Hypothyroidism Diagnosis and Treatment in Dogs

• Canine hypothyroidism is a challenging but common endocrine disease to diagnose due to variation in clinical presentations.
• Selection of the most appropriate diagnostic test and the confusion over interpretation of the results further complicate diagnosis.

Physiology

• The thyroid gland is a vascular bilobed structure located lateral to the proximal tracheal rings.
• Thyroxine (T4) and triiodothyronine (T3) are produced under the control of thyrotropin (thyroid stimulating hormone or TSH) in the pituitary gland.
• Thyrotropin releasing hormone (TRH) from the hypothalamus also plays a role.
• Hypothyroidism can arise from a defect in any of these areas.

Etiology

• Lymphocytic thyroiditis or idiopathic thyroidal atrophy (spontaneous hypothyroidism) is primary in nature, resulting from pathology in the thyroid gland itself.
• Central hypothyroidism (secondary hypothyroidism) results from disorders of the pituitary gland or hypothalamus.
• Space-occupying lesions or tumors of the pituitary can also lead to central hypothyroidism.

Lymphocytic Thyroiditis

• Greater than 95% of hypothyroidism cases are primary, where lymphocytic thyroiditis is believed to be immune-mediated.
• It is progressive in nature, taking months to years to manifest.
• Clinical signs only develop when approximately 75% of the gland is destroyed.

Lymphocytic Thyroiditis Epidemiology

• It is prevalent in medium to large sized breeds.
• The age group of 4-10 years is commonly affected.
• It occasionally occurs in animals as young as 2 years.
• Doberman Pinschers, Golden Retrievers, spaniels, cockers spaniels, Irish setters, and terrier breeds are more prone.
• Boxers and Great Danes are also susceptible, with a higher risk in spayed females.

Idiopathic Thyroidal Atrophy

• Accounts for ≤ 5% of hypothyroidism cases.
• Histology shows degeneration of follicular cells with a reduction in follicular size and replacement of normal parenchymal tissue with adipose connective tissue.
• Appears to be a non-inflammatory degenerative process, which is distinct from lymphocytic thyroiditis.
• The cause is not known.
• Degeneration has been suggested as the end stage of lymphocytic thyroiditis, potentially progressing to non-inflammatory idiopathic atrophy.

Central Hypothyroidism

• Caused by failure of normal TSH secretion by the thyrotropic cells of the pituitary gland.
• It can occur due to suppression of pituitary TSH secretion by exogenous glucocorticoid administration or spontaneous hyperadrenocorticism.

Congenital Hypothyroidism

• It is reported in dogs, but it is uncommon.
• The true incidence may be higher than reported, as many affected puppies die early and are categorized as having "fading puppy" syndrome.
• It is caused by thyroid hypoplasia or aplasia.
• Affected puppies may present with disproportionately wide skulls, macroglossia, and delayed dental eruption genesis, or dyshormonogenesis

Clinical Signs

• Dermatological signs include hair thinning, poor quality/dry/brittle hair coat, rat tail, hyperpigmentation, pyoderma, seborrhea sicca, seborrhea oleosa, otitis, skin thickening.
• Metabolic signs include lethargy, weight gain, exercise intolerance, mental dullness, bradycardia, and generalized weakness.
• Neuromuscular signs include polyneuropathies, peripheral vestibular disease, facial nerve paralysis, central nervous system (CNS) signs, seizures, ataxia, circling, and weakness.
• Other signs include corneal lipidosis, keratoconjunctivitis sicca, reduced myocardial function, reproductive abnormalities, small intestinal bacterial overgrowth (SIBO) and diarrhea, and concurrent immune-mediated endocrinopathies.
• Obesity affects approximately 25% of the canine population; hypothyroidism is estimated at 0.2-0.6%.
• Hypothyroidism is a rare cause of canine obesity.
• Weight gain is a common finding in affected dogs, occurring in approximately 40% of cases during the few months before presentation.

Cardiac & Reproductive Involvement

• Thyroid hormones have a direct positive inotropic effect on the myocardium.
• Dogs with pre-existing heart disease are worsened by concurrent hypothyroidism.
• Canine hypothyroidism is linked to dilated cardiomyopathy.
• Reproductive abnormalities such as anestrus, galactorrhea, infertility, and a prolonged interestrus interval in females and decreased fertility/libido in males have all been attributed to hypothyroidism.

