Hypothyroid associated polyneuropathy in dogs ... - ResearchGate

285have been reported in Doberman pinschers. 4A subclinical myopathy has beenreported in mature dogs with primaryhypothyroidism. 9,10 Occasionally, signs ofneuromuscular disorders can occur with orwithout cutaneous signs, and these includeweakness, stiffness, decreased consciousproprioception and muscle wasting. 3,10,11 Theetiopathogenesis of this endocrine myopathyis unknown. A disturbance in carbohydratemetabolism has been proposed to explainthe preferential type II fiber atrophy, whichoccurs in humans and canine muscle. 10,11A hypothyroid-associated neuropathydoes appear to exist in mature to middleageddogs, usually in large breeds, and maybe recognized without the usual signs ofhypothyroidism. 3,12,13 Peripheral neuropathiesmay also affect the cranial nerves causingabnormalities such as head tilt, facial nerveparalysis, strabismus, nystagmus, decreasedfacial sensitivity and laryngealparalysis. 3,7,14,15,16,17,18,19 Although thepathogenesis of this neuropathy is not clear,metabolic alterations would determineabnormalities in the transport axonal and inthe functionality of Schwann cells. 3,7 Theearly stages are often missed because thesigns are mild. 13 The occurrence ofmegaesophagus, intermitent lameness,paraparesis and tetraparesis have all beenassociated with hypothyroidism. 14,15,18,19,20Clinical signs such as progressive weakness,muscle atrophy (mainly appendicular),hypotonia and depressed spinal reflexes maybe seen. 11,17 Nerve fibers studies arecharacterized by both demyelinationremyelinationand axonal necrosis.Electrodiagnostic studies have revealedmultifocal patterns of fibrillation potentials,positive sharp waves and decreased motornerve conduction velocity. 3,11 This clinicalsigns usually resolve with L-thyroxine (T4)supplementation. Dogs improve rapidlywithin a few days after the start of treatment,and most dogs are neurologically normalafter one to two months of treatment. 3 Insome animals there is a lack of correlationbetween the degree of electromyographicabnormalities and the severity ofclinical signs. 20Results of hemogram, biochemicalpanel and urinalysis may support a diagnosisof hypothyroidism and rule out otherdiseases. A mild nonregenerative anemia andfasting hypercholesterolemia occur in 30 and75 per cent of hypothyroid dogs,respectively. Less common abnormalitiesinclude mild increases in alkalinephosphatase, alanine aminotransferase andcreatine kinase. 6Despite the routine a regular use ofthyroid function tests in veterinary medicine,the practitioner is still plagued with theproblem of making an accurate diagnosisof hypothyroidism. While in primaryhypothyroidism TSH levels should increaseto stimulate the glands to produce morehormone, in secondary or tertiaryhypothyroidism levels are low. Because themajority of hypothyroid dogs have primarydisease, elevated TSH levels are to beexpected in most of them . To increase thediscriminating value of TSH, it has beensuggested that the assay be run in conjunctionwith TT4 or free T4 (fT4). In hypothyroidism4, 21the TT4 or fT4 would have to be low.Because not all laboratories may use the sameassay kit or technique to determine theirresults, normal ranges can vary fromlaboratory to laboratory. Values of TSH lessthan 0,5 ng/ml and from fT4 varying from0,3 to 1,7 ng/dl are considered diagnosticof hypothyroidism. 4 The present reportconcerns six cases of hypothyroid-associatedpolineuropathy in Doberman Pinscher.Case ReportsSix Doberman Pinscher (two malesand four females), between six and eight yearsof age, were presented to the VeterinaryHospital from Faculty of Veterinary Scienceof The University of Buenos Aires withdiagnosis of Wobbler syndrome. Accordingto the owners, the diagnosis was made basedon clinical signs and radiological studies ofcervical column with lateral incidence and inforced flexion of the neck. The problem hasprogressed slowly, varying from one to threeBraz. J. vet. Res. anim. Sci., São Paulo, v. 45, n. 4, p. 284-288, 2008

