Titanium and Other Metal Hypersensitivity Diagnosed by MELISA® Test: Follow-Up Study
Language English Country United States Media electronic-ecollection
Document type Clinical Trial, Journal Article
PubMed
34124241
PubMed Central
PMC8192180
DOI
10.1155/2021/5512091
Knihovny.cz E-resources
- MeSH
- Hypersensitivity diagnosis MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Surveys and Questionnaires * MeSH
- Aged MeSH
- Titanium adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Names of Substances
- Titanium MeSH
This study is aimed at proving the clinical benefit of the MELISA® test in the minimization or complete elimination of health problems in patients with confirmed hypersensitivity to metals used for tissue replacements. A group of 305 patients aged 20-75 years with previously proven metal hypersensitivity (initial MELISA® test), mainly to titanium and then to another fifteen metals, was chosen from the database at the Institute of Dental Medicine. From these patients, a final group of 42 patients agreed to participate in the study, 35 of which were female and 7 were male. The patients completed a special questionnaire aimed at information regarding change of health status from their last visit and determining whether the results of the initial MELISA® test and recommendations based on it were beneficial for patients or not. They were clinically examined, and peripheral blood samples were taken to perform follow-up MELISA® tests. Questionnaire data was processed, and the follow-up MELISA® test results were compared with the results of the initial MELISA® tests. For statistical analysis, the Fisher's exact test and paired T-test were used. Thirty-two patients reported that they followed the recommendations based on the results of the initial MELISA® tests, and of these, 30 patients (94%) confirmed significant health improvement. Six patients did not follow the recommendation, and from these, only one patient reported an improvement in his health problems. By comparison of the initial and follow-up MELISA® test results, it can be stated that the hypersensitivity to the given metal decreased or disappeared after the therapeutic interventions performed based on the initial MELISA® test results. The evaluation of the data obtained from patients in this study confirmed a significant clinical benefit of MELISA® test.
See more in PubMed
Jurczak P., Witkowska J., Rodziewicz-Motowidło S., Lach S. Proteins, peptides and peptidomimetics as active agents in implant surface functionalization. Advances in Colloid and Interface Science. 2020;276, article 102083 doi: 10.1016/j.cis.2019.102083. PubMed DOI
Catauro M., Bollino F., Papale F. Preparation, characterization, and biological properties of organic-inorganic nanocomposite coatings on titanium substrates prepared by sol-gel. Journal of Biomedical Materials Research PART A. 2014;102(2):392–399. doi: 10.1002/jbm.a.34721. PubMed DOI
Eraković S., Janković A., Ristoscu C., et al. Antifungal activity of Ag:hydroxyapatite thin films synthesized by pulsed laser deposition on Ti and Ti modified by TiO2 nanotubes substrates. Applied Surface Science. 2014;293:37–45. doi: 10.1016/j.apsusc.2013.12.029. DOI
Strakowska P., Beutner R., Gnyba M., Zielinski A., Scharnweber D. Electrochemically assisted deposition of hydroxyapatite on Ti6Al4V substrates covered by CVD diamond films -- Coating characterization and first cell biological results. Materials Science and Engineering: C. 2016;59:624–635. doi: 10.1016/j.msec.2015.10.063. PubMed DOI
