3 CE Credits

Neurologic Manifestations of
Hypothyroidism in Dogs
Abigail Bertalan, VMD
University of Pennsylvania

Marc Kent, DVM, DACVIM (Internal Medicine, Neurology)

University of Georgia

Eric Glass, MS, DVM, DACVIM (Neurology)

Red Bank Veterinary Hospital
Tinton Falls, New Jersey

Abstract: Hypothyroidism is a common endocrine disease in dogs. A variety of clinicopathologic abnormalities may be present; however,
neurologic deficits are rare. In some instances, neurologic deficits may be the sole manifestation of hypothyroidism. Consequently, the
diagnosis and management of the neurologic disorders associated with hypothyroidism can be challenging. This article describes several
neurologic manifestations of primary hypothyroidism in dogs; discusses the pathophysiology of hypothyroidism-induced neurologic
disorders affecting the peripheral and central nervous systems; and reviews the evidence for the neurologic effects of hypothyroidism.

T
he reported prevalence of hypothyroidism in middle-aged to Nonneurologic Clinical Signs and Diagnosis
older dogs is 0.2% to 0.8%.1 The clinical syndrome results from of Hypothyroidism
a deficiency of the active thyroid hormones triiodothyronine A variety of clinicopathologic abnormalities are present in affected
(T3) and thyroxine (T4), which are synthesized in the thyroid gland dogs. Typical physical manifestations include dermatologic changes
from the protein thyroglobulin. All circulating T4 is derived from the such as nonpruritic, symmetrical truncal and distal tail alopecia and
thyroid gland, but 80% of T3 is produced by nonthyroidal tissues superficial pyoderma. Other physical examination findings include
after deiodination of T4. The thyroid gland synthesizes thyroid bradycardia, lethargy, weight gain, and hypothermia. Anestrus,
hormone after being stimulated by thyroid-stimulating hormone testicular atrophy, loss of libido, and gynecomastia have also been
(TSH), which is released from the adenohypophysis (pituitary gland) reported.1
in response to thyrotropin-releasing hormone (TRH) released by A complete blood count may reveal a nonregenerative anemia
the hypothalamus. Hypothyroidism may be due to dysfunction that is the result of reduced erythropoietin production consequent
of the hypothalamus, pituitary gland, or thyroid gland. The most to reduced T4 levels.1 Hypercholesterolemia is often present and
common presentation occurs in adult dogs with disease affecting is primarily due to the role of thyroid hormone in stimulating
the thyroid gland (primary hypothyroidism), with 50% of these lipid synthesis, mobilization, and degradation via its actions on
dogs having evidence of lymphocytic thyroiditis and 50% having hepatic and lipoprotein lipase as well as on hepatic low-density
idiopathic atrophy of the thyroid gland.1 Lymphocytic thyroiditis lipoprotein (LDL) receptors.3 In 20% to 30% of hyperthyroid dogs,
is an autoimmune disease in which (1) lymphocytic-plasmacytic the serum creatine kinase level is elevated due to hypothyroid
infiltrates exist within the glandular tissue and (2) circulating auto- myopathy or changes in muscle metabolism; creatine kinase activity
antibodies directed against thyroglobulin, T4, or T3 are present. has been shown to be inversely proportional to thyroid hormone
Certain breeds, such as pointers, English setters, boxers, and beagles, activity in humans.1
are predisposed to having antithyroid hormone antibodies.2 How- Therapy for hypothyroidism is straightforward and involves
ever, the presence of autoantibodies does not confirm the presence thyroid hormone supplementation. However, in some instances,
of clinical hypothyroidism. the diagnosis can be challenging, as a number of non–thyroid-
With idiopathic atrophy of the thyroid gland, the parenchyma is related diseases affect thyroid hormone metabolism. As a result,
replaced with adipose tissue. Clinical signs are a result of decreased serum concentrations of T4 may be low despite normal thyroid
synthesis and secretion of T3 and T4. function. This is referred to as euthyroid sick syndrome.1 Similarly,

