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Basics ⬇

Basics

Definition

Clinical manifestations that result from inadequate production of thyroxine (T4) and 3,5,3';-triiodothyronine (T3) by the thyroid gland. Characterized by a generalized decrease in cellular metabolic activity.

Pathophysiology

Acquired Hypothyroidism

  • In dogs acquired hypothyroidism can be primary, secondary, or tertiary.
  • Primary hypothyroidism is associated with a defect localized to the thyroid gland. The thyroid tissue has been destroyed or replaced and thus becomes less responsive to TSH and T3 and T4 levels gradually decline, with a compensatory increase in TSH.
  • There are two common forms of primary hypothyroidism. Lymphocytic thyroiditis is an immune-mediated process characterized by chronic and progressive lymphocytic infiltration and destruction of the thyroid gland. This process is gradual and accounts for the slow onset of clinical signs associated with hypothyroidism. The immune-mediated process is associated with production of auto-antibodies, predominantly against thyroglobulin; however, auto-antibodies against T3 and T4 have been reported.
  • Idiopathic thyroid atrophy is a separate form of thyroid destruction that does not demonstrate an inflammatory component and is caused by the replacement of normal thyroid tissue with adipose tissue.
  • Together, these processes account for 95% of the clinical cases of hypothyroidism in dogs, each account for 50% of reported cases. Rare causes of primary hypothyroidism include neoplastic destruction of thyroid tissue, iodine deficiency, infection, and iatrogenic destruction secondary to drugs, surgery, or radioiodine treatment.
  • Secondary acquired hypothyroidism is rare. The defect is localized to the pituitary, where the ability to synthesize and secrete TSH is impaired. Secondary hypothyroidism may be caused by pituitary tumors, congenital malformation of the pituitary, infection, or TSH suppression. Drugs, hormones, or concurrent illness can cause TSH suppression.
  • Tertiary hypothyroidism (not reported in the veterinary literature) is hypothalamic in origin, and production of TRH is either decreased or non-existent.

Congenital Hypothyroidism

  • Congenital hypothyroidism is a rare disease that is categorized as goitrous or non-goitrous. Goiter (enlargement of the thyroid gland) develops when there is increased release of TSH, along with an intact thyroid TSH receptor.
  • An autosomal recessive form of congenital hypothyroidism has been reported in toy fox terriers, giant schnauzers, and Abyssinian cats. Affected animals have a thyroid peroxidase deficiency.
  • Congenital hypothyroidism is also noted as an element of panhypopituitarism.

Systems Affected

  • Behavioral
  • Cardiovascular
  • Endocrine/Metabolic
  • Gastrointestinal
  • Nervous
  • Neuromuscular
  • Ophthalmic
  • Reproductive
  • Skin/Exocrine

Genetics

  • No known genetic basis for heritability associated with primary hypothyroidism in dogs.
  • An autosomal recessive form of congenital hypothyroidism has been reported in toy fox terriers, giant schnauzers, and Abyssinian cats.

Incidence/Prevalence

  • Primary hypothyroidism is the most common endocrinopathy in dogs. Prevalence appears to average about 1:250.
  • Hypothyroidism is rare in cats.

Geographic Distribution

Worldwide

Signalment

Species

Dog, rarely cat

Breed Predilections

Larger-breed dogs are more likely to develop hypothyroidism (golden retriever, Doberman pinscher, Great Dane, Irish setter), though several smaller-breed dogs do appear to also be predisposed (miniature schnauzer, cocker spaniel, poodle, dachshund).

Mean Age and Range

Most commonly seen in middle age dogs, with the average age of onset being 7 years.

Predominant Sex

None

Signs

General Comments

Clinical signs associated with hypothyroidism are vague and involve many different systems.

Historical Findings

  • Lethargy, weight gain, and hair loss are the most common signs reported by owners (40–50% of all cases).
  • Pyoderma (often recurrent), hyperpigmentation of the skin and a dry, brittle hair coat (10% of cases).
  • Rarely (<5% of cases) facial paralysis, weakness, or conjunctivitis.

