UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Neurologic manifestations of hyperthyroidism and Graves' disease

Author
Devon I Rubin, MD
Section Editors
Michael J Aminoff, MD, DSc
Douglas S Ross, MD
Deputy Editor
Janet L Wilterdink, MD

INTRODUCTION

Hyperthyroidism is a common medical condition in the general population. The most common cause of hyperthyroidism is Graves' disease, but elevated thyroid hormone levels may occur due to thyroiditis, multinodular goiter, toxic thyroid nodule, or excess thyroid hormone supplementation.

Common systemic features of hyperthyroidism include palpitations, heat intolerance, and weight loss. A number of central and peripheral nervous system manifestations may also occur in patients with hyperthyroidism (table 1). In many cases, the neurologic manifestations occur in conjunction with the systemic features of the disease, but these may be the presenting symptom in some patients.

This topic reviews the neurologic manifestations of hyperthyroidism. Other clinical features of hyperthyroidism are discussed separately. (See "Overview of the clinical manifestations of hyperthyroidism in adults" and "Clinical manifestations and diagnosis of hyperthyroidism in children and adolescents".) The diagnosis of hyperthyroidism is also discussed separately. (See "Diagnosis of hyperthyroidism".)

COGNITIVE DYSFUNCTION AND SEIZURES

Cognitive impairment is common in hyperthyroidism and may present as one or more different syndromes. In one review of elderly patients with hyperthyroidism, dementia and confusion was found in 33 percent and 18 percent of patients, respectively [1]. Studies in younger individuals with newly-diagnosed or induced hyperthyroidism have found lower cognitive scores compared with controls [2-4].

There is also inconclusive evidence suggesting that mild hyperthyroidism may be a risk factor for dementia. Case control and population-based cohort studies have had conflicting results, with some finding a positive association between low thyrotropin (TSH) levels and others not [5-9]. Low TSH in this setting may represent subclinical hyperthyroidism, but may instead be associated with hypothyroidism if it is the result of decreased thyrotropin-releasing hormone production, itself a consequence of neurodegeneration. (See "Neurologic manifestations of hypothyroidism", section on 'Alzheimer disease'.)

                      