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 Neurologic Manifestations of Hypothyroidism in Dogs

drugs may alter thyroid hormone metab-

olism, which can result in an inaccurate
Table 1. Commonly Used Medications in Veterinary Neurology and
diagnosis of hypothyroidism (TABLE 1).
4
Their Effect on Thyroid Axis Testing
Among commonly used medications, Drug Use Mechanism Effect on Thyroid Testing
phenobarbital and corticosteroids may
Phenobarbital Anticonvulsant Increases hepatic metabolism, • Decreased TT4
alter thyroid hormone levels. Likewise, decreases T4 5' deiodinase
trimethoprim-sulfonamides can result in activity • Decreased fT4
true hypothyroidism.2 As a result, mea- • Increased TSH
surement of free T4 (fT4) concentration,
which is not affected by nonthyroidal Potassium bromide Anticonvulsant Suspected to interfere with None
illness, is recommended for patients iodide transport
with clinical signs of hypothyroidism.1 Carprofen Antiinflammatory Displaces thyroid hormone • Decreased TT4
A definitive diagnosis of hypothy- from serum-binding proteins,
decreases hepatic uptake • Decreased fT4
roidism is established by demonstrating
a serum fT4 concentration below 90% • Decreased TSH
of the reference range, in addition to
Glucocorticoids Antiinflammatory Decreases TSH secretion, • Decreased TT4
clinical suspicion of disease.1 Endoge- T4 5' deiodinase activity, and
nous TSH levels can help strengthen T4-binding globulin levels • Decreased fT4
the diagnosis and are 80% diagnostic • Increased TSH
for hypothyroidism; however, measure-
ment of endogenous TSH concentration Opioids Analgesia Unknown • Decreased TT4
is more specific in the presence of a • Decreased fT4
low fT4 level than if interpreted alone.1
Ultimately, the decision to treat dogs • Decreased TSH
suspected of being hypothyroid de- fT4 = free thyroxine, TSH = thyroid-stimulating hormone, T4 = thyroxine, TT4 = total thyroxine.
pends on the clinical signs, combined
with the results of thyroid function testing. A complete thyroid influences the expression of dynein and tubulin proteins, which
panel, including measurement of total thyroxine (TT4), fT4 and are involved with microtubule functions necessary for axonal
TSH, is recommended. Affected dogs are treated with synthetic transport. Altered microtubule formation and function can lead
T4 at a dosage of 0.02 mg/kg twice daily. Six to 8 weeks should be not only to slowed axonal transport, but also to degradation of
allowed to observe an improvement in clinical signs, and lethargy the axon and impaired regeneration.14
and dullness may improve sooner than dermatologic and repro-
ductive abnormalities. Neurologic signs may show improvement Ischemia
rapidly. However, cases of myopathy may take weeks to months Ischemic events are some of the most frequently cited causes of
to improve.5–7 CNS signs in hypothyroid dogs, but they have also been postulated
to play a role in clinical signs related to the peripheral nervous
Pathogenesis of Hypothyroid-Induced Neurologic Signs system.3,8,10,15 In hypothyroid animals, ischemia and secondary
Neurologic signs occur in 7.5% of hypothyroid dogs. Neurologic
8
infarction of tissue may be the result of atherosclerosis. Hyperlip-
deficits may implicate the involvement of the peripheral nervous idemia, which is the accumulation of plasma lipid and cholesterol,
system and the central nervous system (CNS).3,9,10 A causal rela- occurs commonly in dogs with hypothyroidism and is secondary
tionship between hypothyroidism and neurologic dysfunction to a reduction in the uptake of triglycerides due to T4 deficiency.16
has not been definitively established; however, the literature Atherosclerosis is characterized by thickening of the tunica media/
strongly suggests that hypothyroidism plays a role in the devel- interna of arterial walls, associated with lipid deposition. Smooth
opment of neurologic deficits. Although not fully understood, muscle and lipid-filled macrophages known as foam cells proliferate
the pathophysiologic mechanisms underlying the development of in the tunica media/interna, and a fibrous plaque forms around a
neurologic signs may involve, among other processes, alterations core of lipid (atheroma).16 In humans, plasma LDL concentrations
in axonal transport and ischemia. have been positively correlated with the risk of developing athero-
sclerosis.16 Several reasons may explain this correlation. LDLs
Abnormal Axonal Transport easily penetrate the subintimal space of vessels, have greater sus-
Thyroid hormone induces activity of adenosinetriphosphatase ceptibility to oxidation than other plasma lipoproteins, bind intimal
(ATPase), which is used by the sodium/potassium pumps necessary proteoglycans, are toxic to endothelial cells, and stimulate the
for axonal transport of ATP and molecular proteins. Consequently, production and secretion of plasminogen activator inhibitor 1 and
in hypothyroidism, ATPase activity is decreased, resulting in a thromboxane by endothelial cells.16 LDLs also bind to scavenger
decreased activity of these pumps. Additionally, thyroid hormone
11–13
receptors, thereby contributing to the formation of foam cells.16