Physical Examination Findings

  • The most commonly findings include dermatologic abnormalities, weight gain, lethargy, and weakness. Most changes appear to be secondary to decreased metabolism due to a lack of circulating thyroid hormones.
  • Dermatologic changes are common but are not noted in every patient.
  • A dry, lackluster hair coat may be seen. Bilateral symmetrical non-pruritic truncal alopecia is reported in 88% of hypothyroid dogs. Hair loss is noted in areas of increased wear and usually includes the ventral thorax and neck, ventral abdomen, elbows and tail. Loss of primary hair is most common, with retention of guard hairs, resulting in a short, fine hair coat.
  • Seborrhea is common and may be localized or have a more generalized distribution pattern.
  • Pyoderma is noted in 14% of hypothyroid dogs and may be recurrent in nature. A lack of thyroid hormone will decrease T-cell function and humoral immunity, causing the skin to become more susceptible to infection. Generalized demodicosis and Malassezia spp. infections are common. Though primary dermatologic conditions are non-pruritic, pruritis may accompany secondary parasitic, yeast, or bacterial infections. Chronic changes to the skin can result in thickening and hyperpigmentation.
  • Otitis externa.
  • Weight gain.
  • Decreased activity level.
  • Most neurologic signs are associated with polyneuropathy and include weakness, facial nerve paralysis, vestibular signs (usually peripheral), and hyporeflexia. No data support an association between megaesophagus or laryngeal paralysis and hypothyroidism.
  • Central nervous system signs, including seizures, ataxia and coma (myxedema coma) are rare.
  • In males, decreased fertility, testicular atrophy, poor semen motility, and decreased libido have been reported in hypothyroid dogs. In females, hypothyroidism has been suggested to be associated with prolonged interestrous periods, failure to cycle, decreased libido, and inappropriate mammary gland development. However, data are lacking to support an association between decreased thyroid hormone levels and reproductive failure in males or females.
  • Cardiovascular abnormalities, are rare. Bradycardia, arrhythmias, decreased conduction, decreased contractility, and diastolic dysfunction have been reported.
  • Ocular changes including corneal cholesterol deposits, KCS, and conjunctivitis are seen in less than 1% of hypothyroid dogs.

Congenital Hypothyroidism

  • Lethargy and general inactivity
  • Dwarfism
  • Alopecia
  • Constipation (more common in cats)

Causes

  • Lymphocytic thyroiditis
  • Idiopathic thyroid atrophy
  • Neoplasia
  • Pituitary disease
  • Congenital abnormalities
  • Iodine deficiency (dietary)
  • Iatrogenic (secondary to surgery or radiation)

Risk Factors

Surgical removal (bilateral) of the thyroid gland

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Primary dermatologic disease
  • Other endocrinopathies (hyperadrenocorticism, diabetes mellitus, growth hormone deficiency)
  • Pancreatitis
  • Nephrotic syndrome
  • Hepatobiliary disease

CBC/Biochemistry/Urinalysis

  • Useful to rule out non-thyroidal illness.
  • Normochromic, normocytic, and nonregenerative anemia is a common finding. 28–32% of hypothyroid dogs demonstrate anemia. The hypothyroid state does not affect erythrocyte lifespan.
  • Hyponatremia.
  • Hypercholesterolemia is present in over 75% of hypothyroid dogs.
  • Hypertriglyceridemia.
  • Elevated levels of cholesterol and triglycerides have been associated with atherosclerosis in dogs, although this is rare.
  • No specific changes are noted on urinalysis.

