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Neurologic Manifestations of Thyroid Disease
THYROID DISORDERS
0195-5616/94 $0.00 + .20
NEUROLOGIC MANIFESTATIONS OF THYROID DISEASE Andre Jaggy, Dr.med.vet., and John E. Oliver, DVM, MS, PhD
Primary hypothyroidism due to lymphocytic thyroiditis or idiopathic atrophy of the thyroid gland22 is a relatively common endocrine disorder with characteristic signs and symptoms, including lethargy, weight gain, alopecia, dry hair coat, hyperpigmentation, cold intolerance, anestrus, bradycardia, and weakness?· 8 Hypothyroidism may also result from impaired ability of the pituitary gland to secrete thyrotropin (TSH), resulting in secondary thyroid atrophy. 1 More than 95% of clinical cases of hypothyroidism seem to result from destruction or atrophy of the thyroid gland itself. There is also, however, a neurologic manifestation of primary hypothyroidism with neuromuscular symptoms. 14- 16 Several syndromes, in which clinical signs of peripheral nervous dysfunctions and thyroid abnormalities occur together, have been described in dogs. 2-6· s-13 Such abnormalities included lower motor neuronal and peripheral vestibular disease, laryngeal paralysis, and megaesophagus. Diagnosis is confirmed by determining serum levels of thyroxine (T4 ) before and after thyroid gland stimulation. 10 Once diagnosis is established, the patients are treated with thyroid hormone supplementation for the rest of their life. Although the clinical signs are usually reversible in most cases after months, the therapeutic success is less evident in cases of megaesophagus and laryngeal paralysis associated with primary hypothyroidism. From the Institute for Veterinary Neurology, University of Bern (AJ), Bern, Switzerland; and Department of Small Animal Medicine, The University of Georgia College of Veterinary Medicine (JEO), Athens, Georgia VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 24 • N UMBER 3 • MAY 1994
487
488
JAGGY & OLIVER
LOWER MOTOR NEURON DISEASE
Dogs with lower motor neuron signs associated with primary hypothyroidism are primarily older animals. 9' 14' 15 Although small- and large-breed dogs are affected, mixed-breed dogs are the most commonly seen. These patients may experience generalized weakness, decreased appetite, and exercise intolerance at presentation. Some dogs may also be presented with lameness in one limb and generalized muscle pain on palpation. The course of the disease is reported to be 2 weeks to 8 weeks from the first appearance of clinical signs. 2' 16 The disease is usually progressive, although fluctuations in clinical signs are frequently seen. On neurologic examination most dogs are depressed and show weakness with generalized mild muscle atrophy. Generalized ataxia, predominant in the posterior limbs, is initially characterized by knuckling of the toes, wearing of the nails, and stumbling. In later stages, the dogs may drag the forelimbs as well the hindlimbs. In a few cases, tetraparesis is observed. Proprioceptive positioning deficits and segmental spinal reflexes are decreased or absent in all four limbs. Other signs of lower motor neuronal dysfunction, including unilateral or bilateral facial nerve paralysis, develop over time.16 A diagnosis of primary hypothyroidism should be suspected in small- and large-breed dogs, with progressive generalized ataxia and weakness. This is supported in most cases by neurologic findings of diffuse lower motor neuronal dysfunction. In the early stage of the disease, a few dogs may not show any neurologic signs with the exception of impaired pain sensation. It has been reported that electrodiagnostic testing is very useful in these cases to confirm lower motor neuronal involvement. 16 Nonregenerative normocytic normochromic anemia, elevated creatine kinase and serum cholesterol levels are found in most cases. 16 The diagnosis is confirmed by the abnormal low T4 levels before and after TSH-stimulation. In one study of 11 cases16 it has been shown that pre-T4 levels ranged between 0.5 J.Lg/dL and 0.9 J.Lg/ dL and post-T4 levels were between 0.6 J.Lg/ dL and 2.1 f,Lg/ dL,l 6 Findings of electromyographic examinations including electromyography (EMG) and motor nerve conduction velocity (MNCV) are abnormal in most cases. The examinations may be characterized by either fibrillation potentials and positive sharp waves in all spinal muscles, the distal extensor muscles being more affected than the proximal extensor muscles; in muscles of the tail; facial muscles; and complex repetitive discharges in a few distal extensor and lumbar muscles. Although the cause of canine hypothyroidism associated with lower motor neuron disease is still unknown, it is possible that the histologic changes observed in muscle biopsy specimens are contributing factors. Muscular changes are variable for most cases. Type-I and type-11 myofiber atrophy, hallmarks of denervation atrophy, are described in some cases. On the other hand, only type-11 myofiber atrophy and focal aggregation and accumulation of some substances in type-I myofibers w ere found in one dog. 14
NEUROLOGIC MANIFESTATIONS OF THYROID DISEASE
489
Figure 1. Lymphocytic thyroiditis in a dog with lower motor neuronal signs and primary hypothyroidism. Follicular collapse, dissociation, and infiltration of the thyroid gland with lymphocytic and plasmocytic cells.
