Contributors: David Bruyette, David Scarff, Robert Shiel

 Species: Canine   |   Classification: Diseases

Introduction Pathogenesis Diagnosis Treatment Outcomes Further Reading

Introduction

  • Cause: congenital or acquired metabolic condition.
  • Signs: alopecia, lethargy, weight gain.
  • Diagnosis: laboratory tests, response to therapy.
  • Treatment: thyroxine supplementation.
  • Prognosis: good but will require life-long therapy.
Print off the owner factsheet Hypothyroidism (Thyroid hormone deficiency) to give to your client.

Presenting Signs

Age Predisposition

  • Most dogs with acquired primary hypothyroidism are middle aged.
  • Acquired primary hypothyroidism is rare in dogs less than two years old.
  • Dogs with lymphocytic thyroiditis tend to be younger than those with thyroidal atrophy.
  • Dogs with congenital hypothyroidism usually present within the first six months of life.

Breed Predisposition

Pathogenesis

Etiology

  • In healthy animal, thyroid hormone production is under control of the hypothalamic-pituitary-thyroid axis Hypothalamic-pituitary-thyroid axis diagram. In most cases, disease affects the thyroid gland itself (primary hypothyroidism). Secondary hypothyroidism occurs due to diseases that reduce thyroid stimulating hormone (TSH) production by the pituitary gland. Tertiary hypothyroidism develops due to decreased thyrotropin releasing hormone (TRH) production by the hypothalamus. Due to difficulty distinguishing secondary and tertiary causes, they are often grouped as “central hypothyroidism”.

Primary hypothyroidism

  • >95% of cases.
  • May be acquired (common) or congenital (rare).
  • The most common causes of acquired primary hypothyroidism are lymphocytic thyroiditis and idiopathic thyroid atrophy, which occur with approximately equal frequency. It is possible that lymphocytic thyroiditis may progress to idiopathic atrophy in at least some cases.
  • Thyroid tumors: are rare causes of acquired primary hypothyroidism. In such cases, destruction of both thyroid lobes is necessary.
  • Lymphocytic thyroiditis: characterized by diffuse infiltration of the thyroid gland by lymphocytes, plasma cells and macrophages, resulting in progressive destruction of thyroid follicles and secondary fibrosis.
  • Idiopathic atrophy: is characterized by loss of thyroid parenchyma without inflammatory infiltration, and replacement by adipose tissue.
  • Primary hypothyroidism can also be caused by administration of inhibitors of thyroid hormone synthesis such as thiamazole (methimazole) or potentiated sulfonamides.
  • Congential primary hypothyroidism represents a group of rare disorders that cause decreased thyroid hormone production because of altered thyroid hormone synthesis or thyroid gland development.
  • Iodine deficiency can cause endemic hypothyroidism, but this is extremely rare in dogs.

Secondary hypothyroidism

  • <5% of cases.
  • Decreased secretion of TSH from the pituitary gland leads to → decreased thyroidal follicular cell atrophy.
  • Causes: pituitary tumors, hypophysectomy, congenital dysfunction of pituitary gland (secondary hypothyroidism frequently accompanies pituitary dwarfism in the German Shepherd dog German Shepherd Dog, which is caused by a mutation of the LHX3 gene).

Tertiary hypothyroidism

  • Poorly defined in the dog.
  • Deficient production or release of TRH, which causes reduced TSH secretion and effects on the thyroid gland as described for secondary hypothyroidism.

Pathophysiology

  • In early cases, lymphocytic thyroiditis may be present without impairment of thyroid hormone secretory ability. This is known as silent thyroiditis.
  • If destruction of the thyroid gland becomes more widespread, thyroid hormone concentrations tend to decrease. However, adequate thyroid hormone concentrations may be maintained by increased TSH secretion. This is known as subclinical or compensating hypothyroidism.
  • When more than 75% of gland is destroyed, increased TSH secretion is no longer capable of maintaining adequate thyroid hormone secretion. Thyroid hormone concentrations decline, and clinical hypothyroidism develops. Once thyroid tissue is destroyed, the stimulus for autoimmunity is removed, leading to resolution of the lymphocytic thyroiditis in the gland and development of thyroidal atrophy. Transition from lymphocytic thyroiditis to thyroidal atrophy has been documented in a small number of dogs. It is possible that two separate pathophysiological processes may be involved in some cases.

