Canine Hypothyroidism

Chapter 42


Canine Hypothyroidism



Clinical signs of hypothyroidism result from decreased production of thyroxine (T4) and triiodothyronine (T3) by the thyroid gland. Acquired primary hypothyroidism is most common in dogs and usually is caused by either lymphocytic thyroiditis or idiopathic thyroid atrophy. Secondary hypothyroidism (deficiency of thyroid-stimulating hormone [TSH]) is less commonly recognized in dogs.



Cause


Approximately 50% of cases of primary hypothyroidism are caused by lymphocytic thyroiditis. Grossly, the thyroid gland may be normal or atrophic, whereas histologically there is multifocal or diffuse infiltration of the thyroid gland by lymphocytes, plasma cells, and macrophages. As thyroiditis progresses, the parenchyma is destroyed and replaced by fibrous connective tissue. Initially, thyroiditis may be subclinical, but progression to overt hypothyroidism can occur. Idiopathic thyroid atrophy, in which there is loss of thyroid parenchyma and replacement by adipose and connective tissue, may represent end-stage thyroiditis rather than a separate disease process. Canine thyroiditis is believed to be immune mediated, and antithyroglobulin antibodies (ATAs) are a sensitive marker of thyroid inflammation. Approximately 50% of hypothyroid dogs have ATAs; however, the prevalence varies widely among breeds, which reflects a familial tendency for thyroiditis and resultant hypothyroidism.



Signalment


Any breed can develop hypothyroidism; however, some breeds, such as the golden retriever and the Doberman pinscher, have been reported to be at higher risk. Thyroiditis is clearly heritable in the beagle and the borzoi, and many other common breeds, such as the golden retriever, Great Dane, Irish setter, Doberman pinscher, and Old English sheepdog, have a high prevalence of ATAs. The rate of clinical progression of thyroiditis also varies among breeds. In beagles, the prevalence of thyroiditis can reach 40%, but if thyroiditis progresses to hypothyroidism, it occurs in middle age or later (Scott-Moncrieff et al, 2006). In other breeds, such as golden retrievers, thyroiditis appears to progress more rapidly, with some dogs diagnosed at 2 years of age. Middle-aged dogs generally are at increased risk of hypothyroidism. In one study, mean age at diagnosis was 7 years (range, 0.5 to 15 years).



Clinical Signs


Clinical features of hypothyroidism are insidious in onset, and hypothyroidism is commonly misdiagnosed because of nonspecific clinical signs affecting multiple body systems. Clinical signs attributable to decreased metabolic rate include lethargy, mental dullness, weight gain, unwillingness to exercise, and cold intolerance.


Dermatologic findings include dry scaly skin, changes in hair coat quality or color, symmetrical alopecia, seborrhea, and superficial pyoderma. Hyperkeratosis, hyperpigmentation, comedo formation, hypertrichosis, ceruminous otitis, poor wound healing, increased bruising, and myxedema also may occur. Alopecia is usually bilaterally symmetrical (see Chapter 39) and is first evident in areas of wear, whereas the head and extremities tend to be spared. The hair may be brittle and easily epilated, and loss of undercoat or primary guard hairs may result in a coarse appearance or a puppy-like hair coat. Fading of coat color may occur, and failure of hair regrowth after clipping is common. Hypothyroid dogs are also predisposed to recurrent bacterial infections of the skin.


Reproductive dysfunction has been attributed to hypothyroidism. There is little evidence for male reproductive dysfunction associated with hypothyroidism; however, bitches with radioactive iodine (131I)–induced hypothyroidism have reduced fertility, prolongation of parturition, and higher periparturient mortality compared with euthyroid bitches (Panciera et al, 2007).


Both the peripheral nervous system and the central nervous system may be affected by hypothyroidism. Subclinical myopathy is well documented in hypothyroid dogs (Rossmeisl, 2010). Peripheral nerve dysfunction also has been described in association with hypothyroidism. Affected dogs have exercise intolerance, generalized weakness, ataxia, tetraparesis or paralysis, deficits of conscious proprioception, and decreased spinal reflexes. Some affected dogs have multifocal dysfunction of cranial nerves (facial, trigeminal, vestibulocochlear). Clinical signs resolve with levothyroxine sodium (l-thyroxine) supplementation. Rarely, central neurologic dysfunction (seizures, central vestibular dysfunction, disorientation, and mentation changes) is observed as a result of cerebral or cerebellar infarction, atherosclerosis, myxedema, coma, and blood viscosity changes secondary to hyperlipidemia. Overall, hypothyroidism is a rare cause of seizure disorders in dogs (Higgins et al, 2006). Although laryngeal paralysis and megaesophagus have been reported in association with hypothyroidism, treatment of hypothyroidism does not consistently result in resolution of clinical signs, and a causal relationship has not been established. Behavioral abnormalities that have been attributed to canine hypothyroidism include aggression and cognitive dysfunction; however, evidence for a causal association between behavioral problems and hypothyroidism is lacking.