The histologic examination of teased nerve preparations showed segmental demyelination/remyelination, supporting the · diagnosis of polyneuropathy with secondary neurogenic myopathy. 14- 16 Biopsies of the thyroid gland show lymphocytic thyroiditis (Fig. 1). 15, 16 The diagnosis of primary hypothyroidism is based, in most cases, on neurologic findings, clinicopathologic changes in some cases, and electromyographic abnormalities and low responses following hormonal evaluation of T4 in all cases. It has been suggested by the authors that dogs with lower motor neuronal disease and primary hypothyroidism must show on thyroid evaluation that the post-TSH T4 serum level has not doubled or it is below 2.4 1-Lg/ dL (32 nmoles/L). The treatmentprogram includes supplementation therapy with levothyroxine (0.02 mg-0.04 mg/kg of body weight), which is commonly divided into two separate doses and given orally at 12-hour intervals. The clinical signs are usually reversible after 2 months of thyroid hormone replacement therapy.
PERIPHERAL VESTIBULAR DISEASE
Peripheral vestibular disease with primary hypothyroidism occurs mainly in older dogs with predilection for neither sex, nor breed
490
JAGGY & OLIVER
predisposition.2' 16 The onset of clinical signs is, in most cases, acute and nonprogressive; however, the course of the disease is reported to be chronic progressive in a few cases. 15' 16 Neurologic signs of peripheral vestibular disease are evident and include head tilt and positional vestibular strabismus.2 The gait abnormalities are characterized by drifting or circling to one side, and generalized ataxia. Postural reactions and segmental spinalreflexes are normal. In some cases, a~ditional signs of lower motor neuronal dysfunction may be seen.2' 16 Although these patients account for fewer than 5% of the total number of dogs wit,h peripheral vestibular disease associated with hypothyroidism, the presence of lower motor neuronal signs suggest that a polyneuropathy of the cranial nerves may generalize and involve spinal nerves. These patients have the same abnormalities, with the addition of generalized lower motor neuron signs, characterized by decreased tendon reflexes and proprioceptive positioning deficits.16 Otoscopic examination of the external ear canal and tympanic membranes and radiographic examination of the bulla ossea are normal. Results of clinicopathologic examinations are generally in normal limits, except for a mild elevation of protein in cerebrospinal fluid and high serum cholesterol levels in a few cases, Results of TSH response test are reported to be always abnormal. In one study of 9 cases16 with peripheral vestibular disease, the mean value of pre-T4 serum levels was 0.9 f.Lg/dL (11.6 runol/L), and mean post-T4 serum level was 1.2 f.Lg/dL (15.4 runol/ L).
Electrodiagnostic tests include brainstem auditory evoked responses (BAER). Decreased amplitudes and increased latencies of the BAER suggest decreased peripheral acoustic perception. Findings on electromyographic examinations are characterized by fibrillation potentials and positive sharp waves of the proximal extensor muscles, These findings are reported not only in dogs with vestibular signs and diffuse lower motor neuronal disease, but also in cases with vestibular deficits alone. 16 Therefore, vestibular signs in dogs frequently may be only one clinical sign of an underlying, more generalized, polyneuropathy and clinical expression, The exact pathogenesis of vestibular and facial nerve paralysis that can develop is not known, but such neuropathies are likely to result from compression by mucinous deposits in and around the affected nerves as they pass through the internal acoustic meatus of the temporal bone, The diagnosis of primary hypothyroidism with vestibular disease is based on clinical signs and abnormal thyroid function testing. The dogs are supplemented with levothyroxine. 16 Vestibular signs resulting from polyneuropathy associated with hypothyroidism are at least partially (after one to two months) and often totally (after four months) reversible with thyroid supplementation and so must be differentiated from other causes of vestibular diseases.