Diagnosis

• Biochemical and hematological abnormalities in both humans and dogs inclide hyperlipidemia and anemia.
• Hypercholesterolemia is commonly reported occurring in up to 80% of affected dogs, the presence of Hypertriglyceridaemia is also present in a similar proportion of cases.
• Mild increases in liver enzymes, particularly alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), are present in about 30% of hypothyroid dogs.
• Fructosamine concentrations are known to be increased in human hypothyroid patients, however little attention has been given to this test in dogs

Diagnostic Testing

• Serum total T4 estimation has traditionally been used as the first-line diagnostic test.
• Routine diagnostic protocol involves T3, T4, and TSH assays by electro-chemiluminescence immunoassay (ECLIA).
• Free T4 has more diagnostic value.
• TSH response test and biopsy of thyroid has been suggested to rule out Pituitary dependant hypothyroidism

Canine TSH (cTSH)

• Measurement of cTSH in isolation is not recommended; it should be tested together with a total T4 estimation to differentiate the low T4 of hypothyroidism from other causes.
• A combined decreased total T4 and increased cTSH has a specificity of >95%.
• This combination of tests has become the hallmark for the initial laboratory diagnosis of hypothyroidism.

Free T4

• The metabolically active fraction of total T4, representing the hormone fraction available for tissue uptake.
• Specificity and sensitivity of free T4 is approximately >90% and 80%.
• Free T4 measurement is a second-line diagnostic test.
• Consider results of cTSH when using T4 to diagnose.

Other Tests

• Not all dogs with hypothyrdism have lympnocytic thyroiditis and even in those that do.
• TgAA positive dogs eventually become TgAA negative with time
• A positive TgAA result strongly indicates thyroid disease, a negative result does not rule it out

Therapeutic Trial

• It is appropriate when the index of suspicion for hypothyroidism remains high, but where diagnostic testing has repeatedly proven equivocal
• Therapeutic trials should be considered a 'last resort' in these situations.

Treatment

• Synthetic sodium levothyroxine therapy is the treatment of choice.
• Re-establishment of normal circulating T4 and T3 concentrations is best achieved by administration of synthetic products that have consistent bioavailability and a longer shelf life.
• Thyroxin is administered at 20-40 μg/kg body weight in single or divided doses, without food, on an empty stomach, subsequent adjustments are made based on the monitoring test.
• The changes in coat and body weight should only assessed after 1-2 month of therapy.

Post-Treatment

• Use laboratory monitoring to identifying peak circulating total T4 concentration and confirm the expected decrease in cTSH values.
• Total T4 measurements are preferred over free T4 for monitoring purposes as clinical resolution is correlated with specific therapeutic ranges.
• Also, Total T4 determinations less expensive than free T4 measurement.

Other Considerations

• Dogs receiving once a day treatment have a marked increase in circulating total T4 values which peaks approximately 6 hours post-treatment & gradually declines until the next day's dose is administered.
• Optimal peak circulating total T4 concentrations should be in the region of 50-60 nmol/l in dogs receiving sid therapy but if values are <35 nmol/l are usually associated with an inadequate clinical response and an increase in dosage is indicated.
• If Marked increases in peak total T4 to 90-100 nmol/l or greater these are unnecesarary and could be thyrotoxic.
• Routiene serum biochemistry and Haematology

Complications

• Dogs are relatively resistant to thyrotoxic effects
• Studies show it requires up to 20x the standard dose of T4 to induce clinical thyrotoxicosis
• When clinical signs of thyrotoxicosis do occur, they may include polydipsia, polyuria, polyphagia, panting, weight loss, hyperactivity, tachycardia, and pyrexia.
• Most signs should resolve within a few days of withdrawing therapy.

Explore the reasons for preferring synthetic thyroid hormones, the role of free T4 in diagnosis, and appropriate use of therapeutic trials. Learn about thyroxine dosage, monitoring treatment effectiveness, and reproductive abnormalities associated with hypothyroidism in dogs.