Hypothyroidism

Hypothyroidism describes inappropriately reduced function of the thyroid gland that results in a state of thyroid hormone deficiency.

Central hypothyroidism encompasses secondary or tertiary hypothyroidism or both. This term should be used when secondary and tertiary hypothyroidism are not distinguished.

Congenital hypothyroidism refers to hypofunction of the thyroid gland present from birth. Affected animals may not display clinical signs until later in life. It is caused by abnormal development or function of any part of the hypothalamic–pituitary–thyroid axis.

Genetic hypothyroidism is a form of congenital hypothyroidism that results from a genetic mutation. Although rare, mutations in the T4 peroxidase gene have been described in dogs and cats.

Thyroid dysgenesis refers to a structural developmental defect of the thyroid gland.

Thyroid dyshormonogenesis refers to a developmental or acquired abnormality of thyroid hormone synthesis.

Primary thyroid disease characterised by replacement of normal parenchymal tissue with adipose or fibrous connective tissue, but without significant inflammatory infiltration. In some cases, this may represent an end stage of lymphocytic thyroiditis. The definitive test for thyroid atrophy is thyroid biopsy. However, this is uncommonly performed. The disease is often assumed by demonstration of primary hypothyroidism without the presence of circulating antibodies against thyroglobulin, T4, or T3. In such cases, other potential causes of primary hypothyroidism must be excluded (including iatrogenic, neoplastic, drug-induced, or congenital causes).

Primary thyroid disease characterised by multifocal or diffuse infiltration of the thyroid tissue by lymphocytes, macrophages, and plasma cells. This can lead to progressive destruction of thyroid follicles. The definitive test for lymphocytic thyroiditis is thyroid biopsy. However, this is uncommonly performed. Alternatively, the presence of disease can be inferred by demonstration of circulating antibodies against thyroglobulin or thyroid hormones (T4 or T3). The presence of anti-thyroid antibodies does not provide evidence of thyroid dysfunction.

Hypothyroidism caused by neoplasia destroying normal thyroid parenchyma.

Hypothyroidism caused by trauma to any component of the hypothalamic–pituitary–thyroid axis.

The presence of lymphocytic thyroiditis without alteration of thyroid function. This is typically identified as thyroid autoantibody positivity without increased TSH or decreased T4 concentrations or clinical signs. This condition may or may not progress to subclinical/compensating hypothyroidism or clinical hypothyroidism. Lymphocytic thyroiditis may resolve in some dogs.

Myxoedema is the increased deposition of glycosaminoglycans within the dermis and when present is strongly suggestive of hypothyroidism in dogs. This can lead to the clinical appearance of non-pitting oedema and a tragic facial expression. This most commonly affects the head but can involve other areas of the body.

• Decreased total T4 with increased cTSH concentrations are consistent with a diagnosis of primary hypothyroidism (observed in approximately 70% of cases).
• Decreased total T4 with reference interval cTSH concentrations are observed in approximately 30% of dogs with primary hypothyroidism. However, this combination of results can also be observed with non-thyroidal illness, in dogs receiving thyroid suppressive medications, and in some healthy dogs, particularly within certain breeds.

A diagnosis of canine hypothyroidism should only be pursued in the presence of clinical or clinicopathological changes considered consistent with the disease. First-line testing should include concurrent measurement of at least total T4 and cTSH concentrations. Suspicion of central hypothyroidism is increased in dogs with documented pituitary diseases (e.g., neoplasia, hypophysitis, or congenital abnormalities) or following pituitary surgery or radiotherapy. A diagnosis of central hypothyroidism should be considered when first-line testing reveals decreased total T4 and reference interval or undetectable cTSH concentrations. This condition can be difficult to distinguish from primary hypothyroidism with reference interval TSH concentrations and non-thyroidal illness. Free T4 may be useful to distinguish between hypothyroidism and non-thyroidal illness. Additional tests to distinguish between primary and central hypothyroidism may include TRH stimulation testing or neuroimaging if pituitary or hypothalamic pathology is suspected.

Primary subclinical hypothyroidism is a state of increased TSH concentration with reference interval thyroid hormone concentrations (in the absence of interfering autoantibodies) and absence of clinical signs. This is presumed to represent a stage of thyroid disease, where adequate thyroid reserve capacity prevents the development of overt clinical signs. In some cases, progression to clinical hypothyroidism may occur. TSH concentrations may normalise or remain persistently elevated without apparent progression of disease. Treatment of subclinical hypothyroidism is not recommended at this time. Reference interval total T4 (in the absence of interfering autoantibodies) with increased cTSH concentrations may be consistent with subclinical hypothyroidism, primary hypoadrenocorticism, recovery from nonthyroidal illness, or the response following removal of thyroid suppressive medication.

Hypothyroidism-inducing medications can cause clinical hypothyroidism due to effects on the synthesis of thyroid hormones as an intended or unintended effect. These drugs include methimazole, carbimazole, and potentiated sulphonamides.

Transient hypothyroidism refers to a temporary abnormality of the pituitary–thyroid axis resulting in high TSH and low T4 concentrations that is not due to primary hypothyroidism. Transient hypothyroidism may be induced by a number of possible causes including a recovery phase from concurrent non-thyroidal illness, untreated hypoadrenocorticism, removal of thyroid suppressive medications, or the administration of drugs that block thyroid hormone synthesis.