The Ingestion of Compounds That Inhibit the Uptake or Organic Binding of Iodine Blocks the Thyroid's Ability to Secrete Thyroid Hormones and Causes Goiter

An inability to secrete adequate amounts of thyroid hormone often leads to the enlargement of the thyroid gland, a con­dition known as goiter. In many places in the world, this con­dition is, or has been, caused by a deficiency of iodine in the diet.

Hypothyroidism in Dogs

Hypothyroidism is most common in the dog, and the usual etiology of primary hypothyroidism is lymphocytic thyroid­itis. Congenital hypothyroidism may be caused by thyroid dysgenesis, dyshormonogenesis, T₄ transport defects, goitro- gens, or in rare cases, iodine deficiency. Secondary hypo­thyroidism may be a secondary effect of pituitary tumors, radiation therapy, or ingestion of endogenous or exogenous glucocorticoids. Tertiary hypothyroidism can be acquired, as in the case of hypothalamic tumors, or can be congenital as a result of defective TRH or TRH receptor defects.

The signalment of hypothyroid dogs carries a distinct breed predisposition; high-risk breeds manifest symptoms as early as 2 to 3 years of age, and low-risk breeds manifest symp­toms at a slightly older age (4-6 years).

Clinical signs of hypothyroidism are gradual and subtle in onset; lethargy and obesity are most common. Dermatological evidence of hypothyroidism is the next most common clinical finding. Symmetric truncal or tail head alopecia is a classic finding in hypothyroid dogs. The skin is often thickened because of myxedematous accumulations in the dermis. Com­mon hair coat changes seen in the hypothyroid dog include dull dry hair, poor hair regrowth after clipping, and presence or retention of puppy hair.

Cardiovascular signs of hypothyroidism include brady­cardia, decreased cardiac contractility, and atherosclerosis, but these are uncommon presenting complaints. Neuromuscular signs such as myopathies and megaesophagus are also uncom­mon manifestations of canine hypothyroidism. Neuropathies, including bilateral or unilateral facial nerve paralysis, vestib­ular disease, and lower motor neuron disorders, are occa­sionally seen in hypothyroid dogs. Myxedema coma is an unusual finding in hypothyroid dogs and is secondary to myxedematous fluid accumulations in the brain and severe hyponatremia. Less common signs Ofhypothyroidism include reproductive disorders in female dogs, such as prolonged interestrous intervals, silent heat, and delivery of weak or stillborn puppies. Corneal lipid deposits and gastrointestinal problems such as constipation are occasionally observed in hypothyroid dogs.

Clinicopathologica) findings, such as anemia resulting from erythropoietin deficiency, decreased bone marrow activity, and decreased serum iron and iron-binding capacity, are observed in about 25% to 30% of hypothyroid dogs. Hypercholesterole-

Table 34-1

SerumT₄ andT₃ Values by Radioimmunoassay

From McDonald LE, Pineda MG, editors: Veterinary endocrinology and reproduction, ed 4, Philadelphia, 1989, Lea & Febiger.

*∕V= 10, for all species listed.

T_z, Triiodothyronines; T_λ, thyronine; M± SD, median plus/minus standard deviation.

mia is seen in approximately 75% of hypothyroid dogs because of altered lipid metabolism, decreased fecal excretion of choles­terol, and decreased conversion of lipids to bile acids. Hypo­natremia, a common finding in humans with hypothyroidism, is observed as a mild decrease in serum sodium in about 30% of hypothyroid dogs in one study. Hyponatremia is caused by an increase in total body water as a result of impaired renal excretion of water and by retention of water by hydrophilic deposits in tissues. An unusual Clinicopathological feature of hypothyroidism is increased serum creatine phosphokinase levels, possibly as a result of hypothyroid myopathy.

Diagnosis is based on measurement of serum basal total thyroxine (T₁) and triiodothyronine (T₃) concentrations, serum free T₄ and T₃ concentrations, and endogenous canine serum thyrotropin (TSH) levels (Table 34-1) and/or results of dynamic thyroid function tests, including the TRH and TSH stim­ulation tests. The many variables that affect T₄ include age, breed, environmental and body temperature, diurnal rhythm, obesity, and malnutrition. Specifically, affected greyhounds have approximately half the normal total thyroxine (TT₄) and free thyroxine (unbound) (FT₄) concentrations of normal dogs. Obese dogs have mild increases in serum TT₄ concen­trations. In puppies the serum TT₄ concentration is two to five times higher than in adult dogs. Furthermore, there is an age- related decline in serum TT₄ concentrations and response to TSH stimulation in dogs. Euthyroid sick syndrome is charac­terized by a decrease in serum TT₄ and increase in reverse T₃. Concurrent illnesses such as diabetes mellitus, chronic renal failure, hepatic insufficiency, and infections can cause euthyroid sick syndrome, resulting in decreases in serum TT₄ concentrations.

