HASHIMOTO THYROIDITIS IN PEDIATRICS: INSIGHTS INTO PATHOGENESIS, DIAGNOSIS, AND MANAGEMENT WITH CONSIDERATIONS OF CANCER RISK
Main Article Content
Abstract
This systematic review comprehensively examines the pathogenesis, diagnosis, management, and cancer risk of Hashimoto's thyroiditis in pediatric populations. We searched the literature using PubMed, Web of Science, and critical medical journals, focusing on studies published within a specified timeframe. Inclusion criteria targeted studies on pediatric populations, while exclusion criteria filtered out irrelevant studies. Data extraction and synthesis highlighted key findings: genetic predispositions and environmental triggers such as selenium levels and gut microbiota alterations contribute to Hashimoto’s Thyroiditis pathogenesis. Diagnostic challenges arise from the often subtle and nonspecific clinical presentation, necessitating thorough clinical evaluations and diagnostic testing, including TSH, free T4, thyroid antibodies, and ultrasound. Management strategies involve levothyroxine therapy, dietary considerations, and lifestyle modifications tailored to individual patient needs. Additionally, the review discusses the controversial but significant potential association between Hashimoto’s Thyroiditis and increased thyroid cancer risk, emphasizing the need for vigilant long-term monitoring. This synthesis provides critical insights to inform clinical practice and future research directions.
Keywords:
Hashimoto Thyroiditis, Pediatrics, Pathogenesis, Diagnosis, Management, Thyroid Cancer Risk, Genetic Predisposition, Environmental Triggers, Levothyroxine Therapy, Long-term Monitoring
Article Details
How to Cite
RODRIGUEZ-REYES, Derick et al.
HASHIMOTO THYROIDITIS IN PEDIATRICS: INSIGHTS INTO PATHOGENESIS, DIAGNOSIS, AND MANAGEMENT WITH CONSIDERATIONS OF CANCER RISK.
Medical Research Archives, [S.l.], v. 12, n. 6, june 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5427>. Date accessed: 21 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i6.5427.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Mincer DL, Jialal I. Hashimoto Thyroiditis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 29, 2023.
2. Hiromatsu Y, Satoh H, Amino N. Hashimoto's thyroiditis: history and future outlook. Hormones (Athens). 2013;12(1):12-18. doi:10.1007/BF03401282.
3. Leung AKC, Leung AAC. Evaluation and management of the child with hypothyroidism. World J Pediatr. 2019;15(2 ):124-134. doi:10.1007/s12519-019-00230-w.
4. De Luca F, Santucci S, Corica D, et al. Hashimoto's thyroiditis in childhood: presentation modes and evolution over time. Ital J Pediatr. 2013;39(1):8. doi:10.1186/1824-7288-39-8.
5. Ilicki A, Marcus C, Karlsson FA. Hyperthyroidism and hypothyroidism in monozygotic twins: detection of stimulating and blocking TSH receptor antibodies using the FRTL5-cell line. J Endocrinol Invest. 1990; 13(4):327-331. doi:10.1007/BF03349571.
6. Wasniewska M, Vigone MC, Cappa M, et al. Acute suppurative thyroiditis in childhood: relative frequency among thyroid inflammatory diseases. J Endocrinol Invest. 2007;30(4):346-347. doi:10.1007/BF03346303.
7. Penta L, Cofini M, Lanciotti L, Leonardi A, Principi N, Esposito S. Hashimoto's Disease and Thyroid Cancer in Children: Are They Associated?. Front Endocrinol (Lausanne). 2018;9:565. Published 2018 Oct 9. doi:10.3389/fendo.2018.00565.
8. Hu X, Wang X, Liang Y, et al. Cancer Risk in Hashimoto's Thyroiditis: a Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2022;13:937871. Published 2022 Jul 12. doi:10.3389/fendo.2022.937871.
9. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked?. Free Radic Biol Med. 2010;49(11):1603-1616. doi:10.101 6/j.freeradbiomed.2010.09.006.
10. Skov J, Eriksson D, Kuja-Halkola R, et al. Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study. Eur J Endocrinol. 2020;182(5):473-480. doi:10.1530/EJE-20-0049.
11. Jabrocka-Hybel A, Skalniak A, Piątkowski J, et al. How much of the predisposition to Hashimoto's thyroiditis can be explained based on previously reported associations?. J Endocrinol Invest. 2018;41(12):1409-1416. doi:10.1007/s40618-018-0910-4.
12. Berteau F, Rouvière B, Nau A, et al. A20 haploinsufficiency (HA20): clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease. Ann Rheum Dis. 2019;78(5):e35. doi:10.1136/annrheumdis-2018-213347.
13. Zaghlol RY, Haghighi A, Alkhayyat MM, et al. Consanguinity and the Risk of Hashimoto's Thyroiditis. Thyroid. 2017;27(3):390-395. doi: 10.1089/thy.2016.0495.
