Hyperthyroidism is considered to be the most common endocrine disorder of cats and a disease frequently encountered in small animal practice. The clinical syndrome results from excessive circulating concentration of the active thyroid hormones, thyroxine (T4) and triiodothyronine (T3) produced by an abnormally functioning thyroid lobe. The underlying pathology in over 98 % of cases is benign adenomatous hyperplasia (adenoma) and as such the disease carries a favourable prognosis with effective therapy. Failure to institute therapy leads to progression of thyrotoxicosis, emaciation and severe cardiac and metabolic dysfunction and eventual death. However, although severe cases are rarely seen in practice today, there are a number of consequences and complications associated with hyperthyroidism that must be considered in individual cats.

Effects on the cardiovascular system

Cardiovascular abnormalities are relatively common in hyperthyroid cats and can include systolic murmurs, powerful apex beat, gallop rhythm, tachycardia and other arrhythmias determined at physical examination, mild to severe cardiomegaly on radiographic examination, sinus tachycardia, increased R-wave amplitude (lead II), premature complexes, intraventricular conduction disturbances and atrial and ventricular arrhythmias on electrocardiographic examination and left ventricular hypertrophy, thickening of the interventricular septum, left atrial and ventricular dilation and myocardial hypercontractility on echocardiographic ^(6,22,23,27). Although these abnormalities are still relatively common, their severity and prevalence has decreased in recent years presumably because of earlier diagnosis^(7,13).

The cardiac abnormalities are related to direct effects of thyroid hormone on cardiac muscle and indirect effects mediated through the interaction of thyroid hormone with the adrenergic nervous system, or occur to compensate for altered peripheral tissue perfusion. While hyperthyroidism most commonly induces a reversible form of hypertrophic cardiomyopathy, a dilative type has also been described and overt congestive cardiac failure can arise form either, albeit uncommonly^(17,19). In affected cats, treatment of the underlying cardiac disease is required together with antithyroid medication. In many cases, on-going treatment of the cardiac disease is required even when euthyroidism is induced suggesting either irreversible thyroid hormone induced damage or pre-existing cardiac disease. Cats with the dilative form of hyperthyroidism tend to exhibit more severe cardiac disease.

Mild to moderate hypertension is relatively common in hyperthyroid cats and in one study was diagnosed in 34 of 39 (87 %) hyperthyroid cats⁽¹⁸⁾. The mechanism is unclear but presumably is related to increased beta adrenergic activity with subsequent increase in heart rate and cardiac output and stimulation of renin release. It is largely reversible but when severe can induce ocular abnormalities including haemorrhage, oedema and retinal detachment ultimately leading to blindness^(20,25). However, overt retinopathy is less commonly seen with hyperthyroidism than with other causes of hypertension such as renal failure^{(11,20,25,28)}.

Effects on routine clinicopathological analyses

Hyperthyroidism has been associated with a variety of routine clinicopathological abnormalities such as mild to moderate erythrocytosis, macrocytosis, Heinz body anaemia and higher mean platelet size^(8,23,26,27). However, the most striking abnormalities are elevations in the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALKP), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST). At least one of these enzymes is elevated in over 90 % of hyperthyroid^(7,23,27). The elevations in these enzymes can be dramatic but serum ALKP and total T4 concentrations are significantly correlated⁽¹²⁾. Despite these elevations, histological examination of hyperthyroid cat livers has revealed only modest and non-specific changes. Several recent reports have shown that both liver and bone contribute to increased ALKP activity in hyperthyroid cats. ^(3,4,12,16).

Hyperphosphataemia, in the absence of azotaemia, was originally reported in approximately 20 % of cases and this has more recently been reported in a higher percentage (36-43 %) of hyperthyroid cats particularly when compared to an age-matched control group^(3,4,23). This together with the elevation in the bone isoenzyme of ALKP is suggestive of altered bone metabolism in hyperthyroidism. Circulating osteocalcin concentration, used as a measure of osteoblastic activity and bone remodeling, although variable, was elevated in 16 of 36 (44 %) hyperthyroid cats compared to values from 10 healthy cats. In human thyrotoxic patients, there is an increased risk of osteoporosis because of a direct effect of thyroid hormone on bone. The net bone loss leads to the release of calcium and a tendency towards hypercalcaemia, hyperphosphataemia, hypoparathyroidism and reduced concentrations of activated vitamin D. Early reports suggested that circulating calcium concentration was largely unaffected by hyperthyroidism, but only total calcium was measured. In two separate studies 18 of 36 (50 %)⁽³⁾ and 4 of 15 (27 %)⁽⁴⁾ hyperthyroid cats had serum ionised calcium concentrations below the reference range. In addition, hyperparathyroidism appears to be common in hyperthyroid cats. In 30 hyperthyroid cats, circulating parathormone concentration was elevated in 23 (77 %) cases⁽⁴⁾. Of 8 hyperthyroid cats in which plasma 1,25 Vitamin D concentration was measured, 3 values were above the reference range but there was no overall significant difference between this group and 20 healthy cats⁽⁴⁾. The aetiology and clinical consequence of hyperparathyroidism, hyperphosphataemia and ionised hypocalcaemia remain unclear.

A number of other unusual or significant clinicopathological abnormalities have been described in hyperthyroid cats. Hypokalaemia with associated clinical signs has been reported in four hyperthyroid cats but the aetiology remains unclear⁽²¹⁾. Two separate studies have examined the effect of hyperthyroidism on circulating fructosamine concentration and found significantly lower concentrations in hyperthyroid compared with healthy cats presumably as a result of increased protein turnover^(14,24). As a consequence, caution is advised in interpreting serum fructosamine concentration in hyperthyroid cats particularly if concurrently diabetic.

Effects on the renal system

The presence of hyperthyroidism can increase glomerular filtration rate (GFR), decrease serum creatinine concentration and mask underlying renal disease⁽¹⁾. Decreased GFR, increased serum urea and creatinine concentration and development of overt clinical signs of renal disease have all been reported after successful treatment of hyperthyroidism, irrespective of therapeutic modality (antithyroid medication, surgical thyroidectomy or radioiodine)^(2,5,9,15). Assessment of GFR before treatment can act as a predictor of post-treatment renal failure with a low GFR in hyperthyroidism indicating an increased risk for adverse clinical outcome⁽²⁾. However, techniques for assessment of GFR are impractical as they typically involve use of radioisotopes. Estimation of GFR is also possible using a plasma iohexol clearance test which requires no special licensing⁽⁵⁾. In the absence of such estimations, careful evaluation of serum urea and creatinine concentration and urine specific gravity is required prior to treatment of hyperthyroidism. If both serum parameters are normal and the urine is concentrated, the risk of developing renal failure after therapy is minimised. Serum creatinine should be evaluated in light of the animal's muscle mass with lower values expected in emaciated cats⁽¹⁰⁾. If the serum creatinine and urea concentrations are higher than expected and the urine isosthenuric, then there is a risk of developing renal failure. In such cases, trial therapy using either methimazole or carbimazole, should be attempted and renal function reassessed once euthyroidism is achieved. Initially low and then increasing doses of antithyroid medication have been suggested in suspect cases but there is little scientific evidence to support this. If there is no deterioration after treatment of the hyperthyroidism, then a more permanent therapeutic option may be selected. If renal function declines, therapy should be instituted for renal failure and the dose of antithyroid medication adjusted to maximise renal function whilst attempting to control clinical signs. Maintenance of a mildly hyperthyroid state may be beneficial in some individuals but this has not yet been evaluated. Avoidance of hypothyroidism is important because it may have its own detrimental effects on GFR⁽¹⁰⁾.

References

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