Introduction

A definitive diagnosis of hypothyroidism in dogs can often be very challenging and it may be a disease that we are over-diagnosing due to a lack of understanding of what the different tests and methods actually tell us. Most common mistake made is over-interpreting low total T4 levels. Often these levels are low due to medications or due to nonthyroidal illness syndrome and not due to hypothyroidism.

Clinical Presentation

Hypothyroidism is more commonly seen in Boxers, Dachshunds, Dobermans, Golden Retrievers, Great Danes, Irish Setters, Miniature Schnauzers and Poodles. There is no real sex predilection. Most dogs are between 4–6 years of age at time of onset of clinical signs.

There are four types of hypothyroidism in dogs. The first three are "true" hypothyroidism:

1.  Primary hypothyroidism accounts for over 90% of cases and is due to destruction of the thyroid gland (lymphocytic thyroiditis). This is most commonly caused by immune-mediated destruction of the thyroid gland or due to the presence of antithyroglobulin antibodies. Thyroiditis has been shown to be hereditary in Beagles and Borzois.

2.  Secondary hypothyroidism is caused by impaired secretion of thyroid-stimulating hormone (TSH). This is very rare and accounts for less than 5% of cases. Causes include congenital malformation (German Shepherds), pituitary destruction or due to medications (glucocorticoids).

3.  Tertiary hypothyroidism is due to decreased secretion of thyroid-releasing hormone (TRH). This can be due to congenital defects, tumours or abnormal binding of TRH in the pituitary. It has not been reported in dogs.

4.  Nonthyroidal illness syndrome (euthyroid sick syndrome). There is no real dysfunction of the thyroid gland, but rather a deregulation of thyrotropic feedback control. This is often seen in a variety of acute and chronic diseases (e.g., sepsis, trauma, pneumonia, chronic renal failure, starvation, ketoacidotic diabetics, inflammatory bowel disease or patients with heart failure).

Clinical signs of primary hypothyroidism can include a combination of any of the following:

 Systemic: Lethargy, exercise intolerance, increased weight without polyphagia

 Dermatological: 60–80% of cases will show some form of skin disease. Bilaterally symmetrical truncal alopecia or sometimes focal on the tail (rat tail). Usually nonpruritic unless they have a secondary infection. They may also have a dull, brittle and dry hair coat. Some cases show evidence of hyperkeratosis, hyperpigmentation or thickness (myxedema). Myxedema is rare and is characterised as non-pitting thickening of the skin, especially of the face.

 Cardiovascular: Bradycardia and arrhythmias

 Neuromuscular: Peripheral neuropathy and weakness including laryngeal paralysis. Some cases may also have facial paralysis. Seizures have been reported due to atherosclerosis causing infarcts in the brain.

 Ocular: Corneal lipid deposits and dry eye

 Reproductive: Irregular oestrus intervals in females

 Gastrointestinal: Mega-oesophagus has been reported in dogs with hypothyroidism, but remains controversial as clinical signs did not reverse with treatment.

 Congenital hypothyroidism: Young animals showing dwarfism. They may also have a variety of clinical signs similar to those seen in adult dogs described above, including mental impairment.

 Clinical signs with secondary or tertiary hypothyroidism will reflect the degree of involvement of the rest of the pituitary gland - these could include signs of hyperadrenocorticism, diabetes insipidus, hypoadrenocorticism or reproductive problems.

Diagnostic Testing

a. Routine Haematology and Serum Chemistry

A mild nonregenerative anaemia is found in about 30% of cases with hypothyroidism. An elevated cholesterol level is found in 75% of hypothyroid cases and up to 88% of cases will have hypertriglyceraemia. Some other minor changes on serum chemistry may also be evident.

b. Total T4 or T3

Measuring basal levels of total T4 or T3 can lead to over-diagnosis of hypothyroidism. Basal T3 levels are of little use as the majority of T3 is intracellular. Low levels of T4 do not confirm hypothyroidism. Many other factors can lead to low T4 levels - e.g., hourly fluctuations, fasting, age, concurrent illness and a vast majority of drugs (glucocorticoids, phenobarbitone, other).

c. Free T4

Determination of free T4 by equilibrium dialysis (fT4ED) correlates very well with a TSH stimulation test for the diagnosis of canine hypothyroidism and is currently the test used most often. Free T4 is the biologically active form of thyroid hormone and is less affected by nonthyroidal illnesses. Please note that there are many fT4 assays available, but only the methods that use a dialysis step are valid in dogs.

d. TSH

A canine-specific TSH (cTSH) kit is available. cTSH has a high specificity, but a low sensitivity for hypothyroidism and therefore a normal value does not exclude hypothyroidism. Combining cTSH with a free T4 measurement by dialysis will increase the sensitivity of confirming a diagnosis of hypothyroidism. A dog with hypothyroidism will have an elevated (or high normal) cTSH level with a concurrent decreased fT4 level.

