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Association of Cognitive Dysfunction with Thyroid Autoantibody

갑상선 자가항체와 인지기능 저하의 연관성

  • Han, Dong Kyun (Department of Psychiatry, Kosin University College of Medicine) ;
  • Cheon, Jin Sook (Department of Psychiatry, Kosin University College of Medicine) ;
  • Choi, Young Sik (Department of Internal Medicine, Kosin University College of Medicine) ;
  • Kim, Ho Chan (Department of Psychiatry, Kosin University College of Medicine) ;
  • Oh, Byoung Hoon (Department of Psychiatry, Yonsei University College of Medicine)
  • 한동균 (고신대학교 의과대학 정신건강의학교실) ;
  • 전진숙 (고신대학교 의과대학 정신건강의학교실) ;
  • 최영식 (고신대학교 의과대학 내과학교실) ;
  • 김호찬 (고신대학교 의과대학 정신건강의학교실) ;
  • 오병훈 (연세대학교 의과대학 정신건강의학교실)
  • Received : 2016.11.16
  • Accepted : 2016.12.19
  • Published : 2016.12.31

Abstract

Objectives : The aims of this study were to know the frequency of cognitive dysfunction among patients with autoimmune thyroid disorders, and to reveal influencing factors on it, especially to clarify association with autoimmune thyroid antibodies. Methods : From sixty-five female patients with autoimmune thyroid disorders, demographic data were obtained by structured interview. Their cognitive funtions were measured using the MMSE-K and the MoCA-K tests. Depression was evaluated by the K-HDRS. Results : 1) Among patients with autoimmune thyroid disorders, 7.69% of them were below 24 on the MMSE-K, while 10.77% were below 22 on the MoCA-K. The frequency of cognitive deficit was not significantly different according to having positivity to antimicrosomal antibodies or not. 2) The antimicrosomal antibody-positive patients had significantly higher antithyroglobulin antibody titers, antimicrosomal antibody titers, and TSH concentration, while had significantly lower free T4 levels(p<0.05, respectively). 3) The total scores of the MMSE-K and the MoCA-K had significant correlation with age, marital status, antithyroglobulin antibody titers and K-HDRS(p<0.05, respectively). 4) The regression analysis revealed that variables such as age, education, autoimmune thyroid antibodies, thyroid function and depression did not influence on cognitive function of patients with autoimmune thyroid disorders. Conclusions : Our results could not support that cognitive function of patients with autoimmune thyroid disorders had correlation with autoimmune thyroid antibodies.

연구목적 본 연구의 목적은 자가면역 갑상선장애 환자에서 인지결함의 발생 빈도를 알아보고, 이에 영향 미치는 변인을 규명하며, 특히 갑상선 자가항체와의 연관성을 알아보기 위함이다. 방 법 여성 자가면역 갑상선장애 환자 65명을 대상으로 구조적 면담을 통해서 인구학적 정보를 얻었으며, 한국판 Mini-Mental State Examination(Korean Version of the Mini-Mental State Examination, MMSE-K)와 한국판 Montreal Cognitive Assessment(Korean Version of the Montreal Cognitive Assessment, MoCA-K)를 사용해서 인지기능을 평가하였고, 한국판 Depression Rating Scale(Korean Version of the Hamilton Depression Rating Scale, K-HDRS)를 사용해서 우울증을 평가하였다. 결 과 1) MMSE-K 총점 24점 이하는 7.69%, MoCA-K 총점 22점 이하는 10.77%였다. 인지기능 저하의 빈도는 antimicrosomal 항체 양성군(N=38, 58.46%)과 음성군(N=27) 간에 유의한 차이가 없었다. 2) Antimicrosomal 항체 양성군과 음성군의 변인별 차이를 비교한 결과, 음성군보다 양성군에서 antithyroglobulin 항체 수치, antimicrosomal 항체 수치, TSH 농도는 유의하게 높았고, free T4는 유의하게 낮았다(각각 p<0.05). 3) 자가면역 갑상선장애 환자의 인지기능과 여러 변인의 연관성을 분석한 결과, MMSE-K 검사와 MoCA-K 검사의 총점은 연령, 결혼상태, antithyroglobulin 항체 수치, K-HDRS 총점과 각각 유의한 상관관계가 있었다(각각 p<0.05). 4) 회귀분석 결과, 연령, 교육수준, 갑상선 자가항체, 갑상선기능, 우울증은 자가면역 갑상선장애 환자의 인지기능에 영향을 미치지 않았다. 결 론 본 연구의 결과는 자가면역 갑상선장애 환자의 인지기능과 갑상선 자가항체의 연관성을 지지할 수 없었다.

