Hypothyroidism, the most frequently diagnosed endocrinopathy in the dog, is a deficiency of the thyroid follicular hormone cell hormones thyroxine (T4) and triiodothyronine (T3). Most cases of hypothyroidism are due to acquired, primary, destructive processes of the thyroid, namely idiopathic thyroid atrophy and lymphocytic thyroiditis. Rare causes include iodine deficiency (all meat or liver diets), congenital defects, neoplastic-mediated thyroid destruction and brain disease, affecting the hypothalamus and/or pituitary gland. Commonly used medications that affect the thyroid axis are phenobarbital, carprofen, sulfonamides, glucocorticoids and opioids. More than 75% of both thyroid lobes must be rendered non-functional in order for clinical hypothyroidism to become apparent.
Neurologic Manifestations of Hypothyroidism
The Motor Unit
Central Nervous System
Neuroanatomic site of ischemia/infarction
Facial Nerve Paralysis
Peripheral Vestibular Disease
Central Vestibular Disease
Signs of hypothyroidism in the dog include integument-related disease (non-pruritic, symmetrical truncal/distal tail alopecia and/or superficial pyoderma), inappropriate mentation (preserved wakefulness, reduced awareness), intolerance to a cold environment and weight gain (although not necessarily obese). Reproductive signs, ocular signs (rare), decreased renal function secondary to decreased glomerular filtration rate, cardiovascular dysfunction (bradycardia, heart block), possible increase in risk of developing a gallbladder mucocele and polyglandular endocrinopathy (concurrent hypoadrenocorticism, Diabetes Mellitus) have all been reported to correlate with hypothyroidism.
Neurologic signs occur in ~ 7% of hypothyroid dogs, affecting the central nervous system and/or the peripheral nervous system. Pathophysiologic mechanisms of neuromuscular disease include:
Abnormal axonal transport, secondary to decreased ATPase activity and altered microtubule formation and function
Ischemia (+/- infarction), secondary to hyperlipidemia, atherosclerosis and thromboembolic events
Miscellaneous causes, such as immune-mediated demyelination of nerves, deposition of glycogen around nerves and myxedematous deposits.
We can compartmentalize the neurologic manifestations of hypothyroidism into those signs implicating dysfunction of the peripheral nervous system and those attributed to dysfunction of the central nervous system. In the former, generalized polyneuropathy, myasthenia gravis, isolated or multiple cranial neuropathies and myopathies can be seen. In the latter group, central vestibular disease and forebrain dysfunction are the most common.
Facial paresis/paralysis can become evident secondary to hypothyroidism. Myxedematous deposits surrounding the nerves as they pass through the internal acoustic meatus and decreased vascular perfusion of the inner ear, secondary to flow disturbances within the labyrinthine artery, are 2 possible pathophysiologic mechanisms explaining facial neuropathy. Decreased or absent menace response, decreased or absent palpebral reflex, facial asymmetry and/or decreased tear production can be seen. Facial neuropathy secondary to hypothyroidism can occur either unilaterally or bilaterally. If hypothyroid-mediated facial neuropathy is recognized, an improvement is typically seen within weeks of starting appropriate supplementation.
The onset of peripheral vestibular disease, regardless of the underlying cause, is often shocking to the owner(s) and is one of the most common neurologic emergencies we see. In brief, the vestibular system is responsible for; maintaining equilibrium and balance; coordinating head, eye, trunk and limb movements; and, detecting the static position of the head as well as its acceleration, deceleration and rotational movements. Despite the severity and debilitating nature of profound loss of balance, establishing a neuroanatomic diagnosis is crucial to both differential diagnoses and prognosis, namely, determining whether such dysfunction is of peripheral or central cause. If such a diagnosis cannot be reached, due to the extreme vertigo, supportive care is instituted in order to perform a second assessment a day later, allowing time for compensation to better evaluate the patient. Such time given to reach such a diagnosis, based solely on examination, may make the difference between quality of life decisions and the recommendation for continued supportive care.
