The thyroid glands, hyper and hypothyroidism
The Thyroid Glands
The thyroid glands are paired glands located in the ventral neck, either side of the trachea, at the level of the 5-6th tracheal rings.
The glands consist of thyroid epithelial cells and parafollicular cells. Epithelial cells synthesize the two thyroid hormones thyroxine (T4) and triiodothyronine (T3), from dietary iodine. The main role of the thyroid hormones is to increase the body’s basal metabolic rate.
Parafollicular cells secrete calcitonin, which counteracts the effects of parathyroid hormone, reducing circulating calcium levels.
Hyperthyroidism
Feline hyperthyroidism is the most common endocrine disease in cats, and is a multisystemic disorder resulting from excessive production and secretion of thyroid hormones.
It most commonly affects middle-aged to older cats and has no gender or significant breed predisposition. In 97-99% of cases, hyperthyroidism is caused by a benign thyroid tumour – either adenomatous hyperplasia, a thyroid adenoma, or a multinodular adenoma. The remaining 1-3% of cases have a malignant tumour (thyroid carcinoma). Over 70% have bilateral involvement.
Clinical Signs and Examination
Clinical signs classically include cachexia (wasting of general physical condition, muscle mass and extreme weight loss associated with an underlying disease) and polyphagia.
This is seen as the high levels of circulating thyroid hormones cause a hypermetabolic state, which results in the cat not being able to consume enough calories to compensate for the speed at which they are being burned off.
Other signs include tachycardia, potentially with a cardiac murmur +/- arrhythmia (gallop rhythm), gastrointestinal signs, PU/PD, poor coat quality, hyperactivity and behavioural changes such as vocalisation and irritability or increased socialisation.
Hyperthyroidism is generally diagnosed through a combination of clinical history, physical examination and laboratory results.
On physical exam, tachycardia (often exceeding 220bpm), systolic heart murmurs, and arrhythmias (gallop rhythm) are often identified. Weight loss, poor muscle mass and reduced body condition score are also often seen, as are reductions in skin and coat quality.
Thyroid nodules (goitres) may also be palpable, when running a finger and thumb down either side of the trachea. Placing the thumb and finger either side of the trachea, and with the cat in a sitting position, the examiner moves their thumb and finger from the larynx down to the thoracic inlet, and back up again. Often, a goitre will be pushed down as the area is palpated, and then ‘slip’ up back into position.
As hyperthyroidism is associated with hypertension, signs of target organ damage may also be seen; common target organs include the eyes, kidneys and CNS. The most classic sign of this is blindness caused by retinal detachment.
Diagnostic Tests
Diagnostic testing includes biochemistry, haematology and endocrine testing +/- urine analysis.
On biochemistry, elevations in the liver enzymes alanine aminotransferase (ALT) and alkaline phosphatase (ALP) may be present. Haematological analysis also frequently reveals increases in red blood cells, neutrophils and lymphocytes.
Total T4 is the most common test used to diagnose the condition, with elevations typically reliable in confirming the diagnosis. However, as thyroid hormone levels can fluctuate throughout the day, and due to the risk of concurrent diseases or medications lowering T4 levels, a free T4 (assessed via equilibrium dialysis which is more specific than total T4) may be required. This should be performed where total T4 results are within normal limits, but hyperthyroidism is still suspected.
Other diagnostic procedures in cats include nuclear scintigraphy; in this procedure, the cat is injected with an intravenous radionuclide which is concentrated by thyroid tissue, before being imaged with a gamma camera, to evaluate any areas where the radionuclide is concentrating. This procedure requires specialised equipment and is typically not performed outside of large university hospitals (if required).
As many cats with hyperthyroidism have concurrent cardiac changes, echocardiography is recommended. Cardiomegaly may be seen on ultrasound examination, and in cases of chronic hyperthyroidism, left ventricular hypertrophy may be apparent.
Arterial blood pressure should also be assessed, due to the high incidence of systemic hypertension in hyperthyroid cats.
Treatment
Hyperthyroidism is managed medically, surgically or using radioactive iodine therapy.
Medical management includes administration of methimazole or carbimazole, either systemically or topically. These medications inhibit the synthesis of thyroid hormones, but do not prevent the tumour from growing, so dose adjustments may be required in the future. Many cats respond well to these medications; however, some do experience adverse effects such as vomiting, inappetence, lethargy and dermatological changes such as alopecia and erythema.
Prior to surgical or radioiodine therapy, hyperthyroid patients should be treated medically until a euthyroid state is achieved, to assess for occult renal disease.
Following appropriate control of hyperthyroidism, biochemistry and urinalysis should be repeated to ensure BUN, creatinine and urine specific gravity remain normal following the reduction in renal perfusion (associated with resolved hypertension and tachycardia).