e. TSH Stimulation Test

The TSH stimulation test is currently the best single test for diagnosing canine hypothyroidism and excluding euthyroid sick syndrome. The TSH stimulation test uses recombinant human TSH which can be expensive, hence the use of free T4 by equilibrium dialysis. T4 levels are measured at 0 and 6 hours post-TSH administration. With primary hypothyroidism, both pre- and post-TSH T4 will remain low.

f. TRH Stimulation Test

TRH stimulation test helps to differentiate secondary from tertiary hypothyroidism and is normally only used in patients that show other abnormalities in pituitary-releasing hormones. The test evaluates release of TSH in response to TRH.

g. Antithyroglobulin and Anti-T3, Anti-T4 Antibodies Testing

Antithyroglobulin antibodies indicate lymphocytic thyroiditis. Dogs with thyroiditis do not always have hypothyroidism but will develop it over time. Antibody testing is especially helpful in diagnosing early thyroiditis and hypothyroidism and is a recommend test to rule out hereditary thyroiditis.

h. Thyroxine Trial

A trial therapy of thyroxine has been advocated as a diagnostic tool for hypothyroidism. Patients may show some improvement of clinical signs even if they do not have hypothyroidism due to thyroxine's anabolic effect. Thyroxine is unlikely to be harmful, but may delay a definitive diagnosis for the patient if they are not hypothyroid.

i. Scintigraphy

Scintigraphy can differentiate hypothyroidism from nonthyroidal illness but is not readily available. Scintigraphy has been helpful also in finding the cause of congenital hypothyroidism by differentiating pituitary disease from thyroid agenesis.

j. Thyroid Ultrasound

Thyroid ultrasound may be helpful but greatly depends on the ultrasonographer's experience. The thyroid gland in a hypothyroid dog will be less echogenic than normal.

Summary

As evident from above, a combination of clinical signs and testing should be used to confirm a diagnosis of hypothyroidism. Hypothyroidism has a wide range of clinical signs, and further testing should be considered if routine biochemistry shows high fasting levels of triglycerides and/or cholesterol. It is also important to find out which tests/methods for hypothyroidism are used by your laboratories. There is a great difference in the accuracy of the results obtained by the different methods, and canine-specific assays should be used where possible.

Below is a table taken from: Ettinger SJ, et al. Textbook of Veterinary Internal Medicine, 7th ed. (2010). It summarises the performance of the different diagnostic tests for hypothyroidism.

Table 287-1. Performance of various diagnostic tests for hypothyroidism in dogs

The specificity is greatly increased by combining TSH with either TT4 or fT4 than either test alone. For this reason, the Orthopaedic Foundation of Animals requires patients to undergo an extensive thyroid panel to rule out hypothyroidism before adding them to the thyroid registry. The thyroid panel for the registry includes: TT4, fT4ED, cTSH and antithyroglobulin antibody test - hence by combining a few tests greatly enhances the chances of an accurate diagnosis or exclusion of hypothyroidism.

Stimulation testing (TSH or TRH) is still considered to be the gold standard by many clinicians especially when basal thyroid test results (TT4, fT4ED, cTSH) are equivocal. Unfortunately, these tests can be expensive and not always readily available. Best is to contact your laboratory or a specialist centre if you want to pursue any of these tests.

In patients where cost is a concern, a free T4 level by equilibrium dialysis may be money well spent, but again has to be interpreted with other parameters (e.g., clinical signs, breed, etc.). Most clinicians currently will test fT4ED and cTSH simultaneously as their preferred method of diagnosing hypothyroidism.

There is a helpful diagnostic algorithm for hypothyroidism in: Ettinger SJ, et al. Textbook of Veterinary Internal Medicine, 7th ed. 2010:1756.

Feline Hypothyroidism

Hypothyroidism in cats is very rare with only a few documented cases existing of naturally occurring disease - mostly congenital disease seen in Abyssinian cats and DSH cats. Hypothyroidism is more commonly seen in cats secondary to treatment for hyperthyroidism (post radiation or surgery). Iodine deficiency as a cause for hypothyroidism is not readily seen anymore due to adequate levels of iodine in commercial cat foods. Euthyroid sick syndrome in cats has not yet been described.

Clinical signs include lethargy, weight gain and obesity. Constipation and cold intolerance are also noticed. Cats also display dermatological changes including thinning of the hair coat, alopecia and dry skin. Kittens can also display delayed tooth eruption.

Diagnosis of hypothyroidism in cats is complicated by the lack of species-specific assays. In general, the same tests that are used in dogs for the diagnosis of hypothyroidism are also employed in cats.

Treatment is the same as for dogs - synthetic levothyroxine, and it is very effective. Dose 0.05–0.1 mg/cat given orally daily.

References

1.  Ettinger SJ, Feldman EC. Textbook of Veterinary Internal Medicine. 7th ed. Saunders Elsevier; 2010.

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5.  Higgins MA, Rossmeisl JH, Panciera DL. Hypothyroid-associated central vestibular disease in 10 dogs: 1999–2005. J Vet Intern Med. 2006;20:1363–1369.

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10. Greco DS. Diagnosis of congenital and adult-onset hypothyroidism in cats. Clin Tech Small Anim Pract. 2006;21(1):40–44.