14. Hori T, Ohnishi H, Kadowaki T, et al. Autosomal dominant Hashimoto's thyroiditis with a mutation in TNFAIP3. Clin Pediatr Endocrinol. 2019;28(3):91-96. doi:10.1297/cp e.28.91.
15. Song RH, Wang Q, Yao QM, et al. TNFSF4 Gene Variations Are Related to Early-Onset Autoimmune Thyroid Diseases and Hypothyroidism of Hashimoto's Thyroiditis. Int J Mol Sci. 2016;17(8):1369. Published 2016 Aug 20. doi:10.3390/ijms17081369.
16. Brčić L, Barić A, Gračan S, et al. Genome-wide association analysis suggests novel loci for Hashimoto's thyroiditis. J Endocrinol Invest. 2019;42(5):567-576. doi:10.1007/s406 18-018-0955-4.
17. Roberts GHL, Santorico SA, Spritz RA. The genetic architecture of vitiligo. Pigment Cell Melanoma Res. 2020;33(1):8-15. doi:10.1 111/pcmr.12848.
18. Lo MS, Towne M, VanNoy GE, et al. Monogenic Hashimoto thyroiditis associated with a variant in the thyroglobulin (TG) gene. J Autoimmun. 2018;86:116-119. doi:10.1016/ j.jaut.2017.09.003.
19. Wang Y, Zhu YF, Wang Q, et al. The haplotype of UBE2L3 gene is associated with Hashimoto's thyroiditis in a Chinese Han population. BMC Endocr Disord. 2016;16:18. Published 2016 Apr 19. doi:10.1186/s12902-016-0098-6.
20. Weetman AP. An update on the pathogenesis of Hashimoto's thyroiditis. J Endocrinol Invest. 2021;44(5):883-890. doi:10 .1007/s40618-020-01477-1.
21. Negro R, Attanasio R, Grimaldi F, Marcocci C, Guglielmi R, Papini E. A 2016 Italian Survey about the Clinical Use of Selenium in Thyroid Disease. Eur Thyroid J. 2016;5(3):164-170. doi:10.1159/000447667.
22. Thvilum M, Brandt F, Brix TH, Hegedüs L. Month of birth is associated with the subsequent diagnosis of autoimmune hypothyroidism. A nationwide Danish register-based study. Clin Endocrinol (Oxf). 2017;87(6):832-837. doi:10.1111/cen.13425.
23. Ishaq HM, Mohammad IS, Guo H, et al. Molecular estimation of alteration in intestinal microbial composition in Hashimoto's thyroiditis patients. Biomed Pharmacother. 2017;95:865 -874. doi:10.1016/j.biopha.2017.08.101.
24. Zhao F, Feng J, Li J, et al. Alterations of the Gut Microbiota in Hashimoto's Thyroiditis Patients. Thyroid. 2018;28(2):175-186. doi:10. 1089/thy.2017.0395.
25. Faustino LC, Lombardi A, Madrigal-Matute J, Owen RP, Libutti SK, Tomer Y. Interferon-α Triggers Autoimmune Thyroid Diseases via Lysosomal-Dependent Degradation of Thyroglobulin. J Clin Endocrinol Metab. 2018;103(10):3678-3687. doi:10.1210/jc.2018-00541.
26. Urwyler P, Earnshaw I, Bermudez M, et al. Mechanisms of checkpoint inhibition-induced adverse events. Clin Exp Immunol. 2020;200 (2):141-154. doi:10.1111/cei.13421.
27. Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr Rev. 2019;40(1):17-65. doi:10.1210/er.2018-00006.
28. Kotwal A, Gustafson MP, Bornschlegl S, et al. Immune Checkpoint Inhibitor-Induced Thyroiditis Is Associated with Increased Intrathyroidal T Lymphocyte Subpopulations. Thyroid. 2020;30(10):1440-1450. doi:10.1089 /thy.2020.0075.
29. Wichman J, Winther KH, Bonnema SJ, Hegedüs L. Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis. Thyroid. 2016;26(12):1681-1692. doi :10.1089/thy.2016.0256.
30. Winther KH, Rayman MP, Bonnema SJ, Hegedüs L. Selenium in thyroid disorders - essential knowledge for clinicians. Nat Rev Endocrinol. 2020;16(3):165-176. doi:10.1038/ s41574-019-0311-6.
31. Scappaticcio L, Castellana M, Virili C, et al. Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis. J Endocrinol Invest. 2020;43(2): 219-229. doi:10.1007/s40618-019-01105-7.
32. Jokisch F, Kleinlein I, Haller B, Seehaus T, Fuerst H, Kremer M. A small subgroup of Hashimoto's thyroiditis is associated with IgG4-related disease. Virchows Arch. 2016;46 8(3):321-327. doi:10.1007/s00428-015-1893-6.
33. Rodríguez-Muñoz A, Vitales-Noyola M, Ramos-Levi A, Serrano-Somavilla A, González -Amaro R, Marazuela M. Levels of regulatory T cells CD69(+)NKG2D(+)IL-10(+) are increased in patients with autoimmune thyroid disorders. Endocrine. 2016;51(3):478-489. doi :10.1007/s12020-015-0662-2.
