Feline Hyperthyroidism is a common disease seen in feline patients. Every technician should understand pathophysiology of the thyroid gland including how the gland affects the body in a normal and abnormal state. As well as diagnostic and treatment options which will help the technician become a better patient advocate and help educate clients on those options.
Physiology of the Thyroid Gland
The thyroid gland helps regulate many different parts of the body. It is one of many glands in the body that makes up the endocrine system. The thyroid gland is located below the larynx on each side of the trachea and is one of the largest endocrine glands in the body. (1) Secretion of the hormones thyroxine (T4) and triiodothyronine (T3) is the primary function of the thyroid gland. These hormones control the rate of metabolism within the body. When the body secretes too much of the thyroid hormones it is termed “hyperthyroidism” and when the body does not secrete enough of the thyroid hormones it is termed “hypothyroidism”. When the thyroid gland needs to secrete more of the thyroid hormones, the anterior pituitary gland will release thyroid-releasing hormone (TSH). TSH will be secreted to the thyroid gland and in return the thyroid gland releases the hormones. Both T4 and T3 are as equally as important within the body even though T4 is secreted at a much higher rate than T3. T3 is four times more potent and but lasts a shorter amount of time than T4.
Iodine is needed to complete the formation of T4. Only a small amount is needed in the weekly diet. In humans, this was the reason why iodine was added to table salt. (1) When iodides are ingested, they are secreted from the gastrointestinal tract into the blood and then thyroid gland will then transform it into an oxidized state and use them to complete the formation of T4. Once the hormone is released it binds with plasma proteins that are synthesized by the liver. The hormones are then introduced to the tissues of the body slowly. T4 is introduced every 6 days and T3 every day. Once they are introduced to tissue, they will bind again with intracellular proteins.
Calcitonin is the third hormone that is secreted from the thyroid gland. (1) Calcitonin, Vitamin D and the parathyroid hormone (PTH) are all closely intertwined to help control the formation and regulation of calcium and phosphate metabolism as well as bone and teeth formation. Calcium specifically plays a role in this activity by decreasing plasma calcium concentrations and has opposing effects of PTH. (For the purposes of this lecture, specific effects of the PTH will not be discussed.) Increased calcium in the extracellular fluid is the primary stimulus for secretion of calcitonin. It only takes a 10% increase of calcium to cause secretion of calcitonin. (1) The immediate effect of calcitonin is to change the amount of absorbed and deposited calcium, especially in the young animal. The long term effects of calcitonin is to decrease the amount of new osteoclasts being formed.
Increasing metabolic rate in almost every tissue of the body
Increases the amount and activity of the mitochondria that will cause an increase the rate of formation of adenosine triphosphate (ATP). So in return the body uses more energy
Effects the Na-K-ATPase which will increase transportation of sodium and potassium ions through cell membranes of tissue in the body. This causes more energy to be used and will increase the core body temperature.
Growth- promotes growth and development of the brain during fetal life and for the first few years after birth. Growth and maturation can be decreased in the event of not enough of the hormones and vice versa if there is too much of the hormones present.
Carbohydrate metabolism- stimulation of most aspects of carbohydrate metabolism is effected by thyroid hormone secretion. Rapid glucose uptake of the cells, glycolysis, gluconeogenesis, rate of absorption of the gastrointestinal tract and insulin secretion are all effected by the rate of carbohydrate metabolism in which the thyroid hormones play a role in.
Fat metabolism- they thyroid gland can alter almost every step of fat metabolism. The lipids will be mobilized rapidly from the fat tissue which will decrease the amount of fat stores in the body and this will affect the free fatty acid concentration in the plasma and cause oxidation of free fatty acids to increase with an increase in thyroid hormone secretion.
Concentrations of cholesterol, phospholipids and triglycerides will be affected with increased amounts of thyroid hormones. And they will be increased with lesser amounts of thyroid hormones in the body.
Increased blood flow and cardiac output- because the metabolic rate is increased in the body this will cause the oxygen consumption to increase as well. This will cause vasodilation causing an increase in blood flow peripherally. Vasodilation will occur in the skin to aid in normalization of the increased body temperature. To compensate for the increased blood flow, the body will increase the cardiac output.
Increased heart rate- The increased heart rate is not only due to the body trying to meet the needs of increased oxygen consumption and cooling the body. The rate at which the heart is beating is increased more than to be expected. It is believed that the increased secretion of thyroid hormone has a direct effect on the excitability of the heart. (1)
Increased heart strength- Enzymatic activity of the increased flow of thyroid hormone will increase the strength of the heart even if the hormone secretion is only slightly increased. With excessive amounts of hormone in the body the heart will become weak due to long term increased production of protein catabolism.
Respiratory system- The respiratory system is effected due to the increase rate of oxygen consumption and formation of carbon dioxide. The rate and depth of respiration will be increased with hyperthyroidism.
Gastrointestinal system- GI motility and rate of secretion of digestive enzymes will be increased to help aid the body in the increased metabolism.
