Hyperthyroidism

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Enlarged thyroid gland in a Domestic shorthair cat

Hyperthyroidism is the most common endocrine disorder affecting the thyroid gland of older cats, characterized classically by elevated total thyroxine (T4) above the reference range of 20 - 40 nmol/L. Since the late 1970s, there has been a significant increase in the prevalence of this disease, which resembles toxic nodular goiter of older humans in iodine-deficient areas[1].

Cause

Iodine content of the diet has been suggested as a likely etiologic factor in feline hyperthyroidism[2] (particularly fish-based diets). Disparities in commercial-diet iodine content appears to exacerbate the problem, particularly if cats consume diets that are at first iodine-deficient and later contain excessive iodine[3]. Current feline dietary iodine levels recommended by the Association of American Feed Control Officials (AAFCO) is a basal dry-diet level of 0.35 mg I/kg dry feed[4]. Iodine-restricted diets in geriatric cats has shown to correct the disorder in short-term studies[5].

It is uncommon to see hyperthyroidism in cats under 10 years of age, and is commonly associated with benign thyroid adenoma or adenomatous hyperplasia present in one or both lobes of the thyroid gland. Fewer than 2% of cases occur as a result of a functional thyroid carcinoma[6].

Extensive epidemiological studies over the last two decades have revealed that certain factors appear to contribute to feline hyperthyroidism:

  • Age - the majority of cases occur in cats over 10 years of age
  • Dramatic disparities in iodine concentrations in feline tinned foods[7]
  • Goitrogenic compounds - primarily in commercial food[8], household cleaners, and topical insecticides[9]

The combination of persist exposure to goitrogens repeatedly over time, often years, appears to be the primary etiological agent of this disease in cats. The pathogenesis of hyperthyroidism, especially due to thyroid adenomas, is complex and not entirely clear, but factors such as dietary iodine content, autoimmune thyroiditis and lymphocytic thyroiditis have been disproved or no longer in flavor as theories to explain hyperfunctional thyroid tissue.

A complicating issue associated with this disease is hyperthyroid-masking of underlying chronic renal disease due to hyperthyroid induced increase in renal blood flow and glomerular filtration rate, masking a potential azotemia[10].

Clinical signs

Hyperthyroidism affects older cats most commonly. It is seen occasionally in cats as young as 4 years of age. The clinical signs include weight loss, increased activity, polyphagia, vomiting or diarrhoea, increased vocalisation, increased drinking and increased urination.

Much is written concerning hyperthyroidism as a cause of hypertension, chronic renal disease and cardiac dysfunction. It is difficult to critically review the published literature, as many cats with hyperthyroidism have concurrent renal and cardiac disease that may or may not have a causal relationship with their endocrinopathy. It is well established that hyperthyroidism is associated with increased glomerular filtration rates (GFR) in cats, and that GFR declines after treatment of hyperthyroidism. Although the exact mechanism is not known, it is likely that increased cardiac output and decreased peripheral vascular resistance associated with hyperthyroidism cause increased GFR by enhancing renal plasma flow[11].

Hyperthyroidism per se is rarely a cause of symptomatic hypertension; said another way, most cats with hypertension and hyperthyroidism have persistent hypertension after their thyroid disease is controlled. Cardiac disease is quite different, in that there is no doubt that hyperthyroidism induces a high cardiac output state, which in time can result in direct and indirect damage to the myocardium and eventually signs of congestive heart failure.

Cats which develop CHF as a result of thyrotoxicosis have a characteristic echocardiographic picture, with features of both hypertrophic and dilatative cardiomyopathy. In other words, they have biatrial dilatation, left ventricular hypertrophy, obvious ventricular chamber dilatation, and variable contractility (sometimes with a reduced fractional shortening)[12].

Diagnosis

The diagnosis of feline hyperthyroidism by veterinarians usually requires the combination of a detailed medical history, thorough physical examination, and confirmation of disease via laboratory testing. The medical history should note any changes in activity, behaviour, or appearance that are suggestive of hyperthyroidism. Hyperthyroidism is commonly diagnosed by showing an elevated level of T4 in the blood. However, cats with hyperthyroidism can have normal serum thyroid hormone concentrations, normal hematocrits, and normal serum concentrations of creatinine despite the presence of disease that affects these parameters[13].

Testing for hyperthyroidism is done by;

  • Thyroid manual palpation is important in the detection of thyroid gland abnormalities.
  • Total thyroxine (T4) and triiodothyronine (T3) levels - the total T4 is the first test used to assess thyroid function. In most cats with hyperthyroidism, these levels will be above normal. Total T4 values may fall within normal reference ranges in early hyperthyroidism, or where there is concurrent non-thyroidal illness present ('euthyroid sick syndrome). In house testing of T4 has been shown to be inaccurate for measurement of real T4 in cats. Free T4 can be helpful in diagnosing hyperthyroidism in a patient with high normal T4 along with clinical signs suggestive of hyperthyroidism. It must be noted that non-thyroidal illness can (in <1% of cats) cause artificial elevation of T4 resulting in misdiagnosis.
  • Thyrotropin-releasing hormone (TRH) stimulation test - has good accuracy but there is a 50% chance of transient malaise during testing.
  • T3-suppression test - a relatively easy test to perform but has a grey zone in that it is unclear which results signify hyperthyroidism or not.
  • TSH stimulation test - attempts to measure feline TSH in hyperthyroid cats using commercially available canine TSH assays have not shown the necessary sensitivity to clearly distinguish between low and normal concentrations.
  • Radioisotope scanning/Technetium scanning - requires a facility and personnel able to perform and interpret radio-uptake. This has led to the revelation that 20-25% of hyperthyroid cats have ectopic functional thyroid tissue located elsewhere (often intrathoracic) and thus warrants investigation and often precludes use of surgical intervention.