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 Neurologic Manifestations of Hypothyroidism in Dogs

Although dogs with naturally occurring hypothyroidism are blocks exist.7 It is important to note that affected dogs may have
relatively resistant to the development of atherosclerosis, dogs concurrent myopathy. Histopathologic demonstration of wallerian-
made hypothyroid through thyroid ablation or thyroidectomy that like degeneration with intercalated internodes and myelin irreg-
are fed a diet high in cholesterol may develop atherosclerosis.5 ularities in nerve tissue provides definitive evidence of a poly-
Hypothyroidism is the most common cause of atherosclerosis in neuropathy.26
dogs, but plaques may also form in dogs with hypertension, diabetes Ultrasonography of the vasculature supplying the affected
mellitus, and hyperlipidemia.17 Cerebrovascular accidents may limbs may detect thrombi. In one study, emboli were identified in
also be caused by intravascular neoplasia or underlying diseases the internal iliac and the femoral arteries of hypothyroid dogs.27
that cause hypercoagulability, such as hyperadrenocorticism, Response to thyroid supplementation is often rapid in dogs
pheochromocytoma, diabetes mellitus, cardiac disease, and protein- with a polyneuropathy. Affected dogs may show improvement in
losing enteropathy/nephropathy. 24 hours, with complete resolution occurring within 1 to 2
Dogs that have hyperlipidemia and develop atherosclerosis have months.5,11,14,22
increased lipoprotein levels, primarily in the β and α2 fractions
consistent with LDLs, which may suggest an underlying patho- Myasthenia Gravis
genesis for ischemia and infarction similar to that in humans.5 In humans, a link between hypothyroidism and myasthenia gravis
Additionally, an increase in triglyceride and cholesterol concen- (MG) has been reported.28 Approximately 10% to 20% of people
trations increases blood viscosity and the risk of thromboembolic with MG also have thyroid disorders.29 Hypothyroidism also has
events.16,18,19 Multifocal thromboemboli and lipid emboli involving been observed in dogs with MG.12,22 It is hypothesized that the auto-
the brain and muscle tissue have been observed antemortem and antibodies directed at the acetylcholine (ACh) receptor cross-react
at necropsy in hypothyroid dogs.3,18 with self-antigens present in the thyroid gland.12 Embryologically,
the thyroid gland arises from the endoderm of the floor of the
Miscellaneous Causes foregut and migrates caudally. Ectopic migration may result in
Secondary immune-mediated demyelination of nerves, primary the presence of myoepithelial cells expressing ACh receptors, the
inherited Schwann cell demyelination,20 and deposits of glycogen target for autoantibodies in MG, in thyroid tissue. Such a patho-
around nerves have been reported in humans,11,12,21,22 and nerve genesis has been documented for disorders of the thymus.26 The
compression by myxedematous deposits has been described in occurrence of hypothyroidism before development of MG or
humans and dogs.14,20 Lipid granulomas have been reported in vice versa has not been studied, and a causal relationship in dogs
cats with hyperchylomicronemia.23 Affected cats have elevated remains to be established.
cholesterol and LDL levels, which is a condition also seen in hypo-
thyroid dogs. The pathogenesis for these findings remains undefined. Cranial Nerve Disorders
Isolated or multiple cranial neuropathies involving the vestibular
Peripheral Nervous System Disorders branch of the vestibulocochlear nerve, the facial nerve, and the
The most commonly encountered neurologic disorders related to sensory branch of the trigeminal nerve may be observed in dogs
hypothyroidism include neuropathic and myopathic disease. In with hypothyroidism. However, other cranial nerves can also be
both, neurologic examination abnormalities may include abnormal affected.
postural reactions, decreased patellar and withdrawal reflexes, There are many reports of hypothyroid dogs with facial nerve
and decreased muscle tone and atrophy. dysfunction.3,14,22,30–32 Facial nerve paralysis is present in up to 70%
of dogs with hypothyroidism and nerve dysfunction.33 Neurologic
Generalized Polyneuropathy abnormalities may include decreased or absent palpebral reflexes,
Hypothyroidism is associated with polyneuropathy.1,6,24,25 Large- lip droop, ear droop, or decreased tear production. Unilateral or
and giant-breed dogs are usually affected and can present with bilateral facial paresis/paralysis was reported in four dogs in
pelvic limb paresis progressing to tetraparesis over the course of which clinical signs improved over a 2-week period during which
1 to 2 months.14 Neurologic deficits include postural reaction thyroid supplementation was administered.22 In another study,
deficits, hyporeflexia, hypotonia, and muscle atrophy.11 absent corneal and palpebral reflexes were observed in 88% of
The diagnosis of hypothyroid-induced polyneuropathy begins hypothyroid dogs examined over a 3-year period.14 Unilateral facial
with documenting hypothyroidism in a dog with signs of neuro- nerve paralysis in hypothyroid dogs has been reported.30,31
muscular dysfunction. More definitive diagnosis includes electro- In addition to typical neurologic defects, bilateral stapedial reflex
physiological testing. Electromyography (EMG) may reveal fibril- deficits were detected by impedance audiometry, and EMG revealed
lation potentials, positive sharp waves, increased insertional activity, fibrillation potentials and positive sharp waves in the facial muscles
and complex repetitive discharges from the proximal appendicular in two dogs in one report.30 Both dogs experienced improvement
muscles.7,26 Since these findings can be present with disorders of in facial nerve paralysis after 2 weeks of thyroid hormone supple-
nerve or muscle, more suggestive evidence of polyneuropathy is mentation and were free of neurologic deficits by 4 weeks.
found with direct evoked motor potentials, in which motor nerve Myxedematous deposits surrounding the nerves as they pass
conduction velocities are decreased and, in some cases, conduction through the internal acoustic meatus has been suggested as a likely