Himmlova L., Kubies D., Hulejova H., et al. Effect of blood component coatings of enosseal implants on proliferation and synthetic activity of human osteoblasts and cytokine production of peripheral blood mononuclear cells. Mediators of Inflammation. 2016;2016:15. doi: 10.1155/2016/8769347.8769347 PubMed DOI PMC
Nishio K., Neo M., Akiyama H., et al. The effect of alkali- and heat-treated titanium and apatite-formed titanium on osteoblastic differentiation of bone marrow cells. Journal of Biomedical Materials Research. 2000;52(4):652–661. doi: 10.1002/1097-4636(20001215)52:4<652::AID-JBM9>3.0.CO;2-W. PubMed DOI
Lusquiños F., de Carlos A., Pou J., et al. Calcium phosphate coatings obtained by Nd: YAG laser cladding: physicochemical and biologic properties. Journal of Biomedical Materials Research PART A. 2003;64(4):630–637. doi: 10.1002/jbm.a.10440. PubMed DOI
Yang Y. C., Chang E. The bonding of plasma-sprayed hydroxyapatite coatings to titanium: effect of processing, porosity and residual stress. Thin Solid Films. 2003;444(1-2):260–275. doi: 10.1016/S0040-6090(03)00810-1. DOI
Xiong J., Li Y., Hodgson P. D., Wen C. Nanohydroxyapatite coating on a titanium-niobium alloy by a hydrothermal process. Acta Biomaterialia. 2010;6(4):1584–1590. doi: 10.1016/j.actbio.2009.10.016. PubMed DOI
Ansar E. B., Ravikumar K., Suresh Babu S., et al. Inducing apatite pre-layer on titanium surface through hydrothermal processing for osseointegration. Materials Science and Engineering: C. 2019;105, article 110019 doi: 10.1016/j.msec.2019.110019. PubMed DOI
Zykova A., Safonov V., Yanovska A., et al. Formation of solution-derived hydroxyapatite coatings on titanium alloy in the presence of magnetron-sputtered alumina bond coats. The Open Biomedical Engineering Journal. 2015;9(1):75–82. doi: 10.2174/1874120701509010075. PubMed DOI PMC
Bai X., Sandukas S., Appleford M. R., Ong J. L., Rabiei A. Deposition and investigation of functionally graded calcium phosphate coatings on titanium. Acta Biomaterialia. 2009;5(9):3563–3572. doi: 10.1016/j.actbio.2009.05.013. PubMed DOI
Choi J.-M., Kim H.-E., Lee I.-S. Ion-beam-assisted deposition (IBAD) of hydroxyapatite coating layer on Ti- based metal substrate. Biomaterials. 2000;21(5):469–473. doi: 10.1016/S0142-9612(99)00186-6. PubMed DOI
Yoon H.-J., Song J.-E., Um Y.-J., et al. Effects of calcium phosphate coating to SLA surface implants by the ion-beam-assisted deposition method on self-contained coronal defect healing in dogs. Biomedical Materials. 2009;4(4, article 044107) doi: 10.1088/1748-6041/4/4/044107. PubMed DOI
Su Y., Cockerill I., Zheng Y., Tang L., Qin Y. X., Zhu D. Biofunctionalization of metallic implants by calcium phosphate coatings. Bioactive Materials. 2019;4:196–206. doi: 10.1016/j.bioactmat.2019.05.001. PubMed DOI PMC
Eto S., Kawano S., Someya S., Miyamoto H., Sonohata M., Mawatari M. First clinical experience with thermal-sprayed silver oxide-containing hydroxyapatite coating implant. Journal of Arthroplasty. 2016;31(7):1498–1503. doi: 10.1016/j.arth.2015.12.034. PubMed DOI
Harrasser N., Jüssen S., Obermeir A., et al. Antibacterial potency of different deposition methods of silver and copper containing diamond-like carbon coated polyethylene. Biomaterials Research. 2016;20(1):1–10. doi: 10.1186/s40824-016-0062-6. PubMed DOI PMC
Vlcak P., Jirka I. Protective Sliding Carbon-Based Nanolayers Prepared by Argon or Nitrogen Ion- Beam Assisted Deposition on Ti6Al4V Alloy. Journal of Nanomaterials. 2016;2016:9. doi: 10.1155/2016/1697090.1697090 DOI
Vlcak P. The effect of ion irradiation and elevated temperature on the microstructure and the properties of C/W/C/B multilayer coating. Applied Surface Science. 2016;365:306–313. doi: 10.1016/j.apsusc.2016.01.003. DOI
