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Hyperthyroidism

duddyBy Jean Duddy, DVM
www.angell.org/internalmedicine
internalmedicine@angell.org
617-541-5186

Hyperthyroidism is the most common endocrinopathy seen in our older cat population today.  It was first described in 1913 for humans and not until 1979 in cats.  The cats we see today are vastly different from the ‘bag of bones’ cats originally seen in the early 80’s with hyperthyroidism.  Their signs were severe as the disease progressed much further by the time of diagnosis.  With feline senior screening programs and better recognition of the signs, this disease is now suspected sooner and diagnosed earlier.

Signs: (not all cats will have signs and many are vague)

  • Weight loss despite a good or increased appetite (polyphagia)
  • Hyperactivity
  • Panting/dyspnea
  • Unkempt Hair Coat
  • Polyuria/Polydipsia
  • Vomiting
  • Diarrhea
  • Aggression

Physical exam (PE) for these patients can be a challenge as they are often constantly in motion andmay become aggressive at times, but are often fragile with restraint, so caution is needed.

Figure 1

Figure 1

PE findings- some have no changes  (Figure 1)

  • Thin / poor body condition
  • Thyroid nodule
  • Cardiac changes (tachycardia, murmur, arrhythmias )
  • Unkempt Hair Coat or matted hair coat
  • Alopecia
  • Increased nail growth
  • Ventral neck flexion

10% of cats will present with weakness, lethargy and anorexia.  This form of hyperthyroidism has been called “Apathetic Hyperthyroidism”.  These catsmay have a history of polyphagia and now have more advanced disease with concurrent illness such as severe cardiac changes (congestive heart failure).

The etiology of feline hyperthyroidism has not been clearly identified, but the pathological findings associated with this disease have been well documented. Most thyroid nodules (95+%) are benign, functional thyroid adenomatous hyperplasia (or adenoma).  Many contain multifocal nodules ranging from 1mm to 3cm dispersed throughout the gland.  Approximately 70% are bilateral which becomes important if surgery is considered for treatment of the condition.Carcinomas do occur but are much less frequent (<5%).

Recent findings have shown that some hyperthyroid cats have areas of adenomas next to an area of carcinoma within the same thyroid lobe biopsy.  This finding has led to the suggestion that some cats with thyroid hyperplasia or thyroid adenoma may, over time, transform into thyroid carcinoma.  Cats with benign adenomatous hyperplasia, even those well controlled with methimazole, may also transform to carcinomas.  As much as 10% of benign adenomas may transform to carcinoma by 2 years and 20% after 4 years of medical management.  This should be taken into consideration along with the patient’s age and other concurrent diseases when decisions are made about therapy to control the signs and symptoms versus surgery or radioiodine treatment to eliminate the tumor burden.

Adenomatous thyroid tissues produce excessive amounts of thyroid hormones, thyroxine (T4) and tri-iodothyronine (T3).  These increased levels of thyroid hormones cause the metabolic rate to increase and cause the signs and physical findings of hyperthyroidism.

Since many of the signs and physical exam findings are vague, laboratory testing is needed to make the diagnosis of hyperthyroidism.  Most hyperthyroid cats are diagnosed using a T4 level, but because this is a disease of our elderly cat population, a general biochemical profile, CBC, and urinalysis are also recommended for evaluation.  These are the tests most commonly included in geriatric screening panels.

  • CBC – often normal but may show increased hematocrit (40-50%) or a stress leukogram
  • Profile – increases in ALT and ALP are common (75%) while hyperphosphatemia is seen in about 20% as well as reduced ionized calcium. Stress hyperglycemia and azotemia (pre-renal or concurrent renal disease) are common findings.
  • Urinalysis – often normal, but helps rule out diabetes, urinary tract infections, or proteinuria.
Figure 2: Bilateral Thyroid Scan

Figure 2: Bilateral Thyroid Scan

Additional testing may be warranted for full evaluation of our patients or those suspected to be hyperthyroid when the initial test, Total T4 (T4)is inconclusive.