Diagnosis

Presenting Problems

  • Alopecia.
  • Thinning of the hair coat.
  • Weight gain.
  • Lethargy.
  • Reproductive cycle abnormalities (decreased fertility, galactorrhea).
  • Neurological abnormalities (central vestibular disease, neuropathies).
  • Corneal lipidosis Cornea: lipidosis.
  • Gall bladder mucocele Gallbladder: mucocele.

Client History

  • Lethargy/mental dullness.
  • Increased hair shedding.
  • Weight gain.
  • Irregular estrus, anestrus, reproductive failure, gynecomastia, galactorrhea.
  • Heat seeking.
  • Secondary pruritic or seborrheic skin conditions.
  • Coat color changes.

Clinical Signs

  • In general, dermatological signs are seen in approximately 80% of cases, and metabolic signs are seen in approximately 80% of cases.

Decreased basal metabolic rate

  • Lethargy.
  • Mental dullness.
  • Weight gain.

Skin abnormalities

  • Non-pruritic alopecia, often first seen around areas of friction, such as the ventral neck Hypothyroidism atypical , ventral thorax, tail, and dorsal nose.
  • Alopecia can become bilaterally symmetrical and affect the flanks. The extremities are usually spared.
  • Thinning of hair coat.
  • Dull, dry, brittle, easily epilated hair coat.
  • Scaling/seborrhea Hypothyroidism Dachshund.
  • Failure of hair regrowth after clipping.
  • Hyperpigmentation Skin: pigmentary disorders  Hypothyroidism hyperpigmentation.
  • Secondary pyoderma Skin: deep pyoderma Hypothyroidism Shar Pei , malasseziosis and demodicosis Skin: demodectic mange.
  • Otitis externa Ear: otitis externa Hypothyroidism cerumen.
  • Myxedema (non-pitting, thickening of the skin), seen as a 'tragic' facial expression.
  • Comedone formation, especially ventral abdomen Comedone.
  • Hypertrichosis (usually in Boxer Boxer and Irish Setters Irish Setter).

Cardiovascular system

Neuromuscular and central nervous system abnormalities

  • Central vestibular disease.
  • Myxedema coma. This is a very rare presentation of hypothyroidism. Affected dogs are often stuporous or comatose, bradycardic, hypotensive and hypothermic. Hypoventilation may also occur.
  • Peripheral polyneuropathy Peripheral neuropathies may be associated with weakness or proprioceptive deficits.
  • Myopathy is usually subclinical but may contribute to exercise intolerance and weakness.
  • Links with other neurological disorders have been suggested including peripheral vesibular disease, laryngeal paralysis, seizures Seizures, individual cranial neuropathies and megaesophagus Megaesophagus. However, casual associations appear are largely unsubstantiated or are very rare.

Reproductive abnormalities

  • Galactorrhea.
  • Gynecomastia Gynaecomastia in male dogs.
  • Decreased fertility.

Growth and maturation

  • Disproportionate dwarfism, and impaired mental development (cretinism) in congenital hypothyroidism.

Ocular abnormalities

Signs which may be associated with hypothyroidism

Diagnostic Investigation

  • Thyroid hormone concentrations are markedly affected by the presence of the non-thyroidal illness and certain drug therapies. Therefore, it is essential to test the appropriate case. When possible:
    • Dogs should not be tested in the presence of non-thyroidal illness.
    • Dogs should not be tested while receiving thryoid-suppressive medications.
  • Trial therapy should not be used to make a diagnosis of hypothyroidism:
    • The response to treatment can be slow and subjective.
    • Non-specific hair growth may occur.
    • A diagnosis can be reached in most cases with appropriate testing.
For diagnostic plan see Hypothyroidism: diagnosis.