NEUROLOGIC MANIFESTATIONS OF THYROID DISEASE
491
LARYNGEAL PARALYSIS
Canine laryngeal paralysis has been recognized primarily in old dogs of large or giant breeds and in young Bouvier des Flandres. Clinical signs depend on the severity of airway obstruction. Coughing, change in voice, and slight to mod~rate decrease in exercise tolerance are frequently reported. Clinical signs are often minimal until the animal is stressed.n-!3, 17 Recently it has been emphasized that laryngeal paralysis may be associated with primary hypothyroidism.5' 15' 16 Clinical signs consist of respiratory distress with stridor and cough, generalized weakness, and in a few cases weight gain. The neurologic examination revealed hindlimb weakness and hyporeflexia of extensor and flexor reflexes of the pelvic limbs. Other lower motor neuronal deficits included decreased proprioceptive positioning in posterior limbs. · Electrodiagnostic evidence of involvement of all four limbs and laryngeal muscles (i.e., fibrillation potentials and positive sharp waves) was found in these cases. Although the brainstem auditory evoked responses showed increased latencies and decreased amplitude, np clinical evidence of impaired acoustic perception was noted. Motor-nerVe conduction velocities were slowed in the proximal (mean = 37m/ s) and distal (mean = 32m/s) segments of the tibial nerve. These results sub~tantiate an acquired cause of generalized polyneuropathy in older qogs with laryngeal paralysis.16 ·· · In addition, O'Brien and cqauthors21 have described neurogenic atrophy of laryngeal musculature in large-breed dogs with laryngeal p
492
JAGGY & OLIVER
ism, thyroxine supplementation is essential in the return of a functional companion animal.
MEGAESOPHAGUS Megaesophagus in the dog is a disorder of esophageal transport or lower esophageal sphincter function which results in retention of food and dilation of the esophagus. It has been reported in purebreed and mixed-breed dogs. The German Shepherd, Great Dane, and Newfoundland appear to have familial predisposition. Usual recognition of the disease is in the puppy at weaning, and is thus considered congenital.19• 20 The acquired form may be the result of a secondary disorder such as myasthenia gravis, systemic lupus erythematosus, giant axonal neuropathy, hypoadrenocorticism, and lead intoxication. 19• 20 After the problem of regurgitation has been confirmed by a history, physical examination, and observation of eating, a definitive diagnosis of megaesophagus is determined by radiographs. Survey and contrast radiographs along with esophageal motility studies are used to differentiate megaesophagus from other dilation of the esophagus. Laboratory evaluation is in most cases nonspecific. Inflammatory leukocytosis with or without a left shift may be found in the complete blood count, depending on the severity of aspiration pneumonia present. Edrophonium (Tensilon) testing, measurement of blood lead levels, adrenocorticotropic hormone-stimulation testing, and immune function testing including Coomps' test, antinuclear antibody, lupus erythematosus preparation, and rheumatoid factors determine the presence of an extra-esophageal disorder. Most cases of megaesophagus, however, remain idiopathic as no origin is ever determined. Although megaesophagus has previously been reported to occur in dogs with primary hypothyroidism/ 6 little is known about pathophysiology in these patients. Physical examination verified the historical findings, including regurgitation and coughing. On neurologic examination, no significant abnormality other than weakness in the hind limbs was noted. The results of clinicopathologic examinations were within normal limits except that the TSH-stimulation test showed low pre-T4 (mean = 12.8 nmol/L) and post-T4 (mean = 15.4 nmol/L) values. Based on the history, clinical signs, results of the TSH-stimulation test, and radiographs, the diagnosis of acquired megaesophagus associated with primary hypothyroidism was established.16 All dogs were managed by feeding in an upright position with a liquid diet three times daily. In addition, treatment consisted of thyroxine supplementation with levothyroxine. Although significant improvement of clinical signs have been reported, the prognosis remains poor for dogs with megaesophagus and primary hypothyroidism.20
NEUROLOGIC MANIFESTATIONS OF THYROID DISEASE
493
SUMMARY
