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Feline Hyperthyroidism

Thomas K. Graves, DVM, PhD, Diplomate ACVIM

Endocrinology & Metabolic Diseases

|March 2006|Peer Reviewed

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Feline Hyperthyroidism

DEFINITION
• Multisystemic clinical condition caused by high circulating concentrations of thyroid hormone and resultant derangement in basal metabolism and other thyroid hormone-dependent processes
• Most common endocrine disease of cats; true prevalence is unknown
• Common in North America, Europe, Australia, New Zealand

SIGNALMENT
• No sex predilection
• Siamese and Himalayan may be at decreased risk
• Average age is 10 to 13 years; fewer than 5% are younger than 8 years of age

CAUSES
• Autonomous hyperfunctional adenoma of the thyroid gland
• Most are benign tumors, but 1% to 2% may be adenocarcinoma

RISK FACTORS/PATHOPHYSIOLOGY
• Canned food might play a role1,2
• Excess thyroid hormone raises basal metabolic rate and increases expression of gene products that affect an array of metabolic processes
• Excess metabolism causes weight loss and loss of body condition despite food intake
• Thyroid hormone can lead to hypertension and myocardial changes
• Excess thyroid hormone increases renal blood flow and glomerular filtration rate

SIGNS
History of weight loss, hyperactivity, anxiety, normal or increased appetite, inappetence (uncommon), polyuria/polydipsia, behavioral changes, vomiting, diarrhea, large fecal volume, signs of congestive heart failure (severe cases); however, signs may be nonspecific.

PAIN INDEX
Not necessarily a painful condition, but complications of hyperthyroidism (e.g., congestive heart failure) could be associated with discomfort.

Diagnosis

PHYSICAL EXAMINATION
Thin body condition, unilateral or bilateral thyroid nodules (not always palpable), heart murmur, tachycardia, unkempt appearance, thickened claws; or findings may be normal.

DEFINITIVE DIAGNOSIS
• Finding of a high serum concentration of total T4 confirms a diagnosis in a cat with clinical signs
• Total T4 concentrations may be within the normal range
• Elevated free T4 may be diagnostic in these cats, but some cats with nonthyroidal illness have elevated free T4 levels
• Repeated total T4 testing can confirm the diagnosis in some cases
• Measurement of serum total T3 is not useful

DIFFERENTIAL DIAGNOSIS
• Several common disorders of middle-aged and older cats share clinical features with hyperthyroidism
• Chronic renal failure can cause weight loss, inappetence, gastrointestinal signs, polyuria/polydipsia
• Diabetes mellitus can cause polyphagia with weight loss, polyuria/polydipsia
• Inflammatory bowel disease can cause weight loss, vomiting, diarrhea
• Neoplasia can be associated with cachexia; alimentary lymphoma especially can be associated with vomiting, diarrhea, and weight loss

LABORATORY FINDINGS/IMAGING
• Total T4 is elevated in most cats with hyperthyroidism
• Increased alanine aminotransferase and alkaline phosphatase levels occur in more than 80% of cases
• Azotemia can occur in cats with concurrent renal disease or dehydration; more than 20% have high serum creatinine levels
• True renal function can be masked by
the increased glomerular filtration rate caused by hyperthyroidism (i.e., azotemia may be absent on initial evaluation but may become apparent once the cat becomes euthyroid)
• Isosthenuria is common
• Increased hematocrit occurs in roughly half of cases
• Thoracic radiographs can show cardiomegaly or signs of pulmonary edema in cats with thyroid-induced myocardial disease

• No specific findings on abdominal radiography or ultrasonography, but ultrasonography may be useful in investigating other differential diagnoses and to evaluate renal architecture
• Thyroid scintigraphy can identify a more precise anatomical location of thyroid nodules, can identify hyperactive tissue that is not enlarged or that is ectopic, and can sometimes be used to diagnose the disease
• Blood pressure should be measured in cats suspected of having hyperthyroidism; it is typically elevated3 and can be high enough to cause severe consequences, such as retinal detachment

POSTMORTEM FINDINGS
Nodular lesions involving one or both lobes of the thyroid gland; other findings can include poor body condition and myocardial thickening.