Hypothyroidism can cause cardiovascular changes, such as sinus bradycardia, weak apex beat, low QRS voltage, and inverted T waves. Reduced left ventricular pump function has been documented in hypothyroidism and may exacerbate clinical signs in dogs with underlying cardiac disease. Although hypothyroidism is rarely the primary cause of myocardial failure in dogs, dilated cardiomyopathy and hypothyroidism may occur concurrently.


Congenital hypothyroidism results in mental retardation and stunted, disproportionate growth caused by epiphyseal dysgenesis and delayed skeletal maturation. Affected dogs are mentally dull and have large broad heads, short thick necks, short limbs, macroglossia, hypothermia, delayed dental eruption, ataxia, and abdominal distention. A palpable goiter may be present, depending on the cause of the congenital defect. Other clinical signs include gait abnormalities, stenotic ear canals, sealed eyelids, and constipation. Congenital hypothyroidism with goiter (CHG) caused by a nonsense mutation in the thyroid peroxidase gene has been recognized in toy fox terriers and rat terriers (Fyfe et al, 2003; Dodgson et al, 2012). A different missense mutation of the thyroid peroxidase gene causes CHG in Tenterfield terriers. Both defects are autosomal-recessive traits, and a deoxyribonucleic acid test that detects carriers of the defects is available through the laboratory of comparative medical genetics at Michigan State University.



Diagnosis


Hypothyroidism is clinically suspected based on evaluation of the signalment; history and physical examination; and results of a hemogram, biochemical panel, and urinalysis. Clinicopathologic changes that are commonly observed in dogs with hypothyroidism are normocytic, normochromic, nonregenerative anemia; fasting hypertriglyceridemia; and hypercholesterolemia.


Measurement of total T4 concentration is a sensitive initial screening test for hypothyroidism. Additional tests that may aid in confirmation of the diagnosis include measurement of free T4 and TSH concentration, provocative thyroid function testing, antibody tests for thyroiditis, and diagnostic imaging. In some equivocal cases, evaluation of response to thyroid hormone supplementation is necessary to confirm the diagnosis.



Basal Thyroid Hormone Concentrations


T4 is the major secretory product of the thyroid gland, whereas most serum T3 is derived from the extrathyroidal deiodination of T4. Both T3 and T4 are highly protein bound to serum carrier proteins. Only unbound (free) hormone penetrates cell membranes, binds to receptors, and has biologic activity. Protein-bound hormone acts as a reservoir and buffer to maintain a steady concentration of free hormone in the plasma despite rapid alterations in release and metabolism of T3 and T4 and changes in plasma protein concentrations. Free T4 is monodeiodinated within cells to T3, which binds to receptors and induces the cellular effects of thyroid hormone. Basal thyroid hormone measurements used in the diagnosis of canine hypothyroidism are shown in Table 42-1.



Factors such as age, breed, drug therapy, and concurrent illness influence thyroid hormone concentrations without altering metabolically active free thyroid hormone concentrations. Not only do thyroid hormone concentrations in healthy dogs commonly fluctuate out of the reference range, but also numerous breeds have been identified as having thyroid hormone concentrations different than established laboratory reference ranges (Table 42-2). There is also a significant decline in thyroid hormone concentrations with age in dogs (Table 42-3), and many drugs have a marked influence on the thyroid axis (Table 42-4) (Daminet et al, 2003). Dogs treated with phenobarbital that have clinical signs of hypothyroidism are particularly challenging to evaluate for hypothyroidism because phenobarbital treatment causes both a decrease in thyroid hormone concentrations and sometimes an increase in TSH. Options include reevaluation after withdrawal of phenobarbital (and, if necessary, transition to an alternative drug) or consideration of a therapeutic trial (see later).



< div class='tao-gold-member'>

Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Canine Hypothyroidism

Full access? Get Clinical Tree

Get Clinical Tree app for offline access