Thyroid diseases are common in a variety of species, including humans, and have been well characterized and documented for many decades. In the case of felines, however, thyroid abnormalities have only been recognized since the late 1970's. In the early years, most diagnostics and treatments were borrowed from the research done in human medicine. As the prevalence in cats increases, however, considerations for treatment protocols have become more species specific.
In cats, hyperthyroidism (over-active thyroid hormone production) is far more common than hypothyroidism (under-active thyroid). Peak prevalence of hyperthyroidism in cats is around the age of 12 to 13 years of age (Nichols), but is not uncommon in cats as young as 7 (Hines).
A unique dilemma in feline medicine is the high incidence of concurrent renal disease, which also tends to occur at nearly the same time or soon after hyperthyroidism is diagnosed and/or treated (DiBartola, 2006). This is quite possibly the greatest area of interest at this time, as the connection between the two is slowly becoming less of a mystery. It is still unknown whether a true cause and effect relationship exists between the two, or if they are simply common in the geriatric feline independently. What is known, however, is that treatment decisions for hyperthyroidism do affect existing renal disease when present. As a result, the study of hyperthyroid treatment goes hand in hand with renal function in the feline species.
The purpose of this discussion is to outline the basic function of the thyroid, what hyperthyroidism means to the cat, and what the treatment options and considerations are at this stage of our medical understanding. While renal function must be considered when determining the appropriate treatment protocol, the scope of this paper will only address what is currently known and well understood, without speculating about relationships that are still uncertain.
The normal thyroid glands are located just caudal to the larynx, ventrolaterally adhered to the trachea, and attached to the medial aspect of the sternothyroideus muscles of the neck. The two symmetrical glands are often referred to as a single bi-lobed structure with an isthmus joining the two lobes. Each lobe has two closely associated parathyroid glands. In response to hormonal signals (thyroid stimulating hormone) from the pituitary gland, the thyroid produces the hormones thyroxine (T4) and triiodothyronine (T3), which are required by every cell in the body for metabolic regulation. An additional hormone produced by the thyroid gland, thyrocalcitonin, stimulates calcium uptake by the skeleton, thus reducing free calcium in the blood. Calcium regulation appears to be a minor function of the thyroid gland, however. Calcium homeostasis is primarily regulated by the parathyroid glands (Evans).
The thyroid gland uses iodine as a precursor for the production of T4 and T3. This becomes extremely important in the process of diagnostics and treatment considerations of thyroid diseases. Thyroid tissue is the only tissue in the body that takes up and uses iodine, which makes systemic targeting possible without invasive surgical techniques (Becker).
When excessive amounts of T3 and T4 are produced, the overall effect is an increase in metabolic function throughout the body. Temperature tends to increase, tachycardia and hypertension are often present, calories are burned at a higher than normal rate, and appetite often increases to accommodate, but stool production is also increased. The increased blood flow is especially significant in regard to the kidney, because the added filtration may have helpful and harmful effects on the kidney at the same time. With everything running at a faster pace, most cats will display the typical symptoms of weight loss in spite of increased appetite, poor coat condition, increased water intake and urine output, and voluminous stools. In rare cases, weight gain may occur. Additional symptoms that may be seen include a croaky voice, vomiting, diarrhea, and ocular abnormalities (Hines).
Hyperthyroidism is a single disease that is caused by an overactive thyroid, but there are multiple conditions that may cause the thyroid to become hyper-functional. Most commonly, in cats, hyperthyroidism is caused by an adenoma which causes an overall enlargement of the thyroid gland(s). Adenomas are usually benign, and therefore usually remain local (Little). In some cases, although not commonly seen in cats, malignant tumors may be the culprit. Also less common in cats, hot nodules may be present. Hot nodules are isolated areas within the gland that become overactive and are usually non-cancerous.
Severe hyperthyroidism can lead to a complete wasting away or malnourishment condition and death, or it may simply cause extreme stress on organs such as the heart and kidney, which could also be fatal. With the current treatment options, most hyperthyroid cats can be managed or cured, but they are still at risk of complications that are even more challenging, particularly kidney failure (DiBartola, 2006).
Three major treatment approaches are currently used to treat hyperthyroidism in cats. Daily medication to decrease thyroid hormone production, surgical removal of all or part of the thyroid gland, and radioactive iodine treatment are all equally important treatment options for the patient.
