Hypothyroidism in a boxer dog

Abstract

A 6-year-old boxer was presented with head tilt and facial nerve paralysis. Hypothyroidism was diagnosed and treated appropriately. Hypothyroidism can have an affect on almost any organ system, so the practitioner must be familiar with all clinical signs in order to select appropriate tests and treatment.

A 6-year-old, 30-kg, intact male boxer dog was presented for evaluation of acute onset of a profound head tilt and unilateral facial nerve paralysis. There was no known trauma or exposure to a toxic agent. The dog had received all of its vaccinations and had no previous medical problems, other than a recurring cyst on his back.

On presentation, the dog was bright and responsive. A physical and neurological examination revealed no abnormalities other than excessive drooling; drooping of the left ear, eyelid, and lip; and a pronounced head tilt to the left that was assumed to be vestibular in origin. The differential diagnoses were neoplasia (nerve sheath tumor, osteosarcoma), metabolic disorders (hypothyroidism, cranial nerve polyneuropathy), inflammation (otitis media and interna, infection, foreign body), idiopathic diseases (canine geriatric vestibular disease), head trauma, and exposure to a toxic agent (aminoglycosides, lead). Neoplasia, trauma, and exposure to a toxicant were ruled out based on the dog's history.

A complete blood cell (CBC) count (QBC VetAutoread Hematology System; IDEXX Laboratories, Toronto, Ontario), serum biochemical profile (Vet-test; IDEXX Laboratories), and urinalysis revealed eosinophilia (5.2 ×10⁹ cells/L; reference range, 0.5 to 1.5 × 10⁹ cells/L) and no other abnormalities. Lateral and dorsoventral radiographs of the skull and tympanic bullae were normal. Otoscopic examination revealed that the tympanic membranes were intact and normal in appearance. Since the tympanic bullae and membrane were normal and there was no indication of Horner's syndrome, inflammation (otitis media or interna) was ruled out. Canine geriatric vestibular disease was ruled out based on the dog's age and the facial nerve involvement. Thyroid function tests (Vita-Tech Canada, Markham, Ontario) revealed low serum thyroxine (T4) (7.7 nmol/L; reference range, 19.0 to 58.0 nmol/L) and an increased serum level of endogenous thyrotropin (thyroid-stimulating hormone; TSH) (0.95 nmol/L; reference range, 0.04 to 0.35 nmol/L). A diagnosis of hypothyroidism was made.

The dog was treated with levothyroxine sodium (Synthroid; Knoll, Pharma, Markham, Ontario), 20 μg/kg body weight (BW), PO, q12h. The owner was informed that serum T4 levels should re-assessed in 4 to 8 wk (1). A bacitracin, neomycin, and polymyxin eye ointment (BNP; Vetcom, Upton, Quebec), was dispensed for treatment of the left cornea, q6h, as the dog was unable to close the eye.

Two weeks after the onset of clinical signs and initiation of treatment, the owner reported an improvement in the head tilt and drooping facial features, except when the dog panted. Seven weeks after initiating treatment, the owner reported that the dog was still exercise intolerant and lethargic.

Eight weeks after initiation of thyroxine supplementation, the T4 levels were within normal range (28.2 nmol/L; reference range, 19.0 to 58.0 nmol/L), as was the endogenous TSH level (0.18 nmol/L; reference range, 0.04 to 0.35 nmol/L). The recommendation was that the dog should be maintained on levothyroxine sodium, q12h, until all clinical signs are resolved, before an attempt is made to medicate once daily (1). In this case, the dog was kept on levothyroxine sodium, q12h, even though the clinical signs had resolved.

Hypothyroidism is one the most common endocrine disorders of the dog (2). Most affected dogs have primary hypothyroidism, which may be caused by lymphocytic thyroiditis, idiopathic thyroid atrophy, or, more rarely, neoplastic destruction, resulting in loss of functional thyroid tissue and impaired thyroxine (T4) production (3). Secondary hypothyroidism, which is less common, is caused by reduced secretion of thyrotropin (TSH) by the pituitary gland (3). Tertiary hypothyroidism is caused by a deficiency of hypothalamic thyrotropin-releasing hormone (TRH), and has not been documented in dogs (3). On the basis of the thyroid function tests, the diagnosis for this dog was primary hypothyroidism.

Hypothyroidism occurs most commonly in 4- to 8-year-old, mid- to large-sized purebred dogs. Although several breeds are listed as being predisposed (4), this may reflect a referral population bias. The boxer has been shown, in some studies, to be one such predisposed breed (2,4). There is no clear gender predilection for hypothyroidism, although 1 study did note a greater risk for spayed females (4).