Biochemistry

Hematology

Hormone assay

  • Serum Total T4:
    • Total T4 concentration Thyroid: T4 is usually measured in conjunction with canine TSH (cTSH) concentration (see below) Thyroid: TSH assay.
    • Total T4 has high sensitivity (>95%). Therefore, a reference interval value makes hypothyroidism very unlikely.
    • Total T4 has low specificity; therefore, decreased total T4 values must be interpreted with caution, particularly in the presence of non-thyroidal illness, while administering thyroid-suppressive medications, and in certain breeds.
    • Total T4 concentration may be reduced by non-thyroidal illness (euthyroid sick syndrome). The magnitude of decrease is proportional to the severity and type of illness.
    • The administration of certain drugs decreases total T4 concentrations. These drugs include glucocorticoids and phenobarbitone Phenobarbital. Potentiated sulfonamides can block thyroid hormone synthesis and may result in decreased total T4 concentrations, increased TSH concentrations and clinical hypothyroidism.
    • Total T4 concentrations are often decreased below non-breed specific reference intervals in healthy dogs of certain breeds, most notably sighthounds. For example, >90% of greyhounds Greyhound have total T4 concentrations below non-breed-specific reference intervals. The use of breed-specific reference intervals may not avoid this problem because values in healthy dogs may be below the limit of quantification of commonly used assays.
  • Serum cTSH:
    • Results should be interpreted in combination with total (or free) T4.
    • cTSH concentrations are commonly increased in primary hypothyroidism.
    • cTSH has a sensitivity of approximately 75%, and specificity of approximately 80%, for the diagnosis of hypothyroidism.
    • A transient increase in TSH may be seen during recovery from non-thyroidal illness and following discontinuation of thyroid-suppressive medication. Values can also be increased in dogs with primary hypoadrenocorticism Hypoadrenocorticism prior to treatment.
  • Combined serum total T4 and cTSH:
    • Increased cTSH concentration with decreased total T4 concentration supports primary hypothyroidism.
    • Reference interval total T4 and cTSH concentrations make hypothyroidism extremely unlikely.
    • Increased cTSH concentration with reference interval total T4 concentration is most consistent with subclinical hypothyroidism or primary hypothyroidism if T4 autoantibodies are interfering with the measurement of total T4.
    • Increased cTSH concentrations are also described in dogs with primary hypoadrenocorticism Hypoadrenocorticism, and a transient increase may be observed following discontinuation of thyroid-suppressive medication or during recovery from non-thyroidal illness. In such cases, the history should be reviewed to identify recent illness or thyroid-suppressive therapies. If identified, testing could be repeated at a later date. If not identified, free T4 measurement (by equilibrium dialysis) and measurement of autoantibodies against T4 or thyroglobulin may confirm the diagnosis. Clinical signs are not expected in dogs with subclinical thyroid disease.
    • A pattern of decreased total T4 concentration and reference interval cTSH concentration is seen in approximately 25% of hypothyroid dogs. Similar results can occur in dogs with central hypothyroidism or non-thyroidal illness, dogs receiving thyroid suppressive medications and in healthy dogs of certain breeds such as sighthounds. The signalment and recent history should be reviewed. Free T4 measurement may allow confirmation of a diagnosis.
  • Serum free T4:
    • Serum free T4 concentration should ideally be measured by equilibrium dialysis. Some other methods may measure a proportion of total T4 rather than free T4, and as a result, offer limited advantage over total T4 measurement. However, measurement of free T4 by equilibrium dialysis is time consuming and requires use of radioimmunoassay. As a result, it is not widely available and relatively expensive. For these reasons, it is often reserved as a second-line test if thyroid function remains uncertain following measurement of total T4 and cTSH concentrations.
    • Less sensitive (80%) but more specific (>90% compared to total T4 for a diagnosis of hypothyroidism.
    • Free T4 (by equilibrium dialysis) is not affected by the presence of autoantibodies against T4 that can artificially increase total T4 concentrations.
    • Free T4 concentrations are less affected by non-thyroidal illness compared to total T4. However, decreased free T4 concentrations can occur particularly in dogs with severe non-thyroidal illness.
    • Certain drugs, including glucocorticoids and phenobarbitone Phenobarbital, can decrease free T4 concentrations.
    • Decreased free T4 concentrations can be seen in healthy dogs of certain breeds, such as greyhounds Greyhound.
  • TSH response test:
    • Decreased or no T4 response to TSH administration of human recombinant TSH is consistent with hypothyroidism.
    • The most accurate and reliable means of diagnosis, and traditionally considered the gold standard test.
    • Severe non-thyroidal disease or drugs may reduce the T4 response.
    • The test is rarely necessary and the high costs of human recombinant TSH is usually prohibitive.
  • Serum total T3 Thyroid: T3 assaybaseline total T3 is of little value in diagnosis of hypothyroidism because is it less sensitive than total T4, and values are decreased in many cases by the presence of even mild non-thyroidal illness.

