Small Animal Endocrinology

Canine Hypothyroidism

• Impaired production and secretion of thyroid hormone results in canine hypothyroidism.
• The destruction of the thyroid gland itself causes 95% of cases, making it a common canine endocrine disease.
• Diagnosis is typically not difficult, but treatment is costly.
• Prognosis is good with treatment.

Physiology of the Thyroid Gland

• The thyroid gland follicles synthesize thyroglobulin, the precursor to thyroid hormone.
• Iodine is incorporated into thyroglobulin's tyrosine residues, leading to the synthesis of T3 and T4.
• T4 is the gland's primary secretory product which is then deiodinated to T3 in peripheral tissues.
• TSH modulates thyroid hormone release, which is modulated by a negative feedback mechanism from thyroid hormone.
• Hypothalamic TRH release controls TSH.
• Thyroid hormones are mainly bound to thyroid-binding globulin (TBG) in plasma.
• Less than 1% of T4 and T3 circulate in their free form, which cells can access.
• Thyroid hormone controls metabolic rate, impacting all tissues.

Classification

• Primary hypothyroidism is the most prevalent form, characterized by the thyroid gland's destruction.
• Idiopathic atrophy of the thyroid and immune-mediated (lymphocytic) thyroiditis are common causes of thyroid gland loss.
• Congenital hypothyroidism, neoplastic destruction, and iatrogenic causes exist, but are less common.
• Secondary or pituitary hypothyroidism: It is caused by the pituitary gland's impaired ability to secrete TSH.
• This mechanism is responsible for <5% of cases, with pituitary tumors, malformation, and isolated TSH deficiency as possible causes.
• Tertiary or hypothalamic hypothyroidism: Deficient production or release of TRH due to traumatic, infiltrative, or destructive lesions.
• Secondary and tertiary hypothyroidism are collectively referred to as central hypothyroidism

Clinical Findings

• This is typically a disease where middle-aged, large breed dogs are at increased risk, usually around 7 years old (range 0.5 - 15 years).
• Neutered animals, particularly females, are at higher risk and small breeds are rarely affected.
• Clinical signs: The metabolic function of organs are affected, leading to diffuse, variable and nonspecific signs.
• Metabolic signs: Dogs experience mental and physical lethargy, weight gain despite normal appetite, along with "heat-seeking" behavior.
• Symptoms often develop slowly and usually improve within two weeks of commencing the treatment.
• Skin diseases, especially bilaterally symmetrical, non-pruritic alopecia are the most common dermatological signs which mainly affect the trunk.
• The coat is dry and lustreless and seborrhea is common, which can lead to secondary bacterial infections due to immunosuppression.
• Skin thickens and facial folds become prominent "tragic" facial expression which results in poor wound healing.
• Reproductive signs: Reproductive failure and hyperprolactinaemia are seen in some cases, which will cause lactation in intact bitches.
• The elevation in TRH stimulates prolactin release and causes neurological signs which are rarely seen in isolation.
• Central disease can be linked to demyelination or atherosclerosis, whereas peripheral disease is associated with mucopolysaccharide accumulation pressuring nerves.
• Cardiac signs: Animals present with bradycardia related to myocardial hypokinesis and cardiac failure can cause euthyroid sick syndrome (ESS).
• Ocular signs: Corneal lipid deposits may be seen.
• Gastrointestinal signs: Constipation and diarrhea which are rarely megaoesophagus and megacolon.
• Myxoedematous coma: Rare syndrome that requires intravenous hormone replacement.
• Congenital hypothyroidism (cretinism): Associated with growth retardation and mental dullness.

Clinicopathologic Abnormalities

• The degree of abnormality correlates with the severity and chronicity of the disease: recognized clinical pathological abnormalities.
• Haematology: Mild normocytic, normochromic, non-regenerative anaemia.
• Occasionally reduced iron absorption from the gut causes hypochromic microcytic anaemia.
• Lipid metabolism abnormalities increase leptocytes.

Biochemistry

• Fasting hypercholesterolaemia is present in 75% of cases.
• Liver enzymes may show mild elevation (ALP, ALT) and muscle enzymes like CK may elevate rarely.
• Urinalysis: Usually normal - a urinary tract infection may be seen.

Thyroid Function Tests

• Diagnosis requires many features which are consistent with the disease.
• Cases are worked up to the point where hypothyroidism is high on the dd list before running specific hormone assays.
• This is termed "increasing your index of suspicion".
• Never base a diagnosis on a single test result since interpretation of thyroid hormone assay results can be difficult.
• Thyroid hormone is very stable and it will resist degradation by freezing/thawing, standing at room temperature.
• Samples can be drawn in serum or heparin tubes.
• Serum total T4 (TT4) levels: It is a good (highly sensitive) screening test - rule out diseases.
• In most cases, Low TT4 distinguishes euthyroid from hypothyroid patients.
• TT4 is often low in the presence of concurrent disease, thereby making the test less specific.
• TT4 can be spuriously elevated in true hypothyroidism if there are high circulating levels of anti-T4 antibody that reacts with the T4 assay.
• Endogenous TSH analysis improves the low specificity of this test.

Serum Free fT4 Levels

• Unbound fraction of T4 is measured, but may be some advantage for ESS and hypothyroidism.

Canine Serum TSH

• It increases because thyroid hormone production drops due to immune-mediated destruction and the negative feedback of TSH decreases.
• True primary hypothyroidism will classically have a low T4 and a high TSH whereas ESS cases will have low T4.
• There are poor poor sensitivity for canine TSH with between 13 and 38% of hypothyroid dogs.
• The combination of TT4 and TSH must be used to diagnose the disease since dogs can have TSH concentrations inside of the reference range.

Euthyroid Sick Syndrome

• Concurrent disease lowers baseline T4 levels.
• A dog is euthyroid, however its TT4 value is below normal.
• Correction of the ESS with thyroid hormone supplementation is contraindicated.
• The interpretation of T4 results are affected by ESS which is probably the most important reason not to base a diagnosis on a TT4 assay.
• Conditions commonly associated wih ESS include dermatologic disorders, and Systemic diseases.

Treatment of Hypothyroidism

• Thyroid hormone replacement will need to be administered life long to ensure a correct diagnosis.
• When diagnostic testing is repeatedly equivocal, yet the index of suspicion for hypothyroidism remains high, a trial of replacement therapy may be used.
• Synthetic T4 (Eltroxin or Leventa) is the drug of choice.
• Dosing: 20 µg/kg twice daily - is a higher dose in man.
• After around 8 weeks, dose drops to once daily - however, some dogs need twice daily treatment.
• Step dose up drug gradually from 10 to 20 µg/kg dose over 3 – 4 weeks in patients with concurrent illness as to not overload the heart.
• A few weeks will improve the well-being, dermatological signs will improve, myocardial function and weight loss may require 2-3 months.
• Response to treatment is often the only therapeutic monitoring required.
• Post pill testing may be necessary in some cases and is measured 4 - 8 weeks after initiating treatment.
• Draw samples at trough.
• Monitor the TSH levels, normal range should return with supplemented T4.
• Monitor Serum T4 concentrations for the first year every 8 weeks, metabolizing T4 as the metabolic rate normalizes and reduce to twice yearly thereafter.
• Prognosis is excellent if treated adequately.