Hyperthyroidism

A multisystemic disease caused by excessive secretion of thyroid hormones: Interpretation of thyroxine (T4) and triiodothyronine (T3) tests. Secretion is increased due to a thyroid hyperplasia or neoplasia. It is more common in cats than dogs.

• Feline hyperthyroidism: of unknown aetiology. Usually affects middle-aged or older animals. The clinical picture is typically adenomatous hyperplasia, which is bilateral in 70% of cases. In some cats, it is caused by a solitary adenoma and very rarely a carcinoma (usually non-functioning).
• Canine hyperthyroidism: usually associated with thyroid carcinoma, although functional adenomas have occasionally been found. Thyroid carcinoma is a relatively common tumour, but less than 5% are functioning and cause hyperthyroidism. These tumours are highly malignant with a high capacity for metastasis.

Symptoms

Feline hyperthyroidism: The most common symptom is weight loss, caused in part by an increase in the basal metabolic rate. Other common symptoms include:

Polyphagia / vomiting / polyuria-polydipsia / behavioural changes (nervousness, hyperactivity) / diarrhoea due to malabsorption / heat intolerance / poor hair quality.

Conflicting symptoms can also appear, such as decreased appetite, weakness, anorexia, and dyspnoea.

In 80% of cases, the enlarged thyroid gland can be palpated (unilateral or bilateral). In the remaining cases, it is not palpable because it is located at the entrance to the thoracic cavity. Heart murmurs, tachycardia, and other cardiovascular abnormalities are common findings on auscultation. The cat may present muscle tremors, muscle weakness and ventroflexion of the neck, and in advanced stages, retinal haemorrhage and retinal detachment.

Canine hyperthyroidism: Most common symptoms:

Weight loss / polyphagia / polyuria-polydipsia / behavioural disturbances (nervousness, hyperactivity) / frequent defecation.

Symptoms appear early, when the tumour is relatively small, and as it grows, the animal may present dyspnoea, cough, dysphagia, and stridor due to compression and invasion of adjacent tissues.

Interpretation of laboratory tests

General tests:

• Complete blood count: Red blood cells: mild or moderate polycythaemia, with elevated haematocrit, haemoglobin and MCV; sometimes anaemia. Leukocytes: stress leukogram. Platelets: increased platelet size.
• Blood biochemistry ALT/AST/Alkaline phosphatase/LDH: Mild to moderate elevation. Glucose: increase might be due to stress or associated diabetes mellitus. Urea/creatinine: elevated if accompanied by nephropathy or dehydration. Hyperphosphataemia (even without kidney impairment). Hypokalaemia. Hypocalcaemia (ionized calcium).
• Urine test: Urine-specific gravity is elevated in 50% of cases; 3% decrease or normal values in others. Possible glucosuria due to stress hyperglycaemia or diabetes mellitus. Elevated cortisol/creatinine ratio in cats.

Specific tests. Hormone tests:

• Baseline serum total T4:
  Advantages: test of first choice. Values are elevated in 95% of hyperthyroid cats.
  Drawbacks: if the test is negative in a suspected animal (hidden hyperthyroidism), the test must be repeated 7-14 days later due to fluctuations in hormonal levels. Some non-thyroidal diseases or the administration of some drugs can decrease serum T4 values to normal or low levels in hyperthyroid cats.
• Serum free T4:
  Advantages: highly sensitive and particularly useful in suspected cases with normal total T4 values. Free T4 does not decrease due to the presence of non-thyroid diseases or drug administration.
  Drawbacks: May be unreliable if used as a sole test. Not as specific as total T4 determination, and free T4 values can be elevated in some euthyroid cats with non-thyroidal diseases.
  In general, elevated free T4 values together with normal or elevated baseline T4 levels are indicative of hyperthyroidism.
• TSH:
  In dogs with functional thyroid tumours, endogenous TSH levels are low or at the lower limit of normal; however, this test is less sensitive than other tests and should not be used as a sole test. There are as yet no over-the-counter tests for determining TSH in cats.

Specific tests. Functional tests:

• T3-suppression test:
  T3 inhibits the secretion of TSH by the pituitary gland, and consequently reduces T4 secretion in a healthy animal. In hyperthyroid animals, hormone secretion occurs independently of TSH, so the administration of T3 hardly affects the secretion of T4.
  Protocol:
  • Day 1: measure baseline levels of T3 and T4.
  • Days 2-3: administer 25 μg of T3 (liothyronine or triiodothyronine) orally every 8 hours, 7 doses in total.
  • Day 4: 2-4 hours after administering the 7th dose, determine T3 and T4 levels.
  Interpretation
  • Euthyroid cat: T4 < 1.5 μg/dL or T4 ≤ 50% of baseline values.
  • Hyperthyroid cat: T4 > 1.5 μg/dL.
  Serum T3 levels are not useful for diagnosis, but they are useful for assessing whether the treatment has been administered correctly. Advantages: Very useful for diagnosing hyperthyroidism, particularly in animals with other concomitant diseases and in cases of hidden hyperthyroidism.
  Drawbacks: Difficulty obtaining the drug. It is important to confirm that the owner will be able to correctly administer the drug.
• TSH stimulation assay:
  In normal cats, TSH administration stimulates the release of T3 and T4; in hyperthyroid cats, it will reduce T3 and T4 levels.
  The test is not recommended due to the poor response obtained and the difficulty of interpreting the results.
• TRH stimulation assay:
  In normal cats, TRH stimulates the release of TSH, which in turn increases T4 secretion; in hyperthyroid cats, TRH does not affect T4 values due to chronic TSH suppression.
  Protocol:
  • Draw a blood sample to determine baseline T4 levels.
  • Administer 0.1 mg/kg intravenous TRH (TRH PREM®, Novartis)
  • Draw a blood sample 4 hours after administering TRH and determine T4 levels.
  Interpretation: Apply the formula:
  Ratio = (T4 post TRH - T4 baseline) / T4 baseline x100
  • • Euthyroid: Ratio > 60%
    • Inconclusive: Ratio 50% – 60%
    • Hyperthyroid: Ratio < 50%
  Advantages: reliable test for the diagnosis of hyperthyroidism.
  Drawbacks: TRH administration causes significant but transient side effects (salivation, vomiting, tachypnoea, defecation).

Other tests.

• Thyroid biopsy:
  Characterises the cells responsible for over-secretion of thyroid hormone and distinguishes between hyperplasia, a benign tumour, or a malignant tumour. It is important to perform a biopsy because it will determine the therapeutic approach. Obtaining a sample from the border of the mass is preferable to a Tru-cut biopsy, because it is difficult to obtain good quality samples using the Tru-cut needle, and there is a risk of bleeding. Fine needle aspiration cytology is not recommended due to the difficulty of interpreting the results.
• Determination of anti T3 and T4 autoantibodies:
  In dogs, the presence of anti-T3 and T4 autoantibodies can artificially elevate baseline T4 levels, but not free T4 levels.

Bibliography

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