Other Laboratory Tests

  • Diagnosing hypothyroidism is complex. The TSH stimulation test is a reliable single test used to diagnose hypothyroidism and is considered the gold standard. However, there is limited access to test reagents and the cost is often prohibitive.
  • Several tests are available to assess thyroid function, thyroid hormone levels, and antithyroglobulin antibody levels. These tests include the total T4, free T4, endogenous TSH, antithyroglobulin antibodies, anti-T3 antibodies, anti-T4 antibodies, total T3, reverse T3, and free T3.
  • Combination testing will yield a highly reliable result.

Total T4

  • Initial screening (high sensitivity) test of thyroid function.
  • This test measures both protein-bound and free T4 levels.
  • Test is a direct assessment of the ability of the thyroid gland to produce hormone.
  • A decreased total T4 level is a common finding in hypothyroid animals but is not diagnostic of hypothyroidism as concurrent illness can cause an artificial decrease in total T4 level.
  • Total T4 level can be measured by ELISA, chemiluminescence, or radioimmunoassay. There is indication that in-house ELISA is less reliable than radioimmunoassay.

Free T4

  • Most valuable as a screening test (high sensitivity).
  • Measures metabolically active portion of the total T4 level.
  • Hypothyroid animals would be expected to have a low free T4 level.
  • Concurrent illness has less effect on the free T4 level compared with the total T4 level.
  • Measurement by equilibrium dialysis (fT4ED) has been demonstrated to be more reliable than radioimmunoassay because it mitigates the influence of antithyroglobulin antibodies.
  • Newer methods of fT4 analysis utilize chemiluminescent technology with comparable sensitivity and specificity to fT4ED.

Endogenous TSH Level

  • Measurement of endogenous TSH is available using a canine assay.
  • Cross-reactivity allows this assay to be used in cats; however, it may be accurate only 50% of the time in cats.
  • This test has high specificity and low sensitivity, best used as a confirmatory test and not as a screening test.
  • TSH level is expected to be elevated in primary hypothyroid animals due to loss of negative feedback.
  • Interpretation of the TSH level requires knowledge of the total or free T4 level.
  • Methods of assessing TSH levels are less sensitive at low levels and evaluation of endogenous TSH cannot be used to diagnose secondary hypothyroidism.

Antithyroglobulin Antibodies

  • Antithyroglobulin antibodies include antithyroglobulin, anti-T3, and anti-T4 antibodies.
  • A positive titer is predictive of immune-mediated thyroiditis, and suggestive of hypothyroidism.
  • Anti-T3 and -T4 antibodies are similar to T3 and T4 and can cross-react to falsely elevate these assay levels. In animals who are slightly hypothyroid (as measured by total T4), the presence of anti-T4 antibodies will make it appear as if these animals are euthyroid, leading to a delay in the diagnosis and treatment of hypothyroidism.

TSH Stimulation Test

  • Historically considered the gold standard for diagnosing hypothyroidism.
  • Pharmaceutical-grade bovine TSH was used to conduct this test; however, production has been halted.
  • Recombinant human TSH can be used safely in both dogs and cats to effectively conduct the test, but is expensive. Therefore, this test is unlikely to become routine and replace the total and free T4 tests and the TSH assay as the preferred diagnostics.

Total T3, Reverse T3, and Free T3

  • Total T3 measurement is an unreliable indicator of thyroid function.
  • The total T3 level has been demonstrated to be normal in up to 90% of hypothyroid dogs.
  • The reverse T3 level has not been validated in companion animals.
  • Evaluation of total T3, reverse T3, and free T3 levels is not recommended to assess thyroid function.