Free thyroid hormone concentrations, or unbound T₄ and T₃, are used in human medicine to differentiate between euthyroid sick syndrome and true hypothyroidism. In humans the diagnostic accuracy of a single FT₄ measurement is approximately 90%. Measurement of FT₄ concentrations is achieved by equilibrium dialysis (“gold standard”) or analogue immunoassays. Theoretically, FT₄ is not subject to spontaneous or drug-induced changes that occur with TT₄. Results of early studies, classifying dogs as hypothyroid on the basis of TSH stimulation tests, indicated that FT₄ measure­ments by equilibrium dialysis were 90% accurate, whereas other FT₄ assays (analogue assays) were no better than TT₄. Glucocorticoids decrease both FT₄ fraction and TT₄ in dogs.

With the advent of the endogenous canine TSH assay, veterinarians now have a method of assessing the thyroid­pituitary axis in dogs without dynamic testing. With thyroid gland failure, decreases in serum FT₄ and TT₄ are sensed by the pituitary gland, resulting in an increase in serum endogenous TSH concentration. Initial studies in dogs with experimentally induced hypothyroidism have been encourag­ing. In humans, when endogenous TSH concentrations are increased and FT₄ concentrations are decreased, diagnostic accuracy for primary hypothyroidism approaches 100%. As FT₄ concentration falls, there is a logarithmic increase in serum endogenous TSH concentration, which makes the TSH assay the most sensitive test for the detection of early hypo­thyroidism. The use of endogenous TSH alone is not recom­mended as a method of assessing thyroid function.

The antithyroglobulin autoantibody test (ATAA) appears promising on the basis of initial study results.

For many years the TSH stimulation test was considered the gold standard for diagnosis of hypothyroidism in dogs. Unfortunately, this test does not differentiate between early hypothyroidism and euthyroid sick syndrome and does not identify dogs with secondary or tertiary hypothyroidism. Fur­thermore, exogenous bovine TSH is no longer commercially available. Other thyroid function tests include the TRH stimulation test, thyroid scan, and thyroid biopsy. However, each test has drawbacks (expense, inaccuracy, or invasiveness).

In summary, diagnosis of canine hypothyroidism is based on signalment, historical findings, physical examination findings, Clinicopathological features, and confirmation with a battery of thyroid function tests. The author uses TT₄ and endogenous TSH (eTSH) initially, followed by FT₄ by dialysis. If all measurements are abnormal, the dog is hypothyroid. If two of the three are abnormal, secondary hypothyroidism (low FT₄) low TSH) or early primary hypothyroidism (high TSH, low FT₄) is possible. If only one of the three thyroid measurements is abnormal, the dog should be reevaluated in 3 to 6 months.

Hyperthyroidism in Cats

Hyperthyroidism is the most common endocrinopathy of cats and is caused by adenomatous hyperplasia of the thyroid gland. Middle-aged to older cats are typically affected, and there is no predilection for breed or gender. Hyperthyroidism is characterized by hypermetabolism; therefore, polyphagia, weight loss, polydipsia, and polyuria are the most prominent features of the disease. Activation of the sympathetic nervous system is also seen; hyperactivity, tachycardia, pupillary dilation, and behavioral changes are characteristic of the disease in cats.

Clinicopathological features of hyperthyroidism include erythrocytosis and an excitement Ieukogram (neutrophilia, lymphocytosis) caused by increased circulating catecholamine concentrations. Increased catabolism of muscle tissue in hyperthyroid cats may result in increased levels of blood urea nitrogen (BUN) but not creatinine. In fact, glomerular filtration rate (GFR) is increased in hyperthyroid cats, and this increase may mask underlying renal insufficiency. Although hyperthyroidism increases GFR, the effect of thyroid hor­mone excess on the urinalysis is variable. Most cats, however, have decreased urine specific gravity, particularly if they are exhibiting polyuria as a clinical sign. Increased metabolic rate results in liver hypermetabolism; therefore, serum activities of liver enzymes (alanine aminotransferase, aspartate amino­transferase) increase in 80% to 90% of hyperthyroid cats. Serum cholesterol decreases, not because of decreased syn­thesis, but rather because of increased hepatic clearance mediated by thyroid hormone excess.

Feline hyperthyroidism is diagnosed through measure­ment of TT₄; TT₃ measurement is generally noncontributory to a diagnosis. Because the disease has become more common and recognized in its early stages, FT₄ concentrations have been shown to be more diagnostic of early or “occult” hyperthyroidism. However, FT₄ concentrations should be interpreted in light of the TT₄ because nonthyroidal illness (chronic renal failure) can result in spurious elevations of FT₄ as well. Free triiodothyronine (FT₃) concentrations do not provide any further advantage over FT₄.