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Treatment Options for Hyperthyroidism in Cats
by Andrea Jensen
Fall 2006
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Introduction
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.
Normal Thyroid Function
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).
Hyperthyroidism
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).
Treatment Options
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 131I 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.
REFERENCES
Becker, David V. "Radioactive Iodine Treatment for Hyperthyroidism."
Thyrobulletin 1993;14(3).
Birchard, S.J. "Thyroidectomy in the Cat." Clinical Techniques in
Small Animal Practice. 2006 Feb; 21(1): 29-33.
DiBartola, Stephen P. "Feline Hyperthyroidism and Renal Disease."
Lecture, The Ohio State University. 28 Nov. 2006.
Evans, Howard E. Miller's Anatomy of the Dog, Third Ed.
Philadelphia: WB Saunders Company, 1993.
Fischetti, Anthony J., et al. "Effects of Methimazole on Thyroid
Gland Uptake of 99MTC-Pertenchnetate in 19 Hyperthyroid Cats.
Veterinary Radiology and Ultrasound 2
Flanders, J.A. "Surgical Options for the Treatment of
Hyperthyroidism in the Cat." Journal of Feline Medicine and Surgery
1
Hines, Ron. "Hyperthyroidism in Cats, Cause and Treatment." 29 Apr.
2006. www.2ndchance.info/hyperthyroid.htm
"Hyperthyroidism, Overactivity of the Thyroid Gland." Norman
Endocrine Surgery Clinic. 30 Jan. 2005. www.endocrineweb.com/hyper4.html
Little, Susan. "Feline Hyperthyroidism." The Winn Feline Foundation.
2006 www.winnfelinehealth.org/health/hyperthyroidism.html
Naan, E.C., et al. "Results of Thyroidectomy in 101 Cats with
Hyperthyroidism." Veterinary Surgery 2
Nelson, Richard W. "Diagnosis and Management of Feline
Hyperthyroidism." Western Veterinary Conference 2004.
Peterson, M.E. "Radioiodine Treatment of Hyperthyroidism." Clinical
Techniques in Small Animal Practice 2
Ruslander, David. "What Every Practitioner Should Know About
Radiation Therapy." ACVIM Conference 2002.
Welches, C.D., et al. "Occurrence of Problems After Three Techniques
of Bilateral Thyroidectomy in Cats." Veterinary Surgery 1989
Sept-Oct;18(5):392-6.
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