Hyperthyroidism

• Most common endocrine disease of cats.
• First reported in 1979.
• Cause: functional thyroid adenoma, ademomatous hyperplasia or rarely thyroid carcinoma  Thyroid gland: neoplasia    →   excessive concentrations of thyroxine (T4) Thyroxine assay and tri-iodothyronine (T3) Endocrinology: tri-iodothyronine (T3).
• Signs: weight loss, polyphagia; lethargy, vomiting, diarrhea, hyperactivity, vocalization, inappetence less commonly.
• Diagnosis: laboratory demonstration of elevated T4.
• Treatment: carbimazole Carbimazole, methimazole Methimazole, radioactive iodine, surgical removal of tumor.
• Prognosis: good with treatment and careful aftercare.
  Print off the Owner factsheet on hyperthyroidism  Hyperthyroidism - disease and treatment to give to your client.

• Weight loss with polyphagia     .
• Vomiting, diarrhea.
• Hyperactivity (restlessness), increased vocalization.
• Polyuria/polydipsia.
• Complications associated with congestive heart failure Heart: congestive heart failure, eg tachypnea, dyspnea, acute onset hindlimb paralysis (thromboembolism).
• Complications associated with hypertension Hypertension, eg hypertensive retinopathy (detached retina, retina hemorhage, hyphaema), neurological signs.
• Unkempt coat.
• Rare cases show 'apathetic disease' with depression, lethargy, anorexia and weight loss (</=10% cases).

• Signs associated with hypertrophic cardiomyopathy Heart: hypertrophic cardiomyopathy: cardiac failure Heart: congestive heart failure, thromboembolism Thromboembolism: aorta.
• Signs associated with hypertensive complications - acute onset blindness, seizures Seizures.
• Thyroid storm-episodic dyspnea.

• Middle-aged to old cats (mean 12-13 years, range 4-22 years).

• Siamese Siamese and Himalayans less likely to develop disease.

• Medical treatment - cost of drugs and routine monitoring for complications of drugs and primary disease, eg hypertension.
• Surgical costs.
• Radio-iodine therapy - cost of evaluation to determine suitability and boarding fees Hyperthyroidism: radio-iodine treatment.

• Danger of arrhythmia development during anesthesia if pre-stabilization not achieved.
  Period of stabilization (minimum of 2 weeks) recommended pre-operatively using anti-thyroid drugs +/- beta-blockers.Warn owner of risk associated with anesthesia.
• Post-operative:
  • Risks of iatrogenic hypoparathyroidism Hypoparathyroidism if bilateral thyroidectomy performed.
  • Rare risk of laryngeal paralysis Larynx disease.
• Unmasking renal disease Kidney: chronic kidney disease with permanent treatment methods (surgery and radio-iodine) (due to decreased glomerular filtration rate as euthyroidism achieved).
• Severely affected hyperthyroid cats can be very fragile - ensure gentle handling and restraint performed by trained staff to avoid excessive stress upon the patient (collapse, syncope, fatal arrhythmias can occur if severely hyperthyroid and put under undue stress).
• Accelerated insulin catabolism in pre-existing diabetic cats may necessitate increased insulin dose.

• Functional thyroid adenomas/carcinoma in one or both thyroid glands   →   elevated [T4] and [T3]   →   increased metabolic rate and heat production   →   weight loss and increased appetite.
• Elevated [T4] and [T3]   →   increased sympathetic stimulation   →   tachycardia and hypertrophic cardiomyopathy Heart: hypertrophic cardiomyopathy and behavioral changes.
• Benign adenomatous change in 98% cases - functional malignant carcinoma is rare (<3% cases).

• In normal thyroid hormone production is under control of hypothalamic-pituitary-thyroid axis    .
• Increased [T4] affects many body systems.

