Hypothyroidism is the condition that results from thyroid hormone deficiency. Diagnosis is based on clinical signs such as lethargy, weight gain, obesity, and coat changes, as well as low serum thyroid hormone concentrations. The treatment is lifelong, daily oral thyroid hormone replacement.
Hypothyroidism results from thyroid hormone deficiency and is most common in dogs but also develops rarely in other species, including cats, horses, and other large domestic animals.
Etiology of Hypothyroidism in Animals
Although dysfunction anywhere in the hypothalamic-pituitary-thyroid axis may result in thyroid hormone deficiency, > 95% of clinical cases of hypothyroidism in dogs appear to result from destruction of the thyroid gland itself (primary hypothyroidism). The two most common causes of adult-onset primary hypothyroidism in dogs are lymphocytic thyroiditis and idiopathic atrophy of the thyroid gland. (Also see Autoimmune Thyroiditis in the Immunologic Diseases chapter.)
Lymphocytic thyroiditis is likely immune-mediated and is characterized histologically by a diffuse infiltration of the gland by lymphocytes, plasma cells, and macrophages, resulting in progressive destruction of follicles and secondary fibrosis.
Idiopathic atrophy of the thyroid gland is characterized histologically by loss of thyroid parenchyma and replacement by adipose tissue.
In dogs, secondary hypothyroidism is uncommon and usually results from destruction of pituitary thyrotrophs by an expanding, space-occupying tumor. Because of the nonselective nature of the resulting compressive atrophy and replacement of pituitary tissue by such large tumors, deficiencies of other (one or more) pituitary hormones also usually occur.
Other rare forms of hypothyroidism in dogs include neoplastic destruction of thyroid tissue and congenital (or juvenile-onset) hypothyroidism.
Congenital primary hypothyroidism may result from one of various forms of thyroid dysgenesis (eg, athyreosis, thyroid hypoplasia) or from dyshormonogenesis (usually an inherited inability to organify iodide).
Congenital secondary hypothyroidism (associated with clinical signs of disproportionate dwarfism, lethargy, gait abnormalities, and constipation) has been reported in Giant Schnauzers, Toy Fox Terriers, and Scottish Deerhounds. Congenital secondary hypothyroidism also has been reported in German Shepherd Dogs, with pituitary dwarfism associated with a cystic hypophyseal diverticulum (Rathke pouch). The extent of thyroid-stimulating hormone (TSH) deficiency in these dogs is variable, and clinical signs are usually caused mainly by deficiency of growth hormone (rather than thyroid hormone).
In cats, iatrogenic hypothyroidism is the most common form. Hypothyroidism develops in these cats after treatment for hyperthyroidism with radioiodine, surgical thyroidectomy, or use of an antithyroid drug. Although naturally occurring hypothyroidism is an extremely rare disorder in adult cats, congenital or juvenile-onset hypothyroidism does occur.
Recognized causes of congenital hypothyroidism in cats include dyshormonogenesis, an inability of the thyroid gland to respond to TSH, and thyroid dysgenesis. All reported cats with hypothyroidism have had a primary (thyroidal) disorder. Secondary (pituitary) or tertiary (hypothalamic) hypothyroidism has not been well described in either juvenile or adult cats but has been reported after severe head trauma.
In foals, congenital hypothyroidism may develop when pregnant mares graze plants that contain goitrogens or are fed diets either deficient in or containing excessive amounts of iodine. Most commonly, congenital hypothyroidism develops in association with a specific syndrome of neonatal foals characterized by thyroid gland hyperplasia together with multiple congenital musculoskeletal anomalies. This syndrome, reported most commonly in western Canada, has been referred to as either thyroid hyperplasia and musculoskeletal deformities syndrome or as congenital hypothyroidism and dysmaturity syndrome and may be related to feeding a high-nitrate diet to pregnant mares. In adult horses, hypothyroidism appears to be rare but, as in other species, is commonly misdiagnosed.
Clinical Signs of Hypothyroidism in Animals
Although onset is variable, hypothyroidism is most common in dogs 4–10 years old. There does not appear to be a sex predilection. It usually affects mid- to large-size breeds, although the number of breeds affected is vast.
Breeds reported to be predisposed to hypothyroidism include the following:
Golden Retriever
Doberman Pinscher
Irish Setter
Miniature Schnauzer
Dachshund
Cocker Spaniel
Airedale Terrier
A deficiency of thyroid hormone affects the function of all organ systems; as a result, clinical signs are diffuse, variable, often nonspecific, and rarely pathognomonic.