34. Vitales-Noyola M, Serrano-Somavilla A, Martínez-Hernández R, et al. Patients With Autoimmune Thyroiditis Show Diminished Levels and Defective Suppressive Function of Tr1 Regulatory Lymphocytes. J Clin Endocrinol Metab. 2018;103(9):3359-3367. doi:10.1210/jc.2018-00498.
35. Ajjan RA, Weetman AP. The Pathogenesis of Hashimoto's Thyroiditis: Further Developments in our Understanding. Horm Metab Res. 2015;47(10):702-710. doi:10.1055 /s-0035-1548832.
36. Zake T, Skuja S, Kalere I, Konrade I, Groma V. Heterogeneity of tissue IL-17 and tight junction proteins expression demonstrated in patients with autoimmune thyroid diseases. Medicine (Baltimore). 2018;97(25):e11211. doi:10.1097/MD.0000000000011211.
37. Vitales-Noyola M, Ramos-Levi AM, Martínez-Hernández R, et al. Pathogenic Th17 and Th22 cells are increased in patients with autoimmune thyroid disorders. Endocrine. 2017;57(3):409-417. doi:10.1007/s12020-017-1361-y.
38. Guan LJ, Wang X, Meng S, et al. Increased IL-21/IL-21R expression and its proinflammatory effects in autoimmune thyroid disease. Cytokine. 2015;72(2):160-165. doi:10.1016/j.cyto.2014.11.005.
39. Guo Q, Wu Y, Hou Y, et al. Cytokine Secretion and Pyroptosis of Thyroid Follicular Cells Mediated by Enhanced NLRP3, NLRP1, NLRC4, and AIM2 Inflammasomes Are Associated With Autoimmune Thyroiditis. Front Immunol. 2018;9:1197. Published 2018 Jun 4. doi:10.3389/fimmu.2018.01197.
40. Álvarez-Sierra D, Marín-Sánchez A, Ruiz-Blázquez P, et al. Analysis of the PD-1/PD-L1 axis in human autoimmune thyroid disease: Insights into pathogenesis and clues to immunotherapy associated thyroid autoimmunity. J Autoimmun. 2019;103:10228 5. doi:10.1016/j.jaut.2019.05.013.
41. Marelli-Berg FM, Weetman A, Frasca L, et al. Antigen presentation by epithelial cells induces anergic immunoregulatory CD45RO+ T cells and deletion of CD45RA+ T cells. J Immunol. 1997;159(12):5853-5861.
42. Nishihara E, Amino N, Kudo T, et al. Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases. Endocr J. 2017;64(10):955-961. doi:10.1507/ endocrj.EJ17-0164.
43. Bektas Uysal H, Ayhan M. Autoimmunity affects health-related quality of life in patients with Hashimoto's thyroiditis. Kaohsiung J Med Sci. 2016;32(8):427-433. doi:10.1016/j.kj ms.2016.06.006.
44. Barić A, Brčić L, Gračan S, et al. Thyroglobulin Antibodies are Associated with Symptom Burden in Patients with Hashimoto's Thyroiditis: A Cross-Sectional Study. Immunol Invest. 2019;48(2):198-209. doi:10.1080/0882 0139.2018.1529040.
45. Guldvog I, Reitsma LC, Johnsen L, et al. Thyroidectomy Versus Medical Management for Euthyroid Patients With Hashimoto Disease and Persisting Symptoms: A Randomized Trial. Ann Intern Med. 2019;170 (7):453-464. doi:10.7326/M18-0284.
46. Diana T, Krause J, Olivo PD, et al. Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease. Clin Exp Immunol. 2017;189(3):304-309. doi:1 0.1111/cei.12980.
47. Kahaly GJ, Diana T, Glang J, Kanitz M, Pitz S, König J. Thyroid Stimulating Antibodies Are Highly Prevalent in Hashimoto's Thyroiditis and Associated Orbitopathy. J Clin Endocrinol Metab. 2016;1 01(5):1998-2004. doi:10.1210/jc.2016-1220.
48. Foley TP Jr, Abbassi V, Copeland KC, Draznin MB. Hypothyroidism caused by chronic autoimmune thyroiditis in very young infants. N Engl J Med. 1994;330(7):466-468. doi:10.1056/NEJM19940217330070.
49. Gunther DF, Chiu HK, Numrych TE, Kletter GB. Onset of acquired autoimmune hypothyroidism in infancy: a presentation of delayed gross-motor development and rhabdomyolysis. Eur J Pediatr. 2006;165(5):32 0-322. doi:10.1007/s00431-005-0051-6.
50. Mittnacht J, Schmidt F, Ebinger F, Bettendorf M. Unusual clinical presentation of primary hypothyroidism in a very young infant caused by autoimmune thyroiditis: case report and update of the literature. Eur J Pediatr. 2007;166(8):881-883. doi:10.1007/s0 0431-006-0323-9.