• Development of disease poorly understood and likely multifactorial. Several theories proposed:
  • Some thyroid follicular cells have higher growth potential   →     focal hyperplasia and adenoma development.
  • Circulating factors, eg iodine levels in diet or immunoglobulins stimulate thyroid development.
  • Environmental goitrogens   →   thyroid pathology.
  • Oncogene mutations.
• Epidemiological risk factors:
  • Use of a litter box.
  • >50% wet food in the diet.
  • Diet including fish, liver or giblets.
  • Exposure to canned foods.
  • Increasing age.
  • Non-pure breed.

• Months to years.

• Weight loss.
• Polyuria/polydipsia.
• Polyphagia.
• Increased activity/restlessness, increased vocalization.
• Vomiting, diarrhea.
• Cardiac associated abnormalities - dyspnea, tachypnea, signs related to thromboembolism.
• Hypertensive associated complications - hypertensive retinopathy, neurological signs.
• Coat alterations - unkempt, seborrheic, matted, patchy alopecia.
• Less commonly weakness, lethargy and inappetence - 'apathetic hyperthyroidism'.
• Heat intolerance.

• Weight loss.
• Polyphagia.

• Polyuria/polydipsia.
• Restlessness, vocalization.
• Reduced grooming activity.

• Vomiting Vomiting.
• Diarrhea.
• Coughing/sneezing.
• Episodic tachypnea - 'thyroid storm'.

• Intermittent anorexia in some cases.
• Decreased activity in some cases.
• Signs related to cardiac disease, eg thromboembolism   Thromboembolism: aorta  , dyspnea.
• Signs related to hypertension, eg acute onset blindness and neurological complications (seizures, ataxia).

• Thin body condition/emaciated in chronic cases       .
• Tachycardia (heart rate >240 bpm)       .
• Palpably enlarged thyroid gland    .
  Thyroid tissue can also be intra-thoracic - 'ectopic'.

• Murmurs, gallop rhythm Heart sound: gallop rhythm (hyperthyroid cat), arrhythmias Heart: dysrhythmia .
• Difficult to examine.
• Matted/ill-kept coat    .
• Tachypnea.

• Mild pyrexia.
• Congestive heart failure Heart: congestive heart failure.
• Anxious facial expression    .

• Ventral neck flexion.
• Increased nail growth.
• Lethargy, generalized weakness (muscle weakness and atrophy).

Hematology

• Erythrocytosis Hematology: red blood cell count 40-50% cases, usually mild.
• Increased MCV (44% cases), RBC count (21%) and hemoglobin concentration (17%).
• Leukocyte changes common but are non-specific - mature neutrophilia Hematology: neutrophil, lymphopenia Hematology: lymphocyte, eosinopenia Hematology: eosinophil. Reflects stress leukogram.
• Eosinophilia Hematology: eosinophil and lymphocytosis occasionally.

Biochemistry

• Elevation of one or more hepatic enzyme (ALT and ALKP +/- AST)  Blood biochemistry: aspartate aminotransferase  Blood biochemistry: alkaline phosphatase  Blood biochemistry: alanine aminotransferase (SGPT, ALT) - typically reversible with correction of hyperthyroidism:
  • Dynamic bile acids usually normal, if elevated suggests concurrent hepatopathy.
• Elevation of urea Blood biochemistry: urea and creatinine Blood biochemistry: creatinine   (26% cases) - likely reflects concurrent renal disease (differential diagnosis reduced perfusion due to concurrent cardiac disease).
• Reduced creatine common - loss of  muscle mass.
• Mild hyperglycemia Blood biochemistry: glucose  - most commonly due to stress hyperglycemia.
• Hyperphosphatemia (18% cases) - due to altered bone metabolism +/- concurrent renal disease.
• NB Fructosamine Blood biochemistry: fructosamine may be lower in hyperthryoidism due to increased protein turnover, therefore interpretation of fructosamine levels is more difficult.

Urinalysis

• Urine specific gravity variable (may be reduced due to hyperthyroidism +/- concurrent renal disease, diabetes etc).
• Trace ketonuria may be identified.
• Check for proteinuria Proteinuria (urine protein: creatinine ratio) - especially relevant if concurrent renal disease.
• Bacterial UTI may develop as secondary complication.