Many of the clinical signs associated with canine hypothyroidism are directly related to slowing of cellular metabolism, which results in development of mental dullness, lethargy, exercise intolerance, and weight gain without a corresponding increase in appetite. Obesity develops in some dogs.
Difficulty maintaining body temperature may lead to heat seeking or hypothermia.
Alterations in the skin and coat are common. Dryness, excessive shedding, and retarded regrowth of hair are early dermatological changes. Nonpruritic hair thinning or alopecia (usually bilaterally symmetric) of the ventral and lateral trunk, caudal surfaces of the thighs, dorsum of the tail, ventral neck, and the dorsum of the nose is observed in approximately two-thirds of dogs with hypothyroidism. Alopecia, sometimes associated with hyperpigmentation, often starts over points of wear. Occasionally, secondary pyoderma (which may be associated with pruritus) occurs.
In moderate to severe cases, thickening of the skin occurs secondary to accumulation of glycosaminoglycans (mostly hyaluronic acid) in the dermis. This myxedema is most common on the forehead and face, producing a puffy appearance and thickened skin folds above the eyes, along with slight drooping of the upper eyelid, resulting in a characteristic appearance (described as a tragic facial expression).
In sexually intact dogs, hypothyroidism may cause various reproductive disturbances: in females, failure to cycle (anestrus) or sporadic cycling, infertility, abortion, or poor litter viability; and in males, lack of libido, testicular atrophy, hypospermia, or infertility.
A variety of neurological disorders, including megaesophagus, laryngeal paralysis, facial nerve paralysis, and vestibular disease, have been described in dogs with hypothyroidism. However, peripheral and central nervous system clinical signs are uncommon, compared with the metabolic and dermatological changes. Associated neurological clinical signs do not always resolve after thyroid hormone replacement therapy.
Myxedema coma, a rare syndrome, is the extreme expression of severe hypothyroidism. Lethargy can rapidly progress to stupor and then coma. The common clinical signs of hypothyroidism (eg, hair loss) are usually present; however, other signs (eg, hypoventilation, hypotension, bradycardia, and profound hypothermia) are usually also present.
During the fetal period and in the first few months of postnatal life, thyroid hormones are crucial for growth and development of the skeleton and CNS. Therefore, in addition to the well-recognized clinical signs of adult-onset hypothyroidism, disproportionate dwarfism and impaired mental development (cretinism) are prominent clinical signs of congenital and juvenile-onset hypothyroidism. In primary congenital hypothyroidism, enlargement of the thyroid gland (goiter) may also be detected, depending on the cause of the hypothyroidism. Radiographic clinical signs of epiphyseal dysgenesis of long bones, shortened vertebral bodies, and delayed epiphyseal closure are common.
In dogs with congenital hypopituitarism (pituitary dwarfism), there may be variable amounts of thyroidal, adrenocortical, and gonadal deficiency; however, clinical signs are primarily related to growth hormone deficiency, and include the following:
proportionate dwarfism (rather than the disproportionate form of dwarfism characteristic of congenital hypothyroidism)
loss of primary guard hairs with retention of the puppy coat
hyperpigmentation of the skin
bilaterally symmetric alopecia of the trunk
In adult cats, clinical signs of hypothyroidism are very uncommon, occur with advanced disease, and include the following:
lethargy
dull mentation
nonpruritic seborrhea sicca
hypothermia
decreased appetite
bradycardia (occasionally)
Obesity may develop, especially in cats with iatrogenic hypothyroidism, but it is not a consistent clinical sign. Bilaterally symmetric alopecia does not develop; however, focal areas of alopecia over the pinnae, craniolateral carpi, caudal hocks, and tail base have occasionally been observed. However, in many cats with mild iatrogenic hypothyroidism, mild or no obvious clinical signs are noted. In young cats with congenital or juvenile-onset hypothyroidism, the clinical signs are more obvious and include disproportionate dwarfism, severe lethargy, mental dullness, constipation, inappetence, and bradycardia.
Diagnosis of Hypothyroidism in Animals
Clinical signs
Serum thyroid hormone testing
Hypothyroidism is probably one of the most overdiagnosed diseases in dogs. Many diseases and conditions can mimic clinical signs of hypothyroidism, and even in euthyroid dogs, some clinical signs improve after administration of exogenous thyroid hormone. In addition, a variety of nonthyroidal factors (eg, nonthyroidal illness and prior administration of certain drugs) can lead to low serum thyroid hormone measurements in euthyroid dogs, cats, and other species.