Animals with polyneuropathy associated with primary hypothyroidism have clinical neurologic signs that range from peripheral vestibular signs, lower motor neuronal deficits, laryngeal paralysis, to megaesophagus; however, a few affected animals also show evidence of a more generalized polyneuropathy with cranial (facial more than vestibular nerve) and spinal nerves being affected most commonly. Confirmation of the diagnosis will depend on neurologic signs, clinicopathologic results including an abnormally low T4 response to TSH and electrodiagnostic findings. Successful treatment is based on thyroxine supplementation therapy. In severe cases with laryngeal paralysis, additional surgical treatment is indicated. Some animals with megaesophagus may develop permanent neurologic disabilities. References 1. Belshaw BE: Thyroid diseases. In Textbook of Veterinary Internal Medicine. Philadel-
phia, WB Saunders, 1983, p 1592 2. Bichsel P, Jacobs G, Oliver JE: Neurologic manifestations associated with hypothyroidism in four dogs. JAm Vet Med Assoc 192:1745, 1988 3. Boudrieau RJ, Rogers WA: Megaesophagus in the dog: A review of 50 cases. J Am Anim Hosp Assoc 21:33, 1985 4. Braund KG: Myopathies in dogs and cats: Recognizing endogenous causes. Pet Pract 803, 1986 5. Braund KG, Steinberg HS, Shores A, et a!.: Laryngeal paralysis in immature and mature dogs as one sign of a more diffuse polyneuropathy. J Am Vet Med Assoc 194:1735, 1989 6. Cardinet GH, Holliday TA: Neuromuscular diseases of domestic animals: A summary of muscle biopsies from 159 cases. Ann NY Acad Sci 317:290, 1979 7. Chastain CB: Canine hypothyroidism. JAm Vet Med Assoc 181:349, 1982 8. Duncan ID, Griffiths IR: Peripheral neuropathies of domestic animals. In Dyck PJ, Thomas PK, Lambert EH, and Bunge RO (eds): Peripheral Neuropathy. Philadelphia, WB Saunders, 1984, p 707 9. Dyer KR, Duncan ID, Hammang JP, eta!.: Peripheral neuropathy in two dogs: Correlation between clinical, electrophysiological, and pathological findings. J Small Anim Pract 27:133, 1986 10. Ferguson DC: Thyroid function tests in the dog: Recent concepts. J Small Anim Pract 14:783, 1984 11. Gaber CE, Amis TC, LeCouteur A: Laryngeal paralysis in dogs: A review of 23 cases. J Am Vet Med Assoc 186:377, 1985 12. Greenfield CL: Canine laryngeal paralysis. Comp Small Anim 9:1011, 1987 13. Harvey HJ, Irby NL, Watrous BJ: Laryngeal paralysis in hypothyroid dogs. In Kirk RW (ed): Current Veterinary Therapy VIII, Small Animal Practice. Philadelphia, WB Saunders, 1983, p 694 14. Indrieri RJ, Whalen LR, Cardinet GH, et a!.: Neuromuscular abnormalities associated with hypothyroidism and lymphocytic thyroiditis in three dogs. JAm Vet Med Assoc 190:544, 1987 15. Jaggy A.: Primary hypothyroidism associated with neurological deficits in the dog. XVI.WSAVA, Vienna, October 1991 16. Jaggy A, Oliver JE: Neurological manifestations of hypothroidism in dogs. In ACVIM Meeting, Washington, DC, 1990, p 1037 17. LaHue TR: Treatment of laryngeal paralysis in dogs by unilateral criocoarytenoid laryngoplasty. JAm Anim Hosp Assoc 25:317, 1989
494
JAGGY & OLIVER
18. Lane JG: Canine laryngeal surgery. Vet Ann 18:239, 1978 19. Leib MS: Megaesophagus in the dog, part I: Anatomy, physiology, and pathophysiology. Comp Cont Educ 5:825, 1983 20. Leib MS: Megaesophagus in the dog, part II: Clinical aspect. Comp Cont Educ 6:11, 1984 21. O'Brien JA, Harvey CE, Kelly AM, et al.: Neurogenic atrophy of the laryngeal muscles of the dog. J Small Anim Pract 14:521, 1973 22. Peterson ME, Ferguson OC: Thyroid diseases. In Ettinger SJ (ed): Textbook of Veterinary Internal Medicine, Philadelphia, WB Saunders, 1989, p 1632
Address reprint requests to John Oliver, DVM, PhD Department of Small Animal Medicine The University of Georgia College of Veterinary Medicine Athens, GA 30602
0195-5616/94 $0.00 + .20
NEUROLOGIC MANIFESTATIONS OF THYROID DISEASE Andre Jaggy, Dr.med.vet., and John E. Oliver, DVM, MS, PhD