Radiography

• Thoracic radiographs Radiography: thorax may show signs of congestive heart failure, ie pulmonary edema, venous congestion, pleural effusion.
• Cardiomegaly seen in 50% of cases in absence of other signs of CHF:
  • Absence of cardiomegaly does not exclude hypertrophic changes however. 
• Occasionally intra-thoracic thyroid tissue or pulmonary metastasis seen   .
• Abdominal radiography Radiography: abdomen may show hepatomegaly   due to congestive heart failure.

2-D Ultrasonography

• Echocardiography Ultrasonography: heart to show hypertrophic cardiomyopathy or occasionally left atrial and ventricular dilation.

Electrocardiography

• Tachycardia - usually sinus tachycardia     .
• Atrial and ventricular arrhythmias.
• Intraventricular conduction disturbances.
• Increased R wave amplitude.

Other

• Thyroid hormone assay:
  • Serum thyroxine T4  Thyroxine assay (elevated in 90-95% of cases):
    • Serum levels fluctuate through day.
    • May be suppressed by non-thyroidal illness:
      • Cannot exclude hyperthroidism on basis of single T4 if supporting clinical signs   →   retest 1-2 weeks later +/- measure free T4 Blood biochemistry: free thyroxine assay.
  • Tri-iodothyronine T3 Endocrinology: tri-iodothyronine (T3) (elevated in approximately 70-75% cases):
    • Not routinely measured.
• Free T4  Blood biochemistry: free thyroxine assay:
  • Measure by equilibrium dialysis.
  • Less affected by non-thyroidal illness.
  • Look for elevation in conjunction with assessing T4 (T4 usually in mid-high end of reference range if sick euthyroid effect on hyperthyroidism).
• TSH stimulation test:
  • Protocol described using human recombinant TSH  Thyroid stimulating hormone however interpretation can be problematic due to low specificity of the test.
  • Limited increase in T4 following TSH administration (overlap between normal and hyperthyroid cats).
• TRH stimulation test  Thyrotropin releasing hormone (TRH) stimulation test:
  • Little increase in T4 after TRH administration in hyperthyroidism.
  • Limited value due to difficulty in interpreting results (lacks specificity) and adverse effects of TRH (cholinergic type signs).
• T3 suppression test  T3 suppression test:
  • T4 levels not suppressed by T3 administration in hyperthyroidism.
  • Preferred dynamic test for assessment of thyroid function.
  • Requires administration of medication over 3 days. 
• Scintigraphic thyroid imaging Scintigraphy: overview:
  • Specialized imaging technique using radioactive iodine or technetium pertechnate.
  • Increased uptake in affected hyperfunctional gland.
  • Also useful for detecting ectopic tissue and metastases         .

• Enlarged thyroid gland    .
• Hypertrophic cardiomyopathy  .

• Adenomatous hypertrophy of thyroid tissue: multifocal hyperplastic nodules 1-3 mm surrounded by normal thyroid tissue.
• Occasionally carcinomatous thyroid tissue - metastases to local lymph nodes, lungs, liver and CNS.
• Centrilobular fatty infiltration of liver with mild hepatic necrosis.
• Symmetrical hypertrophy of left ventricular free wall and interventricular septum.

For weight loss and polyphagia

• Diabetes mellitus Diabetes mellitus.
• Malabsorptive disease (EPI Exocrine pancreatic insufficiency, inflammatory bowel disease   Inflammatory bowel disease: overview  , intestinal lyphocytic lymphoma) and lymphocytic cholangitis.
• Other causes of weight loss more typically associated with anorexia, eg chronic renal failure  Kidney: chronic kidney disease, cardiac disease Heart: congestive heart failure, neoplasia.