Medication. In feline medicine, the drug of choice for the treatment of hyperthyroidism is methimazole, either in generic form or the familiar brand name Tapazole. Methimazole renders the thyroid gland less efficient at producing thyroid hormone, and therefore decreases the rate of production and release regardless of the cause of overproduction. Approximately 15% of patients on methimazole experience side effects such as vomiting, lethargy, and skin reactions, but most are mild (Little). In rare cases extreme immune reactions occur. The biggest challenge for the clinician is determining the appropriate dose, which is accomplished partially through trial and error. A dose guideline is used to determine the initial dose, and blood screens are evaluated at regular intervals to assess thyroid function. The dose is adjusted until the desirable result is obtained. The main disadvantage to the pet owner is the need for daily or twice daily pilling. Transdermal delivery is available but makes dose consistency an impossibility (DiBartola, 2006).
The largest advantage to using methimazole is that it is completely reversible. Since the thyroid hormone affects every organ in the body, an active hyperthyroid condition can have a masking effect on underlying kidney disease by augmenting glomerular filtration. By giving a reversible medication and potentially "unmasking" kidney disease and normalizing the glomerular filtration rate, a more informed decision can be made regarding the most appropriate treatment protocol.
As stated before, the correlation between thyroid disease and kidney disease is not completely understood. However, it is known that increased thyroid hormone, increased blood flow to the kidney, and increased filtration rate does, at the very least, have a short term protective effect when kidney disease is already present (DiBartola, 2006). As a result, it has become common practice to use medication before attempting a more permanent cure for an overactive thyroid. If kidney disease is revealed, then medication becomes the long term treatment of choice and is used to control thyroid hormone at a higher than normal rate, thus producing a level that is less dangerous to the patient but still high enough to protect the kidneys. However, if the kidneys prove to be healthy, then a more permanent cure may be considered, such as surgical removal or radioactive iodine treatment.
Surgical. Thyroidectomy is a common procedure and is usually curative. All or part of one or both thyroid lobes are surgically removed. The first surgical technique that was recommended was a complete thyroparathyroidectomy, which removed all thyroid and parathyroid glands (Flanders). It was quickly discovered that complete removal was contraindicated due to the parathyroid role in calcium homeostasis. Without a parathyroid, patients immediately suffered from potentially fatal cases of hypocalcaemia. Since most feline cases of hyperthyroidism are caused by benign growth, complete removal is not necessarily required. A variety of surgical techniques are now used, all of which preserve at least two lobes of the parathyroid (Flanders).
Since 1980, veterinarians have been seeking a surgical technique which would be curative with a low incidence of recurrence and low side effects. The primary post-operative complications of concern are recurrence, hypocalcaemia, and hypothyroidism. In 1999, a comprehensive review of surgical techniques over the preceding two decades was published in the Journal of Feline Medicine and Surgery by Dr. J.A. Flanders of Cornell University. The review describes six surgical techniques by multiple veterinarians, and evaluates recurrence rate as well as incidence of hypocalcaemia. Hypothyroidism is not evaluated in this review, and is considered to be relatively uncommon because most surgical techniques preserve at least a small amount of thyroid tissue. Recurrence rates in all cases were low, under 10% with one exception, but hypocalcaemia rates ranged from a low of zero to a high of 82% depending on the technique used.
As mentioned previously, the parathyroid glands are positioned in close association with the thyroid gland. This has been an important challenge in the development of surgical techniques, because it is difficult to remove the thyroid gland without affecting the parathyroid glands. Each thyroid gland is encapsulated in a "sack" of parenchyma together with one parathyroid gland. The parenchymal sack is usually referred to as the thyroid capsule. Each thyroid capsule has one parathyroid gland solidly attached to its external surface. The parathyroid glands located inside and outside the thyroid capsule are called the internal and external parathyroid glands, respectively. The six surgical techniques reviewed by Dr. Flanders are based on finding the best way to access the thyroid gland without disturbing the delicate parathyroid glands or their vascular and neurological supply.