Central Nervous System- altered amounts of thyroid hormone will affect the patient’s ability to think. Hyperthyroidism will cause the patient to be nervous, fidgety or find it hard to sit still. Hypothyroidism will cause the patient to become dull or even lethargic.
Muscles- a slight increase in hormone secretion the muscles of the body with react with increased reaction time. When the hormone secretion is excessive they will react slowly because the body is in a continuous state of protein catabolism. If decreased, the body will be sluggish to react.
Feline Hyperthyroidism is the most common endocrinopathy in feline patients over the age of 8 years old. (2) It is a multi-systemic disease resulting in increased production and secretion of the thyroid hormone, T4 and T3 within the body. Typically lateral or bilateral small thyroid masses are palpable on physical examination. The mass causing the disease typically contains an adenoma or adenomatous hyperplasia cells. It is less common for the enlarged lobe to be caused by thyroid carcinoma. (2) There is not a sex related predisposition to the disease. It has been reported that Siamese and Himalayans are at a decreased risk for development of Hyperthyroidism. And domestic long and short hair breed are most commonly affected. (2)
Clinical Signs include the following;
Hair coat changes
Clinical signs can be variable and consist of the non-traditional findings listed above if the disease has progressed. The clinical signs of a progressed state could include anorexia, emaciation and severe dehydration.
Upon physical exam, it is important to do a thorough thyroid palpation. Not every patient with hyperthyroidism will have a palpable thyroid in the author’s experience. In the author’s opinion, a positive enlarged thyroid lobe and a matching history for hyperthyroidism is a positive start to diagnosis of the disease. Techniques for a proper thyroid palpation will be discussed during the lecture hour. Other physical exam findings can include; poor body condition, dull hair coat, dehydration, tachycardia and hyperactivity. In her experience, the author has noted that commonly the hyperthyroid cat will be aggressive, fidgety or vocalizing during examination.
Common abnormalities on a biochemistry panel include increased alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, BUN, creatinine and hyperphosphatemia. On urinalysis the urine specific gravity is typically greater than 1.035. (2)
Diagnosis of hyperthyroidism can be made on positive palpation of an enlarged node, matching history, clinical signs and documentation of an elevated total T4 on blood work. A total T4 should be ran on serum and can be sent to ay commercial laboratory for evaluation. In cases that the Total T4 levels are not conclusive other testing should be pursued to determine a definitive diagnosis.
A T3 Suppression test can be performed if the serum total T4 is indecisive. This test evaluates the responsiveness of TSH that is secreted by the pituitary gland and if the synthetic T3 that was given suppresses its secretion. When the synthetic T3 is administered it should suppress pituitary TSH secretion. This would then cause a decrease in the serum T4 concentration in a normal cat. But if the patient has hyperthyroidism it will still have secretion of the thyroid hormone that has is not related to the pituitary gland. So the administration of synthetic T3 will have no effect on the hyperthyroid patient. To perform the test, collect a baseline serum total T4 and T3, the owner will administer 25 mg of sodium liothyronine three times a day for 2 days starting the next morning. The morning of day 3 the last dose of sodium liothyronine will be administered and a final serum T4 and T3 will be collected 2-4 hours after administration of the last dose.
Lastly a radioactive thyroid scan can be done to diagnose an enlarged thyroid lobe and the presence or absence of metastatic cancer. At the author’s facility, the scan is performed by injecting 2 millicuries (mCi) of technetium intravenously. After waiting 20 minutes for the technetium to take effect, ventral, left and right lateral images of the thyroid and thoracic regions are acquired. A radiologist will read the scans and determine if I131 is an appropriate treatment for the patient.
Treatment options for feline hyperthyroidism include; drug therapy, thyroidectomy and radioactive iodine therapy. The mode of treatment will ultimately be determined by several different factors including; the age and health status of the patient, owner wishes, renal function, cardiac function, the presence or lack of hyperplasia, adenoma or carcinoma, the allowance of the patient to receive oral medications, the availability of I131 treatment and the availability of a surgeon to perform a thyroidectomy.
Initially the patient should be treated with antithyroid drugs to help control the side effects of excessive amounts of the hormone in the body. If surgery was chosen it will help reverse the effects on the body and make that patient a better anesthetic candidate. Oral therapy will also help reverse any cardiac or renal hyperthyroid induced derangements. Renal function abnormalities can be masked in the face of hyperthyroidism so when treated with antithyroid drugs any renal abnormalities will be uncovered and will help aid in final treatment options for the patient.
Antithyroid oral drugs include methimazole, propylthiouracil and carbimazole. Methimazole is the drug of choice for daily oral hyperthyroidism treatment in the feline patient. It can be given orally or placed topically on the pinna of the ear. Typical starting doses of methimazole is 1.25 to 2.5 mg/cat every 12 hours. (3) Methimazole does not block the release of thyroid hormone it blocks the oxidation of iodine once the hormone is released. It typically takes 2 to 4 weeks before T4 concentrations normalize after beginning treatment. Side effects of methimazole include; neutropenia, thrombocytopenia scabbing lesions on the pinna of the ear, hepatotoxicity, anorexia, vomiting, lethargy, renal decompensation and rarely Myasthenia Gravis. Monitoring the CBC, biochemistry panel and serum T4 levels should be done at weeks 2, 4 and 6 initially. (3) If owners choose to give the transdermal methimazole, it is important to educate them on proper administration and the importance of wearing gloves to not allow the medication to absorb into their skin and alter their thyroid levels.