51. Marzuillo P, Grandone A, Perrotta S, et al. Very early onset of autoimmune thyroiditis in a toddler with severe hypothyroidism presentation: a case report. Ital J Pediatr. 2016;42:61. doi:10.1186/s13052-016-0270-7.
52. Tang S, Yang M, Zhang D, Tong YJ, Xin Y. Clinical characteristics and follow-up of 19 children with Hashimoto’s thyroiditis aged below 3 years: a single-center retrospective analysis. Front Endocrinol (Lausanne). 2021;12 :737527. doi:10.3389/fendo.2021.737527.
53. Rose SR, Wassner AJ, Wintergerst KA, et al. Congenital hypothyroidism: screening and management. Pediatrics. 2023;151(1):e20220 60419. doi:10.1542/peds.2022-060419.
54. Wasniewska M, Corrias A, Salerno M, et al. Thyroid function patterns at Hashimoto's thyroiditis presentation in childhood and adolescence are mainly conditioned by patients' age. Horm Res Paediatr. 2012;78(4): 232-236. doi:10.1159/000343815.
55. de Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child. 2009;94(1):33-37. doi:10.1136/adc.2007.134841.
56. Weber G, Vigone MC, Stroppa L, Chiumello G. Thyroid function and puberty. J Pediatr Endocrinol Metab. 2003;16:253-257.
57. Bauman A, Novello L, Kreitzer P. Endocrine Disorders and Delayed Puberty. In: Abnormal Female Puberty: A Clinical Casebook. 2016:87-107.
58. Wassner AJ. Pediatric Hypothyroidism: Diagnosis and Treatment. Paediatr Drugs. 2017;19(4):291-301. doi:10.1007/s40272-017-0238-0
59. Lee SJ, Lim GY, Kim JY, Chung MH. Diagnostic performance of thyroid ultrasonography screening in pediatric patients with a hypothyroid, hyperthyroid or euthyroid goiter. Pediatr Radiol. 2016;46:104-111.
60. Vukovic R, Zeljkovic A, Bufan B, Spasojevic-Kalimanovska V, Milenkovic T, Vekic J. Hashimoto Thyroiditis and Dyslipidemia in Childhood: A Review. Front Endocrinol (Lausanne). 2019;10:868. Published 2019 Dec 10. doi:10.3389/fendo.2019.00868.
61. Watemberg N, Greenstein D, Levine A. Encephalopathy associated with Hashimoto thyroiditis: pediatric perspective. J Child Neurol. 2006;21(1):1-5. doi:10.1177/0883073 8060210010201.
62. Rodriguez L, Dinauer C, Francis G. Treatment of hypothyroidism in infants, children and adolescents. Trends Endocrinol Metab. 2022;33(7):522-532. doi:10.1016/j.te m.2022.04.007.
63. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1 670-1751. doi:10.1089/thy.2014.0028.
64. Radetti G, Salerno M, Guzzetti C, et al. Thyroid function in children and adolescents with Hashimoto's thyroiditis after l-thyroxine discontinuation. Endocr Connect. 2017;6(4):2 06-212. doi:10.1530/EC-17-0023.
65. Gopalakrishnan S, Chugh PK, Chhillar M, Ambardar VK, Sahoo M, Sankar R. Goitrous autoimmune thyroiditis in a pediatric population: a longitudinal study. Pediatrics. 2008;122(3):e670-e674. doi:10.1542/peds.2008-0493.
66. Osowiecka K, Myszkowska-Ryciak J. The Influence of Nutritional Intervention in the Treatment of Hashimoto's Thyroiditis-A Systematic Review. Nutrients. 2023;15(4):104 1. doi:10.3390/nu15041041.
67. Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13(4-5):391-397. doi:10.1016/j.autrev.2014.01.007.
68. Vincent A, Bouvattier C, Teinturier C, et al. Evaluation of catch-up growth in severe pediatric Hashimoto's hypothyroidism. Arch Pediatr. 2023;30(3):142-148. doi:10.1016/j.ar cped.2023.01.001.
69. Brain L, Jellinek EH, Ball K. Hashimoto’s disease and encephalopathy. Lancet. 1966;2( 7462):512-514. doi:10.1016/s0140-6736(66)92876-5.
70. Mocellin R, Walterfang M, Velakoulis D. Hashimoto’s encephalopathy: epidemiology, pathogenesis and management. CNS Drugs. 2007;21(10):799-811. doi:10.2165/00023210-200721100-00002.
71. Ruggeri RM, Trimarchi F, Giuffrida G, Certo R, Cama E, Campennì A, Alibrandi A, De Luca F, Wasniewska M. Autoimmune comorbidities in Hashimoto's thyroiditis: different patterns of association in adulthood and childhood/adolescence. Eur J Endocrinol. 2017;176(2):133-141.
72. Penta L, Cofini M, Lanciotti L, Leonardi A, Principi N, Esposito S. Hashimoto's Disease and Thyroid Cancer in Children: Are They Associated?. Front Endocrinol (Lausanne). 2018;9:565. Published 2018 Oct 9. doi:10.338 9/fendo.2018.00565.
