Hypothyroidism in cats
In hypothyroidism, impaired production and secretion of the thyroid hormones result in a decreased metabolic rate. This disorder is most common in dogs but also develops rarely in other species, including cats.
Aetiology
Although dysfunction anywhere in the hypothalamic-pituitary-thyroid axis may result in thyroid hormone deficiency, >95% of clinical cases of hypothyroidism in dogs appear to result from destruction of the thyroid gland itself (primary hypothyroidism). The two most common causes of adult-onset primary hypothyroidism in dogs include lymphocytic thyroiditis and idiopathic atrophy of the thyroid gland. Lymphocytic thyroiditis, probably immune-mediated, is characterized histologically by a diffuse infiltration of the gland by lymphocytes, plasma cells, and macrophages, and results in progressive destruction of follicles and secondary fibrosis. Idiopathic atrophy of the thyroid gland is characterized histologically by loss of thyroid parenchyma and replacement by adipose tissue. (See also autoimmune thyroiditis, Diseases Involving Cell-mediated Immunity.)
In dogs, the most common cause of secondary hypothyroidism is destruction of pituitary thyrotrophs by an expanding, space-occupying tumour. Because of the non-selective nature of the resulting compressive atrophy and replacement of pituitary tissue by such large tumors, deficiencies of other (one or more) pituitary hormones also usually occur.
Other rare forms of hypothyroidism in dogs include neoplastic destruction of thyroid tissue and congenital (or juvenile-onset) hypothyroidism. Congenital primary hypothyroidism may result from one of various forms of thyroid dysgenesis (eg, athyreosis, thyroid hypoplasia) or from dyshormonogenesis (usually an inherited inability to organify iodide). Congenital secondary hypothyroidism (associated with clinical signs of disproportionate dwarfism, lethargy, gait abnormalities, and constipation) has been documented in a family of Giant Schnauzers. Congenital secondary hypothyroidism also has been reported in German Shepherds with pituitary dwarfism associated with a cystic Rathke’s pouch. However, the degree of TSH deficiency in these dogs is variable, and clinical signs are usually caused primarily by deficiency of growth hormone (rather than thyroid hormone).
In cats, iatrogenic hypothyroidism is the most common form. Hypothyroidism develops in these cats after treatment for hyperthyroidism with radioiodine, surgical thyroidectomy, or use of an antithyroid drug. Although naturally occurring hypothyroidism is an extremely rare disorder in adult cats, congenital or juvenile-onset hypothyroidism does also occur. Recognized causes of congenital hypothyroidism in the cat include intrathyroidal defects in thyroid hormone biosynthesis (dyshormonogenesis), an inability of the thyroid gland to respond to TSH, and thyroid dysgenesis. All reported cats with hypothyroidism have had the primary (thyroidal) disorder. Secondary (pituitary) or tertiary (hypothalamic) hypothyroidism have not been described in either the juvenile or adult cat.
Clinical signs
In adult cats, clinical signs associated with hypothyroidism usually include lethargy, dullness, non-pruritic seborrhoea sicca, hypothermia, and occasionally bradycardia. Obesity may develop, especially in cats with iatrogenic hypothyroidism, but it is not a consistent sign. Bilaterally symmetric alopecia, with the exception of pinnal involvement, does not appear to develop, but focal areas of alopecia over the craniolateral carpi, caudal hocks, and dorsal and lateral tail base have occasionally been observed. In young cats with congenital or juvenile-onset hypothyroidism, the clinical signs include disproportionate dwarfism, severe lethargy, mental dullness, constipation, and bradycardia.
Diagnosis
In dogs, hypothyroidism is probably one of the most over-diagnosed diseases. Many diseases and conditions can mimic hypothyroidism, and some of the clinical signs, even in dogs with normal thyroid function, can improve following administration of exogenous thyroid hormone. In addition, a variety of nonthyroidal factors (eg, nonthyroid illness and prior administration of certain drugs) can lead to low serum thyroid hormone measurements in euthyroid dogs, cats, and other species. Definitive diagnosis of canine hypothyroidism requires careful attention to clinical signs, routine laboratory testing, and demonstration of low serum concentrations of total or free thyroid hormones that are unresponsive to TSH administration.
There are well-recognized clinicopathologic abnormalities associated with hypothyroidism, the severity of which usually correlates with the severity and chronicity of the hypothyroid state. These alterations are nonspecific and may be associated with many other diseases in dogs. Their presence, however, adds supportive evidence for a diagnosis of hypothyroidism in a dog with appropriate clinical signs. The classic hematologic finding associated with hypothyroidism is a normocytic, normochromic, nonregenerative anaemia. The classic serum biochemical abnormality is hypercholesterolemia, which occurs in ~80% of dogs with hypothyroidism. The value of serum cholesterol determination as a screening test for hypothyroidism cannot be overemphasized, as cholesterol concentrations represent a sensitive but inexpensive biochemical marker for this disease in dogs. Other clinicopathologic abnormalities may include high serum concentrations of triglycerides, alkaline phosphatase, and creatine kinase.