Horazdovsky T., Vrbova R. Tribomechanical properties of a carbon-based nanolayer prepared by nitrogen ion beam assisted deposition for finger joint replacements. Journal of Nanomaterials. 2018;2018:9. doi: 10.1155/2018/3749309.3749309 DOI
Evans E. M., Freeman M. A., Miller A. J., Vernon-Roberts B. Metal sensitivity as a cause of bone necrosis and loosening of the prosthesis in total joint replacement. The Journal of Bone and Joint Surgery. 1974;56-B(4):626–642. doi: 10.1302/0301-620X.56B4.626. PubMed DOI
Merritt K., Rodrigo J. J. Immune response to synthetic Materials. Clinical Orthopaedics and Related Research. 1996;326:71–79. doi: 10.1097/00003086-199605000-00009. PubMed DOI
Lalor P. A., Revell P. A., Gray A. B., Wright S., Railton G. T., Freeman M. A. Sensitivity to titanium. A cause of implant failure? The Journal of Bone and Joint Surgery. British volume. 1991;73(1):25–28. doi: 10.1302/0301-620X.73B1.1991768. PubMed DOI
Fernandes M. H. Effect of stainless steel corrosion products on in vitro biomineralization. Journal of Biomaterials Applications. 1999;14(2):113–168. doi: 10.1177/088532829901400202. PubMed DOI
Hallab N. J., Jacobs J. J. Biologic effects of implant debris. Bulletin of the NYU Hospital for Joint Diseases. 2009;67(2):182–188. PubMed
Granchi D., Cenni E., Tigani D., Trisolino G., Baldini N., Giunti A. Sensitivity to implant materials in patients with total knee arthroplasties. Biomaterials. 2008;29(10):1494–1500. doi: 10.1016/j.biomaterials.2007.11.038. PubMed DOI
Mitchelson A. J., Wilson C. J., Mihalko W. M., et al. Biomaterial hypersensitivity: is it real? Supportive evidence and approach considerations for metal allergic patients following total knee arthroplasty. BioMed Research International. 2015;2015:10. doi: 10.1155/2015/137287.137287 PubMed DOI PMC
Hallab N. J. Biologic responses to Orthopedic Implants. Spine. 2016;41(7S):S30–S31. doi: 10.1097/BRS.0000000000001436. PubMed DOI
Hallab N. J., Merritt K., Jacobs J. J. Metal sensitivity in patients with orthopaedic implants. The Journal of Bone and Joint Surgery. 2001;83(3):428–436. doi: 10.2106/00004623-200103000-00017. PubMed DOI
Belohlavek J., Belohlavkova S., Hlubocky J., Mrazek V., Linhart A., Podzimek S. Severe allergic dermatitis after closure of foramen ovale with Amplatzer occluder. The Annals of Thoracic Surgery. 2013;96(3):e57–e59. doi: 10.1016/j.athoracsur.2013.01.079. PubMed DOI
Prikrylova J., Prochazkova J., Podzimek S. Side effects of dental metal implants: impact on human health (metal as a risk factor of implantologic treatment) Biomed Research International. 2019;2019:5. doi: 10.1155/2019/2519205.2519205 PubMed DOI PMC
Sykaras N., Iacopino A. M., Marker V. A., Triplett R. G., Woody R. D. Implant materials, designs, and surface topographies: their effect on osseointegration. A literature review. The International Journal of Oral & Maxillofacial Implants. 2000;15(5):675–690. PubMed
Frisken K. W., Dandie G. W., Lugowski S., Jordan G. A study of titanium release into body organs following the insertion of single threaded screw implants into the mandibles of sheep. Australian Dental Journal. 2002;47(3):214–217. doi: 10.1111/j.1834-7819.2002.tb00331.x. PubMed DOI
Akagawa Y., Abe Y. Titanium: the ultimate solution or an evolutionary step? The International Journal of Prosthodontics. 2003;16(28-9):47–51. PubMed
Assad M., Chernyshov A., Leroux M. A., Rivard C.-H. A new porous titanium-nickel alloy: part 1. Cytotoxicity and genotoxicity evaluation. Bio-medical Materials and Engineering. 2002;12(3):225–237. PubMed
Ryhänen J., Niemi E., Serlo W., et al. Biocompatibility of nickel-titanium shape memory metal and its corrosion behavior in human cell cultures. Journal of Biomedical Materials Research. 1997;35(4):451–457. doi: 10.1002/(SICI)1097-4636(19970615)35:4<451::AID-JBM5>3.0.CO;2-G. PubMed DOI