Serology for thyroid autoantibodies

  • Antibodies against T4 Thyroid gland: T4AA assay and T3 Thyroid gland: T3AA assay are seen in approximately 8 and 28% of hypothyroid dogs, respectively.
  • These tests do not assess thyroid function.
  • Thyroglobulin autoantibodies are seen in approximately 50% of hypothyroid dogs, and their presence supports the diagnosis of lymphocytic thyroiditis.
  • Thyroglobulin autoantibodies can be used to detect dogs with silent thyroiditis. This allows identification of dogs at risk for developing hypothyroidism at an earlier age (before hormone changes are apparent), which can be advantageous, for example, in breeding programs. Not all dogs with silent thyroiditis progress to clinical hypothyroidism. In dogs with thyroglobulin autoantibody positivity without any thyroid hormone or TSH abnormalities, approximately one in five will have additional evidence of thyroid dysfunction within a year, and one in twenty will be clinically hypothyroid.
  • Thyroid hormone autoantibodies can interfere with the measurement of total thyroid hormone concentrations, most commonly resulting in inappropriately high values in dogs with hypothyroidism (within or above the reference interval). Therefore, measurement of T4 or T3 autoantibodies can help to explain these inappropriately high values. Thyroglobulin autoantibody assays are more widely available and can be used to support the presence of thyroid hormone autoantibodies indirectly. Only 5% of dogs have thyroid hormone autoantibodies without thyroglobulin autoantibodies.

Histopathology

  • Skin biopsy Biopsy: skin typical of endocrine dermatopathy.
  • Hyperplastic and hyperkeratotic epidermis, follicular infundibular atrophy of deeper portion of hair follicle, most hairs in telogen. Increased melanin throughout the epidermis with hyperpigmentation Skin: pigmentary disorders. Extensive follicular plugging.
  • Skin biopsy rarely provides a definitive diagnosis of hypothyroidism and is therefore not routinely performed.
  • Thyroid gland biopsy is rarely performed unless thyroid neoplasia is suspected (in which case, excisional biopsy is usually recommended).

Additional tests

  • Thyroid scintigraphy:
    • Thyroid scintigraphy Scintigraphy: overview is an accurate test to differentiate between dogs with non-thyroidal illness and hypothyroidism.
    • Thyroidal uptake of pertechnetate (99mTcO4) is usually measured. Uptake is decreased in dogs with hypothyroidism.
    • Equivocal results may be seen in dogs with non-thyroidal illness and receiving certain therapies such as glucocorticoids.
    • Not widely available.
  • Thyroid ultrasonography Ultrasonography: thyroid and parathyroid gland:
    • Not a test of thyroid function; however, decreased thyroid volume and altered thyroid echogenicity have been described in hypothyroid dogs.
    • Requires adequate equipment and training. Further studies required to determine the diagnostic utility of this test.

Differential Diagnosis

Treatment

Initial Symptomatic Treatment

For myxedema coma

All of Thyroxine sodium Levothyroxine (ideally IV).

And Respiratory support.

And Intravenous fluid and electrolyte support.

And Rewarming.

Standard Treatment

  • Thyroxine sodium Levothyroxine:
    • A dose range from 10-20 mcg/kg SID-BID is commonly cited. However, 20 mcg/kg SID PO is sufficient in most cases. This is usually administered in the morning to facilitate therapeutic monitoring.
    • Concurrent feeding or administration of other medications can decrease the absorption of T4. Higher doses may be necessary if T4 is administered in food.
    • Higher doses or twice daily therapy may be necessary depending on clinical response and serum T4 concentrations.
    • Some authors suggest commencing with a lower dose in older dogs or those with cardiac disease or hypoadrenocorticism to decrease the likelihood of thyrotoxicosis. Thyrotoxicosis is uncommon when a dose of 20 mcg/kg SID is used. In dogs with concurrent hypoadrenocorticism Hypoadrenocorticism and hypothyroidism, hypoadrenocorticism should be treated before commencing levothyroxine therapy to avoid induction of an adrenal crisis (associated with increased steroid hormone clearance).