Primary hypothyroidism due to lymphocytic thyroiditis or idiopathic atrophy of the thyroid gland22 is a relatively common endocrine disorder with characteristic signs and symptoms, including lethargy, weight gain, alopecia, dry hair coat, hyperpigmentation, cold intolerance, anestrus, bradycardia, and weakness?· 8 Hypothyroidism may also result from impaired ability of the pituitary gland to secrete thyrotropin (TSH), resulting in secondary thyroid atrophy. 1 More than 95% of clinical cases of hypothyroidism seem to result from destruction or atrophy of the thyroid gland itself. There is also, however, a neurologic manifestation of primary hypothyroidism with neuromuscular symptoms. 14- 16 Several syndromes, in which clinical signs of peripheral nervous dysfunctions and thyroid abnormalities occur together, have been described in dogs. 2-6· s-13 Such abnormalities included lower motor neuronal and peripheral vestibular disease, laryngeal paralysis, and megaesophagus. Diagnosis is confirmed by determining serum levels of thyroxine (T4 ) before and after thyroid gland stimulation. 10 Once diagnosis is established, the patients are treated with thyroid hormone supplementation for the rest of their life. Although the clinical signs are usually reversible in most cases after months, the therapeutic success is less evident in cases of megaesophagus and laryngeal paralysis associated with primary hypothyroidism. From the Institute for Veterinary Neurology, University of Bern (AJ), Bern, Switzerland; and Department of Small Animal Medicine, The University of Georgia College of Veterinary Medicine (JEO), Athens, Georgia VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 24 • N UMBER 3 • MAY 1994
487
488
JAGGY & OLIVER
LOWER MOTOR NEURON DISEASE
Dogs with lower motor neuron signs associated with primary hypothyroidism are primarily older animals. 9' 14' 15 Although small- and large-breed dogs are affected, mixed-breed dogs are the most commonly seen. These patients may experience generalized weakness, decreased appetite, and exercise intolerance at presentation. Some dogs may also be presented with lameness in one limb and generalized muscle pain on palpation. The course of the disease is reported to be 2 weeks to 8 weeks from the first appearance of clinical signs. 2' 16 The disease is usually progressive, although fluctuations in clinical signs are frequently seen. On neurologic examination most dogs are depressed and show weakness with generalized mild muscle atrophy. Generalized ataxia, predominant in the posterior limbs, is initially characterized by knuckling of the toes, wearing of the nails, and stumbling. In later stages, the dogs may drag the forelimbs as well the hindlimbs. In a few cases, tetraparesis is observed. Proprioceptive positioning deficits and segmental spinal reflexes are decreased or absent in all four limbs. Other signs of lower motor neuronal dysfunction, including unilateral or bilateral facial nerve paralysis, develop over time.16 A diagnosis of primary hypothyroidism should be suspected in small- and large-breed dogs, with progressive generalized ataxia and weakness. This is supported in most cases by neurologic findings of diffuse lower motor neuronal dysfunction. In the early stage of the disease, a few dogs may not show any neurologic signs with the exception of impaired pain sensation. It has been reported that electrodiagnostic testing is very useful in these cases to confirm lower motor neuronal involvement. 16 Nonregenerative normocytic normochromic anemia, elevated creatine kinase and serum cholesterol levels are found in most cases. 16 The diagnosis is confirmed by the abnormal low T4 levels before and after TSH-stimulation. In one study of 11 cases16 it has been shown that pre-T4 levels ranged between 0.5 J.Lg/dL and 0.9 J.Lg/ dL and post-T4 levels were between 0.6 J.Lg/ dL and 2.1 f,Lg/ dL,l 6 Findings of electromyographic examinations including electromyography (EMG) and motor nerve conduction velocity (MNCV) are abnormal in most cases. The examinations may be characterized by either fibrillation potentials and positive sharp waves in all spinal muscles, the distal extensor muscles being more affected than the proximal extensor muscles; in muscles of the tail; facial muscles; and complex repetitive discharges in a few distal extensor and lumbar muscles. Although the cause of canine hypothyroidism associated with lower motor neuron disease is still unknown, it is possible that the histologic changes observed in muscle biopsy specimens are contributing factors. Muscular changes are variable for most cases. Type-I and type-11 myofiber atrophy, hallmarks of denervation atrophy, are described in some cases. On the other hand, only type-11 myofiber atrophy and focal aggregation and accumulation of some substances in type-I myofibers w ere found in one dog. 14
NEUROLOGIC MANIFESTATIONS OF THYROID DISEASE
489
Figure 1. Lymphocytic thyroiditis in a dog with lower motor neuronal signs and primary hypothyroidism. Follicular collapse, dissociation, and infiltration of the thyroid gland with lymphocytic and plasmocytic cells.