Keywords

References

  1. Davis JD, Tremont G. Neuropsychiatric aspects of hypothyroidism and treatment reversibility. Minerva Endocrinol 2007;32:49-65.
  2. Beydoun MA, Beydoun HA, Kitner-Triolo MH, Kaufman JS, Evans MK, Zonderman AB. Thyroid hormones are associated with cognitive function: moderation by sex, race, and depressive symptoms. J Clin Endocrinol Metab 2013;98:3470-3481. https://doi.org/10.1210/jc.2013-1813
  3. Samuels. Thyroid disease and cognition. Endocrinol Metab Clin North Am 2014;43:529-543. https://doi.org/10.1016/j.ecl.2014.02.006
  4. Akintola AA, Jansen SW, van Bodegom D, van der Grond J, Westendorp RG, de Craen AJM, van Heemst D. Subclinical hypothyroidism and cognitive function in people over 60 years: a systematic review and meta-analysis.Front Aging Neurosci 2015;7:150(11 pages). doi: 10.3389/fnagi.2015.00150.
  5. Samuels. Cognitive function in untreated hypothyroidism and hyperthyroidism. Curr Opin Endocrinol Diabetes Obes 2008;15:429-433. https://doi.org/10.1097/MED.0b013e32830eb84c
  6. Noda M. Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders. Front Cell Neurosci 2015;9:194. doi: 10.3389/fncel.2015.00194.
  7. Forti P, Olivelli V, Rietti E, Maltoni B, Pirazzoli G, Gatti R, Gioia MG, Ravaglia G. Serum thyroid-stimulating hormone as a predictor of cognitive impairment in a elderly cohort. Gerontology 2012;58:41-49. https://doi.org/10.1159/000324522
  8. Goh KK, Chiu Y-H, Shen WW. Hashimoto's encephalopathy mimicking presenile dementia. Gen Hosp Psychiatr 2014;36:360.e9-360.e11. https://doi.org/10.1016/j.genhosppsych.2014.01.006
  9. Quinque EM, Karger S, Arelin K, Schroeter ML, Kratzsch J, Villringer A. Structural and functional MRI study of the brain, cognition and mood in long-term adequately treated Hashimoto's thyroiditis. Psychoneuroendocrinology 2014;42:188-198. https://doi.org/10.1016/j.psyneuen.2014.01.015
  10. Grigorova M, Sherwin BB. Thyroid hormones and cognitive functioning in healthy, euthyroid women: A correlational study. Horm Behav 2012;61:617-622. https://doi.org/10.1016/j.yhbeh.2012.02.014
  11. Zettinig G, Asenbaum S, Fueger BJ, Hofmann A, Diemling M, Mittlboeck M, Dudczak R. Increased prevalence of subclinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto's encephalitis? Clin Endocrinol 2003;59:637-643 https://doi.org/10.1046/j.1365-2265.2003.01901.x
  12. Leyhe T, Ethofer T, Bretscher J, Kule A, Sauberlich A-L, Klein R, Gallwitz B, Haring H-U, Fallgatter A, Klingberg S, Saur R, Mussig K. Low performance in attention testing is associated with reduced grey matter density of the left ingerior frontal gyrus in euthyroid patients with Hashimoto's thyroiditis. Brain Behav Immun 2013;27:33-37. https://doi.org/10.1016/j.bbi.2012.09.007
  13. Leyhe T, Mussig K. Cognitive and affective dysfunctions in autoimmune thyroiditis. Brain Behav Immun 2014;41:261-266. https://doi.org/10.1016/j.bbi.2014.03.008