The surgical techniques reviewed by Dr. Flanders were: extracapsular, modified extracapsular, intracapsular, modified intracapsular, staged intracapsular, and staged with parathyroid reimplantation. Overall, the techniques have improved as veterinarians have gained experience with what is now a relatively common procedure, the side effects have diminished. A brief description of some of the techniques will shed light on the complexity of the surgical approach to the treatment of hyperthyroidism.
Extracapsular thyroidectomy requires meticulous dissection of the external parathyroid gland from the thyroid capsule, and then removal of the entire capsule. Incidence of hypocalcaemia was as high as 82% with this procedure, so a modified extracapsular approach was attempted to preserve both the external and internal parathyroid glands. In the modified extracapsular technique, cautery was used to divide the thyroid capsule between the thyroid gland and the internal parathyroid, with special care to preserve the blood supply to the parathyroid. This method preserved all four parathyroid glands, although some amount of disturbance may have occurred. Hypocalcaemia was improved at 23%.
In contrast, the intracapsular approach was performed by opening the thyroid capsule and bluntly dissecting the thyroid gland out with a sterile swab, hence avoiding destruction of the blood supply to the parathyroid. Recurrence rates ranged from 8% to 22%, and hypocalcaemia incidence ranged from 15% to 26% in 129 patients. A modified method was used in a separate group of patients. In the modified approach, post removal of the thyroid gland, the caudal portion of the capsule was removed and the caudal vessels were cauterized. This method resulted in a recurrence rate reduction to 5% but hypocalcaemia incidence went up to 34%. While none of the techniques reviewed were free of risk, careful evaluation and experience has brought about clear improvements in surgical treatment in the feline patient.
Since no surgical technique is perfect, the vote on which technique is the best is far from unanimous. What is clear, however, is that each method that is still used today is being performed with greater expertise than when first introduced. In a 2006 issue of Veterinary Surgery, a team of veterinarians from Utrecht University published a review of 101 feline thyroidectomy patients. In this review, the modified intracapsular approach resulted in post-operative complications in fewer than 10% of patients overall. The modified extracapsular technique is also still used, and was reviewed in a 2006 issue of Clinical Techniques in Small Animal Practice, with promising results. Thyroidectomy is a non-specialty surgery that can be successfully performed in most veterinary hospitals with a low risk of side effects, and is therefore considered a positive option for a hyperthyroid cat in good renal health (Birchard, Flanders, Welches).
Radioactive Iodine Treatment. As mentioned previously, the thyroid gland contains the only tissue in the body that takes up and utilizes iodine. This property provides a unique opportunity to selectively target the thyroid cells for destruction without anesthesia and surgery, and eliminates the risk of hypocalcaemia and peripheral damage to nerves and arteries in the region (DiBartola, 2006). Although radioactive iodine treatment is rapidly becoming the treatment of choice for patients that do not suffer from renal disease, it is a specialty procedure and not as readily available as the surgical approach.
A radioactive isotope of iodine, usually 131I, is injected intravenously. This isotope travels throughout most of the body quickly, and is taken up by thyroid tissue both within the capsule and elsewhere in cases that metastasis has occurred. As expected, the harmful, overactive cells take up the most iodine. Normal thyroid cells that are atrophied or not functioning well do not take up as much iodine and are spared, which helps to prevent total destruction of all thyroid tissue and secondary hypothyroidism. Any iodine that is not taken up by the thyroid tissue is filtered out of the body and shed in the urine (Nelson, Ruslander). The iodine that is abosrbed damages the cells by shedding ionizing radiation, which impacts dividing cells directly, causing fatal errors in the cell cycle and apoptosis. There is some peripheral tissue radiation exposure, but the total effect on non-thyroid tissue is estimated to be no more severe than a standard whole body X-ray (DiBartola, 2006). In most cases a single treatment is needed, but a small percentage of patients require a second treatment.
The success rate for I131 treatment has been high, with 95% of treated cats becoming euthyroid within 6 months. As many as 80% see more immediate results between 1 week and 3 months. Approximately 2% will have a recurrence within 6 years and re-evaluation and possibly re-treatment are necessary, and another 2% will lose too much thyroid tissue and develop secondary hypothyroidism which must be treated with medication for life (Nelson). These risks are not considered life threatening with monitoring and management, and most patients in good renal health are candidates for treatment, provided there is a treatment facility within a reasonable geographic radius.
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