Medical therapy also reverses weight loss, cardiac and metabolic complications, making the patient a better surgical candidate. Medical therapy is recommended for 6-12 weeks prior to surgery in these cases.
In patients who will not tolerate or respond well to long-term medication, surgical or radioactive iodine therapy may be considered.
Thyroidectomy is performed commonly. This involves the surgical removes the thyroid gland(s); however, many cats are found to have ectopic thyroid tissue within the thoracic inlet or mediastinum, and surgical management will not be curative for such
cases. During thyroidectomy, care must be taken not to remove or disrupt the parathyroid glands, as iatrogenic hypoparathyroidism, and therefore hypocalcaemia may result. Postoperatively, these patients should be monitored for signs of hypocalcaemia, and ionised calcium levels should be checked regularly in the acute postoperative period.
Radioactive iodine (I-131) therapy has been shown to be a simple, safe and effective method of treating hyperthyroidism, and where available, is preferred to surgical thyroidectomy. This has a >95% success rate in destroying hyperfunctional thyroid tissue, including ectopic tissue. The radioactive iodine isotope (I-131) is most commonly administered by IV or SC injection, and following administration, the patient must remain in a dedication hospitalisation area until their radiation levels decrease.
Hypothyroidism
Hypothyroidism results from inadequate production of T3 and T4. It is commonly seen in dogs, and rarely seen in cats (congenital hypothyroidism is typically seen in cats, but is a very rare condition).
Primary hypothyroidism is a result of gradual, progressive destruction of the thyroid gland. This occurs due to an immune-mediated process, or by idiopathic atrophy. Immune-mediated destruction is progressive, and clinical signs may not be seen until around 3/4 of the gland has been destroyed.
The condition can be seen in any breed, but retrievers, Dobermans, Daschunds, Schnauzers, Boxers and Old English Sheepdogs are some of the breeds most commonly affected. Neutering is associated with increased risk for developing the disease, and the disease is most commonly reported in middle-aged dogs.
Secondary canine hypothyroidism occurs due to a failure in the development of pituitary cells, which cause the impaired release of thyroid-stimulating hormone (TSH) from the pituitary gland. In cases with pituitary cell failure/dysfunction, secondary atrophy of the thyroid gland is seen, due to inadequate stimulation.
Clinical Signs and Examination Findings
Clinical signs are variable, and depend on the age of the dog when the thyroid hormone deficiencies develop. These signs can also vary between breeds.
The most common clinical signs are associated with a reduction in metabolism, and include dullness, lethargy, exercise intolerance and weight gain. Other clinical signs include alopecia without pruritis, which can be local or generalised and symmetrical or non-symmetrical, but generally does not affect the head or limbs. Other dermatological signs include pyoderma and seborrhoea. Neuromuscular signs, such as weakness, ataxia and vestibular signs, are also reported.
Hypothyroidism is a non-specific condition and is gradual in onset, and so physical examination findings may vary depending on the clinical signs seen.
These findings may include dull mentation, weight gain, dermatological changes, ocular abnormalities, bradycardia, cardiac arrhythmias, ataxia or weakness.
Diagnostic Tests
Biochemistry typically reveals increased cholesterol and triglyceride levels even on a fasted sample, as the body’s ability to degrade lipids is reduced in hypothyroid patients. If the patient is euthyroid sick, abnormalities associated with the underlying disease process will be seen.
Endocrine tests which are typically performed include a total T4, free T4 and TSH level. Total T4 levels will most frequently be below the reference range. A decreased free T4 and increased TSH is seen in dogs with typical hypothyroidism, and confirms the condition. However, it is important to consider the patient’s medical history, as any concurrent disease, or medications may affect the results, particularly if administering antibiotics, NSAIDs, frusemide, steroids or phenobarbital.
Treatment
Hypothyroidism is treated by administering oral levothyroxine (synthetic T4). Rechecking serum T4 levels are recommended at around 4-8 weeks after starting treatment, with dosage adjustments made depending on results and the patient’s status.
When collecting bloods, these should ideally be taken at the trough level (immediately before the dose is due), and/or the peak level (4-6 hours post dose). Ongoing monitoring should take place at around the same time (e.g. always 4-6 hours post pill) to avoid daily T4 fluctuations impacting on results.
References
Merrill L. Small Animal Internal Medicine for Veterinary Technicians and Nurses. Iowa: Wiley-Blackwell, 2012.
Carney H, Ward C, Bailey J, et al. AAFP Guidelines for the Management of Feline Hyperthyroidism. J Feline Med Surg 2016; 18: 400-416.
Taylor S, Sparkes A, Briscoe K, et al. ISFM Consensus Guidelines on the Diagnosis and Management of Hypertension in Cats. J Feline Med Surg 2017; 19: 288-303.