  14. Blanchin S, Coffin C, Viader F, Ruf J, Carayon P, Potier F, Portier E, Comby E, Allouche S, Ollivier Y, Reznik Y, Ballet JJ. Anti-thyroperoxidase antibodies from patients with Hashimoto's encephalopathy bind to cerebellar astrocytes. J Neuroimmunol 2007;192:13-20. https://doi.org/10.1016/j.jneuroim.2007.08.012
  15. 이중서, 배승오, 안용민, 박두병, 노경선, 신현균, 우행원, 이홍식, 한상익, 김용식. 한국판 Hamilton 우울증평가 척도의 신뢰도, 타당도 연구. J Korean Neuropsychiatry Assoc 2005;44:456-465.
  16. 권용철, 박종한. 노인용 한국판 Mini-Mental State Examination(MMSE-K)의 표준화 연구-제1편: MMSE-K의 개발-. 신경정신의학 1989;28:125-135.
  17. 박종한, 권용철. 노인용 한국판 Mini-Mental State Examination(MMSE-K)의 표준화 연구-제2편: 구분점 및 진단적 타당도-. 신경정신의학 1989;28:508-513.
  18. Nasreddine Z, Lee JY. Korean Version of the Montreal Cognitive Assessment. March 1, 2006. Available from:URL:http://www.mocatest.org.
  19. Sapin R, d'Herbomez M, Gasser F, Meyer L, Schlienger J-L. Increased sensitivity of a new assay for anti-thyroglobulin antibody detection in patients with autoimmune thyroid disease. Clin Biochem 2003;36:611-616. https://doi.org/10.1016/S0009-9120(03)00114-0
  20. Liu M, Zhao L, Gao Y, Huang Y, Lu G, Gao Y, Guo X. Epitope recognition patterns of thyroglobulin antibody in sera from patients with Hashimoto's thyroiditis on different thyroid functional status. Clin Exp Immunol 2012;170:283-290. https://doi.org/10.1111/j.1365-2249.2012.04666.x
  21. Sinclair D. Clinical and laboratory aspects of thyroid autoantibodies. Ann Clin Biochem 2006;43:173-183. https://doi.org/10.1258/000456306776865043
  22. Ando T, Latif R, Pritsker A, Moran T, Nagayama Y, Davies TF. A Monoclonal thyroid-stimulating antibody. J Clin Invest 2002;110: 1667-1674. https://doi.org/10.1172/JCI0216991
  23. Bojar I, Bejga P, Witczak M, Lyszcz R, Makara-Studzinska M. Standards for thyroid laboratory testing, and cognbitive functions after menopause. Prz Menopauzalny 2014;13:233-241.
  24. Gilbert ME, Rovet J, Chen Z, Koibuchi N. Developmental thyroid hormone disruption: prevalence, environmental contaminants and neurodevelopmental consequences. Neurotoxicology 2012;33:842-852. https://doi.org/10.1016/j.neuro.2011.11.005
  25. Colborn T. Neurodevelopment and endocrine disruption. Environ Health Perspect 2004;112:944-949. https://doi.org/10.1289/ehp.6601
  26. Wasserman EE, Pillion JP, Duggan A, Nelson K, Rohde C, Seaberg EC, Talor MV, Yolken RH, Rose NR. Childhood IQ, hearing loss, and maternal thyroid autoimmunity in the Baltimore Collaborative Perinatal Project. Pediatr Res 2012;72:525-530. https://doi.org/10.1038/pr.2012.117
  27. Li Y,Shan Z, Teng W, Yu X, Li Y, Fan C, Teng X, Guo R, Wang H, Li J, Chen Y, Wang W, Chawinga M, Zhang L, Yang L, Zhao Y, Hua T. Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25-30 months. Clin Endocrinol 2010;72:825-829.
  28. Gilbert ME, Lasley SM. Developmental thyroid hormone insufficiency and brain development: a role for brain-derived neurotrophic factor(BDNF)? Neuroscience 2013;239:253-270. https://doi.org/10.1016/j.neuroscience.2012.11.022