Treatment

INPATIENT OR OUTPATIENT
• Outpatient therapy is indicated for patients treated with antithyroid drugs
• Cats receiving radioiodine therapy or surgical thyroidectomy require hospitalization
• Cats presenting in congestive heart failure require inpatient therapy, including oxygen therapy, but this is an uncommon occurrence in hyperthyroid cats

ACTIVITY
No activity restrictions are necessary.

SURGERY
• Thyroidectomy, which remains a viable option, is not done as commonly as it was before radioiodine therapy became more widely available
• One or both lobes of the thyroid gland may be removed, but if a unilateral procedure is done, the opposite lobe will probably need treatment at some point
• Complications of surgery include hypocalcemia (iatrogenic hypoparathyroidism) and laryngeal paralysis
• Complications are uncommon with skilled surgeons, but can be life-threatening

RADIOIODINE THERAPY
• Gaining wide acceptance as the treatment of choice
• Concentrates in the thyroid gland and destroys hyperactive tissue
• Side effects are rare, and recurrence rates are low
• Requires special facilities and regulatory licensing

ALTERNATIVE THERAPY
Ipodate: Use of this cholecystographic contrast agent has been shown to reduce transiently increased total T4 concentrations in some cats with hyperthyroidism; long-term use is not recommended and it is not currently available
Intrathyroidal ethanol injection: Ultrasound-guided injection of ethanol into thyroid nodules has resulted in reversal of hyperthyroidism in a small number of cats, but the effect is usually transient and is associated with a high incidence of laryngeal paralysis and sudden death; at present, its use is not recommended
Intrathyroidal heat ablation: Percutaneous, ultrasound-guided radiofrequency heat ablation has been reported to cause transient resolution of hyperthyroidism in cats, but was associated with Horner's syndrome and laryngeal paralysis in some cats

Drug Therapy

Methimazole
• The most commonly used antithyroid drug
• 2.5 to 5 mg PO Q 12 H is the recommended starting dose
• Controls hyperthyroidism but does not cure the disease
• Dose must be adjusted to keep the total T4 concentration in the low-normal range for clinical improvement to occur
• Transdermal preparations (in pleuronic lecithin organogel) can be made by most compounding pharmacies and are useful in cats that do not tolerate oral medication
• No known interactions

Carbimazole
• Similar to methimazole
• Not available in the United States
• Initial dose is 5 mg PO Q 8 H
• Dose is adjusted based on serum total T4 monitoring as for methimazole

Contraindications
• Antithyroid drugs should not be used in cats with known adverse reactions
• Antithyroid drugs should be used with caution in cats with concurrent renal insufficiency because treatment of hyperthyroidism reliably decreases glomerular filtration rate and can exacerbate renal failure

Precautions
• Side effects occur in approximately 15% of cats treated with methimazole, and most occur within 3 months of starting treatment
• Anorexia and vomiting are the most common side effects, and they may either resolve or may require drug cessation
• Vomiting is less likely in cats treated with transdermal methimazole
• Self-induced facial excoriations occur in a small number of cats on methimazole4 and may require drug cessation
• Life-threatening side effects are rare and include hepatic necrosis, agranulocytosis, and thrombocytopenia
• Bleeding disorders occur in a small number of cats treated with methimazole and are not always associated with thrombocytopenia
• Lymphocytosis, eosinophilia, and mild neutropenia can occur; they are often transient and do not always require discontinuation of therapy, but severe leukopenia is an indication to stop therapy

Follow-Up

POSTTREATMENT RENAL DISEASE
• Any method of treatment for hyperthyroidism can be associated with decreased glomerular filtration rate and the unmasking of renal azotemia and chronic renal failure
• Because no long-term studies of renal function in cats treated for hyperthyroidism have been reported, it is not known if the decline in renal function is transient or if renal function stabilizes at any time after treatment
• There are no known predictors of which cats will have unmasking of posttreatment renal failure, so a therapeutic trial with methimazole (which is reversible) may be recommended before more permanent treatment with radioiodine or surgery is pursued
• Renal function should be monitored
frequently after any treatment method
• Cats that show significant renal insufficiency after treatment of hyperthyroidism may need thyroid hormone supplementation, although studies have not been reported

ANTITHYROID DRUG MONITORING
Total T4: Dose should be adjusted to keep total T4 in the low-normal range to achieve clinical euthyroidism
CBC: Should be monitored every 2 to 3 weeks for the first 3 months of therapy to detect blood dyscrasias
Serum chemistry:
- Liver enzyme elevations can occur with drug-induced hepatopathy
- Concentrations of BUN and creatinine can indicate renal failure

Blood pressure
• Treatment should normalize blood pressure
• In cats in which treatment is not possible (e.g., concurrent renal disease, owner refusal), antihypertensive drugs may be needed

PREVENTION
There are no known, proven strategies for preventing hyperthyroidism in cats.