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 Neurologic Manifestations of Hypothyroidism in Dogs

cause for facial neuropathies.22 Decreased vascular perfusion of MG rather than thyroid supplementation. As further evidence for
the inner ear may also be a cause of facial neuropathies in hypo- a lack of correlation between hypothyroidism and megaesophagus,
thyroid dogs.3 The inner ear is supplied by the labyrinthine artery, abnormal esophageal function does not respond to thyroid hormone
which travels along the cochlear aqueduct. This artery is contained supplementation.33 Ultimately, care must be exercised when in-
in a confined space that may be subject to perfusion injury secondary terpreting thyroid function testing in dogs with megaesophagus,
to hyperlipidemia and increased blood viscosity. In addition to as many dogs are likely to have euthyroid sick syndrome rather
facial nerve paralysis, deficits relating to the parasympathetic branch than hypothyroidism.
of the facial nerve may be present.
Muscle Disorders
Peripheral Vestibular Disease Up to 40% of humans with hypothyroidism have clinical signs of
Peripheral vestibular dysfunction may occur secondary to hypo- skeletal muscle weakness at initial diagnosis.29 Similarly, dogs can
thyroidism.3,7,22,25 Signs of peripheral vestibular dysfunction include present with muscle pain and stiffness as well as generalized
head tilt, vestibular ataxia, and rotary or horizontal nystagmus. weakness.6
While not specific for hypothyroid-induced dysfunction, brainstem In one hypothyroid dog, pelvic limb paresis progressed to tetra-
auditory evoked response testing reveals abnormal conduction paresis over the course of 6 weeks.5 The dog was unable to bear
in dogs with peripheral vestibular disease.10 In one dog with hypo- weight without assistance but had motor function. Postural reactions
thyroidism and signs of peripheral vestibular disease with no other were normal when the dog’s weight was supported. The dog was
identified cause, bilateral stapedial reflexes were also dampened.30 hyporeflexive and hypotonic in all four limbs. EMG revealed
Given the prevalence of otitis media/interna, all dogs with signs prolonged insertional activity, fibrillation potentials, positive sharp
of peripheral vestibular dysfunction should undergo an otoscopic waves, and complex repetitive discharges, which are suggestive of
examination. Otoscopic examination, radiographs of the tympanic a myopathy. Abnormalities were detected in the muscles of the
bullae, and computed tomography or magnetic resonance imaging limbs innervated by the femoral, sciatic, obturator, radial, median,
(MRI) of the head should be performed to exclude otitis media/ and ulnar nerves. Motor nerve conduction velocity was decreased
interna and other otic diseases from consideration. (50 m/sec in the femoral branch and 42 m/sec in the tibial branch
of the sciatic nerve; normal range: 52 to 67 m/sec).20 A muscle
Glossopharyngeal/Vagal Neuropathies biopsy revealed angular atrophy of type II muscle fibers, and
Cricopharyngeal achalasia in a hypothyroid dog has been described some type I fibers had vacuoles containing para-aminosalicylic