286months and, according to the owners, noone had thermophilia. Three females hadaltered estrous cycles. All of the dogsreceived dexamethasone without clinicalimprovement in any of them. Physicalexamination revealed rectal temperaturewithin the normal range and normal skin inall dogs. Only a male and a female werepresented with obesity. Neurologicalexamination revealed tetraparesis withinability to walk, decreased muscle tonus andmyotatic reflexes in all dogs. Two of themalso presented disfonia.Complete blood counts (CBC) andbiochemical analysis were performed in alldogs. CBC, blood glucose concentrations,total protein, albumin, total calcium, ureanitrogen and creatinine concentrations as wellas plasma alanine aminotransferase (ALT)and aspartate aminotransferase (AST) activitywere within normal ranges in all dogs. Serumcholesterol levels were elevated in all dogs,with values ranging from 292 to 504 mg/dl(Table 1). Serum creatine kinase and alkalinephosphatase activities were mildly tomarkedly elevated in all dogs, with valuesranging from 160 to 1450 U/L and from180 to 460 U/L, respectively (Table 1).All dogs were submitted toelectroneurographic examination of the tibialnerve. Tibial motor nerve conductionvelocities were slow in all dogs, varying from20 to 38m/s, when compared with normaldogs, which have velocities higher than 6022 23,24,25,26m/s.As the signs were compatible withhypothyroidism, basal measurements of freeT4 and TSH were determined byradioimmunoassay using veterinary kits.Although four from six dogs had fT4 valueswithin normal range, in all dogs TSH valueswere elevated (Table 1). Based on this results,hypothyroidism was suspected and asupplementation therapy was establishedwith oral levothyroxine (T4), adjusting thedose according to each patient’s evolution,to confirm the diagnosis. Two weeks aftertreatment has been started, all patients hadan improvement in clinical signs, and withintwo months thyroid function tests becamenormal, as well as gait, muscular tonus andspinal reflexes.DiscussionAll dogs presented to the VeterinaryHospital had decreased muscle tonus andmyotatic reflexes in the four limbs, suggestinglower motor neuron involvement. Manydiseases may cause signs of lower motorneuron involvement and, among them,polyneuropathy associated withhypothyroidism which can be observed inDoberman Pinschers. Peripheral neuropathyis the best documented neurologicmanifestation of hypothyroidism. DogsTable 1 - Blood chemical data (serum colesterol levels, creatine kinase and alkaline phosphatase activities), tibialmotor nerve conduction velocities and free T4 ( fT4) and TSH basal measurements, in six DobermanPinscher suspected of having hypothyroid-associated neuropathy. Buenos Aires, 2007Braz. J. vet. Res. anim. Sci., São Paulo, v. 45, n. 4, p. 284-288, 2008

287tipically present with exercise intolerance,generalized weakness, ataxia andquadriparesis or paralysis. There is normallya slow progression of clinical signs frommild gait deficits to parapresis or tetraparesisobserved in most dogs. Neurologicexamination typically reveals proprioceptivedeficits of the pelvic and thoracic limbs, anddiminished segmental reflexes. Mostcommonly all four limbs are affected;however, in some dogs, clinical signsprogress from the hind limbs to theforelimbs or affect the hind limbs alone. 