  29. Lasley SM, Gilbert ME. Developmental thyroid hormone insufficiency reduces expressioin of brain-derived neurotrophic factor(BDNF) in adults but not in neonates. Neurotoxicol Teratol 2011;33:464-472. https://doi.org/10.1016/j.ntt.2011.04.001
  30. Prummel MF, Wiersinga WM. Thyroid peroxidase autoantibodies in euthyroid subjects. Best Pract Res Clin Endocrinol Metab 2005;19:1-15. https://doi.org/10.1016/j.beem.2004.11.003
  31. Tomer Y, Ban Y, Concepcion E, Barbesino G, Villanueva R, Greenberg DA, Davies TF. Common and unique susceptibility loci in Graves and Hashimoto diseases: results of wholegenome screening in a data set of 102 multiplex families. Am J Hum Genet 2003;73:736-747. https://doi.org/10.1086/378588
  32. Tomer Y, Davies TF. Searching for the autoimmune thyroid diseases susceptibility genes: from gene mapping to gene function. Endocr Rev 2003;24:694-717. https://doi.org/10.1210/er.2002-0030
  33. Parish NM, Cooke A. Mechanisms of autoimmune thyroid disease. Drug Discov Tod Dis Mechan 2004;1:337-344.
  34. Jacobson EM, Tomer Y. The CD40-, CTLA=4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: Back to the future. J Autoimmun 2007:28:85-98. https://doi.org/10.1016/j.jaut.2007.02.006
  35. Jacobson EM, Huber A, Tomer Y. The HLA gene complex in thyroid autoimmunity: From epidemiology to etiology. J Autoimmun 2008;30:58-62. https://doi.org/10.1016/j.jaut.2007.11.010
  36. Tomer Y, Huber A. The etiology of autoimmune thyroid disease: A story of genes and environment. J Autoimmun 2009;32:231-239. https://doi.org/10.1016/j.jaut.2009.02.007
  37. Leyhe T, Mussig K, Weinert C, Laske C, Haring H-U, Saur R, Klingberg S, Gallwitz B. Increased occurrence of weaknesses in attention testing in patients with Hashimoto's thyroiditis compared to patients with other thyroid illnesses. Psychoneuroendocrinology 2008;33:1432-1436. https://doi.org/10.1016/j.psyneuen.2008.08.009
  38. Mussig K, Leyhe T, Holzmuller S, Klein R, Weinert C, Saur R, Klingberg S, Haring H-U, Gallwitz B. Increased prevalence of antibodies to central nervous system tissue and gangliosides in Hashimoto's thyroiditis compared to other thyroid illnesses. Psychoneuroendocrinology 2009;34:1252-1256. https://doi.org/10.1016/j.psyneuen.2009.03.011
  39. Ai J, Leonhardt JM, Heymann WR. Autoimmune thyroid diseases: Etiology, pathogenesis, and dermatologic manifestations. J Am Acad Dermatol 2003;48:641-659. https://doi.org/10.1067/mjd.2003.257
  40. Fatourechi V. Hashimoto's encephalopathy: myth or reality? An endocrinologist's perspective. Best Pract Res Clin Endocrinol Metab 2005;19:53-66. https://doi.org/10.1016/j.beem.2004.11.006
  41. Mazzu I, Mosti S, Caltagirone C, Carlesimo GA. Hashimoto's encephalopathy: neuropsychological findings. Neurol Sci 2012;33:653-656. https://doi.org/10.1007/s10072-011-0813-z