The most common classic clinical characteristics associated with hypothyroidism are dermatological abnormalities, such as alopecia, seborrhea, and hyperpigmentation, and metabolic signs, particularly lethargy, weight gain, exercise intolerance, and heat seeking (5). However, more unusual clinical signs are also recognized. In most instances, common clinical signs accompany the unusual ones. If a practitioner asks the correct questions pertaining to the animal's history, owners will often remember common metabolic clinical signs that they have simply overlooked or assumed to be due to aging (4). In this particular case, the dog had none of the more common clinical findings associated with hypothyroidism.

Neurologic, reproductive, ocular, hematologic, and cardiovascular abnormalities have been reported in hypothyroid dogs (4). Localized neuropathies often cause vestibular and facial nerve paralysis, as was observed in this case, where the onset of signs was acute and nonprogressive; but the onset of signs may also be chronic, or acute and progressive. Neurologic signs of peripheral vestibular disease include head tilt, positional vestibular strabismus, and facial nerve abnormalities, such as absent menace response, or palpebral or corneal reflexes (5), as in this case. An abnormal gait is often noted, but was not seen in this case (5). The following clinical signs, which were not present in this case, may also be seen: signs of central nervous system neuropathies, including depression, weakness, ataxia, proprioceptive deficits, hemiparesis, and hypermetria (4,5); laryngeal paralysis and megaesophagus (5); reproductive signs in females, including altered duration of estrus and anestrus, and inappropriate galactorrhea (3), but reproductive function is not altered in hypothyroid male dogs (6); ocular abnormalities, including corneal lipid deposits, corneal ulceration, and uveitis (4); hematological abnormalities, including mild nonregenerative anemia, hypercholesterolemia, and hypertriglyceridemia (6); and cardiovascular abnormalities, including bradycardia, arrhythmia, weak apex beat, and poor pulse quality (6).

Testing for hypothyroidism may prove difficult, as subnormal serum T4 levels may occur in normal dogs, in euthyroid dogs with nonthyroidal illness (3), in certain breeds, and after administration of some medications, such as glucocorticosteroids, sulphonamides, anticonvulsants, furosemide, salicylates, phenylbutazone, flunixin, and radiocontrast agents (6). When a dog shows classic clinical signs, a subnormal serum T4 level may be sufficient to make a tentative diagnosis and begin trial treatment with levothyroxine (6). However, if the dog has atypical signs, as in this case, further testing is indicated. A serum free-T4 (fT4) assay, performed by the equilibrium dialysis technique, more accurately identifies true hypothyroid dogs (6,7). The endogenous TSH assay is an accurate and sensitive test in humans but not in dogs, as some hypothyroid dogs have normal endogenous TSH levels and some euthyroid dogs have elevated endogenous TSH levels (6). When clinical signs are atypical, it is best to measure either serum T4 or fT4 in combination with canine endogenous TSH levels. Normal serum T4 or fT4 rule out hypothyroidism. If there is no concurrent illness or history of recent administration of drugs known to decrease serum T4 levels, a diagnosis of hypothyroidism can be considered in a dog with both subnormal serum T4 or fT4 and elevated endogenous TSH, as in this case (8). Other diagnostic tests used to assess thyroid function in humans are not readily available to the veterinary practitioner (5).

Many thyroid hormone supplements are available, but levothyroxine (synthetic T4) is preferred (9). When exogenous levothyroxine is administered, plasma T4 increases. Levothyroxine is converted to triiodothyronine (T3) through deiodination of T4, which is important, as T3 is more metabolically active in peripheral tissues (8,9). Negative feedback on the pituitary by T3 and T4 results in reduced production of TSH (9). In this case, after thyroxine supplementation, endogenous TSH decreased as the dog's serum T4 increased.

Response to treatment is frequently noted within 1 wk of initiating treatment. Often, the first clinical sign noticed is that the dog's activity level increases (9). In cases with uncommon clinical signs, the owners may realize after treatment that the dog had been lethargic before the presenting clinical signs were noticed (4). Although peripheral neuropathies often improve rapidly, some may persist indefinitely (9), and lethargy may persist longer than usual (4). In this case, the head tilt and facial nerve paralysis improved rapidly, but the dog was still lethargic 8 wk after treatment began. Normally, a lack of a response after 6 to 8 wk should be reason to investigate reasons for treatment failure, such as another underlying medical condition (9).