Kumazawa R., Watari F., Takashi N., Tanimura Y., Uo M., Totsuka Y. Effects of Ti ions and particles on neutrophil function and morphology. Biomaterials. 2002;23(17):3757–3764. doi: 10.1016/S0142-9612(02)00115-1. PubMed DOI
Zhao L., Chang J., Zhai W. Effect of crystallographic phases of TiO2 on hepatocyte attachment, proliferation and morphology. Journal of Biomaterials Applications. 2005;19(3):237–252. doi: 10.1177/0885328205047218. PubMed DOI
Mitchell D. L., Synnott S. A., VanDercreek J. A. Tissue reaction involving an intraoral skin graft and CP titanium abutments: a clinical report. The International Journal of Oral & Maxillofacial Implants. 1990;5(1):79–84. PubMed
Revell P. A., Lalor P. A., Bonde H. V. Massive exposition to titanium, but without sensitization. Acta Orthopaedica Scandinavica. 1995;66(5):p. 484. doi: 10.3109/17453679508995595. PubMed DOI
Katou F., Andoh N., Motegi K., Nagura H. Immuno-inflammatory responses in the tissue adjacent to titanium miniplates used in the treatment of mandibular fractures. Journal of Cranio-Maxillo-Facial Surgery. 1996;24(3):155–162. doi: 10.1016/S1010-5182(96)80049-7. PubMed DOI
Lohmann C. H., Hameister R., Singh G. Allergies in orthopaedic and trauma surgery. Orthopaedics & Traumatology: Surgery & Research. 2017;103(1):S75–S81. doi: 10.1016/j.otsr.2016.06.021. PubMed DOI
Valentine-Thon E., Schiwara H.-W. Validity of MELISA® for metal sensitivity testing. Neuro Endocrinology Letters. 2003;24(1-2):57–64. PubMed
Valentine-Thon E., Muller K., Guzzi G., Kreisel S., Ohnsorge P., Sandkamp M. LTT- MELISA® is clinically relevant for detecting and monitoring metal sensitivity. Neuro Endocrinology Letters. 2006;27(1):17–24. PubMed
Mesinkovska N. A., Tellez A., Molina L., et al. The effect of patch testing on surgical practices and outcomes in orthopedic patients with metal implants. Archives of Dermatology. 2012;148(6):687–693. PubMed
Thomas P., von der Helm C., Schopf C., et al. Patients with intolerance reactions to total knee replacement: combined assessment of allergy diagnostics, periprosthetic histology, and peri-implant cytokine expression pattern. BioMed Research International. 2015;2015:9. doi: 10.1155/2015/910156.910156 PubMed DOI PMC
Krecisz B., Kieć-Świerczyńska M., Chomiczewska-Skóra D. Allergy to orthopedic metal implants - a prospective study. International Journal of Occupational Medicine and Environmental Health. 2012;25(4):463–469. doi: 10.2478/S13382-012-0029-3. PubMed DOI
Frigerio E., Pigatto P. D., Guzzi G., Altomare G. Metal sensitivity in patients with orthopaedic implants: a prospective study. Contact Dermatitis. 2011;64(5):273–279. doi: 10.1111/j.1600-0536.2011.01886.x. PubMed DOI
Phillips E. J., Bigliardi P., Bircher A. J., et al. Controversies in drug allergy: testing for delayed reactions. The Journal of Allergy and Clinical Immunology. 2019;143(1):66–73. doi: 10.1016/j.jaci.2018.10.030. PubMed DOI PMC
Hamann D., Bruze M., Fowler J. F., Jr., Hamann C. R., Andersen K. E., Hamann C. P. Excipient and dose per unit area affect sensitivity when patch testing with gold sodium thiosulfate. Dermatitis. 2018;29(5):258–263. doi: 10.1097/DER.0000000000000395. PubMed DOI
Dickel H., Kuhlmann L., Bauer A., et al. Atopy patch testing with aeroallergens in a large clinical population of dermatitis patients in Germany and Switzerland, 2000-2015: a retrospective multicentre study. Journal of the European Academy of Dermatology and Venereology. 2020;34(9):2086–2095. doi: 10.1111/jdv.16250. PubMed DOI