For respiratory signs

• Primary hypertrophic cardiomyopathy Heart: hypertrophic cardiomyopathy and congestive heart failure Heart: congestive heart failure.
• Other cardiomyopathies.
• Primary pulmonary disease, eg neoplasia, pneumonia, chronic airway disease.

• If concurrent heart failure manage congestive disease:
  • Thoracocentesis Drainage: thorax if pleural effusion.
  • Diuresis - frusemide Furosemide 1 mg/kg IV IM q hour until respiratory rate and effort then taper dose to 2 mg/kg PO BID-TID as required.
  • ACE inhibitor ACE inhibitors: overview  - benazepril Benazepril or enalapril  Enalapril.
  • +/- topical nitroglycerine.
  • Beta-blockers are contra-indicated if the cat is in congestive heart failure.
• Stabilization of hyperthyroidism:
  • Initiate oral treatment with carbimazole Carbimazole or methimazole  Methimazole.
  • Reassess effect after 2 weeks of treatment and check renal function:
    • If azotemia Azotemia develops permanent irreversible treatment (surgery or radioiodine) may not be appropriate, since the medical treatment dose can be titrated to help maintain an adequate glomerular filtration rate.
• If not in heart failure and marked tachycardia beta-blockers sometimes used in conjunction with anti-thyroid drugs in preparation for anesthesia and surgery propanolol Propranolol (2.5-5.0 mg TID PO) or atenolol Atenolol (6.25-12.5 mg/cat SID-BID PO).

• Calcium ipodate has been described as a possible adjunct for stabilization (alternative oral medication), however it has limited availability and effects in inhibiting conversion of T4 to T3 are short-lived. This is not currently used in practice.

• Surgical thyroidectomy Thyroidectomy: cats should be medically stabilized for a minimum of 1-2 weeks prior to anesthesia General anesthesia: overview.
• Pre-surgical administration of propranolol reduces risk of arrhythmias under anesthesia. Acepromazine Acepromazine maleate pre-medicant reduces autonomic manifestations of hyperthyroidism.
• Radioactive iodine: a single injection of radio-iodine 131 will restore euthyroidism in 94-98% of cases. Radio-iodine is concentrated by the thyroid gland and irradiates and destroys neoplastic tissue. Suitable treatment for cats with ectopic thyroid tissue. Cats usually achieve euthyroidism within 4-6 weeks therefore not appropriate in cases with congestive heart failure Hyperthyroidism: radio-iodine treatment   . A careful evaluation of each cat  is performed to determine whether they are suitable to receive iodine 131, since the patients need to be 'isolated' for 3 weeks after treatment, with minimal handling (co-morbid disease may exclude patient from treatment, eg diabetes with insulin requirement).
  Methimazole therapy should be withdrawn 1 week before radiotherapy therapy.
• Treatment is only available at a few specialist centers in the UK. For centers that offer radiotherapy treatment for feline hyperthyroidism in the USA, please visit  http://www.veterinarypartner.com and search for radiotherapy facilities.
• Long-term medical management: methimazole Methimazole (2.5 mg, 5 mg) and carbimazole (available in standard form to dose TID or sustained release preparation for SID dosing in the UK).Transdermal formula of methimazole is available in the USA, however absorption can be highly variable and time to reach euthyroidism may be longer versus oral dosing.
• Carbimazole is converted to methimazole following dosing: 3 mg methimazole is approximately equivalent to 5 mg of carbimazole.
• Side-effects may be seen - transient in initial phase of treatment include vomiting, anorexia, and diarrhea. More serious complications include facial excoriation, hepatopathy and blood dyscrasias.

• Propylthiouracil - potential serious adverse reactions preclude recommendation for use.