73. Keefe G, Culbreath K, Cherella CE, et al. Autoimmune Thyroiditis and Risk of Malignancy in Children with Thyroid Nodules. Thyroid. 2022;32(9):1109-1117. doi:10.1089/ thy.2022.0241.
74. Gallant J-N, Weiss VL, Chen SC, Liang J, Belcher RH, Ye F, Correa H, Wang H. Hashimoto’s Thyroiditis and the Risk of Papillary Thyroid Cancer in Children. Cancers. 2023;15(19):4902. doi:10.3390/cancers15194902.
75. Gallant JN, Weiss VL, Chen SC, et al. Hashimoto's Thyroiditis and the Risk of Papillary Thyroid Cancer in Children. Cancers (Basel). 2023;15(19):4902. Published 2023 Oct 9. doi:10.3390/cancers15194902.
76. Seppälä LK, Madanat-Harjuoja LM, Leinonen MK, Lääperi M, Vettenranta K. Maternal Thyroid Disease and the Risk of Childhood Cancer in the Offspring. Cancers (Basel). 2021;13(21):5409. Published 2021 Oct 28. doi:10.3390/cancers13215409.
77. Sur ML, Gaga R, Lazăr C, Lazea C, Aldea C, Sur D. Papillary thyroid carcinoma in children with Hashimoto's thyroiditis - a review of the literature between 2000 and 2020. J Pediatr Endocrinol Metab. 2020;33(12 ):1511-1517. Published 2020 Nov 12. doi:10.1515/jpem-2020-0383.
78. Penta L, Cofini M, Lanciotti L, Leonardi A, Principi N, Esposito S. Hashimoto's Disease and Thyroid Cancer in Children: Are They Associated?. Front Endocrinol (Lausanne). 2018;9:565. Published 2018 Oct 9. doi:10.3389/fendo.2018.00565.
79. Gallant JN, Weiss VL, Chen SC, et al. Hashimoto's Thyroiditis and the Risk of Papillary Thyroid Cancer in Children. Cancers (Basel). 2023;15(19):4902. Published 2023 Oct 9. doi:10.3390/cancers15194902.
80. 80. Lee JH, Kim Y, Choi JW, Kim YS. The association between papillary thyroid carcinoma and histologically proven Hashimoto's thyroiditis: a meta-analysis. Eur J Endocrinol. 2013;168(3):343-349. Published 2013 Feb 15. doi:10.1530/EJE-12-0903.
81. Erbaş İ, Erbaş İ, Evliyaoğlu O. Clinical, biochemical, and radiological follow-up results of children and adolescents with Hashimoto’s thyroiditis: a single-center experience. J Pediatr Endocrinol Metab. 2021;34(8):987-994. doi:10.1515/jpem-2021-0035.
82. Lai X, Xia Y, Zhang B, Li J, Jiang Y. A meta-analysis of Hashimoto's thyroiditis and papillary thyroid carcinoma risk. Oncotarget. 2017;8:62414-62424. doi:10.18632/oncotarget.18620.
83. Iliadou PK, Effraimidis G, Konstantinos M, et al. Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents. Eur J Endocrinol. 2015;173( 6):827-833. doi:10.1530/EJE-14-1046.
84. Ren PY, Liu J, Xue S, Chen G. Pediatric differentiated thyroid carcinoma: The clinicopathological features and the coexistence of Hashimoto's thyroiditis. Asian J Surg. 2019;42(1):112-119. doi:10.1016/j.asjs ur.2017.10.006.
85. Golbert L, de Cristo AP, Faccin CS, et al. Serum TSH levels as a predictor of malignancy in thyroid nodules: A prospective study. PLoS One. 2017;12(11):e0188123. Published 2017 Nov 16. doi:10.1371/journal.pone.0188123.
86. Boi F, Minerba L, Lai ML, Marziani B, Figus B, Spanu F, et al. Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules. J Endocrinol Invest. 2013;36:313-320. doi:103275/8579.
87. Su X, He C, Ma J, Tang T, Zhang X, Ye Z, et al. RET/PTC Rearrangements are associated with elevated postoperative TSH levels and multifocal lesions in papillary thyroid cancer without concomitant thyroid benign disease. PLoS ONE. 2016;11:e016559 6. doi:10.1371/journal.pone.0165596.
88. Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumour microenvironment. J Immunol Res. 2014;2014 :149185. doi:10.1155/2014/149185.
89. Karavanaki K, Karayianni C, Vassiliou I, Tzanela M, Sdogou T, Kakleas K, et al. Multiple autoimmunity, type 1 diabetes (T1DM), autoimmune thyroiditis and thyroid cancer: is there an association? A case report and literature review. J Pediatr Endocrinol Metab. 2014;27:1011-1016. doi:10.1515/jpe m-2013-0370.