3Dysfunctions of multiple cranial nerveshave been reported in hypothyroid dogs,and were observed in the two dogswith disfonia.Early reports suggested an associationbetween hypothyroidism and cervicalspondylomyelopathy, but this association islikely the result of a similar breedpredisposition for both disorders. Althoughcervical spondylopathy (Wobbler syndrome)is a neurologic disorder that appears withgreat frequency in Doberman pinschers, thedisease does not cause lower motor neuroninvolvement. In most Doberman pinschersclinical signs develop between three and eightyears of age. They typically develop mildpelvic limb ataxia that progresses to severebilateral ataxia and hypermetria. Ataxia andparesis in the thoracic limbs may bepronounced in some cases but are sometimesdetected only by careful neurologicexamination. Some dogs have tetraparesis.Neurologic examination evidences uppermotor neuron signs in the pelvic limbs(increase muscle tonus and normal orexaggerate myotatic reflexes), and sometetraparetic dogs may have lower motorneuron signs in the thoracic limbs becauseof cervical gray matter involvement. Thediagnosis of cervical spondylopathy isconfirmed by survey radiographys andmyelography.All of the six examined dogs hadelevated serum cholesterol levels, creatinekinase and alkaline phosphatase activities,besides slow tibial motor nerveconduction velocities which led us thoughtthat hypothyroidism was the cause of thepolyneuropathy, suggested by hormonaldeterminations. It should be kept in mindthat many affected animals do not haveobvious signs of hypothyroidism. Thereare several factors that make it hard todetermine the true relation betweenhypothyroidism and many of the lesscommon clinical associations attributed tothe disease. One factor is the challenge ofconfirming a diagnosis of hypothyroidismin dogs. Diagnosis of hypothyroidism ishampered by the lack of specificity ofthe thyroxine assay as well as the lack ofsensitivity of the thyrothropin assay. Inmany cases it is difficult to make adefinitive diagnosis and a therapeutic trialis necessary. In the present cases weconfirmed hypothyroidism withtherapeutic diagnosis.Polineuropatia associada a hipotireoidismo em cães: Relato de seis casosResumoSeis Dobermans Pinscher, entre seis e oito anos de idade, foramencaminhados ao Hospital Veterinário da Faculdade de CiênciasVeterinárias da Universidade de Buenos Aires. O exame neurológicorevelou tetraparesia com incapacidade para andar, diminuição dotono muscular e de reflexos miotáticos em todos os cães. Os níveisde colesterol, creatina quinase e fosfatase alcalina encontravam-se demoderada a acentuadamente elevados. As velocidades de conduçãonervosa do nervo tibial estavam diminuídas em todos os cães. Osníveis séricos basais de T4 livre e TSH foram determinados porradioimunoensaio e, embora os valores de T4 livre estivessem dentrodos limites de normalidade, em todos os cães o TSH estava elevado.Palavras-chave:Hormônios tireoidianos.Velocidade de conduçãonervosa motora.Neuropatia.Braz. J. vet. Res. anim. Sci., São Paulo, v. 45, n. 4, p. 284-288, 2008

288Baseado nestes resultados, diagnosticou-se hipotireoidismo e iniciouseuma suplementação oral com levotiroxina (T4). Duas semanasapós o início do tratamento todos os pacientes tiveram melhora clínicae, dentro de um mês a locomoção, o tono muscular e os reflexosmedulares tornaram-se normais.References1 GRAHAM, P. A.; REFSAL, K. R.; NACHREINER, R.F. Etiopathologic findings of canine hypothyroidism.Vet. Clin. Small Anim., v. 37, n. 4, p. 617-631, 2007.2 BEALE, K. M.; HALLIWELL, R. E.; CHEN, C. L.Prevalence of antithyroglobulin antibodies detected byenzyme-linked immunosorbent assay of canine serum.J. Am. Vet. Med. Assoc., v. 196, n. 5, p. 745-748,1990.3 SCOTT-MONCRIEFF, J. C. Clinical signs andconcurrent diseases of hypothyroidism in dogs and cats.Vet. Clin. Small Anim., v. 37, n. 4, p. 709-722, 2007.4 SCOTT, D. W.; MILLER, W. H.; GRIFFIN, C. E. Smallanimal dermatology. 