• Cardiac signs should be monitored frequently until condition stabilized.
• Serum thyroxine concentration should be measured 2 weeks after starting medical therapy to confirm euthyroid state (usually takes up to 2 weeks for effect of methimazole to be seen).
• Serum thyroxine, biochemical and hematological measures are recommended generally at 2, 4, 8 and 12 weeks after initiating medical therapy alone, then every 3-6 months thereafter:
  • T4 - adjust medication dose accordingly.
  • Check renal blood parameters (for unmasking of concurrent renal failure) +/- urine SG and hepatic function (potential side-effect of drugs).
  • Check hematology - blood dyscrasias potential complication of drug therapy.
• Monitor blood pressure  - hypertension may become apparent following stabilization.
• Monitor for deterioration in renal function following any of the 3 treatment strategies.

Surgical aftercare

• Post-operative monitoring of calcium Blood biochemistry: total calcium essential if bilateral thyroidectomy performed due to risk of hypocalcemia (typically occurs in first 3-5 days).

Treatment

• 70% of cats have bilateral gland involvement at time of initial diagnosis, common for disease to recur in remaining gland 6 months - 1 year after unilateral surgery:
  • Development of clinical hypothyroidism Hypothyroidism rare (even after bilateral thyroidectomy).
  • Monitor for recurring hyperthyroidism if unilateral thyroidectomy performed (may recur in other gland or be due to intrathoracic ectopic tissue).
  • Development of tumor recurrence or metastases if thyroid carcinoma Thyroid gland: neoplasia.
• Prevalence of side-effects after carbimazole/methimazole therapy is estimated to be 10%; careful monitoring as per data sheet recommendation is required. If facial pruritus, hepatopathy or blood abnormalities develop alternative methods of managing the hyperthyroidism must be sought. These side-effects are generally reversible once the drug is discontinued however severe hematological problems can be seen rarely (eg marked thrombocytopenia and associated bleeding complications).
• Failure to respond to radio-iodine is unusual, and most commmonly due to large volumes of thyroid tissue or thyroid carcinoma. Thyroid carcinomas require 10 x higher doses of radio-iodine Hyperthyroidism: radio-iodine treatment.

• Good following successful bilateral thyroidectomy or radio-iodine treatment.
• Moderate with long-term medical management.
• Guarded if severe congestive heart failure already present.
• Recent work has suggested that thyroid carcinoma may be treated successfully with high-dose radio-iodine and the associated survival times are similar to cats treated for adenoma.
• Poor if not monitored and treated appropriately for development of post-operative hypoparathyroidism Hypoparathyroidism (hypocalcemia).

Acute

• Resting heart rate returns to normal.
• Serum [ALT] Blood biochemistry: alanine aminotransferase (SGPT, ALT)  and [ALP] Blood biochemistry: alkaline phosphatase decreased within 1-2 weeks.
• [Thyroxine] Thyroxine assayreturns to normal.

Chronic

• Weight gain.
• Resolution of clinical signs.

• Failure to remove all thyroid tissue surgically (or presence of ectopic tissue)   →   recurrence of disease:
  • Up to 1 in 5 cats may have intrathoracic ectopic tissue.
• Inadequate dose of methimazole administered or malabsorption of the drug.
• Severe congestive heart failure at diagnosis and failure to stabilize condition prior to surgery.
• Adenocarcinoma - recurrence following surgery or inappropriate dose of radio-iodine administered.