90. Mussa A, Matarazzo P, Corrias A. Papillary thyroid cancer and autoimmune polyglandular syndrome. J Pediatr Endocrinol Metab. 2015; 28:793-795. doi:10.1515/jpem-2014-0268.
2. Hiromatsu Y, Satoh H, Amino N. Hashimoto's thyroiditis: history and future outlook. Hormones (Athens). 2013;12(1):12-18. doi:10.1007/BF03401282.
3. Leung AKC, Leung AAC. Evaluation and management of the child with hypothyroidism. World J Pediatr. 2019;15(2 ):124-134. doi:10.1007/s12519-019-00230-w.
4. De Luca F, Santucci S, Corica D, et al. Hashimoto's thyroiditis in childhood: presentation modes and evolution over time. Ital J Pediatr. 2013;39(1):8. doi:10.1186/1824-7288-39-8.
5. Ilicki A, Marcus C, Karlsson FA. Hyperthyroidism and hypothyroidism in monozygotic twins: detection of stimulating and blocking TSH receptor antibodies using the FRTL5-cell line. J Endocrinol Invest. 1990; 13(4):327-331. doi:10.1007/BF03349571.
6. Wasniewska M, Vigone MC, Cappa M, et al. Acute suppurative thyroiditis in childhood: relative frequency among thyroid inflammatory diseases. J Endocrinol Invest. 2007;30(4):346-347. doi:10.1007/BF03346303.
7. Penta L, Cofini M, Lanciotti L, Leonardi A, Principi N, Esposito S. Hashimoto's Disease and Thyroid Cancer in Children: Are They Associated?. Front Endocrinol (Lausanne). 2018;9:565. Published 2018 Oct 9. doi:10.3389/fendo.2018.00565.
8. Hu X, Wang X, Liang Y, et al. Cancer Risk in Hashimoto's Thyroiditis: a Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2022;13:937871. Published 2022 Jul 12. doi:10.3389/fendo.2022.937871.
9. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked?. Free Radic Biol Med. 2010;49(11):1603-1616. doi:10.101 6/j.freeradbiomed.2010.09.006.
10. Skov J, Eriksson D, Kuja-Halkola R, et al. Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study. Eur J Endocrinol. 2020;182(5):473-480. doi:10.1530/EJE-20-0049.
11. Jabrocka-Hybel A, Skalniak A, Piątkowski J, et al. How much of the predisposition to Hashimoto's thyroiditis can be explained based on previously reported associations?. J Endocrinol Invest. 2018;41(12):1409-1416. doi:10.1007/s40618-018-0910-4.
12. Berteau F, Rouvière B, Nau A, et al. A20 haploinsufficiency (HA20): clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease. Ann Rheum Dis. 2019;78(5):e35. doi:10.1136/annrheumdis-2018-213347.
13. Zaghlol RY, Haghighi A, Alkhayyat MM, et al. Consanguinity and the Risk of Hashimoto's Thyroiditis. Thyroid. 2017;27(3):390-395. doi: 10.1089/thy.2016.0495.
14. Hori T, Ohnishi H, Kadowaki T, et al. Autosomal dominant Hashimoto's thyroiditis with a mutation in TNFAIP3. Clin Pediatr Endocrinol. 2019;28(3):91-96. doi:10.1297/cp e.28.91.
15. Song RH, Wang Q, Yao QM, et al. TNFSF4 Gene Variations Are Related to Early-Onset Autoimmune Thyroid Diseases and Hypothyroidism of Hashimoto's Thyroiditis. Int J Mol Sci. 2016;17(8):1369. Published 2016 Aug 20. doi:10.3390/ijms17081369.
16. Brčić L, Barić A, Gračan S, et al. Genome-wide association analysis suggests novel loci for Hashimoto's thyroiditis. J Endocrinol Invest. 2019;42(5):567-576. doi:10.1007/s406 18-018-0955-4.
17. Roberts GHL, Santorico SA, Spritz RA. The genetic architecture of vitiligo. Pigment Cell Melanoma Res. 2020;33(1):8-15. doi:10.1 111/pcmr.12848.
18. Lo MS, Towne M, VanNoy GE, et al. Monogenic Hashimoto thyroiditis associated with a variant in the thyroglobulin (TG) gene. J Autoimmun. 2018;86:116-119. doi:10.1016/ j.jaut.2017.09.003.
19. Wang Y, Zhu YF, Wang Q, et al. The haplotype of UBE2L3 gene is associated with Hashimoto's thyroiditis in a Chinese Han population. BMC Endocr Disord. 2016;16:18. Published 2016 Apr 19. doi:10.1186/s12902-016-0098-6.
20. Weetman AP. An update on the pathogenesis of Hashimoto's thyroiditis. J Endocrinol Invest. 2021;44(5):883-890. doi:10 .1007/s40618-020-01477-1.
21. Negro R, Attanasio R, Grimaldi F, Marcocci C, Guglielmi R, Papini E. A 2016 Italian Survey about the Clinical Use of Selenium in Thyroid Disease. Eur Thyroid J. 2016;5(3):164-170. doi:10.1159/000447667.