Definitive diagnosis of canine hypothyroidism requires careful attention to clinical signs and results of routine laboratory testing. Tests commonly used to confirm the diagnosis include measurement of the serum concentrations of total thyroxine (T4), free T4 (fT4), and TSH, as well as the patient's response to thyroid hormone supplementation. Selection and interpretation of diagnostic tests are based heavily on the index of suspicion for hypothyroidism.
There are well-recognized clinicopathological abnormalities associated with hypothyroidism. Although these changes are nonspecific and may be associated with many other diseases in dogs, their presence adds supportive evidence for a diagnosis of hypothyroidism in a dog with relevant clinical signs:
The classic hematologic finding associated with hypothyroidism, found in 40%–50% of cases, is normocytic, normochromic, nonregenerative anemia.
The classic serum biochemical abnormality is hypercholesterolemia, which occurs in approximately 80% of dogs with hypothyroidism, and therefore can assist as a screening test for hypothyroidism.
Other clinicopathological abnormalities may include high serum concentrations of triglycerides and elevated activities of alkaline phosphatase and CK.
Total T4 concentration is a good initial screening test for canine hypothyroidism, with a sensitivity of approximately 90% (see hypothyroidism flowchart, dogs). A dog with a T4 concentration well within the reference interval may be assumed to have normal thyroid function. If T4 concentration is at the low end of the reference interval, and hypothyroidism is strongly suspected clinically, measurement of fT4 or TSH concentration can help to characterize the dog's thyroid function.
Courtesy of Dr. Johanna Heseltine.
In contrast, a subnormal T4 concentration alone is not diagnostic for hypothyroidism because it may be impacted by nonthyroidal factors (ie, measurement of T4 concentration alone has low specificity).
Measurement of fT4 concentration has been used to differentiate euthyroid from hypothyroid dogs because fT4 concentration may be less affected by euthyroid sick syndrome, making it more specific than T4 concentration. However, most single-stage solid phase (analogue) commercial assays for fT4 concentration do not appear to be superior to measurement of total T4 concentration in dogs. An fT4 concentration assay that uses an equilibrium dialysis step (direct dialysis) has better accuracy than the analogue methods. In addition, antithyroid hormone antibodies may interfere with measurement of T4 concentration but do not impact fT4 concentration measured using the equilibrium dialysis method.
Because T3 is the most potent thyroid hormone at the cellular level, it would seem logical to measure its concentration for diagnostic purposes. However, serum T3 concentrations may be low, normal, or (occasionally) high in dogs with documented hypothyroidism, so T3 concentration is not usually measured. One exception is Greyhounds, who naturally have a lower reference interval for T4 and fT4 concentrations but not T3 concentration. Therefore, a T3 concentration below the reference interval could support a diagnosis of hypothyroidism in this breed.
Determination of serum TSH concentrations by use of a valid species-specific TSH assay can be a useful adjunctive test for hypothyroidism in dogs, cats, and horses. Animals with primary hypothyroidism (by far the most common type) would be expected to have low serum T4 or fT4 concentrations with high endogenous TSH concentrations. However, serum TSH concentrations remain within the reference range in 20%–40% of dogs with confirmed hypothyroidism, so it has low sensitivity.
Although a few dogs with normal serum TSH concentrations have secondary hypothyroidism, pituitary TSH deficiency is extremely rare, and most hypothyroid dogs with normal TSH concentrations (ie, false-negative results) have primary hypothyroidism. In contrast, falsely high serum TSH concentrations (ie, false-positive results) are occasionally found in euthyroid dogs with nonthyroidal illness. Thus, serum TSH determinations should never be evaluated alone but always in conjunction with the dog’s history and clinical signs, routine laboratory results, and total T4 or fT4 concentration.
The TSH stimulation test evaluates the response of the thyroid gland to exogenously administered TSH and is a test of thyroid reserve. It is an accurate test of thyroid function in dogs; however, its use is limited by the availability of TSH.
Human recombinant TSH is available, although expensive, and may be frozen for at least 8 weeks with no loss of potency. The recommended dose is 75 mcg, IV, with collection of 0- and 6-hour samples. Results may reveal a normal response, a blunted response (sick euthyroid syndrome), or no response (hypothyroidism). Use of bovine TSH has been reported; however, anaphylactoid adverse reactions have been described.