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Mon Jun 06 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Martin FI, Deam DR. Hyperthyroidism in elderly hospitalised patients. Clinical features and treatment outcomes. Med J Aust 1996; 164:200.
  2. Wu T, Flowers JW, Tudiver F, et al. Subclinical thyroid disorders and cognitive performance among adolescents in the United States. BMC Pediatr 2006; 6:12.
  3. Yudiarto FL, Muliadi L, Moeljanto D, Hartono B. Neuropsychological findings in hyperthyroid patients. Acta Med Indones 2006; 38:6.
  4. Schlote B, Schaaf L, Schmidt R, et al. Mental and physical state in subclinical hyperthyroidism: investigations in a normal working population. Biol Psychiatry 1992; 32:48.
  5. Döbert N, Hamscho N, Menzel C, et al. Subclinical hyperthyroidism in dementia and correlation of the metabolic index in FDG-PET. Acta Med Austriaca 2003; 30:130.
  6. Kalmijn S, Mehta KM, Pols HA, et al. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study. Clin Endocrinol (Oxf) 2000; 53:733.
  7. van der Cammen TJ, Mattace-Raso F, van Harskamp F, de Jager MC. Lack of association between thyroid disorders and Alzheimer's disease in older persons: a cross-sectional observational study in a geriatric outpatient population. J Am Geriatr Soc 2003; 51:884.
  8. van Osch LA, Hogervorst E, Combrinck M, Smith AD. Low thyroid-stimulating hormone as an independent risk factor for Alzheimer disease. Neurology 2004; 62:1967.
  9. de Jong FJ, den Heijer T, Visser TJ, et al. Thyroid hormones, dementia, and atrophy of the medial temporal lobe. J Clin Endocrinol Metab 2006; 91:2569.
  10. Stern RA, Robinson B, Thorner AR, et al. A survey study of neuropsychiatric complaints in patients with Graves' disease. J Neuropsychiatry Clin Neurosci 1996; 8:181.
  11. Jabbari B, Huott AD. Seizures in thyrotoxicosis. Epilepsia 1980; 21:91.
  12. Safe AF, Griffiths KD, Maxwell RT. Thyrotoxic crisis presenting as status epilepticus. Postgrad Med J 1990; 66:150.
  13. Lee TG, Ha CK, Lim BH. Thyroid storm presenting as status epilepticus and stroke. Postgrad Med J 1997; 73:61.
  14. Li Voon Chong JS, Lecky BR, Macfarlane IA. Recurrent encephalopathy and generalised seizures associated with relapses of thyrotoxicosis. Int J Clin Pract 2000; 54:621.
  15. Newcomer J, Haire W, Hartman CR. Coma and thyrotoxicosis. Ann Neurol 1983; 14:689.
  16. Fukui T, Hasegawa Y, Takenaka H. Hyperthyroid dementia: clinicoradiological findings and response to treatment. J Neurol Sci 2001; 184:81.
  17. Trasciatti S, Prete C, Palummeri E, Foppiani L. Thyroid storm as precipitating factor in onset of coma in an elderly woman: case report and literature review. Aging Clin Exp Res 2004; 16:490.
  18. Aiello DP, DuPlessis AJ, Pattishall EG 3rd, Kulin HE. Thyroid storm. Presenting with coma and seizures. In a 3-year-old girl. Clin Pediatr (Phila) 1989; 28:571.
  19. SKANSE B, NYMAN GE. Thyrotoxicosis as a cause of cerebral dysrhythmia and convulsive seizures. Acta Endocrinol (Copenh) 1956; 22:246.
  20. Primavera A, Brusa G, Novello P. Thyrotoxic encephalopathy and recurrent seizures. Eur Neurol 1990; 30:186.
  21. Su YH, Izumi T, Kitsu M, Fukuyama Y. Seizure threshold in juvenile myoclonic epilepsy with Graves disease. Epilepsia 1993; 34:488.
  22. Scott TF. Thyrotoxicosis and seizures. South Med J 1988; 81:103.
  23. Duyff RF, Van den Bosch J, Laman DM, et al. Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study. J Neurol Neurosurg Psychiatry 2000; 68:750.
  24. Henderson JM, Portmann L, Van Melle G, et al. Propranolol as an adjunct therapy for hyperthyroid tremor. Eur Neurol 1997; 37:182.