Non-thyroid Factors That Alter Thyroid Function Tests

  • In addition to sick euthyroid syndrome, other factors alter the results of thyroid function tests, which may result in a misdiagnosis.
  • Most non-thyroid factors cause an artificial decrease in thyroid hormone levels.
  • Some drugs can decrease thyroid hormone levels and may result in an animal developing clinical signs of hypothyroidism. Sulfonamides, glucocorticoids, phenobarbital, NSAIDs, and clomipramine can decrease circulating thyroid hormone levels.
  • With sulfonamides this effect is noted to occur within weeks of initiation of therapy and disappears 2 weeks after therapy has been discontinued.
  • Glucocorticoids inhibit the entire hypothalamic-pituitary-thyroid axis and have a direct effect against thyroid hormone.
  • Phenobarbital causes a decrease in thyroid levels only in animals receiving long-term treatment. Phenobarbital should not be administered for 4 weeks prior to thyroid function testing.
  • The influence of NSAIDs is variable and evaluation of thyroid function should be made with caution and preferably after stopping NSAIDs well in advance of testing.
  • Well-conditioned and athletic dogs consistently have lower total and free T4 levels. Certain breeds have normal ranges of thyroid hormones that are different from other breeds. Greyhound, Scottish deerhound, Saluki, and whippet have total T concentrations that are well below the mean concentrations. Alaskan sled dogs have serum T4, T3, and fT4 concentrations below the normal reference range.
  • Recent vaccination causes a transient increase in circulating auto-antibody levels, which may cause a truly hypothyroid animal to appear euthyroid. Thyroid function testing should not be conducted if a patient has been vaccinated within the previous 2 weeks.

Imaging

Radiographic Findings

Developmental bone problems (delayed epiphyseal ossification or dysgenesis) are usually noted with congenital hypothyroidism.

Ultrasonographic Findings

  • Significant differences in thyroid gland volume and echogenicity exist between hypothyroid and euthyroid patients.
  • No significant difference is noted between euthyroid and sick euthyroid subjects.
  • Ultrasonography can be an adjunctive diagnostic tool to assist in the diagnosis of canine hypothyroidism.

Pathologic Findings

  • Lymphocytic thyroiditis is characterized by chronic and progressive lymphocytic infiltration and destruction of the thyroid gland. Cytotoxic T cells initiate inflammation, leading to thyrocyte destruction and parenchymal fibrosis.
  • Idiopathic thyroid atrophy is characterized by the replacement of normal thyroid parenchyma with adipose and connective tissue.
  • Many cutaneous changes are nonspecific. However, certain findings, including dermal thickening, myxedema, and vacuolation of arrector pili muscles, are most characteristic.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

Outpatient medical management

Client Education

  • Life-long therapy required.
  • Easily managed with oral thyroid hormone supplementation.
  • Dose adjustments are common in the early stages of treatment.
  • Most clinical signs will resolve over time with appropriate thyroid hormone supplementation.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

  • Synthetic thyroid hormone supplementation easily treats hypothyroidism.
  • Levothyroxine sodium is available as both human and veterinary products.
  • Generic forms of the drug should be avoided as human studies have demonstrated wide variability in the bioavailability of generic forms. If a generic form is used, always prescribe the same formulation.
  • Hormone supplementation is initiated at 0.02 mg/kg PO q12h. Supplementation levels can be increased to a maximum of 0.8 mg per dog per treatment.
  • Supplementation can often eventually be decreased to once daily once proper control is achieved.
  • Levothyroxine doses for dogs exceed those for humans and may confuse pharmacists or human endocrinologists.

Precautions

Patients with concurrent metabolic conditions (hepatic disease, endocrinopathies, renal disease, cardiac disease) should have supplementation started slowly (about 25% of recommended dose) and slowly increased over time (3 months) to the recommended maintenance level.

Possible Interactions

  • Glucocorticoids, NSAIDs, furosemide may increase metabolism of levothyroxine.
  • GI protectants can decrease absorption and administration should be separated from thyroid hormone supplementation by 2 hours.