in which dysphagia and pytalism resolved after 6 days of treatment acid–stained material that was resistant to amylase digestion.
with synthetic thyroxine.34 A focal neuropathy involving the pha- Amylase removes glycogen within myotubules; therefore, this
ryngeal branches of the glossopharyngeal and vagus nerves was material was not glycogen. However, the presence of stain uptake
suspected. indicated that it could be a product of glycogen metabolism. The
presence of large amounts of glycogen between myofibrils has
Laryngeal Paralysis been shown in muscle biopsy samples from humans with hypo-
Laryngeal dysfunction has been reported in dogs with hypothy- thyroidism.5 The dog was treated with thyroid hormone supple-
roidism.7,9,14 In a study of 140 dogs with laryngeal paralysis, 30 dogs mentation and was able to walk a short distance within 1 week.
were diagnosed with hypothyroidism based on results of a mea- By 3 months, it had a normal gait.
surement of TT4, fT4, and TSH levels or a TSH stimulation test.19 The pathogenesis of hypothyroid myopathy likely involves ab-
However, treatment for laryngeal paralysis usually entails surgical normal cellular metabolism. Through the process of beta oxidation,
intervention, and response to thyroid hormone supplementation which takes place in the mitochondria, myocytes use fatty acids
alone has not been widely reported.7 In one study of 66 hypothyroid for energy. Carnitine is necessary to shuttle fatty acids from the
dogs, two dogs had laryngeal paralysis that was not corrected by cytosol into the mitochondria for beta oxidation. One possible
treatment with thyroid supplementation.22 explanation for the development of a myopathy secondary to hypo-
thyroidism is a decreased skeletal muscle carnitine level. This
Megaesophagus may be due to decreased synthesis of de novo carnitine, leading to
While megaesophagus has been thought to be a consequence of a shift of carnitine from skeletal muscle to the extracellular pool
hypothyroidism, recent evidence has failed to demonstrate an and subsequent increased urinary excretion.6 In an experimental
association between acquired megaesophagus and hypothyroid- model for hypothyroidism, affected dogs had a higher urinary
ism.14,22,33,35 excretion of carnitine and decreased levels of muscle carnitine
In one study, three dogs with megaesophagus and hypothy- after 6 months of uncontrolled disease compared with control
roidism had levels of antibodies directed against the ACh recep- dogs.6 Although none of the dogs developed neuromuscular
tor that were diagnostic for MG and experienced response to signs during the 18-month time period, five out of nine dogs had
cholinergic therapy.12 These dogs also received thyroid hormone abnormal EMG findings.6
supplementation; however, although impossible to determine, The same study compared histopathologic evidence of muscle
clinical improvement likely reflected a response to treatment for pathology.6 At 6 months, nemaline rod inclusions and atrophy of

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 Neurologic Manifestations of Hypothyroidism in Dogs