Wawrzynski J., Gil J. A., Goodman A. D., Waryasz G. R. Hypersensitivity to orthopedic implants: a review of the literature. Rheumatology and Therapy. 2017;4(1):45–56. doi: 10.1007/s40744-017-0062-6. PubMed DOI PMC
Podzimek S., Tomka M., Nemeth T., Himmlova L., Matucha P., Prochazkova J. Influence of metals on cytokines production in connection with successful implantation therapy in dentistry. Neuro Endocrinology Letters. 2010;31(5):657–662. PubMed
Stejskal V. D. M., Cederbrant K., Lindvall A., Forsbeck M. MELISA--an _in vitro_ tool for the study of metal allergy. Toxicology In Vitro. 1994;8(5):991–1000. doi: 10.1016/0887-2333(94)90233-X. PubMed DOI
Stejskal V. D., Forsbeck M., Cederbrant K. E., Asteman O. Mercury-specific lymphocytes: an indication of mercury allergy in man. Journal of Clinical Immunology. 1996;16(1):31–40. doi: 10.1007/BF01540970. PubMed DOI
Stejskal V., Reynolds T., Bjørklund G. Increased frequency of delayed type hypersensitivity to metals in patients with connective tissue disease. Journal of Trace Elements in Medicine and Biology. 2015;31:230–236. doi: 10.1016/j.jtemb.2015.01.001. PubMed DOI
Manousek J., Stejskal V., Kubena P., et al. Delayed-type hypersensitivity to metals of environmental burden in patients with takotsubo syndrome - is there a clinical relevance? PLoS One. 2016;11(11, article e0164786) doi: 10.1371/journal.pone.0164786. PubMed DOI PMC
Bjørklund G., Dadar M., Aaseth J. Delayed-type hypersensitivity to metals in connective tissue diseases and fibromyalgia. Environmental Research. 2018;161:573–579. doi: 10.1016/j.envres.2017.12.004. PubMed DOI
Podzimek S., Tomka M., Sommerova P., Lyuya-Mi Y., Bartova J., Prochazkova J. Immune markers in oral discomfort patients before and after elimination of oral galvanism. Neuro Endocrinology Letters. 2013;34(8):802–808. PubMed
Stathopoulos I. P., Andrianopoulos N., Paschaloglou D., Tsarouchas I. Revision total knee arthroplasty due to bone cement and metal hypersensitivity. Archives of Orthopaedic and Trauma Surgery. 2017;137(2):267–271. doi: 10.1007/s00402-016-2614-6. PubMed DOI
Thomsen M., Rozak M., Thomas P. Pain in a chromium-allergic patient with total knee arthroplasty: disappearance of symptoms after revision with a special surface-coated TKA— a case report. Acta Orthopaedica. 2011;82(3):386–388. doi: 10.3109/17453674.2011.579521. PubMed DOI PMC
Gupta R., Phan D., Schwarzkopf R. Total knee arthroplasty failure induced by metal hypersensitivity. The American Journal of Case Reports. 2015;16:542–547. doi: 10.12659/AJCR.893609. PubMed DOI PMC
Thomsen M., Krenn V., Thomas P. Adverse reaktionen gegenüber orthopädisch-chirurgischen metallimplantaten nach kniegelenkersatz. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2016;67(5):347–351. doi: 10.1007/s00105-016-3793-3. PubMed DOI
Engelhart S., Segal R. J. Allergic reaction to vanadium causes a diffuse eczematous eruption and titanium alloy orthopedic implant failure. Cutis. 2017;99(4):245–249. PubMed
Hosoki M., Nishigawa K., Miyamoto Y., Ohe G., Matsuka Y. Allergic contact dermatitis caused by titanium screws and dental implants. Journal of Prosthodontic Research. 2016;60(3):213–219. doi: 10.1016/j.jpor.2015.12.004. PubMed DOI
Hosoki M., Nishigawa K., Tajima T., Ueda M., Matsuka Y. Cross-sectional observational study exploring clinical risk of titanium allergy caused by dental implants. Journal of Prosthodontic Research. 2018;62(4):426–431. doi: 10.1016/j.jpor.2018.03.003. PubMed DOI
Guenther D., Thomas P., Kendoff D., Omar M., Gehrke T., Haasper C. Allergic reactions in arthroplasty: myth or serious problem? International Orthopaedics. 2016;40(2):239–244. doi: 10.1007/s00264-015-3001-6. PubMed DOI