The histologic examination of teased nerve preparations showed segmental demyelination/remyelination, supporting the · diagnosis of polyneuropathy with secondary neurogenic myopathy. 14- 16 Biopsies of the thyroid gland show lymphocytic thyroiditis (Fig. 1). 15, 16 The diagnosis of primary hypothyroidism is based, in most cases, on neurologic findings, clinicopathologic changes in some cases, and electromyographic abnormalities and low responses following hormonal evaluation of T4 in all cases. It has been suggested by the authors that dogs with lower motor neuronal disease and primary hypothyroidism must show on thyroid evaluation that the post-TSH T4 serum level has not doubled or it is below 2.4 1-Lg/ dL (32 nmoles/L). The treatmentprogram includes supplementation therapy with levothyroxine (0.02 mg-0.04 mg/kg of body weight), which is commonly divided into two separate doses and given orally at 12-hour intervals. The clinical signs are usually reversible after 2 months of thyroid hormone replacement therapy.
PERIPHERAL VESTIBULAR DISEASE
Peripheral vestibular disease with primary hypothyroidism occurs mainly in older dogs with predilection for neither sex, nor breed
490
JAGGY & OLIVER
predisposition.2' 16 The onset of clinical signs is, in most cases, acute and nonprogressive; however, the course of the disease is reported to be chronic progressive in a few cases. 15' 16 Neurologic signs of peripheral vestibular disease are evident and include head tilt and positional vestibular strabismus.2 The gait abnormalities are characterized by drifting or circling to one side, and generalized ataxia. Postural reactions and segmental spinalreflexes are normal. In some cases, a~ditional signs of lower motor neuronal dysfunction may be seen.2' 16 Although these patients account for fewer than 5% of the total number of dogs wit,h peripheral vestibular disease associated with hypothyroidism, the presence of lower motor neuronal signs suggest that a polyneuropathy of the cranial nerves may generalize and involve spinal nerves. These patients have the same abnormalities, with the addition of generalized lower motor neuron signs, characterized by decreased tendon reflexes and proprioceptive positioning deficits.16 Otoscopic examination of the external ear canal and tympanic membranes and radiographic examination of the bulla ossea are normal. Results of clinicopathologic examinations are generally in normal limits, except for a mild elevation of protein in cerebrospinal fluid and high serum cholesterol levels in a few cases, Results of TSH response test are reported to be always abnormal. In one study of 9 cases16 with peripheral vestibular disease, the mean value of pre-T4 serum levels was 0.9 f.Lg/dL (11.6 runol/L), and mean post-T4 serum level was 1.2 f.Lg/dL (15.4 runol/ L).
Electrodiagnostic tests include brainstem auditory evoked responses (BAER). Decreased amplitudes and increased latencies of the BAER suggest decreased peripheral acoustic perception. Findings on electromyographic examinations are characterized by fibrillation potentials and positive sharp waves of the proximal extensor muscles, These findings are reported not only in dogs with vestibular signs and diffuse lower motor neuronal disease, but also in cases with vestibular deficits alone. 16 Therefore, vestibular signs in dogs frequently may be only one clinical sign of an underlying, more generalized, polyneuropathy and clinical expression, The exact pathogenesis of vestibular and facial nerve paralysis that can develop is not known, but such neuropathies are likely to result from compression by mucinous deposits in and around the affected nerves as they pass through the internal acoustic meatus of the temporal bone, The diagnosis of primary hypothyroidism with vestibular disease is based on clinical signs and abnormal thyroid function testing. The dogs are supplemented with levothyroxine. 16 Vestibular signs resulting from polyneuropathy associated with hypothyroidism are at least partially (after one to two months) and often totally (after four months) reversible with thyroid supplementation and so must be differentiated from other causes of vestibular diseases.
