The thyroid gland’s main job is producing the two thyroid hormones: thyroxine (T₄) and triiodothyronine (T₃).These hormones influence cellular metabolism, including increasing cellular oxygen consumption and increasing protein synthesis.
Thyroid hormone production is regulated by the hypothalamic-pituitary-thyroid axis. This axis starts with the hypothalamus releasing thyrotropin-releasing hormone (TRH), which binds to thyrotroph cells in the pituitary gland. The pituitary gland subsequently releases thyroid-stimulating hormone, which will travel through the bloodstream to the thyroid. The thyroid then produces and releasesT₃ andT₄.
Because everything in physiology likes to be backwards to confuse poor vet students,T₃ is actually the more active thyroid hormone. And even more confusing, T₄ is actually the precursor toT₃, not the other way around! The conversion fromT₄ toT₃ occurs in the peripheral tissues whereT₃ is used.
Table of Contents
Hyperthyroidism
As you might expect, hyperthyroidism occurs when the thyroid produces too much thyroid hormone. We most commonly see this condition in cats!
Hyperthyroidism is typically caused by functional tumours of the thyroid gland itself. In cats, thyroid adenomas are the most common tumour. These tumours are considered benign, however due to their ability to produce hormones, become significant. In dogs, the malignant form of these tumours, thyroid carcinomas, are the most common cause.
Clinical Findings
- Palpable thyroid. In cats, some clinicians will describe a “thyroid slip” that occurs when you run your hand down the cat’s neck applying gentle pressure. The enlarged thyroid will feel like a marble as it moves underneath your finger!
- Weight loss despite a normal or increased appetite. This occurs because the high amount of thyroid hormone cranks cellular metabolism to the max, and the body is not able to keep up with the high nutritional demand this causes.
- Cardiovascular issues such as tachycardia, cardiomegaly and congestive heart failure. When the metabolism is cranked up, the heart tries to deliver as much oxygen as possible to the tissues, by increasing its heart rate and contraction strength. This can lead to hypertrophic cardiomyopathy eventually.
- Hyperexcitability. The exact reason for this is unknown, however it seems that thyroid hormones have a role in modulating neuron signalling.
NAVLE tip:
When you think hyperthyroidism, think of a really skinny, angry cat with an enlarged thyroid gland. Also the cat is really, REALLY hungry. Probably why it’s so angry, but that also might be the hyperexcitability.
© Greene licensed under CC BY-SA 4.0.
Diagnosis
The best method of diagnosis is serum totalT₄. BecauseT₄ is the precursor toT₃, it is the form that is most commonly found in the blood. By measuring this hormone, we can get an idea of what’s going on in that animal. Animals with hyperthyroidism will have an elevated serum totalT₄.
But wait! There is one thing that can complicate diagnosis: euthyroid sick syndrome. Basically, sick animals will have lower thyroid hormone levels than healthy animals. So if your suspect hyperthyroid cat has other conditions at the same time (often renal failure), they may actually have a normal serum totalT₄, even though it should be elevated. Wild. In these animals, you can measure freeT₄ concentration, and combine that with your physical exam findings and history to make a diagnosis.
Treatment
The main treatment options for hyperthyroidism are radioiodine therapy, thyroidectomy, antithyroid medication and iodine-deficient diets.
The treatment of choice for these cases is radioiodine therapy, due to its safety and efficacy. In this treatment, the animal is administered radioactive iodine, which will concentrate in the thyroid gland as the thyroid tries to use the iodine to make thyroid hormone. The radiation will damage and destroy the functional thyroid tumour.
Thyroidectomy is surgical removal of the thyroid gland, which can also be a good option in some cases. However, there are two important considerations: hypothyroidism and hypoparathyroidism. In some animals, both lobes of the thyroid gland are overproducing thyroid hormone. If the entire thyroid gland was removed in these animals, they will likely suffer from hypothyroidism. These animals will need to be treated as if they have hypothyroidism (see later). Somewhat similarly, the thyroid gland has some friendly neighbours, the parathyroid glands, that may be accidentally removed as part of the thyroidectomy. This may cause hypoparathyroidism in these animals, requiring treatment with vitamin D and calcium.
Medical management of hyperthyroidism involves the drug methimazole, which blocks thyroid hormone synthesis. Prescription diets with low iodine work on a similar principle. By having extremely low levels of iodine available to the thyroid gland, production of hormone is reduced. However, it is absolutely critical that these cats receive no other food beyond their low-iodine diet. Both the diet and medication will not treat the hyperthyroidism, but can manage it well enough to allow the animal a comfortable life.
Hypothyroidism
Similar to hyperthyroidism, we most commonly see hypothyroidism caused by lesions directly within the thyroid gland. Hypothyroidism most commonly occurs in dogs, and has two major etiologies: lymphocytic thyroiditis and idiopathic atrophy.
Lymphocytic thyroiditis is inflammation of the thyroid gland with lymphocytes and plasma cells, and is thought to be immune-mediated. Over time, the inflammation leads to progressive tissue damage to the thyroid gland, preventing it from producing sufficient thyroid hormone. Idiopathic atrophy is similar, although we don’t know what causes the thyroid gland destruction.