Hofmann S. C., Plett M., Jansen S., Thomas P., Thölken K. F. M. Titanium hypersensitivity causing painful intra-abdominal oedema after staple-fixed inguinal hernia repair. Contact Dermatitis. 2018;79(1):48–49. doi: 10.1111/cod.12985. PubMed DOI
Maňoušek J., Andršová I., Stejskal V., et al. Hypersensitivity to material and environmental burden as a possible cause of late complications of cardiac implantable electronic devices. Europace. 2018;20(9):e140–e147. doi: 10.1093/europace/eux227. PubMed DOI PMC
Kim K. T., Eo M. Y., Nguyen T. T. H., Kim S. M. General review of titanium toxicity. International Journal of Implant Dentistry. 2019;5(1):1–12. doi: 10.1186/s40729-019-0162-x. PubMed DOI PMC
Stejskal V., Hudecek R., Stejskal J., Sterzl I. Diagnosis and treatment of metal-induced side-effects. Neuro Endocrinology Letters. 2006;27(1):7–16. PubMed
Hallab N. Diagnosis of metal hypersensitivity in orthopedics. Operative Techniques in Orthopaedics. 2017;27(3):168–177. doi: 10.1053/j.oto.2017.05.005. DOI
Wiltshire W. A., Ferreira M. R., Ligthelm A. J. Allergies to dental materials. Quintessence International. 1996;27(8):513–520. PubMed
Sterzl I., Procházková J., Hrdá P., Bártová J., Matucha P., Stejskal V. D. Mercury and nickel allergy: risk factors in fatigue and autoimmunity. Neuro Endocrinology Letters. 1999;20(3-4):221–228. PubMed
Rastogi S., Patel K. R., Singam V., Lee H. H., Silverberg J. I. Associations of nickel co-reactions and metal polysensitization in adults. Dermatitis. 2018;29(6):316–320. doi: 10.1097/DER.0000000000000421. PubMed DOI
Fujii Y. Severe dermatitis might be caused by a cross-reaction between nickel and palladium and dental amalgam resolved following removal of dental restorations. Clinical Case Reports. 2017;5(6):795–800. doi: 10.1002/ccr3.938. PubMed DOI PMC
Comino-Garayoa R., Cortés-Bretón Brinkmann J., Peláez J., López-Suárez C., Martínez-González J. M., Suárez M. J. Allergies to titanium dental implants: what do we really know about them? A scoping review. Biology. 2020;9(11):p. 404. doi: 10.3390/biology9110404. PubMed DOI PMC
Black J., Hastings G. Handbook of Biomaterial Properties. 1st ed. London: Chapman & Hall; 1998. DOI
Bijukumar D. R., Segu A., Souza J. C. M., et al. Systemic and local toxicity of metal debris released from hip prostheses: a review of experimental approaches. Nanomedicine: Nanotechnology, Biology, and Medicine. 2018;14(3):951–963. doi: 10.1016/j.nano.2018.01.001. PubMed DOI PMC
Mehulić M., Mehulić K., Kos P., Komar D., Katunarić M. Expression of contact allergy in undergoing prosthodontic therapy patients with oral diseases. Minerva Stomatologica. 2005;54(5):303–309. PubMed
Khamaysi Z., Bergman R., Weltfriend S. Positive patch test reactions to allergens of the dental series and the relation to the clinical presentations. Contact Dermatitis. 2006;55(4):216–218. doi: 10.1111/j.1600-0536.2006.00905.x. PubMed DOI
Lugović-Mihić L., Ilić I., Budimir J., Pondeljak N., Mravak Stipetić M. Common allergies and allergens in oral and perioral diseases. Acta clinica Croatica. 2020;59(2):318–328. doi: 10.20471/acc.2020.59.02.16. PubMed DOI PMC
Manousek J., Felsoci M., Miklik R., et al. Delayed-type hypersensitivity to metals in newly diagnosed patients with nonischemic dilated cardiomyopathy. Cardiovascular toxicology. 2020;20(6):571–580. doi: 10.1007/s12012-020-09582-6. PubMed DOI
Stejskal V., Ockert K., Bjørklund G. Metal-induced inflammation triggers fibromyalgia in metal-allergic patients. Neuroendocrinology Letters. 2013;34(6):559–565. PubMed
Hybenova M., Hrda P., Procházková J., Stejskal V., Sterzl I. The role of environmental factors in autoimmune thyroiditis. Neuroendocrinology Letters. 2010;31(3):283–289. PubMed