Both ultrasonography and scintigraphy of the thyroid gland have been evaluated as diagnostic tests for hypothyroidism in dogs. With an experienced radiologist, use of thyroid ultrasonography (evaluating for decreased echogenicity and decreased thyroid volume) can be an effective ancillary diagnostic tool to differentiate between canine hypothyroidism and euthyroid sick syndrome.
The best imaging technique may be the use of technetium-99m (99mTc) uptake and imaging of the thyroid gland. With quantitative measurement of thyroidal 99mTc uptake, there is little to no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness.
When hypothyroidism is suspected based on a low T4, low fT4, or high TSH concentration, response to a therapeutic trial with levothyroxine helps confirm the diagnosis. Every attempt should be made to exclude nonthyroidal illness before starting a therapeutic trial. There is no evidence that thyroid hormone supplementation is beneficial in dogs with sick euthyroid syndrome, and it may be detrimental.
After appropriate levothyroxine supplementation, improvement in clinical signs should be used to assess the response to treatment. Improvement in lethargy and mentation should occur within 2 weeks. If treatment is unsuccessful, therapeutic monitoring of T4 concentration should be performed to identify the cause of treatment failure. Because an incorrect diagnosis is the most common cause of treatment failure, the clinician should be prepared to withdraw treatment and pursue other diagnoses.
In cats, hypothyroidism can also be diagnosed on the basis of finding low to low-normal serum concentrations of total T4 and free T4, with high serum TSH concentrations. A feline-specific TSH assay is available, and the canine TSH assay has also been used to test for feline hypothyroidism.
Thyroiditis
Measurement of circulating thyroid hormone autoantibodies
Thyroglobulin is a glycoprotein produced by thyroid follicular cells and serves as a precursor to thyroid hormones. Circulating antithyroglobulin autoantibodies (TgAAs) can be detected in up to half of dogs with hypothyroidism and are believed to reflect a state of autoimmune thyroiditis (lymphocytic thyroiditis).
Serum TgAA determination may be a useful adjunctive diagnostic for hypothyroidism if the dog has clinical signs and other test results are supportive of hypothyroidism. However, this test gives no information about thyroid function. Measurement of these antibodies in breeding studs and bitches has been proposed as a method to identify dogs with autoimmune thyroid disease; however, only approximately one-third of dogs with high TgAA eventually develop hypothyroidism.
Although extremely rare in dogs, circulating thyroid hormone autoantibodies (anti-T3 or anti-T4 antibodies) are occasionally detected and also are believed to reflect a state of autoimmune thyroiditis. These antibodies produce a spurious increase in T3 or T4 concentration. This can result in thyroid hormone concentrations that are above reference range and, in a hypothyroid dog, could result in thyroid hormone concentrations within the reference range.
Of all the thyroid hormone assays, only measurement of fT4 concentration by dialysis is not affected by autoantibodies directed at T4 or T3, because the serum autoantibodies are removed in the dialysis step. Therefore, if hypothyroidism is suspected in a dog with circulating thyroid hormone autoantibodies, serum fT4 concentration by equilibrium dialysis should be determined to help confirm the diagnosis.
Nonthyroidal Factors That Affect Interpretation of Thyroid Function Tests
Certain breeds have thyroid hormone reference intervals that are lower than those of most other breeds:
Greyhounds have serum total T4 and fT4 concentrations that are considerably lower than those of most other breeds.
Other breeds that may have lower T4 concentrations than the non–breed-specific reference interval include Basenjis, Salukis, Whippets, and Scottish Deerhounds, although breed-specific reference intervals have not been determined for most breeds.
Alaskan sled dogs have serum total T4, T3, and fT4 concentrations that are below the reference interval of most pet dogs, particularly during periods of intense training or racing.
Illness not involving the thyroid gland can alter thyroid function tests and is referred to as “nonthyroidal illness” or “euthyroid sick syndrome.” A decrease in total T4 and T3 concentrations occurs in proportion to the severity of illness. Serum TSH concentration is increased in 8%–10% of dogs with nonthyroidal illness. Serum fT4 concentration measured by equilibrium dialysis is less likely to be affected by nonthyroidal illness but can be increased or decreased. However, in dogs with substantial nonthyroidal illness, the fT4 concentration can also be decreased, so testing of thyroid function should be postponed until nonthyroidal illness is resolved. If this is not possible, measurement of T4, TSH, and fT4 concentration is indicated and should be interpreted with caution.