  25. Kim HT, Edwards MJ, Lakshmi Narsimhan R, Bhatia KP. Hyperthyroidism exaggerating parkinsonian tremor: a clinical lesson. Parkinsonism Relat Disord 2005; 11:331.
  26. Ristić AJ, Svetel M, Dragasević N, et al. Bilateral chorea-ballism associated with hyperthyroidism. Mov Disord 2004; 19:982.
  27. Baba M, Terada A, Hishida R, et al. Persistent hemichorea associated with thyrotoxicosis. Intern Med 1992; 31:1144.
  28. Fischbeck KH, Layzer RB. Paroxysmal choreoathetosis associated with thyrotosicosis. Ann Neurol 1979; 6:453.
  29. Yen DJ, Shan DE, Lu SR. Hyperthyroidism presenting as recurrent short paroxysmal kinesigenic dyskinesia. Mov Disord 1998; 13:361.
  30. Puri V, Chaudhry N. Paroxysmal kinesigenic dyskinesia manifestation of hyperthyroidism. Neurol India 2004; 52:102.
  31. Klawans HL Jr, Shenker DM. Observations on the dopaminergic nature of hyperthyroid chorea. J Neural Transm 1972; 33:73.
  32. Isaacs JD, Rakshi J, Baker R, et al. Chorea associated with thyroxine replacement therapy. Mov Disord 2005; 20:1656.
  33. Lucantoni C, Grottoli S, Moretti A. Chorea due to hyperthyroidism in old age. A case report. Acta Neurol (Napoli) 1994; 16:129.
  34. Javaid A, Hilton DD. Persistent chorea as a manifestation of thyrotoxicosis. Postgrad Med J 1988; 64:789.
  35. Teoh HL, Lim EC. Platysmal myoclonus in subclinical hyperthyroidism. Mov Disord 2005; 20:1064.
  36. Loh LM, Hum AY, Teoh HL, Lim EC. Graves' disease associated with spasmodic truncal flexion. Parkinsonism Relat Disord 2005; 11:117.
  37. Sheu JJ, Kang JH, Lin HC, Lin HC. Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up study. Stroke 2010; 41:961.
  38. Chaker L, Baumgartner C, Ikram MA, et al. Subclinical thyroid dysfunction and the risk of stroke: a systematic review and meta-analysis. Eur J Epidemiol 2014; 29:791.
  39. Squizzato A, Gerdes VE, Brandjes DP, et al. Thyroid diseases and cerebrovascular disease. Stroke 2005; 36:2302.
  40. Presti CF, Hart RG. Thyrotoxicosis, atrial fibrillation, and embolism, revisited. Am Heart J 1989; 117:976.
  41. Petersen P, Hansen JM. Stroke in thyrotoxicosis with atrial fibrillation. Stroke 1988; 19:15.
  42. Molloy E, Cahill M, O'Hare JA. Cerebral venous sinus thrombosis precipitated by Graves' disease and Factor V Leiden mutation. Ir Med J 2003; 96:46.
  43. Verberne HJ, Fliers E, Prummel MF, et al. Thyrotoxicosis as a predisposing factor for cerebral venous thrombosis. Thyroid 2000; 10:607.
  44. Siegert CE, Smelt AH, de Bruin TW. Superior sagittal sinus thrombosis and thyrotoxicosis. Possible association in two cases. Stroke 1995; 26:496.
  45. Ra CS, Lui CC, Liang CL, et al. Superior sagittal sinus thrombosis induced by thyrotoxicosis. Case report. J Neurosurg 2001; 94:130.
  46. Campos CR, Basso M, Evaristo EF, et al. Bilateral carotid artery dissection with thyrotoxicosis. Neurology 2004; 63:2443.
  47. Pezzini A, Del Zotto E, Mazziotti G, et al. Thyroid autoimmunity and spontaneous cervical artery dissection. Stroke 2006; 37:2375.
  48. Nakamura K, Yanaka K, Ihara S, Nose T. Multiple intracranial arterial stenoses around the circle of Willis in association with Graves' disease: report of two cases. Neurosurgery 2003; 53:1210.
  49. Tendler BE, Shoukri K, Malchoff C, et al. Concurrence of Graves' disease and dysplastic cerebral blood vessels of the moyamoya variety. Thyroid 1997; 7:625.
  50. Marongiu F, Conti M, Murtas ML, et al. Anticardiolipin antibodies in Grave's disease: relationship with thrombin activity in vivo. Thromb Res 1991; 64:745.