22. Thvilum M, Brandt F, Brix TH, Hegedüs L. Month of birth is associated with the subsequent diagnosis of autoimmune hypothyroidism. A nationwide Danish register-based study. Clin Endocrinol (Oxf). 2017;87(6):832-837. doi:10.1111/cen.13425.
23. Ishaq HM, Mohammad IS, Guo H, et al. Molecular estimation of alteration in intestinal microbial composition in Hashimoto's thyroiditis patients. Biomed Pharmacother. 2017;95:865 -874. doi:10.1016/j.biopha.2017.08.101.
24. Zhao F, Feng J, Li J, et al. Alterations of the Gut Microbiota in Hashimoto's Thyroiditis Patients. Thyroid. 2018;28(2):175-186. doi:10. 1089/thy.2017.0395.
25. Faustino LC, Lombardi A, Madrigal-Matute J, Owen RP, Libutti SK, Tomer Y. Interferon-α Triggers Autoimmune Thyroid Diseases via Lysosomal-Dependent Degradation of Thyroglobulin. J Clin Endocrinol Metab. 2018;103(10):3678-3687. doi:10.1210/jc.2018-00541.
26. Urwyler P, Earnshaw I, Bermudez M, et al. Mechanisms of checkpoint inhibition-induced adverse events. Clin Exp Immunol. 2020;200 (2):141-154. doi:10.1111/cei.13421.
27. Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr Rev. 2019;40(1):17-65. doi:10.1210/er.2018-00006.
28. Kotwal A, Gustafson MP, Bornschlegl S, et al. Immune Checkpoint Inhibitor-Induced Thyroiditis Is Associated with Increased Intrathyroidal T Lymphocyte Subpopulations. Thyroid. 2020;30(10):1440-1450. doi:10.1089 /thy.2020.0075.
29. Wichman J, Winther KH, Bonnema SJ, Hegedüs L. Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis. Thyroid. 2016;26(12):1681-1692. doi :10.1089/thy.2016.0256.
30. Winther KH, Rayman MP, Bonnema SJ, Hegedüs L. Selenium in thyroid disorders - essential knowledge for clinicians. Nat Rev Endocrinol. 2020;16(3):165-176. doi:10.1038/ s41574-019-0311-6.
31. Scappaticcio L, Castellana M, Virili C, et al. Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis. J Endocrinol Invest. 2020;43(2): 219-229. doi:10.1007/s40618-019-01105-7.
32. Jokisch F, Kleinlein I, Haller B, Seehaus T, Fuerst H, Kremer M. A small subgroup of Hashimoto's thyroiditis is associated with IgG4-related disease. Virchows Arch. 2016;46 8(3):321-327. doi:10.1007/s00428-015-1893-6.
33. Rodríguez-Muñoz A, Vitales-Noyola M, Ramos-Levi A, Serrano-Somavilla A, González -Amaro R, Marazuela M. Levels of regulatory T cells CD69(+)NKG2D(+)IL-10(+) are increased in patients with autoimmune thyroid disorders. Endocrine. 2016;51(3):478-489. doi :10.1007/s12020-015-0662-2.
34. Vitales-Noyola M, Serrano-Somavilla A, Martínez-Hernández R, et al. Patients With Autoimmune Thyroiditis Show Diminished Levels and Defective Suppressive Function of Tr1 Regulatory Lymphocytes. J Clin Endocrinol Metab. 2018;103(9):3359-3367. doi:10.1210/jc.2018-00498.
35. Ajjan RA, Weetman AP. The Pathogenesis of Hashimoto's Thyroiditis: Further Developments in our Understanding. Horm Metab Res. 2015;47(10):702-710. doi:10.1055 /s-0035-1548832.
36. Zake T, Skuja S, Kalere I, Konrade I, Groma V. Heterogeneity of tissue IL-17 and tight junction proteins expression demonstrated in patients with autoimmune thyroid diseases. Medicine (Baltimore). 2018;97(25):e11211. doi:10.1097/MD.0000000000011211.
37. Vitales-Noyola M, Ramos-Levi AM, Martínez-Hernández R, et al. Pathogenic Th17 and Th22 cells are increased in patients with autoimmune thyroid disorders. Endocrine. 2017;57(3):409-417. doi:10.1007/s12020-017-1361-y.
38. Guan LJ, Wang X, Meng S, et al. Increased IL-21/IL-21R expression and its proinflammatory effects in autoimmune thyroid disease. Cytokine. 2015;72(2):160-165. doi:10.1016/j.cyto.2014.11.005.
39. Guo Q, Wu Y, Hou Y, et al. Cytokine Secretion and Pyroptosis of Thyroid Follicular Cells Mediated by Enhanced NLRP3, NLRP1, NLRC4, and AIM2 Inflammasomes Are Associated With Autoimmune Thyroiditis. Front Immunol. 2018;9:1197. Published 2018 Jun 4. doi:10.3389/fimmu.2018.01197.