Peripheral vestibular dysfunction can be caused by hypothyroidism and if so, can resolve with appropriate supplementation. Signs supportive of peripheral vestibular dysfunction include; vestibular ataxia, characterized by leaning, veering, stumbling, falling and rolling towards the ipsilateral side; a head tilt towards the ipsilateral with increased extensor tone in the contralateral limbs; and, pathologic nystagmus that is either resting or positional. With otitis interna/media being the most common cause of peripheral vestibular syndrome, an otoscopic examination is necessary in all patients presenting with vestibular dysfunction.
General stiffness, weakness and diffuse pain can alert the clinician to hypothyroid-induced myopathy. The neuroanatomic diagnosis will be the diffuse lower motor neuron system, after finding the typical features of decreased reflexes, hypotonia and muscle atrophy. Abnormal cellular metabolism, possibly due to decreased carnitine, impaired carbohydrate metabolism and abnormal triglyceride turnover are only a few of the other proposed mechanisms behind hypothyroid-induced myopathy. Serum markers of myopathy include creatine kinase, aspartate aminotransferase and alanine aminotransferase, all of which may be two to three times the upper reference limit in hypothyroid-induced myopathy. Owners of hypothyroid dogs typically report improvement in activity and exercise tolerance within several weeks of starting appropriate thyroid supplementation.
Although causality has not been established for either megaesophagus or laryngeal paralysis, thyroid supplementation upon recognition of clinicopathologic hypothyroidism offers potential for treatment success in such patients, with response to supplementation serving as the best prognostic indicator along with the absence of an identifiable cause for either of these 2 conditions.
The central nervous system is more resilient than other tissues to the metabolic effects of hypothyroidism and due to such resiliency, a neuroanatomic diagnosis within the central nervous system secondary to hypothyroidism is often related to ischemic injury. Myxedema (accumulation of mucopolysaccharides and hyaluronic acids, binding water and increasing thickness of the respective tissue) occurs in the skin of hypothyroid dogs and is uncommon as the cause of a stuporous or comatose dog (i.e. myxedema coma). Rarely, a space-occupying mass affecting the pituitary gland and/or hypothalamus may translate into hypothyroidism although such a patient would be expected to show clinical signs typical of the particular location of both the mass and perilesional edema.
Within veterinary medicine, the word ‘idiopathic’ is a descriptive term for a particular disease that arises spontaneously without an apparent cause. Such enigmatic diseases are prevalent in both human and veterinary medicine within just about every body system. The prefix ‘idiopathic’ to a given syndrome or disease often confers a sense of familiarity and, at times, complacency with such a diagnosis. To name a few examples, Benign (Idiopathic) Geriatric Vestibular Syndrome, Idiopathic Facial Paresis/Paralysis and Idiopathic Polyneuropathy are particular conditions of unknown cause. Many causes of various disease processes are often discovered through a thorough history and complete general physical examination, with supplementary clinicopathologic and/or radiographic testing. When presented with a patient that shows one of the neurologic syndromes described herein, for which ‘idiopathic’ disease is a differential diagnosis, thyroid testing (fT4, TT4 and TSH) can detect hypothyroidism that has the potential, with appropriate supplementation, to treat the primary presenting complaint.
For more information about Angell’s Neurology service, please call 617-541-5140 or e-mail email@example.com.
Bertalan, A., Kent, M. and Glass, E. Neurologic Manifestations of Hypothyroidism in Dogs. VetLearn Compendium. March 2013. VetStreet 2013.
Kent, M., Platt, S.R. and Schatzberg, S.J. The neurology of balance: Function and dysfunction of the vestibular system in dogs and cats. The Veterinary Journal 185 (2010) 247-258.
Panciera, D.A. Complications and Concurrent Conditions Associated with Hypothyroidism in Dogs. Kirk’s Current Veterinary Therapy XV. Web Chapter 14, pp e84-87. www.currentveterinarytherapy.com