  51. Hofbauer LC, Spitzweg C, Heufelder AE. Graves' disease associated with the primary antiphospholipid syndrome. J Rheumatol 1996; 23:1435.
  52. Bowness P, Shotliff K, Middlemiss A, Myles AB. Prevalence of hypothyroidism in patients with polymyalgia rheumatica and giant cell arteritis. Br J Rheumatol 1991; 30:349.
  53. Thomas RD, Croft DN. Thyrotoxicosis and giant-cell arteritis. Br Med J 1974; 2:408.
  54. Kettaneh A, Prevot S, Biaggi A, et al. Hyperthyroidism in two patients with Crohn disease and Takayasu arteritis. Scand J Gastroenterol 2003; 38:901.
  55. Duhaut P, Bornet H, Pinède L, et al. Giant cell arteritis and thyroid dysfunction: multicentre case-control study. The Groupe de Recherche sur l'Artériteá Cellules Géantes. BMJ 1999; 318:434.
  56. Ratanakorn D, Vejjajiva A. Long-term follow-up of myasthenia gravis patients with hyperthyroidism. Acta Neurol Scand 2002; 106:93.
  57. Weissel M, Mayr N, Zeitlhofer J. Clinical significance of autoimmune thyroid disease in myasthenia gravis. Exp Clin Endocrinol Diabetes 2000; 108:63.
  58. Kiessling WR, Pflughaupt KW, Ricker K, et al. Thyroid function and circulating antithyroid antibodies in myasthenia gravis. Neurology 1981; 31:771.
  59. Aarli JA, Thunold S, Heimann P. Thyroiditis in myasthenia gravis. Acta Neurol Scand 1978; 58:121.
  60. Marinó M, Ricciardi R, Pinchera A, et al. Mild clinical expression of myasthenia gravis associated with autoimmune thyroid diseases. J Clin Endocrinol Metab 1997; 82:438.
  61. Marinò M, Barbesino G, Pinchera A, et al. Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis. Thyroid 2000; 10:799.
  62. Sekiguchi Y, Hara Y, Takahashi M, Hirata Y. Reverse 'see-saw' relationship between Graves' disease and myasthenia gravis; clinical and immunological studies. J Med Dent Sci 2005; 52:43.
  63. Téllez-Zenteno JF, Cardenas G, Estañol B, et al. Associated conditions in myasthenia gravis: response to thymectomy. Eur J Neurol 2004; 11:767.
  64. Hofmann WW, Denys EH. Effects of thyroid hormone at the neuromuscular junction. Am J Physiol 1972; 223:283.
  65. SAHAY BM, BLENDIS LM, GREENE R. RELATION BETWEEN MYASTHENIA GRAVIS AND THYROID DISEASE. Br Med J 1965; 1:762.
  66. HAVARD CW, CAMPBELL ED, ROSS HB, SPENCE AW. Electromyographic and histological findings in the muscles of patients with thyrotoxicosis. Q J Med 1963; 32:145.
  67. Ramsay ID. Electromyography in thyrotoxicosis. Q J Med 1965; 34:255.
  68. Olson BR, Klein I, Benner R, et al. Hyperthyroid myopathy and the response to treatment. Thyroid 1991; 1:137.
  69. Horak HA, Pourmand R. Endocrine myopathies. Neurol Clin 2000; 18:203.
  70. Kaminski, HJ. Ruff, RL. Endocrine myopathies (hyper- and hypofunction of adrenal, thyroid, pistuitary, and parathyroid glands and iatrogenic corticosteroid myopathy). In: Myology, 2nd ed, Enngel, AG, Franzini-Armstrong, C (Eds), McGraw-Hill, New York 1994. p.1726.
  71. Kissel, JT. Mendell, JR. The endocrine myopathies. In: Handbook of clinical neurology myopathies, Rowland, LP, Dimauro, S, (Eds), Elsevier Science, New York 1992. p.527.
  72. Erkintalo M, Bendahan D, Mattéi JP, et al. Reduced metabolic efficiency of skeletal muscle energetics in hyperthyroid patients evidenced quantitatively by in vivo phosphorus-31 magnetic resonance spectroscopy. Metabolism 1998; 47:769.
  73. Sinclair C, Gilchrist JM, Hennessey JV, Kandula M. Muscle carnitine in hypo- and hyperthyroidism. Muscle Nerve 2005; 32:357.
  74. Lleó A, Sanahuja J, Serrano C, et al. Acute bulbar weakness: thyrotoxicosis or myasthenia gravis? Ann Neurol 1999; 46:434.