Because T3 is the most potent thyroid hormone at the cellular level, it would seem logical to measure its concentration for diagnostic purposes. However, serum T3 concentrations may be low, normal, or (occasionally) high in dogs with documented hypothyroidism. The diagnostic value of a serum T3 determination is particularly weak during early thyroid failure because the “failing” thyroid tends to increase the relative synthesis and secretion of T3 versus T4. In the hypothyroid dog in which values for serum T3 are high, anti-T3 antibodies, which produce spurious results in most T3 radioimmunoassays, should be suspected.
The determination of basal serum total T4 concentration by radioimmunoassay techniques may provide important information to rule out a diagnosis of hypothyroidism. Because T4 is produced only by the thyroid gland, hypothyroid animals can, in most cases, be distinguished based on a low resting serum total T4 concentration. However, many nonthyroidal illnesses and administration of various drugs including glucocorticoids, sulfonamides, anticonvulsants (eg, phenobarbital), NSAID, and radiocontrast agents may “falsely” lower serum T4 concentrations in dogs. Even when historical and physical findings do not suggest other factors that would lower serum T4, the diagnosis of hypothyroidism is best confirmed by measuring free T4 concentration (by dialysis), which is affected to a much lesser degree by nonthyroidal illness or drug therapy than is the total T4 concentration.
Free T4 is the fraction of circulating thyroxine that is not bound to plasma proteins (normally 0.1% of total T4). Because the free concentration of T4 reflects the hormone available for entry into cells, free T4 determinations provide a more consistent assessment of thyroid status at the tissue level than measurement of total T4. Furthermore, free T4 is not as likely as total T4 to be affected by nonthyroidal illness or drug therapy. Determination of free T4 is most accurately performed by methods that include a dialysis step (eg, equilibrium dialysis). The finding of a low free T4 concentration is consistent with the diagnosis of hypothyroidism, as concentrations usually remain within the reference range in animals with nonthyroidal illness.
Determination of serum TSH concentrations by use of a valid species-specific TSH assay can be a useful adjunctive test for hypothyroidism in dogs and horses. Animals with primary hypothyroidism (by far the most common type) would be expected to have low serum T4 and/or free T4 concentrations with high endogenous TSH concentrations. Unfortunately, serum TSH concentrations remain within the reference range in 20-40% of dogs with confirmed hypothyroidism. Although a few dogs with normal serum TSH concentrations have secondary hypothyroidism, pituitary TSH deficiency is extremely rare, and most dogs with normal TSH concentrations (ie, a false-negative result) have primary hypothyroidism. In contrast, falsely high serum TSH concentrations (ie, a false-positive result) are occasionally found in euthyroid dogs with nonthyroidal illness. Thus, serum TSH determinations should never be evaluated alone, but always in conjunction with the dog’s history, routine laboratory abnormalities, and total or free T4 concentrations.
Circulating antithyroglobulin antibodies can be detected in up to half of dogs with hypothyroidism and are believed to reflect a state of autoimmune thyroiditis. Measurement of these antibodies in breeding studs and bitches has been proposed as a method to identify dogs with autoimmune thyroid disease. Serum thyroglobulin autoantibody determinations may be a useful adjunctive diagnostic aid for hypothyroidism but should not be used alone. Identification of these autoantibodies support the diagnosis if the dog has clinical signs and other laboratory data consistent with the disorder.
Although extremely rare in dogs, circulating thyroid hormone autoantibodies (anti-T3 or anti-T4 antibodies) are occasionally detected and also are believed to reflect a state of autoimmune thyroiditis. These antibodies, which can be formed against either T3 or T4 (or both), produce a spurious increase in the apparent T3 or T4 concentrations, into the hyperthyroid range in most dogs. Of all the thyroid hormones, only measurement of free T4 (by dialysis) is not affected by autoantibodies directed at T4 or T3 because the serum autoantibodies are removed in the dialysis step. Therefore, if hypothyroidism is suspected in a dog with circulating thyroid hormone autoantibodies, serum free T4 concentration should be determined to help confirm the diagnosis.
Treatment
Thyroxine (T4) is the thyroid hormone replacement compound of choice. With few exceptions, replacement therapy is necessary for the remainder of the amimal’s life; careful initial diagnosis and tailoring of treatment is essential. The reported replacement dosages for Levothyroxine (SyntheticT4) in cats is 20-60 μg/kg daily.
The most important indicator of the success of therapy is clinical improvement. Reversal of changes in coat and body weight should be assessed only after 1-2 mo of therapy. When clinical improvement is marginal or signs of thyrotoxicosis are seen, the clinical observations can be supported by therapeutic monitoring of serum thyroid hormone concentrations (“post-pill testing”). With once-daily administration of T4, the peak serum concentration of T4 generally should be slightly high to high-normal 4-8 hr after dosing and should be low-normal to normal 24 hr after dosing. Animals on bid administration probably can be checked at any time, but peak concentrations can be expected at the middle of the dosing interval (4-8 hr) and the nadir just before the next dose. When the dose is stabilized, serum T4 (with or without T3) concentrations should be checked 1-2 times per year.
If clinical signs of hypothyroidism remain despite the use of reasonable doses of thyroid hormone, the following must be considered: 1) the dose or frequency of administration is improper; 2) the owner is not complying with instructions or is not successfully administering the product; 3) the animal is not absorbing the product well, or is metabolizing and/or excreting it too rapidly; 4) the product is outdated; or 5) the diagnosis is incorrect.