type II fibers were present. Although this indicates denervation and dementia).5,7 Although there is little definitive evidence to
injury, which may also be accompanied by type I fiber atrophy in confirm that hypothyroidism causes seizures, atherosclerosis and
some dogs,21 intramuscular nerve fibers were normal throughout hyperlipidemia are potential underlying mechanisms of prosen-
the length of the study, indicating a myopathy. cephalic signs. Dogs with epilepsy may have euthyroid sick syn-
Total myofiber mass between affected and control dogs was drome as a result of nonthyroidal illness as well as from the effect
not statistically different; however, hypothyroid dogs displayed a of anticonvulsant medications on basal thyroid hormone levels,
decreased type II:type I myofiber area ratio at all of the time further confounding the association between hypothyroidism
points in the study compared with control dogs. These changes and seizures.
mimicked those reported in dogs with naturally occurring hypo- Stupor and coma, referred to as myxedema coma, may be a result
thyroidism.6 of altered neurotransmitter release and reuptake or failure of thyroid
Interference with normal carbohydrate metabolism, an increase hormone transport locally within the brain. Myxedema occurs in
in the proportion of slow myofibrillar proteins, abnormal oxidative the skin of hypothyroid dogs. Myxedema results in the accumu-
phosphorylation, abnormal triglyceride turnover, and abnormal lation of acidic and neutral mucopolysaccharides and hyaluronic
cation transfer across the sarcolemma are other proposed mech- acids, which bind water and result in increased thickness of the skin
anisms of hypothyroid-induced peripheral nerve dysfunction.12 and other tissues.2 Signs of myxedema coma include nonpitting
Additionally, immune-mediated depletion of myofibrillar pro- edema of the face and jowls, bradycardia, and profuse obtundation
teins22 and deposition of glycogen between myofibers have been to coma and may also be responsible for neuronal and tissue
shown in humans.5 compression.7,33,36 When performed, electroencephalography reveals
Owners of hypothyroid dogs often notice an increase in their extremely low-voltage, low-amplitude brain activity, which is
dogs’ activity levels and exercise tolerance within 2 weeks of starting consistent with reduced cerebral metabolism.14,32
thyroid supplementation.6 Infarction involving the prosencephalon may also be the result
of hypothyroidism. In one study, three dogs with hypothyroidism
Central Nervous System Disorders presented with circling, disorientation, stupor, and blindness.
Hypothyroidism has been associated with clinical signs of mental Atherosclerotic plaques and obstructions in the cerebral arterial
dullness, circling, seizures, and central vestibular signs as well as circle were observed at necropsy.18
cognitive dysfunction.3 Mechanisms may include atherosclerosis, Similar findings have been reported in a dog with hypothy-
myxedema coma, or presence of a pituitary tumor. As a whole, the roidism that presented with a 1-day history of seizures and dis-
CNS is more resilient than other tissues to the metabolic effects of a orientation and a 1-year history of peripheral vestibular dysfunc-
decreased T4 level. Therefore, CNS dysfunction is a rare presentation tion.32 At necropsy, changes in the brain vasculature, including
in hypothyroid dogs and is most commonly related to ischemic the basilar, rostral and caudal cerebellar, labyrinthine, internal
pathology. However, the effects on the CNS can be profound, and carotid, and caudal, middle, and rostral cerebral arteries, were
clinicians should be aware of the possibility of involvement of observed. In addition, parietal lobe malacia and a cholesterol
metabolic disease as well as primary neurologic etiologies. granuloma were found.
Despite the essential need for energy and its high metabolic
Central Vestibular Disease demands, the brain is relatively insensitive to metabolic changes
In a recent retrospective report of 10 dogs with central vestibular present in other tissues in hypothyroid animals. A small number of
signs and confirmed hypothyroidism, signs included abnormal thyroid hormone–induced genes are present in the adult canine
nystagmus, postural reaction deficits, tetraparesis/hemiparesis, brain, and it has been shown that the brain increases thyroid
and paradoxical central vestibular dysfunction (typified by a head hormone uptake via an active transport process within the
tilt contralateral to the observed postural reaction deficits). Dogs blood-brain barrier in times of deficiency of thyroid hormone.12
presented with variable disease progression; two had a history of In addition, activities of deiodinases that catalyze the conversion
paroxysms of vestibular dysfunction on a daily or weekly basis, of T4 to T3 are increased, and degradation of thyroid hormone is
and eight had an acute onset of signs.10 In another case, a hypo- decreased. This allows the CNS to function at a relatively normal
thyroid dog presented for acute onset of central vestibular dys- metabolic rate compared with peripheral tissues, even when hypo-
function.3 T2-weighted MRI revealed a focal hyperintense lesion thyroidism is chronic. In hypothyroid rodents, however, it has
in the area of the brainstem. Clinical signs improved in 24 hours been shown that γ-aminobutyric acid (GABA) and benzodiazepine
without treatment. The history, spontaneous improvement, and receptor density is altered, as are the reuptake of GABA and the
MRI features were suggestive of a brainstem infarction. Territorial activities of acetylcholinesterase,10 which may explain the mental
infarction of the cerebellum has also been reported in three dogs dullness observed in some dogs with hypothyroidism.
with central vestibular signs and hypothyroidism.10 Although uncommonly reported in the literature, pituitary
neoplasms that cause secondary hypothyroidism can also lead to
Prosencephalic Signs signs of mental dullness.37–40 Neurologic signs are the predominant
Rarely, dogs may display prosencephalic signs, characterized as clinical signs. In these cases, the compressive effects of the tumor
propulsive circling, seizures, and changes in mentation (aggression on surrounding structures can cause ataxia, seizures, depression,