Alternative Drug(s)

  • If T4 levels do not normalized after attempting monitoring and treatment with several different brands of levothyroxine, treatment can be attempted with liothyronine (4–6 mg/kg PO q8–12h).
  • Monitoring is based on T3 levels. However, there is no reliable method by which to measure T3.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Thyroid function testing is recommended 6 weeks after therapy has begun and then every 6–8 weeks for the first 6–8 months and then once to twice yearly.
  • The total T4 level should be monitored and timed so that blood is taken 6 hours after pill administration.
  • Once stable and well controlled, the total treatment dose may be given once daily with excellent clinical results.
  • For animals receiving supplementation once daily, blood should be taken immediately before the medication is given and then again 6 hours later.
  • When supplementation therapy is appropriate, the total post-dose T4 level should be high normal to slightly above normal.
  • If the total T4 level is significantly increased above normal, the medication dose should be decreased or the frequency of administration reduced.
  • If the total T4 level is low, an increase in the dose may be necessary.
  • Before increasing dose, assess client compliance, evaluate gastrointestinal status to ensure there is no impact on absorption, and confirm there has been no change in the levothyroxine formulation.

Prevention/Avoidance

Adequate hormone supplementation with routine monitoring should avoid recurrence of this condition.

Possible Complications

  • If untreated hypothyroid animals are at increased risk of developing myxedema, myxedema coma and atherosclerosis.
  • Oversupplementation of thyroid hormone can result in iatrogenic hyperthyroidism.

Expected Course and Prognosis

  • Primary hypothyroidism can be easily and successfully controlled, the prognosis for affected animals, when appropriately treated, is excellent. Resolution of clinical signs is an important predictor of adequate supplementation therapy.
  • Significant improvement in attitude, activity level, and alertness should occur within 1 week of starting therapy.
  • Dermatologic abnormalities improve slowly, with complete resolution taking up to 3 months.
  • Polyneuropathies usually begin improving quickly; complete resolution may take several months.
  • Anemia and serum cholesterol levels gradually resolve in the first weeks of therapy.
  • Life expectancy expected to be normal.
  • Congenital hypothyroidism has a guarded-to-poor prognosis.

Miscellaneous ⬆

Miscellaneous

Associated Conditions

May rarely be associated with other endocrinopathies.

Pregnancy/Fertility/Breeding

  • No issues relating to pregnancy.
  • No definitive evidence suggesting an association with altered fertility.

Abbreviations

  • ELISA = enzyme-linked immunosorbent assay
  • GI = gastrointestinal
  • KCS = keratoconjunctivitis sicca
  • NSAID = nonsteroidal anti-inflammatory drug
  • T4 = thyroxine, tetraiodothyronine
  • T3 = liothyronine, 3,5,3';-triiodothyronine
  • TRH = thyrotropin-releasing hormone
  • TSH = thyroid stimulating hormone

Suggested Reading

Bellumori TP, Farnula TR, Bannasch DL, Belanger JM, Oberbauer AM. Prevalence of inherited disorders among mixed-breed and purebred dogs; 27,254 cases (1995–2010). J Am Vet Assoc 2013, 242(11):1549–1555.

Finora K, Greco DS. Hypothyroidism and myxedema coma in veterinary medicine-physiology, diagnosis and treatment. Compend Contin Educ Pract Vet 2007, 29:19–32.

Meeking SA. Thyroid disorders in the geriatric patient. Vet Clin North Am Small Anim Pract 2005, 35:635–653.

Mooney CT. Canine hypothyroidism: a review of aetiology and diagnosis. N Z Vet J. 2011, 59(3):105–114.

Scott-Moncrieff JCR, Guptill-Yoran L. Hypothyroidism. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 6th ed. St. Louis: Elsevier, 2005, pp. 1535–1544.

van Dijl IC, Le Traon G, van de Meulengraaf BD, Burgaud S, Horspool LJ, Kooistra HS. Pharmacokinetics of total thyroxine after repeated oral administration of levothyroxine solution and its clinical efficacy in hypothyroid dogs. J Vet Intern Med 2014, doi: Apr 28. 10.1111/jvim.12363.

Author Deborah S. Greco

Consulting Editor Deborah S. Greco

Acknowledgment The author and editors acknowledge the prior contribution of Kevin Finora.

Client Education Handout Available Online