Subsequent Management

Monitoring

  • Serum total T4 concentrations should be measured 4-6 hours after administration of medication.
  • If serum T4 >90 nmol/l: decrease dose or consider once daily dosage if twice daily therapy is being used.
  • If serum total T4 = 35-90 nmol/l: no change necessary.
  • If serum total T4 <35 nmol/l: increase dose. 
  • Serum cTSH concentrations may be useful to measure in conjunction with total T4 concentrations. The presence of a persistently high cTSH concentration suggests poorer longer-term control, for example due to poor owner compliance. The measurement of cTSH is only of value in dogs in which the cTSH concentration was increased prior to commencing therapy.
  • Monitor for clinical signs of thyrotoxicosis (rare):
  • Serum concentrations should always be interpreted in conjunction with clinical signs. The presence of therapeutic T4 concentrations without an adequate clinical response could be due to inadequate time for an effect to be seen, intermittent poor owner compliance (ie, good owner compliance on the day of testing is not representative) or the presence of another cause of clinical signs.

Outcomes

Prognosis

  • Good: life-long therapy required.

Expected Response to Treatment

  • Increased activity and alertness is usually seen within the first week of treatment.
  • Improved dermatological signs, eg hair growth within 4-6 weeks, although a full response may take 5-6 months.
  • Hair loss may appear increased initially.
  • Approximately 10% weight loss is expected within 3 months. In very obese dogs, exercise and dietary modification are also usually necessary.

Reasons for Treatment Failure

  • Standard reasons Standard reasons for failure in a treatment.
  • Incorrect diagnosis.
  • Insufficient therapy, eg dose, frequency, product with poor bioavailability.
  • Administration of T4 with food or other drugs can decrease absorption.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Bennaim M, Shiel R E, Evans H & Mooney C T (2022) Free thyroxine measurement by analogue immunoassay and equilibrium dialysis in dogs with non-thyroidal illness. ResVet Sci 147, 37-43 PubMed.
  • Aicher K M, Cullen J M, Seiler G S et al (2019) Investigation of adrenal and thyroid gland dysfunction in dogs with ultrasonographic diagnosis of gallbladder mucocele formation. PloS one 14 (2), 0212638 PubMed.
  • Lewis V A, Morrow C M K et al (2018) A pivotal field study to support the registration of levothyroxine sodium tablets for canine hypothyroidism. JAAHA 54 (4), 201-208 PubMed.
  • Shiel R E, Pinilla M, McAllister H & Mooney C T (2012) Assessment of the value of quantitative thyroid scintigraphy for determination of thyroid function in dogs. J Small Anim Pract 53 (5), 278-285 PubMed.
  • Espineira M M D, Mol J A et al (2007) Assessment of thyroid function in dogs with low plasma thyroxine concentration. J Vet Int Med 21 (1), 25-32 PubMed.
  • Taeymans O, Peremans K & Saunders J H (2007) Thyroid imaging in the dog: current status and future directions. J Vet Int Med 21 (4), 673-684 PubMed.
  • Daminet S & Ferguson D C (2003) Influence of drugs on thyroid function in dogs. J Vet Med 17 (4), 463-472 PubMed.
  • Dixon R M, Reid S W J & Mooney C T (2002) Treatment and therapeutic monitoring of canine hypothyroidism. J Small Anim Pract 43 (8), 334-340 PubMed.
  • Kantrowitz L B, Peterson M E, Melián C & Nichols R (2001) Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease. JAVMA 219 (6), 765-769 PubMed.
  • Kantrowitz L B, Peterson M E, Trepanier L A, Melian C & Nichols R (1999) Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in epileptic dogs treated with anticonvulsants. JAVMA 214, 1804-1808 PubMed.
  • Dixon R M & Mooney C T (1999) Evaluation of serum free thyroxine and thyrotropin concentrations in the diagnosis of canine hypothyroidism. JSAP 40 (2), 72-78 PubMed.
  • Hall I A, Campbell K I, Chambers M D, & Davis C N (1993) Effect of trimethoprim/sulfamethoxazole on thyroid function in dogs with pyoderma. JAVMA 202 (12), 1959-1962 PubMed.
  • Kemppainen R J, Thompson F N et al (1983) Effects of prednisone on thyroid and gonadal endocrine function in dogs. J Endocrinology 96 (2), 293 PubMed.

Other sources of information

  • Scott-Moncrieff J C (2015) Hypothyroidism. In: Canine and Feline Endocrinology. 4th edn. Elsevier, USA.
  • Mooney C T & Shiel R E (2012) Canine hypothyroidism. In: BSAVA Manual of Canine and Feline Endocrinology. 4th edn. BSAVA, UK.

Other Sources of Information