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 Neurologic Manifestations of Hypothyroidism in Dogs

and head pressing.32 Tumors of the pituitary region may also neuromuscular disease in four hypothyroid dogs. J Am Vet Med Assoc 1993;202(11):
compress the overlying diencephalon and associated ascending 1859-1860.
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and hypothyroidism. Prog Vet Neurol 1995;6(4):117-123.
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dogs. In addition, these tumors may alter production of TRH and, thyroid rats. J Neurochem 1987;496:1790-1795.
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advanced imaging. dogs. J Vet Intern Med 1994;8(5):328-336.
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18. Liu SK, Tilley LP, Tappe JP, Fox PR. Clinical and pathologic findings in dogs with
nervous system are not definitively proven to have a cause-and- atherosclerosis: 21 cases (1970-1983). J Am Vet Med Assoc 1986;189(2):227-232.
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 Neurologic Manifestations of Hypothyroidism in Dogs

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1. Most dogs with hypothyroidism have _______ hypothyroidism a. central nervous system ischemic events.
caused by _______. b. myxedema coma.
a. primary; lymphocytic-plasmacytic thyroiditis c. neuropathic and myopathic disease.
b. secondary; lymphocytic-plasmacytic thyroiditis d. seizures.
c. primary; lymphocytic thyroiditis or idiopathic atrophy
7. Which describes the presentation of a dog with generalized
d. secondary; lymphocytic-plasmacytic thyroiditis or
idiopathic atrophy polyneuropathy due to hypothyroidism?
a. small-breed dog with increased patellar reflexes and tone
2. The most appropriate diagnostic test(s) to perform in a case
b. large-breed dog with decreased patellar reflexes and
of suspected hypothyroidism is/are measurement of the
normal to decreased tone
a. total thyroxine (T4) level.
c. large-breed dog with increased patellar reflexes and tone
b. total T4, free T4, and thyroid-stimulating hormone (TSH)
d. small-breed dog with decreased patellar reflexes and
levels.
normal to decreased tone
c. total and free T4 levels.
d. total and free T4 levels, plus a TSH stimulation test. 8. Which statement is true regarding peripheral nervous
system disorders in hypothyroid dogs?
3. What is the cause of hyperlipidemia in hypothyroid dogs? a. Generalized polyneuropathies have a poor response to T4
a. increased dietary intake secondary to polyphagia supplementation.
b. inhibition of lipoprotein lipase caused by lack of thyroid b. Myasthenia gravis is thought to be associated with
hormone hypothyroidism due to acetylcholine antibody receptor
c. decreased cholesterol uptake due to oversaturation of displaying cross-reactivity with the thyroid gland.
receptors c. Most cases of megaesophagus resolve after a short
d. lack of thyroid hormone–mediated uptake of plasma course of treatment with T4 supplementation.
triglycerides d. A muscle biopsy is the preferred diagnostic test for
generalized polyneuropathy.
4. The pathophysiology of atherosclerotic damage is initiated by
a. lipid deposition and thickening of the tunica media/interna. 9. Histopathologic evidence associated with myopathies in
b. vascular dilatation secondary to nitrous oxide release. hypothyroid dogs may include a _________ type II:type I
c. fibrosis of the muscular lining of arteries, arterioles, and myofiber area ratio and _________ intramuscular nerve
capillaries. fiber morphology.

d. damage to endothelial lining of small vessels. a. decreased; lengthened

b. increased; shortened
5. Which mechanism is thought to be the one by which
c. increased; normal
plasma low-density lipoproteins (LDLs) cause most of the
vascular damage in hypothyroid dogs? d. decreased; normal
a. LDLs easily penetrate the subintimal space of vessels. 10. Which is the most likely explanation for the pathophysiology
b. LDLs have greater susceptibility to oxidation than other of myxedema coma?
plasma lipoproteins. a. altered GABA and inhibitory neurotransmitters present in
c. LDLs stimulate the production and secretion of plasminogen the central nervous system (CNS)
activator inhibitor 1 and thromboxane by endothelial cells.
b. accumulation of neutral and acidic mucopolysaccharides and
d. all of the above hyaluronic acids in the dermis causing tissue compression

6. The most common manifestation(s) of neurologic disease c. ischemic damage to specific regions of the cerebral cortex
in hypothyroid dogs is/are d. elevated ammonia levels circulating within the CNS

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