Hyperthyroid heart disease and cardiac disturbances also are quite common in hyperthyroid cats. These changes include tachycardia (rapid heart rate), murmurs, premature beats, or gallop rhythms. These findings generally are attributed to the high-output cardiac state caused by the effect of excess thyroid hormone on cardiac muscle as well as its effects on the sympathetic nervous system

Treatment

Because an irreversible decline in renal function occurs with many cases of definitive treatment of hyperthyroidism, it may be prudent to assess renal function before and after the hyperthyroid state has been corrected.

There is also evidence suggesting that cats with normal blood urea and creatinine and USG > 1.035 having a greater risk of developing chronic renal disease after treatment for hyperthyroidism[14].

Pretreatment GFR is also reported to be a predictor of post-treatment renal failure, with one study reporting that a pre-treatment GFR of less than 2.25 ml/kg/min was 100% sensitive and 78% specific for post-treatment renal failure. However, none of these predictors withstand thorough investigation and it is best to manage each case on an ad hoc basis[15].

There are numerous medical methods for managing hyperthyroidism.

  • Carbimazole - popular oral treatment in Australia, Canada and Europe. Active metabolite of methimazole, with fewer reported side-effects.
  • Methimazole - popular oral treatment in the United States for oral treatment of hyperthyroidism
  • Ipodate - an oral medication option in cats intolerant of methimazole or carbimazole. This drug may be beneficial for acute management of thyrotoxicosis in some cats, but is not suitable for long-term management[16].
  • Radiotherapy - radioactive iodine(I131) therapy remains the gold standard for patients in which oral administration is unsuccesful[17].
  • Thyroidectomy - an effective surgical procedure in most cats, but technically demanding.
  • Percutaneous intrathyroidal ethanol injection - primarily for unilateral hyperthyroidism, high skill required, not recommended
  • Percutaneous intrathyroidal heat ablation - effective short-term treatment, an experimental procedure only
  • Herbal supplements - Thyroidinum has shown to resolve clinical signs in three of four cases in cats[18]

Because treatment of hyperthyroidism has the potential to reveal pre-existing chronic renal disease and create iatrogenic hypothyroidism, methimazole should be administered in animals with possible renal compromise.

If worsening of renal failure occurs, hyperthyroidism should not be treated or should be treated with methimazole to bring the T4 into the range of 5 - 6 ug/dL or to the lowest achievable level that stops weight loss and does not cause worsening of the azotemia[19][20].

Once a euthyroid state has been achieved with chemotherapy, surgery or radiation therapy, regular quarterly blood testing of T4 should be performed for the life of the cat[21].

References

  1. Edinboro CH et al (2010) Feline hyperthyroidism: potential relationship with iodine supplement requirements of commercial cat foods. J Feline Med Surg 12(9):672-679
  2. Mumma, RO et al (1986) Toxic and protective constituents in pet foods. Am J Vet Res 47:1633-1637
  3. Edinboro CH et al (2013) Iodine concentration in commercial cat foods from three regions of the USA, 2008-2009. J Feline Med Surg 15(8):717-724
  4. Wedekind KJ et al (2010) The feline iodine requirement is lower than the 2006 NRC recommended allowance. J Anim Physiol Anim Nutr (Berl) 94(4):527-539
  5. van der Kooij M et al (2013) Effects of an iodine-restricted food on client-owned cats with hyperthyroidism. J Feline Med Surg 16(6):491-498
  6. Martin, KM et al (2000) Evaluation of dietary and environmental risk factors for hyperthyroidism in cats. J Am Vet Med Assoc 217:853-856
  7. Edinboro CH et al (2013) Iodine concentration in commercial cat foods from three regions of the USA, 2008-2009. J Feline Med Surg Feb 25
  8. Peterson M (2012) Hyperthyroidism in cats: what's causing this epidemic of thyroid disease and can we prevent it? J Feline Med Surg 14(11):804-818
  9. August, JR (2006) Consultations in feline internal medicine. Vol 5. Elsevier Saunders, USA. pp:211-212
  10. Williams TL et al (2010) Survival and the development of azotemia after treatment of hyperthyroid cats. J Vet Intern Med 24(4):863-869
  11. Bradley, SE et al (1974) The thyroid and the kidney. Kidney Int 6:346
  12. Malik R (1995) Feline hyperthyroidism -- an opinionated perspective The Veterinarian
  13. Graves TK (2011) When normal is abnormal: keys to laboratory diagnosis of hidden endocrine disease. Top Companion Anim Med 26(2):45-51
  14. Williams TL et al (2010) Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. J Vet Intern Med 24(5):1086-1092
  15. Stortz, JS (2009) et al
  16. Gallagher, AE & Panciera, DL (2011) Efficacy of iopanoic acid for treatment of spontaenous hyperthyroidism in cats. JFMS 13:441-447
  17. van Hoek IM et al (2009) Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats. JFMS 11:309-314
  18. Chapman SF (2012) Homeopathic and integrative treatment for feline hyperthyroidism--four cases (2006-2010). Homeopathy 100(4):270-274
  19. Williams TL et al (2010) Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. J Vet Intern Med 24(5):1086-1092
  20. Norsworthy, GD et al (2006) The feline patient. 3rd edition. Blackwell Publishing, Iowa, p:149
  21. Higgs P & Hibbert A (2012) Managing hyperthyroidism in cats. Vet Rec 171(9):225-226
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