6 th ed. Philadelphia:W.B.Saunders, 2001. 1528 p.5 DIXON, R. M.; REID, S. W.; MOONEIJ, C. T.Epidemiological, clinical, haematological andbiochemical characteristics of canine hypothyroidism .Vet. Rec., v. 145, n. 17, p. 481-487, 1999.6 SCOTT-MONCRIEFF, J. C. R.; GUPTILL-YORAN, L.Hypothyroidism. In: ETTINGER, S. J.; FELDMAN, E. C.Textbook of veterinary internal medicine. 5 th ed.Philadelphia: Saunders, 2000. p. 1419-1429.7 PANCIERA, D. L. Conditions associated with caninehypothyroidism. Vet. Clin. North Am. Small Anim.Pract., v. 31, n. 5, p. 935-950, 2001.8 PATTERSON J. S.; RUSLEY, M. S.; ZADAREJ, J. F.Neurologic manifestations of cerebrovascularatherosclerosis associated with primary hypothyroidismin a dog. J. Am. Vet. Med. Assoc., v. 186, n. 5, p. 499-503, 1985.9 BRAUND, K. G. Clinical syndromes in veterinaryneurology. 2 nd ed. St. Louis: Mosby, 1994. 477 p.10 BRAUND, K. G. Degenerative causes ofneuropathies in dogs and cats. Veterinary Medicine, v.91, n. 8, p. 722-739, 1996.11 BRAUND, K. G.; DILLON, A. R.; AUGUST, J. R.;GANJAM, J. K. Hypothyroid myopathy in two dogs.Vet. Pathol., v. 18, n. 5. p. 589-598, 1981.12 HIGGINS, M. A.; ROSSMEISL JUNIOR, J. H.;PANCIERA, D. L. Hypothyroid-associated centralvestibular disease in 10 dogs: 1999-2005. J. Vet. Intern.Med., v. 20, n. 6, p. 1363-1369, 2006.13 LORENZ, M. D.; KORNEGAY, J. N. Handbook ofveterinary neurology. 4 th ed. Philadelphia: W.B.Saunders, 2004. 468 p.14 BICHSEL, P.; JACOBS, G.; OLIVER JUNIOR, J. E.Neurologic manifestations associated withhypothyroidism in four dogs. J. Am. Vet. Med. Assoc.,v. 192, n. 12, p. 1745-1747, 1988.15 BUDSBERG, S. C.; MOORE, G. E.;KLAPPENHACH, K. Thyroxin-responsive unilateralforelimb lameness and generalized neuromusculardisease in four hypothyroid dogs. J. Am. Vet. Med.Assoc., v. 202, n. 11, p. 1859-1860, 1993.16 CHRISMAN, C. L. Problems in small animalneurology. 2 nd ed. Philadelphia: Lea & Febiger, 1991.17 CHRISMAN, C. L. Polyneropathies of cats. SmallAnim. Pract., v. 41, n. 9, p. 384-389, 2000.18 GABER, C. E.; AMIS, T. C.; LeCOUTEUR, R. A.Laryngeal paralysis in dogs: a review of 23 cases. J. Am.Vet. Med. Assoc., v. 186, n. 4, p. 377-380, 1985.19 JAGGY, A.; OLIVER, J. E.; FERGUSON, D. C.;MAHAFFEY, E. A.; GLAUS JR, T. Neurologicmanifestations of hypothyroidism: a retrospective studyof 29 dogs. J. Vet. Intern. Med., v. 8, n. 5, p. 328-336,1994.20 INDRIERI, R. J.; WHALEN, L. R.; CARDINET, G.H.; HOLLIDAY, T. A. Neuromuscular abnormalitiesassociated with hypothyroidism and lymphocyticthyroiditis in three dogs. J. Am. Vet. Med. Assoc., v.190, n. 5, p. 544-548, 1987.21 FERGUSON, D. C. Testing for hypothyroidism indogs. Vet. Clin. Small Anim., v. 37, n. 4, p. 647-669,2007.22 CHRISMAN, C. L.; CLEMMONS, R. M.Electrodiagnostic testing. In: BOJRAB, M. J. Diseasemechanisms in small animal surgery. 2 nd ed. Philadelphia:Lea & Febiger, 1993. p. 1183-1201.23 DAVIS, P. E.; MALIK, R. Motor nerve conductionand spinal reflex measurements as predictors of racingperformance in greyhounds. Aust. Vet. J., v. 71, n. 1, p.24-25, 1994.24 DUNCAN, I. D. Peripheral nerve disease in the dogand cat. Vet. Clin. North Am. - Small Anim. Pract., v.10, n. 1, p. 177-211, 1980.25 FEITOSA, M. M.; LARSSON, M. H. M. A.;USHIKOSHI, W. S.; PERRI, S. H. V. Determinação davelocidade de condução nervosa motora dos nervostibial e peroneal de cães clinicamente sadios. ArsVeterinária, v. 16, n. 2, p. 83-91, 2000.26 MALIK, R.; HO, S.; CHURCH, D. B. A new methodfor recording and analysing evoked motor potentialsfrom dogs. Small Anim. Pract., v. 30, n. 1, p. 13-19,1989.Braz. J. vet. Res. anim. Sci., São Paulo, v. 45, n. 4, p. 284-288, 2008