Hypothyroidism by Mike Herrtage: Part 1

Thyroid Physiology

The thyroid gland actively takes up inorganic iodide, resulting in levels that are 10 to 200 times that of serum.  The inorganic iodide enters the thyroid follicular cells and is transformed into metabolically active thyroid hormones, thyroxine (T4) and triiodothyronine (T3).  The synthesis and secretion of T4 and T3 is controlled by thyroid-stimulating hormone (TSH), a glycoprotein secreted by the thyrotroph cells of the anterior pituitary.  Secretion of TSH is stimulated by thyrotrophin releasing hormone (TRH), a hypothalamic tripeptide.  A classic negative feedback system operates to maintain the plasma concentrations of T4 and T3 within close limits.

In plasma, more than 99 percent of T3 and T4 is bound to plasma proteins, mainly albumin and globulins.  It is the free (unbound) hormones, which are metabolically active.  Although T4 is the major secretory product of the thyroid gland, the metabolic activity of T3 is much greater.  About 80 per cent of the plasma T3 concentration is produced by deiodination of T4 in peripheral tissues, mainly the liver and kidneys.

In catabolic states such as those produced by starvation, anorexia or debilitating disease, T4 is deiodinated to reverse T3 (rT3), an inactive metabolite, at the expense of T3 production.

Thyroid hormones play a dominant role in controlling metabolism.  They increase basal metabolic rate, stimulate cellular oxygen consumption, promote carbohydrate absorption from the intestine and regulate lipid metabolism.  Thyroid hormones are also essential for normal growth and development and they activate the anagen (growth) phase of the hair cycle.  Some effects of thyroid hormones, such as stimulation of the nervous and cardiovascular systems, are mediated by an increased sensitivity to catecholamines.

Hypothyroidism

Hypothyroidism is the most commonly diagnosed endocrinopathy in the dog and estimates of incidence range from 1 in 156 to 1 in 500 depending on the criteria for diagnosis.  Naturally occurring hypothyroidism is an extremely rare clinical disorder in cats.

Primary hypothyroidism is the most common type of hypothyroidism in the dog and usually results from lymphocytic thyroiditis or thyroid atrophy.  Thyroid atrophy can be the end result of lymphocytic thyroiditis.  Thyroid neoplasia may occasionally be associated with hypothyroidism.  Congenital hypothyroidism (cretinism) is rare and may be caused by thyroid agenesis, dysgenesis or dyshormonogenesis.

Secondary hypothyroidism is usually associated with pituitary neoplasia but may also occur with congenital panhypopituitarism.  Tertiary hypothyroidism due to hypothalamic dysfunction, iodine deficiency and serum transport defects are all rare causes of hypothyroidism.

The most common cause of feline hypothyroidism is iatrogenic destruction or removal of the thyroid gland following radioactive iodine therapy or surgery for treatment of hyperthyroidism.  Spontaneous acquired hypothyroidism has been reported in a cat with lymphocytic thyroiditis.  Congenital hypothyroidism has been reported in the cat and may be associated with goitre.

Clinical signs

The clinical signs with hypothyroidism are very variable and often vague.  Some cases present with a classic combination of clinical signs whereas others may exhibit only one sign.  Hypothyroidism usually affects young to middle-aged dogs of the larger breeds.  Golden retrievers, Doberman pinschers, Irish setters appear to be over-represented.

Lethargy, mental dullness, bradycardia, poor exercise tolerance, weight gain without an increase in food intake, intolerance to cold and hypothermia are the most common clinical signs associated with hypothyroidism.

Bilaterally symmetrical, non-pruritic alopecia affecting the flanks, thorax, ventral trunk and neck is associated with inhibition of the hair cycle.  The remaining hair coat is dry and dull.  The skin is often thickened (myxoedematous) and hyperpigmented.  Myxoedema of the skin is most evident on the head resulting in a tragic facial expression.  The skin, particularly on the ventral abdomen, may be cold and clammy to the touch.  Comedones, seborrhoea and recurrent pyoderma may also be noted.

Intact females often have abnormal oestrous cycles and males may show a lack of libido and infertility.  Constipation and corneal lipidosis may occasionally be noted.

Neurological signs may be seen in some dogs with hypothyroidism and include neuromuscular dysfunction with cranial nerve abnormalities, laryngeal paralysis, megaoesophagus, lower motor neurone disease and encephalopathy.  Clinical signs of lameness, dragging of the feet, quadriparesis, hearing impairment and nystagmus have also been reported.  Electromyography may reveal fibrillation potentials and positive sharp waves.  Motor nerve conduction velocities may be decreased and tendon reflexes appear sluggish.

Congenital hypothyroidism has been reported in a number of breeds including the boxer and the giant schnauzer.  Clinical signs of congenital hypothyroidism include hypothermia, lethargy, disproportionate dwarfism with a short, broad skull, short thick limbs and kyphosis, delayed dental eruption, thickened skin and a dry hair coat.  Radiographic changes include delayed epiphyseal ossification and epiphyseal dysgenesis.

Laboratory findings

Hypercholesterolaemia is found in about 70 percent of hypothyroid dogs.  Thyroid hormones stimulate biliary excretion of cholesterol and a deficiency of these hormones results in an increase in the cholesterol content of the liver.  To prevent overloading the liver with cholesterol, the low-density lipoprotein receptors are down-regulated to limit low-density and high-density lipoprotein uptake from the circulation.  Plasma levels of these lipoproteins rise causing hypercholesterolaemia.

Hypercholesterolaemia may also occur with high-fat diets, hyperadrenocorticism, diabetes mellitus, nephrotic syndrome, chronic liver disease and primary hyperlipoproteinaemia.

Mild normocytic, normochromic, non-regenerative anaemia occurs in about 30 percent of hypothyroid dogs and represents a physiological response to the lowered basal metabolic rate.

Mild to moderate increases in serum activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and creatinine kinase (CK) may be noted.  Increased CK activity is particularly associated with myopathy in cases of hypothyroidism.