NEUROLOGIC MANIFESTATIONS OF THYROID DISEASE
491
LARYNGEAL PARALYSIS
Canine laryngeal paralysis has been recognized primarily in old dogs of large or giant breeds and in young Bouvier des Flandres. Clinical signs depend on the severity of airway obstruction. Coughing, change in voice, and slight to mod~rate decrease in exercise tolerance are frequently reported. Clinical signs are often minimal until the animal is stressed.n-!3, 17 Recently it has been emphasized that laryngeal paralysis may be associated with primary hypothyroidism.5' 15' 16 Clinical signs consist of respiratory distress with stridor and cough, generalized weakness, and in a few cases weight gain. The neurologic examination revealed hindlimb weakness and hyporeflexia of extensor and flexor reflexes of the pelvic limbs. Other lower motor neuronal deficits included decreased proprioceptive positioning in posterior limbs. · Electrodiagnostic evidence of involvement of all four limbs and laryngeal muscles (i.e., fibrillation potentials and positive sharp waves) was found in these cases. Although the brainstem auditory evoked responses showed increased latencies and decreased amplitude, np clinical evidence of impaired acoustic perception was noted. Motor-nerVe conduction velocities were slowed in the proximal (mean = 37m/ s) and distal (mean = 32m/s) segments of the tibial nerve. These results sub~tantiate an acquired cause of generalized polyneuropathy in older qogs with laryngeal paralysis.16 ·· · In addition, O'Brien and cqauthors21 have described neurogenic atrophy of laryngeal musculature in large-breed dogs with laryngeal p
492
JAGGY & OLIVER
ism, thyroxine supplementation is essential in the return of a functional companion animal.
MEGAESOPHAGUS Megaesophagus in the dog is a disorder of esophageal transport or lower esophageal sphincter function which results in retention of food and dilation of the esophagus. It has been reported in purebreed and mixed-breed dogs. The German Shepherd, Great Dane, and Newfoundland appear to have familial predisposition. Usual recognition of the disease is in the puppy at weaning, and is thus considered congenital.19• 20 The acquired form may be the result of a secondary disorder such as myasthenia gravis, systemic lupus erythematosus, giant axonal neuropathy, hypoadrenocorticism, and lead intoxication. 19• 20 After the problem of regurgitation has been confirmed by a history, physical examination, and observation of eating, a definitive diagnosis of megaesophagus is determined by radiographs. Survey and contrast radiographs along with esophageal motility studies are used to differentiate megaesophagus from other dilation of the esophagus. Laboratory evaluation is in most cases nonspecific. Inflammatory leukocytosis with or without a left shift may be found in the complete blood count, depending on the severity of aspiration pneumonia present. Edrophonium (Tensilon) testing, measurement of blood lead levels, adrenocorticotropic hormone-stimulation testing, and immune function testing including Coomps' test, antinuclear antibody, lupus erythematosus preparation, and rheumatoid factors determine the presence of an extra-esophageal disorder. Most cases of megaesophagus, however, remain idiopathic as no origin is ever determined. Although megaesophagus has previously been reported to occur in dogs with primary hypothyroidism/ 6 little is known about pathophysiology in these patients. Physical examination verified the historical findings, including regurgitation and coughing. On neurologic examination, no significant abnormality other than weakness in the hind limbs was noted. The results of clinicopathologic examinations were within normal limits except that the TSH-stimulation test showed low pre-T4 (mean = 12.8 nmol/L) and post-T4 (mean = 15.4 nmol/L) values. Based on the history, clinical signs, results of the TSH-stimulation test, and radiographs, the diagnosis of acquired megaesophagus associated with primary hypothyroidism was established.16 All dogs were managed by feeding in an upright position with a liquid diet three times daily. In addition, treatment consisted of thyroxine supplementation with levothyroxine. Although significant improvement of clinical signs have been reported, the prognosis remains poor for dogs with megaesophagus and primary hypothyroidism.20
