Hypothyroidsim is one of the most common canine endocrine disorders (for review, see reference 1). It is a condition that is characterized by the deficiency of active thyroxine (T4) and triiodothyronine (T3) hormones which are produced by the thyroid gland. In dogs, primary hypothyroidism is the most common form of the disease. It results from the destruction of the thyroid gland following lymphocytic thyroiditis or idiopathic atrophy.
In contrast to humans, it is often difficult to make a definitive diagnosis for dogs. The diagnosis of hypothyroidism is based on the presence of clinical signs, thyroid function test results and response to the thyroid hormone replacement therapy. Clinical signs are usually non-specific and indefinite often including lethargy, weight gain and various skin related problems. A low circulating total T4 concentration suggests hypothyroidism. However, in order to reliably evaluate canine thyroid function, the results of the total T4 measurement should be combined with measurements of free T4 and TSH. Dogs with primary hypothyroidism would be expected to have low total T4 and free T4 levels and high TSH concentrations. Furthermore, antithyroglobulin antibodies can be screened as their presence is an indication of lymphocytic thyroiditis which may lead to hypothyroidism.
Biochemical properties of canine TSH
TSH belongs to the glycoprotein hormone family that also includes the luteinizing hormone (LH), the follicle stimulating hormone (FSH) and chorionic gonadotropin (hCG). Each of these hormones consists of two noncovalently linked subunits: Alpha and beta.
The alpha subunit is common for all four hormones of this group. There is a 73% sequence homology between human and canine alpha subunits. The canine alpha subunit consists of 96 amino acid residues (aar), which is four aar longer compared to the human alpha subunit. The calculated molecular weight of the canine alpha subunit derived from the amino acid sequence is 10,693 Da. Similarly to the human alpha subunit, the canine alpha subunit contains two potential N-glycosylation sites at residues 56 and 82 and five intramolecular disulfide bonds (2).
The beta subunits are hormone-specific. The beta subunits of canine and human TSH are highly homologous (91%). Both consist of 118 aar and contain six intramolecular disulfide bonds. The calculated molecular weight of the canine TSH beta subunit (protein part) is 13,517 Da. There is only one potential N-glycosylation site that is located at position 23 in both species. Two allelic variants in the canine beta subunit that differ at position 81 (Val81Ala) have been reported (3).