I-131 excretion. Therefore, it may be prudent to consider lowering the I-131 dose by 5% in cats with USG <1.035 or azotemia.
Subclinical hypothyroidism has been defined as a T4, 1.0–2.5 μg/dL; TSH >0.30 ng/mL. According to Dr. Mark Peterson's unpublished observations, approximately 50% of these cats will regain normal thyroid function after 1 year. The decision to supplement with levothyroxine is based on whether there is azotemia, the magnitude of the TSH increase, and the T4.
Detectable TSH at the time of diagnosis has also been linked with increased odds of the development of hypothyroidism. Bilateral hyperthyroidism also increases the odds of the development of hypothyroidism post-I-131 treatment.
Differentiating between benign or malignant thyroid tumors:
Thyroid scintigraphy has been recommended as the gold standard test for the diagnosis of hyperthyroidism. 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.
Thyroid imaging is the best way to assess tumor functionality and determine the size of the thyroid which will help plan the treatment. This is especially important because conventional doses of I-131 treatment are not effective for thyroid carcinomas. Thyroid carcinomas can be treated via I-131, but much higher doses and longer hospitalization are required.
Hyperthyroidism and chronic kidney disease:
Typically, hyperthyroidism will mask chronic kidney disease because the hyperthyroid state stimulates the heart to beat stronger and faster. This leads to increased blood flow to the kidneys. The increased blood flow will artificially improve kidney function. Unfortunately, the increased blood flow is often times associated with increased pressures, which are detrimental to the kidneys. Therefore, hyperthyroidism should be addressed even in patients with underlying chronic kidney disease because the hyperthyroid state will likely cause chronic kidney disease to progress faster over time.
About 20-25% of all hyperthyroid cats with normal kidney values prior to hyperthyroidism treatment, will have increased kidney values after therapy independently of the therapy method chosen (methimazole, surgical thyroidectomy, or radioactive iodine). This poses a diagnostic dilemma for veterinarians to treat the animal permanently with I-131 or perform a methimazole trial prior to more definitive treatment in cats with concurrent CKD (chronic kidney disease).
In the past, methimazole trials had been recommended routinely 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. In summary, a methimazole trial prior to definitive therapy is not needed in cats without obvious (moderately advanced) chronic kidney disease.
Hyperthyroidism and heart disease:
Other important considerations in a cat with hyperthyroidism include 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 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 I-131 Therapy?
Methimazole (and other anti-thyroid medications) is among the most commonly chosen treatments for hyperthyroidism. It acts by blocking the production of T4 and T3 in the thyroid gland, which improves clinical signs. However, it does not treat the tumor itself. The thyroid tumor will continue to grow and increase its secretion of thyroid hormone. Eventually, most cats will 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 is likely due to the transformation from benign to malignant cancer over time. 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, the treatment of hyperthyroidism with radioiodine (I-131) 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 the 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.
I-131 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 non-invasive (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 I-131.
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.
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.
Prior to I-131 treatment:
We recommend stopping methimazole and Hills Y/D diet prior to I-131 treatment. The number of days to stop methimazole is determined by how severely affected by hyperthyroidism your cat is (typically 4-5 days). Hills Y/D diet should be discontinued 4 weeks prior to treatment. Please, contact 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 normal glands go back to secreting the 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 they will be less affected by I-131 treatment, thus it will be less likely for these cats to become hypothyroid after I-131treatment.
Treatment cost includes:
Consultation with the Internal Medicine Specialist, blood pressure evaluation, CBC, chemistry panel, urinalysis, serum T4, and T3.
Hospitalization with daily visual assessments and measured food intake (2-7 days)
99m TC-pertechnate thyroid scintigraphy (included with thyroid scan)
Calculation of Tc99 thyroid uptake, calculation of hyperactive thyroid volume, 24-hour I-131 uptake
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.
Patient’s care during treatment
After administration of 131 Iodine, your cat is transported to an isolation ward to comply with radiation safety rules. During this time, the owner is not allowed to visit. Dr. Galvao, Dr. Otoni, and the Internal Medicine staff will take care of your cat. Care will consist of daily visual inspection, cleaning the cage, and providing food and water. The patient will be monitored on a regular basis to measure the exposure rate. Usually, cats with benign thyroid adenomas stay an average of 2-7 days in isolation. Cats are allowed to go home when their radiation exposure level is 0.5 mR/hr at 1 foot of the patient.
Patient’s care after release – Owner consent form
Cats are released from the hospital with residual radioactivity that will last several weeks. In addition, your cat will continue to excrete radioactive material in the urine and feces for approximately one month. Co-sleeping is not permitted for 9 weeks. To comply with radiation safety rules, owners are asked to implement radiation safety precautions (see owner consent form) when the cat is back home.
Before release from the hospital, an interview with the owner is conducted by the Internal Medicine staff in order to ensure that the radiation instructions are understood. Instructions are fully explained to the owner and included in the owner's consent form signed before releasing of the patient. Failure or unwillingness to complete the instructions will result in continuing hospitalization of the patient until the exposure rate at the skin surface over the thyroid glands has reached 2 mR/hr at thyroid level (approximately 15 more days). Additional costs will apply.
It is recommended to monitor improvement in clinical signs and recheck serum total T4, TSH, CBC, chemistry panel, and urinalysis at 1, 3, and 6 months after radioiodine administration.
If the patient requires medical care within 1 month following the administration of 131 Iodine the owner should follow the instructions found in the owner's consent form.
VCA Arboretum View Animal Hospital
Internal Medicine, and Nuclear Medicine Department
Telephone: (630) 963-0424
Joao Felipe de Brito Galvao, MV, MS, DACVIM (SAIM)
Cristiane Campos Otoni, MV, DACVIM (SAIM)