  75. Couillard P, Wijdicks EF. Flaccid quadriplegia due to thyrotoxic myopathy. Neurocrit Care 2014; 20:296.
  76. Lichtstein DM, Arteaga RB. Rhabdomyolysis associated with hyperthyroidism. Am J Med Sci 2006; 332:103.
  77. Alshanti M, Eledrisi MS, Jones E. Rhabdomyolysis associated with hyperthyroidism. Am J Emerg Med 2001; 19:317.
  78. Bennett WR, Huston DP. Rhabdomyolysis in thyroid storm. Am J Med 1984; 77:733.
  79. Puvanendran K, Cheah JS, Naganathan N, Wong PK. Thyrotoxic myopathy: a clinical and quantitative analytic electromyographic study. J Neurol Sci 1979; 42:441.
  80. Chiu WY, Yang CC, Huang IC, Huang TS. Dysphagia as a manifestation of thyrotoxicosis: report of three cases and literature review. Dysphagia 2004; 19:120.
  81. McElvaney GN, Wilcox PG, Fairbarn MS, et al. Respiratory muscle weakness and dyspnea in thyrotoxic patients. Am Rev Respir Dis 1990; 141:1221.
  82. Verhagen WI, Schimsheimer RJ. Neurologic disease and thyrotoxic storm. A clinical and electrophysiological study. Electromyogr Clin Neurophysiol 1986; 26:27.
  83. Hardiman O, Molloy F, Brett F, Farrell M. Inflammatory myopathy in thyrotoxicosis. Neurology 1997; 48:339.
  84. Nørrelund H, Hove KY, Brems-Dalgaard E, et al. Muscle mass and function in thyrotoxic patients before and during medical treatment. Clin Endocrinol (Oxf) 1999; 51:693.
  85. Klein I, Ojamaa K. Thyroid (neuro)myopathy. Lancet 2000; 356:614.
  86. Fisher M, Mateer JE, Ullrich I, Gutrecht JA. Pyramidal tract deficits and polyneuropathy in hyperthyroidism, Combination clinically mimicking amyotrophic lateral sclerosis. Am J Med 1985; 78:1041.
  87. Feibel JH, Campa JF. Thyrotoxic neuropathy (Basedow's paraplegia). J Neurol Neurosurg Psychiatry 1976; 39:491.
  88. Sözay S, Gökçe-Kutsal Y, Celiker R, et al. Neuroelectrophysiological evaluation of untreated hyperthyroid patients. Thyroidology 1994; 6:55.
  89. Pandit L, Shankar SK, Gayathri N, Pandit A. Acute thyrotoxic neuropathy--Basedow's paraplegia revisited. J Neurol Sci 1998; 155:211.
  90. Gómez R, Shetty AK, Vargas A, et al. Chronic inflammatory demyelinating polyradiculoneurophathy and Graves' disease in an adolescent with Crohn's disease. J Pediatr Gastroenterol Nutr 1999; 29:91.
  91. BRONSKY D, KAGANIEC GI, WALDSTEIN SS. AN ASSOCIATION BETWEEN THE GUILLAIN-BARR'E SYNDROME AND HYPERTHYROIDISM. Am J Med Sci 1964; 247:196.
  92. Roquer J, Cano JF. Mononeuropathies in thyrotoxicosis. J Neurol Neurosurg Psychiatry 1992; 55:332.
  93. Roquer J, Cano JF. Carpal tunnel syndrome and hyperthyroidism. A prospective study. Acta Neurol Scand 1993; 88:149.
  94. Cakir M, Samanci N, Balci N, Balci MK. Musculoskeletal manifestations in patients with thyroid disease. Clin Endocrinol (Oxf) 2003; 59:162.
  95. Rosati G, Govoni E, Aiello I, et al. Hyperthyroidism as a precipitating factor of amyotrophic lateral sclerosis: a case report. Acta Neurol (Napoli) 1980; 2:166.
  96. RAVERA JJ, CERVINO JM, FERNANDEZ G, et al. Two cases of Graves' disease with signs of a pyramidal lesion. Improvement in neurologic signs during treatment with antithyroid drugs. J Clin Endocrinol Metab 1960; 20:876.
  97. Garcia CA, Fleming RH. Reversible corticospinal tract disease due to hyperthyroidism. Arch Neurol 1977; 34:647.
  98. Rowland LP. Diagnosis of amyotrophic lateral sclerosis. J Neurol Sci 1998; 160 Suppl 1:S6.
  99. Ríos A, Rodríguez JM, Canteras M, et al. Surgical management of multinodular goiter with compression symptoms. Arch Surg 2005; 140:49.
  100. Anders HJ. Compression syndromes caused by substernal goitres. Postgrad Med J 1998; 74:327.