  • Blood pressure – required to rule out hypertension. Left untreated, hypertension can lead to renal damage or even blindness.
  • Radiographs – thoracic views evaluate cardiomegaly (which often needs nothing more than control of the hyperthyroidism), but in advanced cases pleural effusion or pulmonary edema may be present. Both thoracic and abdominal views can be used to evaluate for concurrent diseases.
  • Free T4 – a non protein bound form of thyroxine measured by direct equilibrium dialysis. While free T4 (98.5%) is more sensitive than the Total T4 (91.3%) at detecting positives, it is not as specific so there are false positives with the test. Therefore Free T4 is not considered a test for general screening.
  • Thyroid Scintigraphy – using technetium-99-m, the thyroid glands can be evaluated. The scan can be used to confirm the diagnosis of hyperthyroidism, prior to surgery to determine if the adenomatous tissue is unilateral or bilateral, or to see if there is any  ectopic tissue.  It can also be helpful, but not diagnostic, in determining if a carcinoma is present. Scintigraphy is also used in dose calculations for radioactive iodine treatments.  (See Figures 2  and 3)
Figure 3: Computer images form during thyroid scintigraphy

Figure 3: Computer images form during thyroid scintigraphy

For cats that have signs and physical exam findings consistent with hyperthyroidism, but the T4 is normal, diagnostic options include:

  • Repeating the T4 at a later time (usually 2-8 weeks).
  • Free T4
  • Thyroid Scintigraphy

Once the diagnosis of hyperthyroidism is made, there are many options for treatment.

Treatment:

The historical goal of therapy has been to establish euthyroidism.  This can be accomplished with medication, diet, surgery, or radioactive iodine.  With the knowledge that some cats could transform from benign to malignant carcinoma with time, our new goal of treatment may be to eliminate the tumor burden.

Antithyroidal Drugs (Methimazole and Carbimazole)

Antithyroidal drugs may be used for short term evaluation of the renal status of our patients prior to a more permanent treatment or for long term management of the disease.

  • Methimazole (Tapazole®, Felimazole®) – is likely the most common treatment option. This drug inhibits the synthesis of thyroid hormone.  Methimazole is available in tablet form, flavored liquids as well as in treat forms.  For those clients that cannot give oral medication, methimazole can be made into a transdermal gel that can be placed in the pinna.

Today’s cats are often diagnosed with less severe signs, often through routine geriatric screening.  Most cats are well controlled with the starting dose of 2.5mg twice a day.  Laboratory monitoring is done approximately every two weeks for the first couple of months of treatment.  The daily dose is adjusted to the lowest possible amount to keep the T4 concentration within normal limits.

Reactions to methimazole are more common in the first 3 months and are often GI related (vomiting, anorexia).  These side effects are less likely if the dose is started low (once daily) then increased.  Some cats will develop facial or neck excoriations from intense pruritis.  This does not seem to be dose related and may take a few weeks to clear after stopping the medication.  Laboratory monitoring is also needed as changes in the CBC (leukopenia, thrombocytopenia, anemia) or Biochemical profile (elevations in the liver enzymes and total bilirubin) may occur.  Most of these changes are reversible after stopping the methimazole and providing supportive care.

  • Carbimazole (Neomercazole® ) – Not available in the United states at this time. Carbimazole is converted into methimazole in the body and only the methimazole accumulates in the thyroid gland.  A 5mg dose of carbimazole is equivalent to 3mg of methimazole.  There is also a long acting carbimazole available in Europe (Vidalta ®).

Restricted Iodine Diet – (Hills y/d®)

The overproduction of thyroid hormone is the definition of hyperthyroidism.  Thyroid hormone production requires uptake of sufficient dietary iodine.  Feeding a diet with limited iodine (levels must be at or below 0.32ppm) can cause a reduction of thyroid hormones into the normal range in 8-12 weeks.  The limited iodine diet must be the sole diet fed to the cat for it to be effective.  Hyperthyroid cats with IRIS stage 1 [defined by the International Renal Interest Society as Creatinine below 1.6], managed with y/d diet, have not shown any progression of their renal disease.  Hypothyroidism has not been reported with dietary management alone.

Figure 4: Cat being treated with radioactive iodine

Figure 4: Cat being treated with radioactive iodine

Permanent Therapies:  Should be done after stabilized and evaluated with a methimazole trial whenever possible.

