Definition

A pathologic, sustained, high overall metabolism caused by high circulating concentrations of thyroid hormones.

Pathophysiology

• Hyperthyroidism in cats is most often caused by autonomously hyperfunctioning nodules of the thyroid gland that secrete T₄ and T₃, uncontrolled by normal physiologic influences (e.g., TSH secretion); one or both lobes of the thyroid gland can be affected.
• Rare cases of feline hyperthyroidism (1–2%) are caused by hyperfunctioning thyroid carcinoma.
• Extremely uncommon in dogs, it has been seen in some dogs with thyroid carcinoma (most dogs with thyroid gland neoplasia are euthyroid) and in dogs with oversupplementation of exogenous thyroid hormone.

Systems Affected

• Behavioral.
• Cardiovascular-myocardial hypertrophy and hypertension.
• Gastrointestinal-chronic cellular malnutrition, decreased gastrointestinal transit time, malabsorption, and hepatocellular damage.
• Musculoskeletal-cachexia.
• Nervous.
• Renal/Urologic-high GFR may mask underlying chronic renal failure, possible hyperfiltration injury, and decreased urine-concentrating ability.

Genetics

No known genetic predisposition

Incidence/Prevalence

• Most common endocrine disease of cats; one of the most common diseases in late middle-aged and old cats; true incidence is unknown, but diagnosis of the disease is increasing. In the United Kingdom, overall prevalence is 2-3%, with 9% prevalence in cats over 10 years old.
• Rare in dogs.

Signalment

Signs

Causes

• Cats-autonomously hyperfunctioning nodules; rarely, thyroid carcinoma.
• Dogs-T₄ or T₃ secretion by a thyroid carcinoma or iatrogenic due to oversupplementation of thyroxine.

Risk Factors

• Some reports have linked feline hyperthyroidism to canned food diets.
• Recent studies have implicated endocrine disruptor toxins (e.g., PBDEs) as possible causes of feline hyperthyroidism, but this has not been proven.
• Advancing age increases risk.
• Risk may be decreased in purebred cats.

Differential Diagnosis

The clinical signs of feline hyperthyroidism can overlap with those of chronic renal failure, chronic liver disease, and neoplasia (especially intestinal lymphoma); they can be excluded based on routine laboratory findings and thyroid function tests.

CBC/Biochemistry/Urinalysis

• Erythrocytosis (mild) and, less commonly, leukocytosis, lymphopenia, and eosinopenia-stress response associated with high T₃ and T₄.
• High ALT activity-common.
• High ALP, LDH, AST, BUN, creatinine, glucose, phosphorus, and bilirubin-less common; caused by more severe complications of hyperthyroidism.

Other Laboratory Tests

• Serum total T₄ concentration (TT₄)-measures protein-bound and free (unbound) T₄; high resting concentration confirms the diagnosis of hyperthyroidism.
• Serum total T₃ concentration-not reliable.
• Free T₄ (FT₄) by equilibrium dialysis-sometimes useful to diagnose mild or early hyperthyroidism in cats with normal resting serum TT₄ concentrations.
• In theory, FT₄ more accurately reflects true thyroid gland secretory status, but some cats with non-thyroidal illness exhibit unexplained elevations in FT₄; do not use FT₄ alone as a screening test.
• T₃ suppression test-useful to diagnose mild hyperthyroidism (see Appendix II for protocol and interpretation).
• TRH stimulation test-useful to diagnose mild hyperthyroidism (see Appendix II for protocol and interpretation).

Imaging

• Thoracic radiography and echocardiography may be useful in assessing the severity of myocardial disease.
• Dogs-thoracic radiography to detect pulmonary metastasis.
• Cats-abdominal ultrasound may be useful to explore underlying renal disease.
• Thyroid gland scintigraphy can be used to diagnose hyperthyroidism (thyroid-to-salivary gland ratio is increased in most cases) and to determine the location of abnormal thyroid tissue (mediastinal or sublingual ectopic disease is found in nearly 4% of cases).

Diagnostic Procedures

• Treatment of hyperthyroidism can significantly decrease renal function; pursue any abnormal value revealed by CBC, serum biochemical testing, or urinalysis by bacterial culture of the urine, abdominal radiography, and ultrasonography of the urinary tract.
• Can measure GFR by plasma disappearance of iohexol or 99mTc-DTPA in cats with suspected underlying renal disease. Contrary to some reports, concentrated urine (specific gravity >1.035) does not decrease the risk of post-treatment renal insufficiency.
• Indirect blood pressure measurement may be useful in pretreatment assessment and monitoring of therapy.

Pathologic Findings

• Adenomatous hyperplasia of one or both lobes of the thyroid gland
• Carcinoma in dogs and 1–2% of cats

Appropriate Health Care

• Outpatient management usually suffices for cats, if antithyroid drugs are used.
• Radioiodine treatment and surgical thyroidectomy require inpatient treatment and monitoring.
• Rare cases of overt congestive heart failure require emergency inpatient intensive care.

Activity

No alterations recommended

Diet

• Resolution of thyrotoxicosis obviates the need for modifications.
• Poor absorption of many nutrients and high metabolism suggest the need for a highly digestible diet with high bioavailability of protein in untreated hyperthyroidism.
• A commercial iodine-deficient diet (Hill's y/d) has been advocated for treatment of hyperthyroidism, but studies of disease control and long-term outcomes are lacking.

