Hyperthyroidism

Normal thyroid function as opposed to hypo- or hyperthyroidism. It can apply to animals without or after successful treatment of thyroid disease.

Excess of thyroid hormone production by the thyroid gland.

Phenomenon characterised by increased circulating concentrations of thyroid hormones (total and free thyroxine [T4]), with evidence of thyroid stimulating hormone (TSH) suppression. Almost all affected cats have clinical signs of thyrotoxicosis and palpable goitre.

Clinical manifestations that arise from the effects of excess thyroid hormone concentrations secondary to hyperthyroidism or to exogenous sources (e.g., iatrogenic, dietary).

There is currently no clear scientific evidence that cats or dogs develop thyroid storm. In humans, thyroid storm is an endocrine emergency characterised by multiple organ failure and hyperthermia caused by severe thyrotoxicosis and is often associated with triggering illnesses and a high mortality rate. Some hyperthyroid cats can be intolerant to stress and can present in cardiac or respiratory distress with or without congestive heart failure and require appropriate management. This does not mean they meet the criteria for ‘thyroid storm’.

Some cats with hyperthyroidism are not overtly affected. There may only be subtle clinical signs or a barely palpable goitre with within the reference interval circulating total T4 concentration (usually towards the upper reference interval limit). These cats can be addressed as subclinical and usually have evidence of TSH suppression. Hyperthyroidism can then be confirmed by additional tests (scintigraphy or additional laboratory tests [fT4 via equilibrium dialysis or retest with T4 later]). Caution is advised in starting treatment at this stage.

Hyperfunction of the thyroid gland itself, not caused by stimulation by TSH or thyrotropin-releasing hormone (TRH).

Hyperfunction of the thyroid gland caused by excess stimulation by TSH (secondary) or TRH (tertiary). There are currently no reports of these disorders in cats or dogs.

See central hyperthyroidism.

Hypothyroidism, as defined according to ALIVE criteria, induced by treatment of thyroid disease. Such treatments include thyroidectomy, radioactive iodine, and external beam radiation, which can result in transient or permanent hypothyroidism and anti-thyroid drugs that usually result in transient hypothyroidism.

Oversupplementation (iatrogenic) or inadvertent ingestion of thyroid hormone medications or consumption of diets containing excess thyroid hormones (e.g., contamination or use of rations containing thyroid tissue [dietary]).

Thyrotoxicosis due to oversupplementation of thyroid hormone.

Consumption of diets containing excess thyroid hormones (e.g., contamination or use of rations containing thyroid tissue).

Any enlargement of the thyroid gland. The presence of goitre does not indicate hyper- or hypofunction. In feline hyperthyroidism, terms such as ‘thyroid nodule’ and ‘thyroid slip’ are often used interchangeably to describe palpable goitre.

The classic technique is performed with the cat in a sitting position, the neck extended, and the clinician’s thumb and forefinger sweeping downwards on each side of the trachea from the larynx to the sternal manubrium until the goitre is palpated. The thyroid gland size is scored using a validated semi-quantitative estimation: the scoring system ranges from 0 (non-palpable) to a maximum of 6 (nodule >25 mm), with score 1 = 1–<3 mm, score 2 = 3–<5 mm, score 3 = 5–<8 mm, score 4 = 8–<12 mm, and score 5 = 12–25 mm. If the thyroid glands are not equal in size, thyroid size should be recorded for each nodule.

Refers to a condition where hyperfunctioning thyroid tissue is present outside of the thyroid gland. It results from developmental defects at early stages of thyroid gland embryogenesis. It is usually found between the base of the tongue and the base of the heart and occurs in <5% of cases.

Follicular nodular goitre (previously known as multinodular goitre) is the second most common cause of hyperthyroidism in humans. The condition most closely resembling this human condition and commonly observed in older cats is called adenomatous hyperplasia or adenoma.

It is a multi-system autoimmune disorder characterised by TSH receptor antibodies and bilateral goitre. It is usually associated with hyperthyroidism. This form of hyperthyroidism is the most common type of hyperthyroidism in humans but has not yet been recognised in cats.

Benign, non-cancerous growth of thyroidal epithelial cells. Feline hyperthyroidism is most commonly (approximately 98% of cases) associated with benign adenomatous hyperplasia or adenoma of the thyroid gland (previously referred to as toxic nodular goitre). Left untreated, thyroid tissue in affected cats continues to grow and hyperfunction, resulting in more severe clinical signs over time. This condition in cats most closely resembles follicular nodular disease (previously known as multinodular goitre), which is the second most common cause of hyperthyroidism in humans.

Hyperthyroid cats that have been managed for many months to years with anti-thyroid drugs can develop resistance to anti-thyroid medication and probable malignant transformation of the thyroid gland. The acronym “SHIM-RAD” is used to characterise this sub-group of cats clinically based on their history, clinical features, and scintigraphic findings. These SHIM-RAD cats are defined on the basis of five characteristics: (1) Severe hyperthyroidism (serum T4 > 24 μg/dL or >300 nmol/L); (2) Huge thyroid tumour size or volume; (3) Intrathoracic tumour nodule(s); (4) Multifocal disease pattern [≥three nodules]; and (5) Resistance to Anti-thyroid Drug treatment. As in those that present initially with thyroid carcinoma, most of these cats require very high doses of radioiodine (e.g., 30 mCi, 1100 MBq) in order to completely ablate all thyroid tissue.