NEUROLOGIC MANIFESTATIONS OF THYROID DISEASE
493
SUMMARY
Animals with polyneuropathy associated with primary hypothyroidism have clinical neurologic signs that range from peripheral vestibular signs, lower motor neuronal deficits, laryngeal paralysis, to megaesophagus; however, a few affected animals also show evidence of a more generalized polyneuropathy with cranial (facial more than vestibular nerve) and spinal nerves being affected most commonly. Confirmation of the diagnosis will depend on neurologic signs, clinicopathologic results including an abnormally low T4 response to TSH and electrodiagnostic findings. Successful treatment is based on thyroxine supplementation therapy. In severe cases with laryngeal paralysis, additional surgical treatment is indicated. Some animals with megaesophagus may develop permanent neurologic disabilities. References 1. Belshaw BE: Thyroid diseases. In Textbook of Veterinary Internal Medicine. Philadel-
phia, WB Saunders, 1983, p 1592 2. Bichsel P, Jacobs G, Oliver JE: Neurologic manifestations associated with hypothyroidism in four dogs. JAm Vet Med Assoc 192:1745, 1988 3. Boudrieau RJ, Rogers WA: Megaesophagus in the dog: A review of 50 cases. J Am Anim Hosp Assoc 21:33, 1985 4. Braund KG: Myopathies in dogs and cats: Recognizing endogenous causes. Pet Pract 803, 1986 5. Braund KG, Steinberg HS, Shores A, et a!.: Laryngeal paralysis in immature and mature dogs as one sign of a more diffuse polyneuropathy. J Am Vet Med Assoc 194:1735, 1989 6. Cardinet GH, Holliday TA: Neuromuscular diseases of domestic animals: A summary of muscle biopsies from 159 cases. Ann NY Acad Sci 317:290, 1979 7. Chastain CB: Canine hypothyroidism. JAm Vet Med Assoc 181:349, 1982 8. Duncan ID, Griffiths IR: Peripheral neuropathies of domestic animals. In Dyck PJ, Thomas PK, Lambert EH, and Bunge RO (eds): Peripheral Neuropathy. Philadelphia, WB Saunders, 1984, p 707 9. Dyer KR, Duncan ID, Hammang JP, eta!.: Peripheral neuropathy in two dogs: Correlation between clinical, electrophysiological, and pathological findings. J Small Anim Pract 27:133, 1986 10. Ferguson DC: Thyroid function tests in the dog: Recent concepts. J Small Anim Pract 14:783, 1984 11. Gaber CE, Amis TC, LeCouteur A: Laryngeal paralysis in dogs: A review of 23 cases. J Am Vet Med Assoc 186:377, 1985 12. Greenfield CL: Canine laryngeal paralysis. Comp Small Anim 9:1011, 1987 13. Harvey HJ, Irby NL, Watrous BJ: Laryngeal paralysis in hypothyroid dogs. In Kirk RW (ed): Current Veterinary Therapy VIII, Small Animal Practice. Philadelphia, WB Saunders, 1983, p 694 14. Indrieri RJ, Whalen LR, Cardinet GH, et a!.: Neuromuscular abnormalities associated with hypothyroidism and lymphocytic thyroiditis in three dogs. JAm Vet Med Assoc 190:544, 1987 15. Jaggy A.: Primary hypothyroidism associated with neurological deficits in the dog. XVI.WSAVA, Vienna, October 1991 16. Jaggy A, Oliver JE: Neurological manifestations of hypothroidism in dogs. In ACVIM Meeting, Washington, DC, 1990, p 1037 17. LaHue TR: Treatment of laryngeal paralysis in dogs by unilateral criocoarytenoid laryngoplasty. JAm Anim Hosp Assoc 25:317, 1989
494
JAGGY & OLIVER
18. Lane JG: Canine laryngeal surgery. Vet Ann 18:239, 1978 19. Leib MS: Megaesophagus in the dog, part I: Anatomy, physiology, and pathophysiology. Comp Cont Educ 5:825, 1983 20. Leib MS: Megaesophagus in the dog, part II: Clinical aspect. Comp Cont Educ 6:11, 1984 21. O'Brien JA, Harvey CE, Kelly AM, et al.: Neurogenic atrophy of the laryngeal muscles of the dog. J Small Anim Pract 14:521, 1973 22. Peterson ME, Ferguson OC: Thyroid diseases. In Ettinger SJ (ed): Textbook of Veterinary Internal Medicine, Philadelphia, WB Saunders, 1989, p 1632
Address reprint requests to John Oliver, DVM, PhD Department of Small Animal Medicine The University of Georgia College of Veterinary Medicine Athens, GA 30602