Advantages of I-131 for the treatment of feline hyperthyroidism includes the following: eliminates the difficulty of administering twice a day medication, eliminates the possibility of reactions to anti-thyroid drugs and eliminates the risk of anesthesia during the thyroidectomy. Disadvantages of I-131 treatment includes; the availability of I-131 is limited, it requires knowledge and safety precautions of the radiation therapy, the patient must be hospitalized for a specific period of time to allow the I-131 to be eliminated from the body (the typical hospitalization time is 7 to 10 days), the patient has to be isolated for that period of time without owner visitations, cost, and the patient may not respond properly to a single treatment.
Patient selection for I-131 treatment is very important, the patient must be able to be isolated and unmedicated during the entire duration of hospitalization. If the patient has concurrent medical diseases such as cardiovascular, renal, gastrointestinal, other endocrine or neurological diseases they may be excluded from this particular treatment plan. Pre-radioactive iodine treatment work up should include the following; CBC, biochemistry panel, urinalysis, serum T4, thoracic radiographs, echocardiogram and have been off of methimazole for 7 days. If all requirements are met at that time the patient can have I-131 treatment.
Safety precautions should be followed during hospitalization. They would include the patient being confined to an isolated area of the hospital particularly a nuclear medicine isolation ward, trained personnel should only touch the patient, this team of people should be properly trained on radiation safety and know the proper PPE. Long laboratory coats, disposable plastic gloves and dosimeter monitors are the proper PPE for radiation patients. Every day the radiation level should be monitored and recorded in the patient’s chart to ensure the level of radiation is decreasing. In the author’s facility, daily readings are performed by trained personnel until a measurement of 2.5 millirem per hour (mr/h) is obtained. Upon discharge owners should keep the cat strictly indoors, limit the amount of contact time with the cat and dispose of the cat waste properly. Children and pregnant women should not come into contact with the patient for two weeks after discharge. Typically I-131 will restore euthyroid in a single dose. The hormone concentrations are normal within two weeks of therapy and typically the patient starts to feel better within days after treatment. However, there are approximately 5% of cats who do not respond appropriately to a single dose and must have a second dose of I-131 to become euthyroid. (3, 4)
Patients that are good surgical candidates are considered a low anesthetic risk, the availability of I-131 is low and the availability of funding is low. (4) Advantages of a thyroidectomy is it is 90% efficacious and/or curative. The disadvantages of a thyroidectomy include; high initial expense, the risk of hypoparathyroidism, it is nonreversible and the anesthetic risk of the patient. Post operatively patients should be monitored for 7 days for clinical signs of hypocalcemia. Other post-operative complications include; Horner’s syndrome, laryngeal paralysis, damage to the laryngeal nerve and permanent hypothyroidism. (4)
Iodine restricted diets are available for hyperthyroid patients. If the patient is put on this diet, it must be fed this diet exclusively, physical exams and rechecking blood work must be done every 6 months for the rest of the patient’s life and they must be taken off antithyroid drugs over a course of 2 weeks while the patient is introduced to
the iodine-restricted food. (4) Only cats that are diagnosed with hyperthyroidism can eat the iodine restricted diet.
Euthyroid Sick Syndrome
Euthyroid Sick Syndrome is diagnosed in a patient with a nonthyroidal systemic illness with concurrent decreased serum thyroid level. (5) Severe nonthyroidal illness will decrease serum thyroid levels to the low or undetectable range even in patients without concurrent hyperthyroidism. With concurrent systemic illness, patients with serum thyroid levels in the normal to high range should be suspected to have hyperthyroidism. A second serum thyroid level should be checked approximately 1-2 weeks later. (6) If total T4 levels are still suspicious but inconclusive other diagnostic methods for diagnosis of Hyperthyroidism should be pursued.
References: Guyton and Hall Textbook of Medical Physiology, 12th Edition, Hall, Saunders Elsevier, Philadelphia, PA, 2011.
Small Animal Internal Medicine, 3rd Edition, Nelson and Couto, Mosby, St. Louis, Missouri, 2003.
Kirk’s Current Veterinary Therapy XIV, Bonagura and Twedt, Saunders Elsevier, St. Louis, Missouri, 2009.
Small Animal Internal Medicine for Veterinary Technicians and Nurses, Merrill, Wiley-Blackwell, Ames, Iowa, 2012.
The Merck Manual, 19th Edition, Porter, et al., Merck Sharp & Dohme Corp., Whitehouse Station, New Jersey, 2012.
Consultations in Feline Internal Medicine, 5th Edition, August, Saunders Elsevier, St. Louis, Missouri, 2006.