A risk factor is a factor in the animal’s environment (extrinsic) or in the animal itself (intrinsic) that may contribute to the development of the disease. In feline hyperthyroidism, multiple factors are thought to contribute to the development of the disease.

Signalment, age, sex, and breed are all recognised intrinsic risk factors. Particularly, in feline hyperthyroidism advancing age, sex (female), and breed (non-purebred) are potential intrinsic risk factors. Potential extrinsic risk factors include substances in food, drugs, and the environment. In feline hyperthyroidism, many substances can act as goitrogens (substances that disrupt thyroid hormone production and consequently stimulate TSH release) or as thyroid disruptors (chemicals that interfere with the hypothalamic–pituitary–thyroid axis directly or via thyroid hormone receptors). Disparate dietary iodine content, polybrominated diphenyl ethers (PBDEs), and bis-phenol A are implicated as potential extrinsic risk factors. The level of evidence for other substances (e.g., soy proteins) is low.

Hyperthyroidism is confirmed by demonstration of increased circulating total T4 concentration in association with supportive signalment and clinical signs.

• If total T4 is increased in the absence of supportive signalment and clinical signs, reassessment of clinical status (especially if total T4 is clearly increased) or repeat T4 measurement (if total T4 is marginally increased) is recommended.
• If there are supportive clinical signs, but total T4 is not increased and is in the upper end of the reference interval, hyperthyroidism is possible. In these cases, concurrent non-thyroidal disease can be associated with suppression of total T4 to within reference interval. Subclinical hyperthyroidism is associated with within the reference interval total T4 concentrations. Further diagnostic tests for hyperthyroidism could be considered (demonstration of concurrent suppression of TSH, concurrent increased free T4, increased technetium uptake on thyroid scintigraphy or increased total T4 on repeated testing).

Diagnosis of hyperthyroidism due to exogenous disease is achieved by documenting supportive clinical signs, increased total T4 concentration, and suppressed TSH concentration. There will also be evidence of an exogenous source and reversal of the abnormalities when the source is withdrawn. Thyroid tissue is not well visualised if thyroid scintigraphy is performed.

The TSH stimulation test has not been validated for assessment of hypothyroidism in treated hyperthyroid cats. It is also not recommended for the investigation of hyperthyroidism.

This is defined as a serum TSH concentration that is less than the detection limit (<0.03 mg/mL) when measured by the canine TSH (cTSH) chemiluminescent assay (CLIA), or low (<0.01 ng/mL) when measured by the more sensitive TSH bulk acoustic wave assay (TSH-BAW) [25].

A mild increase in serum creatinine is expected (and normal) with effective treatment of hyperthyroidism. In some cases, this means that the serum creatinine evolves from within to above the reference interval; this is referred to as unmasking CKD. In other words, the cat develops post treatment renal azotaemia that was not apparent before treatment of hyperthyroidism.

The goal is the achievement of euthyroidism. This should be assessed primarily by resolution of reversible clinical and clinicopathological abnormalities associated with the disease whilst avoiding complications as subclinical and clinical hypothyroidism. Total T4 concentrations should ideally be within the lower half of the reference interval because values within the upper half may be associated with persistence of hyperthyroidism. Decreased values should be avoided, as they may indicate hypothyroidism but may be unavoidable in cats with significant concurrent non-thyroidal illness. Concurrent measurement of TSH concentrations is recommended. Undetectable TSH concentrations may support persistence of hyperthyroidism if total T4 concentrations are within the upper half of the reference interval. Increased TSH concentrations support clinical or subclinical hypothyroidism depending on whether the total T4 concentration is below or within the reference interval, respectively.

Medical treatment is defined as a palliative treatment, which has to be given on a daily basis (oral or transdermal). Usually anti-thyroid drugs (thioureylenes) such as methimazole (thiamazole) or carbimazole that block the synthesis of thyroid hormones through inhibition of thyroid peroxidase are used.

Surgical treatment refers to thyroidectomy and can be considered a curative treatment. It can be performed unilaterally or bilaterally. Intra- and extracapsular approaches are possible. Bilateral thyroidectomy can result in hypothyroidism and hypoparathyroidism.

Use of radioactive iodine (radioiodine) is considered the treatment of choice for hyperthyroidism for many cats. Thyroid hormones and thyroglobulin are the only iodinated organic molecules in the body, so any ingested or injected iodine is taken up by the sodium-iodide symporter of thyroid follicular epithelial cells. Thus, radioactive isotopes of iodine are concentrated in the thyroid gland where their beta-particles exert significant local tissue damage, destroying hyperactive thyroid tissue. Adjacent normal tissue can certainly be destroyed as well, but radioiodine is ideally administered at low doses aimed to achieve euthyroidism. Several methods are used for calculating dose of radioiodine needed to treat cats with hyperthyroidism. Hyperthyroidism resolves in 90–95% of radioiodine-treated cats, but many of these cats will develop either overt or subclinical hypothyroidism.

A palliative therapy consisting of the administration of a restricted iodine diet that reduces thyroid hormone production from the thyroid gland.

Radiofrequency heat ablation and ethanol injection are potentially curative procedures. The affected thyroid lobe is permanently damaged by injection of ethanol or heat. Due to questionable efficacy and side effects, these treatments are not recommended.

Two treatment options for malignant thyroid tumours. Chemotherapy involves the use of systemic drugs to target and destroy tumour cells, while external beam radiation is a form of local radiation therapy.

TSH suppression is a treatment administered to attempt to reduce the risk of recurrence after removal of thyroid tumours of follicular cell origin. Common medications include levothyroxine and liothyronine.