COMPLICATIONS
Untreated hyperthyroidism results in severe cachexia, uncontrolled elevation in metabolism, hypertension, and life-threatening cardiovascular complications.

COURSE
Onset is insidious and progression is slow.

AT-HOME TREATMENT
Oral or transdermal medications are given at home. No other at-home treatments are needed.

NUTRITION
There are no studies of nutritional management of cats with hyperthyroidism.

CLIENT EDUCATION
Clients must be advised of the advantages/disadvantages of the various therapeutic options. Inform clients that while leaving the disorder untreated is not advised, all treatment options have possible complications.

FOLLOW-UP EXAMINATIONS
Hyperthyroidism can recur in cats treated by any means, and follow-up examinations at 3- to 6-month intervals are necessary to look for disease recurrence, treatment complications, or the development of other diseases.

In General

RELATIVE COST
• Diagnostic workup ($$)
• Methimazole treatment: Cats treated with methimazole incur costs gradually, over extended periods. While the drug itself is only moderately expensive, frequent monitoring and blood tests eventually add up ($$)
• Surgical thyroidectomy ($$$)
• Radioiodine therapy ($$$)

PROGNOSIS
• Prognosis without treatment is poor
• Prognosis with treatment is excellent
• A large study showed age at diagnosis and sex are best predictors of survival after radioiodine therapy
- 5-year survival rate in cats diagnosed at 10 years of age is 42% for females and 28% for males
- 5-year survival rate in cats diagnosed at 13 years of age is 25% for females and 13% for males


FELINE HYPERTHYROIDISM • Thomas K. Graves

References
1. Evaluation of dietary and environmental risk factors for hyperthyroidism in cats. Martin KM, Rossing MA, Ryland LM, et al. JAVMA 217:853-860, 2000.
2. Epidemiologic study of relationships between consumption of commercial canned food and risk of hyperthyroidism in cats. Edinboro CH, Scott-Moncrieff JC, Janovitz E, et al. JAVMA 224:879-886, 2004.
3. Hypertension in cats with chronic renal failure or hyperthyroidism. Kobayashi DL, Peterson ME, Graves TK. J Vet Intern Med 4:58-62, 1990.
4. Methimazole treatment of 262 cats with hyperthyroidism. Peterson ME, Kintzer PP, Hurvitz AI. J Vet Intern Med 2:150-157, 1988.

Suggested Reading
Changes in renal function associated with treatment of hyperthyroidism in cats. Graves TK, Olivier NB, Nachreiner RF, et al. Am J Vet Res 55:1745-1749, 1994.
Effects of methimazole on renal function in cats with hyperthyroidism. Becker TJ, Graves TK, Kruger JM, et al. JAAHA 36:215-223, 2000.
Efficacy and safety of once versus twice daily administration of methimazole in cats with hyperthyroidism. Trepanier LA, Hoffman SB, Kroll MM, et al. JAVMA 222:954-958, 2003.
Efficacy and safety of transdermal methimazole in the treatment of cats with hyperthyroidism. Sartor LL,Trepanier LA, Kroll MM, et al. J Vet Intern Med 18:651-655, 2004.
Long-term health and predictors of survival for hyperthyroid cats treated with iodine 131. Slater MR, Geller S, Rogers K. J Vet Intern Med 15:47-51, 2001.
Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. Peterson ME, Melian C, Nichols R. JAVMA 218:529-536, 2001.
Pathogenesis of feline hyperthyroidism. Mooney CT. J Feline Med Surg 4:167-169, 2002.
Percutaneous ultrasound-guided radiofrequency heat ablation for treatment of hyperthyroidism in cats. Mallery KF, Pollard RE, Nelson RW, et al. JAVMA 223:1602-1607, 2003.
Use of percutaneous ethanol injection for treatment of bilateral hyperplastic thyroid nodules in cats. Wells AL, Long CD, Hornof WJ, et al. JAVMA 218:1293-1297, 2001.

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