Clinical Signs
- Weight gain without an increase in appetite. Because thyroid hormones control cellular metabolism, their absence turns cellular metabolism levels way down. Thus, animals can gain weight, even if they are being fed the same amount, or less, than they were before.
- Lethargy, exercise intolerance and heat-seeking behaviour. Again, with cellular metabolism at low levels, these animals just don’t have the energy to do much of anything. They also have difficulty regulating their temperature, often causing them to be cold. These animals may show “heat-seeking behaviour”, where they want to lay in warm sun or next to the heater.
- Symmetrical alopecia. Decreased cellular metabolism reduces hair re-growth, leading to these animals becoming alopecic.
- “Tragic expression”. This is probably one of my favourite clinical signs ever. With hypothyroidism, animals can get accumulation of glycosaminoglycans in the skin, causing the skin to become puffy and thickened. This can give the dogs a very sad, droopy facial expression. Poor pup!
NAVLE tip:
When you think of hypothyroidism, think of a fat, sad looking, hairless dog lying in the sun. So tragic.
© Harrington licensed under CC BY-SA 4.0.
Diagnosis
Hypothyroidism
Hypothyroidism can be confirmed by serum thyroid hormone testing, similar to hyperthyroidism. This includes tests like totalT₄, freeT₄ and TSH levels.
Most veterinarians will perform a totalT₄ concentration as an initial screening test. If the animal comes back within reference range on this test, they can be considered normal. If they have lowT₄, they could be normal, hypothyroid, or have euthyroid sick syndrome. FreeT₄ is considered to have better diagnostic value, however most commercially available tests are roughly equivalent to totalT₄.
Measuring TSH can also provide insight into the animal’s thyroid function. Animals with thyroid lesions should have low serum or freeT₄, and high TSH concentrations. This is because the pituitary gland is desperately trying to stimulate the thyroid to do something, so it pumps out a lot of TSH. However, it is important to note that this test should not be interpreted withoutT₄ concentrations. Dogs can have normal TSH levels and be hypothyroid, can have elevated TSH and be normal or have euthyroid sick syndrome.
If the diagnosis is still somewhat murky, a TSH stimulation test can be completed. In this test, TSH is administered to the animal to see what the thyroid gland’s response is 6 hours later. If the animal produces adequate thyroid hormone, they are normal. If they produce some, but not a lot, they have euthyroid sick syndrome. If they have no response, they are truly hypothyroid.
Thyroid hormone testing can also be backed up by hematology/biochemistry findings, if the thyroid testing is somewhat ambiguous. Animals with hypothyroidism classically have a normochromic, normocytic, nonregenerative anemia and hypercholesterolemia on their bloodwork.
Thyroiditis
Once you’ve confirmed the animal has hypothyroidism, you might wonder if the animal has idiopathic or immune-mediated disease. There are blood tests available to look for antithyroglobulin antibodies, anti-T₄ antibodies, and anti-T₃ antibodies. Detection of any of these antibodies on its own does not mean the animal has thyroiditis, but if they are present along with depleted thyroid hormone and no response to a TSH stimulation test, you can diagnose the animal as having immune-mediated thyroiditis.
Treatment
Once you have muddled your way through all the different thyroid hormone tests available, treatment for hypothyroidism is thankfully pretty simple! These animals require daily administration of levothyroxine, a synthetic thyroid hormone.
Goiter
Finally, what the heck is a goiter? Goiter refers to enlargement of the thyroid gland for a non-neoplastic and non-inflammatory reason.
We most commonly associate goiter with iodine deficiency. Iodine is a critical component of thyroid hormones, so if it is not adequately provided to the thyroid gland, thyroid hormone production drops. The pituitary gland will try to compensate by producing more TSH, similar to the situation in hypothyroidism. However, because these animals’ thyroid gland is actually normal, they response to increased TSH by becoming hyperplastic. Often, this increase in glandular production actually produces enough thyroid hormone to give the animal normal thyroid function.
Young newborn animals are most susceptible to iodine deficiency goiter. Prevention by feeding iodized salt to the dam is key, as well as preventing access to goitrogenic plants like Brassica species.
© Hedstrom licensed under CC BY-SA 4.0.
Comparison Table
| Thyroid Dysfunction | Clinical Signs | Diagnostic Test Results | Treatment |
|---|---|---|---|
| Hyperthyroidism | Weight loss Enlarged thyroid Hyperexcitability Tachycardia | Elevated total T₄ Elevated free T₄ | Radioiodine therapy Thyroidectomy Methimazole Iodine-deficient diets |
| Hypothyroidism | Weight gain Lethargy Alopecia Heat-seeking behaviour | Low total T₄ Low free T₄ Elevated TSH No response on TSH stimulation test | Levothyroxine |
| Goiter | Enlarged thyroid | Elevated TSH with normal T₄ | Iodine supplementation Remove goitrogens |
Check Your Understanding
Zachary JF. Pathologic Basis of Veterinary Disease, Sixth Edition.
Peterson ME. The Thyroid Gland. Merck Veterinary Manual 2020.