Refereed papers

• Recent references from PubMed and VetMedResource.
• Carney H C, Ward C R, Bailey S J et al (2016) 2016 AAFP Guidelines for the Management of Feline Hyperthyroidism. J Feline Med Surg 18 (5), 400-416 PubMed.
• Harvey A M, Hibbert A , Barrett E L et al (2009) Scintigraphic findings in 120 hyperthyroid cats. J Fel Med Surg 11 (2), 96-106 PubMed.
• Hibbert A, Gruffyd-Jones T, Barrett E L et al (2009) Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. J Fel Med Surg 11 (2), 116-124 PubMed.
• Wakeling J, Everard A, Brodbelt D et al (2009) Risk factors for feline hyperthyroidism in the UK. J Feline Med Surg 50 (8), 406-414 PubMed.
• Shiel R E, Mooney C T (2007) Testing for hyperthyroidism in cat. Vet Clin North Am Small Anim Pract​ 37 (4), 671-691 PubMed.
• Ward C R (2007) Feline thyroid storm. Vet Clin North Am Small Anim Pract​ 37 (4), 745-754 PubMed.
• Milner R J, Channell C D, Levy J K et al (2006) Survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both: 167 cases (1996-2003). JAVMA 228 (4), 559-563 PubMed.
• Shales C (2005) Feline hyperthyroidism: A review of the literature. UK Vet 10 (5), 27-33.
• Hoffmann G, Marks S L, Taboada J et al (2003) Transdermal methimazole treatment in cats with hyperthyroidism. J Feline Med Surg 5 (2), 77-82 PubMed.
• Mooney C T (2002) Pathogenesis of feline hyperthyroidism. J Feline Med Surg 4 (3), 167-169 PubMed.
• Norsworthy G D, Adams V J, McElhaney M R et al (2002) Relationship between semi-quantitative thyroid palpation and total thyroxine concentration in cats with and without hyperthyroidism. J Feline Med Surg 4 (3), 139-143 PubMed.
• Mooney C T (2001) Feline hyperthyroidism. Diagnostics and therapeutics. Vet Clin North Am Small Anim Pract 31 (5), 963-983 PubMed.
• Slater M R, Geller S & Rogers K (2001) Long-term health and predictors of survival for hyperthyroid cats treated with iodine 131. JVIM 15 (1), 47-51 PubMed.
• Bucknell D G (2000) Feline hyperthyroidism - spectrum of clinical presentations and response to carbimazole therapy. Aust Vet J 78 (7), 462-465 PubMed.
• Martin K M, Rossing M A & Ryland L M et al (2000) Evaluation of dietary and environmental risk factors for hyperthyroidism in cats. JAVMA 217 (6), 853-856 PubMed.
• Flanders J A (1999) Surgical options for the treatment of hyperthyroidism in the cat. J Feline Med and Surg 1 (3), 127-34 PubMed.
• Kass P H, Peterson M E, Levy J et al (1999) Evaluation of environmental, nutritional and host factors in cats with hyperthyroidism. JVIM 13 (4), 323-329 PubMed.
• Peterson M E, Melian C & Nichols C E (1998) Measurement of serum concentrations of total and free T4 in hyperthyroid cats and cats with nonthyroidal disease. JVIM 12, 211.
• Broussard J D, Peterson M E, Fox P R (1995) Changes in clinical and laboratory findings in cat with hyperthyroidism from 1983 to 1993. JAVMA 206 (3), 302-5 PubMed.
• Peterson M E & Becker D V (1995) Radioiodine treatment of 524 cats with hyperthyroidism. JAVMA 207 (11), 1422-1428 PubMed.
• Peterson M E, Kinzter P P, Cavanagh P G et al (1983) Feline hyperthyroidism - Pre-treatment clinical and laboratory evaluation of 131 cases. JAVMA 183 (1), 103-110 PubMed.

Other sources of information

• Stephens M, O'Neill D G, Church D B & Brodbelt D C (2013) Feline hyperthyroidism among UK veterinary practices: prevalence, risk factors and spatial distribution. In: Scientific Proceedings, British Small Animal Veterinary Association Congress,Birmingham, April 4-7, 2013, pp 596-597.
• Mooney C M (2009) Hyperthyroidism. In: Ettinger S J, Feldman E C (eds) Textbook of Veterinary Internal Medicine; diseases of the Dog and Cat. 6th edn. Philadelphia, W B Saunders Co, pp 1761-1779.
• Feldman E C & Nelson R W (2004) Feline hyperthyroidism (thyrotoxicosis). In: Feldman E C, Nelson R W (eds) Canine and Feline Endocrinology and Reproduction. 3rd edn, St Louis, Elsevier. pp 153-215.

Further information

The Webinar Vet - Common challenges and practical solutions in feline hyperthyroidism: Treatment