  • Surgical Thyroidectomy – While surgery is an effective treatment for hyperthyroidism, it is the most invasive. Since more than 70% of the cats have bilateral involvement or ectopic tissue, removing one thyroid lobe leaves a significant chance that the patient will remain hyperthyroid.  Thyroid scintigraphy may help determine if this is an option. Surgical complications can include hemorrhage, Horner’s Syndrome or laryngeal paralysis (voice change) and is highly dependent on the surgeon’s experience.  Bilateral thyroidectomies come with the additional post-operative complication of hypocalcaemia from manipulation of the parathyroid glands during surgery.  Hypocalcemia is most common within 5 days post op and is usually transient, but must be monitored and managed closely as it can become life threatening.  Thyroidectomies are common in very large thyroid nodules suspected to be carcinomas.
  • Radioactive Iodinehas long been stated as the “Gold Standard” of treatments because it is safe and effective.

Iodine is stored in the colloid of the gland while it is being made into thyroid hormone.  Elevated thyroid hormone concentrations suppress iodine uptake by normal thyroid. When given radioactive iodine (131I), the body cannot tell the difference and it too is stored in the colloid.

Radioactive iodine is a beta and gamma emitter and is selectively taken up by hyperfunctioning tissue.  β particles destroy functional thyroid tissue  (where ever it is in the body) but travel a maximum of 2mm so they cause only local destruction within the thyroid gland.  The radioactive iodine destroys this functional tissue without damaging surrounding tissues such as the parathyroid glands.  The normal thyroid tissue is relatively “protected” from the effects of radioiodine.

Side effects of radioactive iodine may include a ‘sore throat’ if the cat has a very large thyroid nodule.  Due to the isolation required after treatment, stress to the patient must also be taken into consideration.  Hypertension, severe tachycardia or other concurrent diseases should be dealt with so the cat is as stable as possible prior to treatment.

Patient selection for radioactive iodine:

The level of nursing care available in the radioiodine ward is limited by our need to reduce human exposure to radiation. Therefore, the ideal patient is stable enough to tolerate isolation with only brief periods of basic nursing care 2-3 times daily. Patients who are anorectic, or have significant hepatic, renal, cardiovascular, gastrointestinal, endocrine, or neurologic dysfunction are considered on a case by case basis.

  • Patients must be off methimazole or other anti-thyroid medication (propylthiouracil) for at least 5-7 days prior to admission.  Removing a patient from methimazole should be done carefully and heart rate should be monitored for possible tachycardia.
  • Some medications or procedures (iodinated contrast studies) can interfere with iodine uptake and decrease success of the treatment.
  • Compensated renal failure may be exacerbated by achieving a euthyroid state due to a reduction in hyperdynamic circulation and thus a reduction in glomerular filtration rate. This could occur as the result of I-131 treatment, surgery, or antithyroid medication, but only the latter therapy is reversible. A trial of methimazole for a few months may help predict those patients who will decompensate. If you have concerns about the renal function of your patient, please discuss this with us prior to the therapy date.

Isolation restrictions post treatment:

Cats released from the I-131 isolation before all restrictions are over are still excreting radioiodine in the urine and feces.  Hospitalization time varies based on which restrictions the owners are comfortable with observing at home.

There are two basic types of restrictions; litter restrictions and contact restrictions.

  • Litter Restrictions require use of flushable litter at home for two weeks.
  • Contact Restrictions require owner to have minimal contact with their cat, to keep the cat inside, and restrict contact with children, pregnant women, and other pets.

Details are given to each owner prior to treatment but cats may remain at the hospital throughout the entire restriction period if an owner chooses.

  • Early Release: is 3 days post treatment.   All cats must be monitored with a Geiger counter and comply with state release regulations prior to their discharge.  (<5mR/hr at 12 inches).
  • To Go Home with No Litter Restrictions: Some clients will want to keep their cats hospitalized until their urine/litter no longer needs to be flushed i.e. when the cat is <1mR/hr at 6 inches.  Minimal contact restrictions still continue until 17 days post treatment.
  • To Go Home with No Restrictions: No restrictions are required 17 days post treatment.

To evaluate the success of the treatment, a T4 concentration and renal panel are recommended 1 and 3 months post treatment.

Figure 5: “Jack” post radioactive iodine treatment

Figure 5: “Jack” post radioactive iodine treatment

The success rate of I-131 is approximately 96%. A few patients may require additional I-131 therapy if they do not return to normal function within 3-6 months. A small number of cats will live long enough to become hyperthyroid years later.

A small percentage of cats will become hypothyroid and this may be a transient phenomenon. In rare cases such cats may require daily supplementation with thyroid hormone.

For more information, please contact Angell’s Internal Medicine service at 617-541-5186 or internalmedicine@angell.org.

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