Client Education

• Inform clients of adverse effects of antithyroid drugs (see below) and surgical complications.
• Clients should be aware of possible (rare) recurrence after treatment.

Surgical Considerations

• Surgical thyroidectomy is one recommended treatment for hyperthyroidism in cats.
• Surgical treatment of thyroid carcinoma (dogs and cats) is usually not curative, but can be palliative.

Drug(s) Of Choice

• Radioiodine therapy is arguably the safest and most effective treatment.
• Methimazole (Tapazole) is most often recommended (5–15 mg/day divided q8–12h).
• Methimazole can be given transdermally (compounded in PLO gel). Resolution of thyrotoxicosis takes longer with transdermal than with oral methimazole.
• -adrenergic blocking drugs-sometimes used to treat some of the cardiovascular and neurologic effects of excess thyroid hormone; can be used in combination with methimazole; mainly used to prepare the patient for surgical thyroidectomy or radioiodine therapy. Atenolol is useful for controlling tachycardia.

Precautions

• Antithyroid drugs have several side effects.
• Anorexia and vomiting are common side effects of methimazole; rare side effects include self-induced excoriation of the face, thrombocytopenia, bleeding diathesis, agranulocytosis, serum antinuclear antibodies, and hepatopathy.
• Side effects usually develop within the first 3 months of treatment and may or may not necessitate drug cessation and alternative treatment (depending on severity).
• Bleeding, jaundice, and agranulocytosis necessitate immediate withdrawal of the drug.
• With the exception of vomiting, side effects can occur with transdermal methimazole as well.

Alternative Drug(s)

• Carbimazole-another useful antithyroid drug; not available in the United States.
• Propylthiouracil-can be useful if methimazole is unavailable; adverse effects may be more common and more severe than with methimazole.
• Ipodate-a radiographic contrast agent; can be used at 15 mg/kg PO q12h to treat some cases of mild hyperthyroidism, but not effective in most hyperthyroid patients; long-term effectiveness has not been established.

Patient Monitoring

• Methimazole (and other antithyroid drugs)-physical examination, CBC (with platelet count), serum biochemical analysis, and serum T₄ determination every 2–3 weeks for the initial 3 months of treatment; adjust the dosage to maintain serum T₄ concentration in the low-normal range.
• Surgical thyroidectomy-watch for development of hypocalcemia and/or laryngeal paralysis during the initial postoperative period; measure serum T₄concentrations in the first week of surgery and every 3–6 months thereafter to check for recurrence.
• Radioiodine-measure serum T₄concentrations 2 weeks after treatment and every 3–6 months subsequently.
• Renal function-GFR declines following treatment in most patients; therefore, perform a physical examination, serum biochemistry, and urinalysis 1 month after treatment and then as indicated by the clinical history.

Possible Complications

• Untreated disease can lead to congestive heart failure, intractable diarrhea, renal damage, retinal detachment (as a result of hypertension), and death.
• Complications of surgical treatment include hypoparathyroidism, hypothyroidism, and laryngeal paralysis.
• Hypothyroidism can occur following radioiodine therapy and during treatment with antithyroid drugs. Evidence suggests that iatrogenic hypothyroidism is associated with decreased renal function and decreased survival.

Expected Course and Prognosis

• Uncomplicated disease-prognosis is excellent; recurrence is possible and is most commonly associated with poor owner compliance with medical management; regrowth of hyperthyroid tissue is possible but uncommon after surgical thyroidectomy or radioiodine treatment.
• Reported mean survival time in cats treated with radioiodine is 4 years; mean survival time with methimazole is 2 years; mean survival time of cats treated with radioiodine and methimazole is 5.3 years.
• Cats with pre-existing renal disease have a poorer prognosis. Renal failure is the most common cause of death in hyperthyroid cats.
• Dogs or cats with thyroid carcinoma-prognosis is poor; treatment with radioiodine, surgery, or both is usually followed by recurrence of disease; adjuvant chemotherapy is of questionable benefit.

Associatedconditions

• In cats with underlying renal disease (either secondary to chronic hypertension or unrelated to thyroid disease), the prognosis is less favorable.
• Renal insufficiency may not become apparent until euthyroidism has been established; for this reason, a reversible form of treatment (i.e., antithyroid drugs) is recommended if renal disease is suspected in a cat with hyperthyroidism. Recent studies show the most significant post-treatment decline in GFR occurs during the first month post-treatment, so 30 days should be sufficient time for a trial with antithyroid drugs prior to use of a more permanent treatment for hyperthyroidism.
• In some patients, hyperthyroidism might be best left untreated.

Synonyms

• Multinodular toxic goiter
• Plummer's disease
• Thyrotoxicosis

See Also

• Cardiomyopathy, Hypertrophic-Cats
• Congestive Heart Failure, Left-Sided
• Hypertension, Systemic
• Hypoparathyroidism

Abbreviations

• ACE = angiotensin converting enzyme
• ALP = alkaline phosphatase
• ALT = alanine aminotransferase
• AST = aspartate transaminase
• FT₄ = free thyroxine
• GFR = glomerular filtration rate
• LDH = lactate dehydrogenase
• T₃ = triiodothyronine
• T₄ = thyroxine
• TRH = thyrotropin-releasing hormone
• TSH = thyroid-stimulating hormone
• TT₄ = total thyroxine

Client Education Handout Available Online