Age also impacts T4 concentration, with concentration progressively declining in elderly dogs, so this should be considered when interpreting thyroid hormone concentration using a reference interval established using young adult dogs.
Multiple drugs, including glucocorticoids, phenobarbital, sulfonamides, clomipramine, tricyclic antidepressants, furosemide, heparin, aspirin, amiodarone, propranolol, and inhalant anesthetics are known to commonly alter thyroid function tests. Mechanisms of interference with thyroid function include the following:
decreased TSH secretion
altered thyroid hormone secretion
decreased oral absorption of levothyroxine
alterations in protein binding and protein transport of thyroid hormones
increased hepatic metabolism
interference with 5′-deiodinase activity responsible for converting T4 to T3
Awareness of these effects is important to avoid misdiagnosing hypothyroidism. Changes in thyroid hormone concentrations are reversible when the medication is discontinued. Dozens of drugs affect thyroid function and thyroid function tests in humans; therefore, many others likely affect animals as well.
Treatment of Hypothyroidism in Animals
Thyroid hormone replacement
The standard treatment for hypothyroidism is daily oral administration of the synthetic thyroid hormone levothyroxine, which is the thyroid hormone replacement compound of choice in dogs and cats. Oral administration of levothyroxine restores adequate circulating thyroid hormone concentrations, reversing the clinical signs of hypothyroidism.
With few exceptions, replacement therapy is necessary for the remainder of the animal's life. For dogs and cats with hypothyroidism, an FDA-approved product for dogs is administered (22 mcg/kg, PO on an empty stomach, every 24 hours [or divided in two daily doses], lifelong). It is important to communicate to pharmacists that the dosage of levothyroxine in dogs is substantially higher than in humans and may be administered more frequently during the day as compared to humans. If it is necessary to administer the levothyroxine with food, the same should be done on days when blood samples are obtained for monitoring.
The most important indicator of the success of treatment is clinical improvement. Improvements in lethargy and mentation occur within 2 weeks. Dermatological clinical signs and body weight may take up to 3 months to improve. The clinical goal is to resolve clinical signs without inducing toxicosis.
When clinical improvement is marginal or clinical signs of thyrotoxicosis are present, the clinical observations can be supported by therapeutic monitoring of serum T4 concentrations, generally performed after 4–8 weeks of supplementation. With administration of levothyroxine every 24 hours, the peak serum concentration of T4 4–6 hours after administration should be at the high end or slightly above the reference interval for T4 concentration. The T4 concentration 24 hours after dosing should be at the low end of the reference interval or normal. T4 concentration for animals on administration every 12 hours can probably be checked at any time of day; however, peak concentrations are expected 4–6 hours after administration. Some laboratories report a postadministration T4 concentration range, which accounts for the target with respect to basal T4 concentration, so careful attention should be paid to the submission and reporting of postadministration samples.
After the dosage is stabilized, serum T4 concentrations should be checked 1–2 times per year. Free T4 and TSH concentrations will also normalize; however, monitoring of these is often not required.
Thyrotoxicosis is rare in dogs and can result in polyuria and polydipsia, weight loss, panting, nervousness, or tachycardia.
Treatment failure is uncommon. If clinical signs of hypothyroidism remain despite achieving the target T4 concentrations with levothyroxine supplementation, an alternate diagnosis should be considered.
Key Points
Hypothyroidism is a common endocrine condition in dogs that results from inadequate production of thyroid hormones. It is less common in other species.
Hypothyroidism causes a decreased metabolic rate. Common clinical signs of the disorder include lethargy, weight gain, and coat and skin changes.
Low T4 concentration alone is inadequate to diagnose hypothyroidism and should be interpreted with fT4 or TSH concentrations.
Hypothyroidism is treated with lifelong daily oral supplementation with synthetic levothyroxine, and serum T4 concentration is monitored.
For More Information
Bugbee A, Rucinsky R, Cazabon S, et al. AAHA selected endocrinopathies of dogs and cats guidelines. J Am Anim Hosp Assoc. 2023;59(3):113-135. doi:10.5326/JAAHA-MS-7368
Bolton TA, Panciera DL. Influence of medications on thyroid function in dogs: an update. J Vet Intern Med. 2023;37(5):1626-1640. doi:10.1111/jvim.16823
Also see pet health content regarding hypothyroidism in dogs and cats.