40. Álvarez-Sierra D, Marín-Sánchez A, Ruiz-Blázquez P, et al. Analysis of the PD-1/PD-L1 axis in human autoimmune thyroid disease: Insights into pathogenesis and clues to immunotherapy associated thyroid autoimmunity. J Autoimmun. 2019;103:10228 5. doi:10.1016/j.jaut.2019.05.013.
41. Marelli-Berg FM, Weetman A, Frasca L, et al. Antigen presentation by epithelial cells induces anergic immunoregulatory CD45RO+ T cells and deletion of CD45RA+ T cells. J Immunol. 1997;159(12):5853-5861.
42. Nishihara E, Amino N, Kudo T, et al. Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases. Endocr J. 2017;64(10):955-961. doi:10.1507/ endocrj.EJ17-0164.
43. Bektas Uysal H, Ayhan M. Autoimmunity affects health-related quality of life in patients with Hashimoto's thyroiditis. Kaohsiung J Med Sci. 2016;32(8):427-433. doi:10.1016/j.kj ms.2016.06.006.
44. Barić A, Brčić L, Gračan S, et al. Thyroglobulin Antibodies are Associated with Symptom Burden in Patients with Hashimoto's Thyroiditis: A Cross-Sectional Study. Immunol Invest. 2019;48(2):198-209. doi:10.1080/0882 0139.2018.1529040.
45. Guldvog I, Reitsma LC, Johnsen L, et al. Thyroidectomy Versus Medical Management for Euthyroid Patients With Hashimoto Disease and Persisting Symptoms: A Randomized Trial. Ann Intern Med. 2019;170 (7):453-464. doi:10.7326/M18-0284.
46. Diana T, Krause J, Olivo PD, et al. Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease. Clin Exp Immunol. 2017;189(3):304-309. doi:1 0.1111/cei.12980.
47. Kahaly GJ, Diana T, Glang J, Kanitz M, Pitz S, König J. Thyroid Stimulating Antibodies Are Highly Prevalent in Hashimoto's Thyroiditis and Associated Orbitopathy. J Clin Endocrinol Metab. 2016;1 01(5):1998-2004. doi:10.1210/jc.2016-1220.
48. Foley TP Jr, Abbassi V, Copeland KC, Draznin MB. Hypothyroidism caused by chronic autoimmune thyroiditis in very young infants. N Engl J Med. 1994;330(7):466-468. doi:10.1056/NEJM19940217330070.
49. Gunther DF, Chiu HK, Numrych TE, Kletter GB. Onset of acquired autoimmune hypothyroidism in infancy: a presentation of delayed gross-motor development and rhabdomyolysis. Eur J Pediatr. 2006;165(5):32 0-322. doi:10.1007/s00431-005-0051-6.
50. Mittnacht J, Schmidt F, Ebinger F, Bettendorf M. Unusual clinical presentation of primary hypothyroidism in a very young infant caused by autoimmune thyroiditis: case report and update of the literature. Eur J Pediatr. 2007;166(8):881-883. doi:10.1007/s0 0431-006-0323-9.
51. Marzuillo P, Grandone A, Perrotta S, et al. Very early onset of autoimmune thyroiditis in a toddler with severe hypothyroidism presentation: a case report. Ital J Pediatr. 2016;42:61. doi:10.1186/s13052-016-0270-7.
52. Tang S, Yang M, Zhang D, Tong YJ, Xin Y. Clinical characteristics and follow-up of 19 children with Hashimoto’s thyroiditis aged below 3 years: a single-center retrospective analysis. Front Endocrinol (Lausanne). 2021;12 :737527. doi:10.3389/fendo.2021.737527.
53. Rose SR, Wassner AJ, Wintergerst KA, et al. Congenital hypothyroidism: screening and management. Pediatrics. 2023;151(1):e20220 60419. doi:10.1542/peds.2022-060419.
54. Wasniewska M, Corrias A, Salerno M, et al. Thyroid function patterns at Hashimoto's thyroiditis presentation in childhood and adolescence are mainly conditioned by patients' age. Horm Res Paediatr. 2012;78(4): 232-236. doi:10.1159/000343815.
55. de Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child. 2009;94(1):33-37. doi:10.1136/adc.2007.134841.
56. Weber G, Vigone MC, Stroppa L, Chiumello G. Thyroid function and puberty. J Pediatr Endocrinol Metab. 2003;16:253-257.
57. Bauman A, Novello L, Kreitzer P. Endocrine Disorders and Delayed Puberty. In: Abnormal Female Puberty: A Clinical Casebook. 2016:87-107.
58. Wassner AJ. Pediatric Hypothyroidism: Diagnosis and Treatment. Paediatr Drugs. 2017;19(4):291-301. doi:10.1007/s40272-017-0238-0
59. Lee SJ, Lim GY, Kim JY, Chung MH. Diagnostic performance of thyroid ultrasonography screening in pediatric patients with a hypothyroid, hyperthyroid or euthyroid goiter. Pediatr Radiol. 2016;46:104-111.
60. Vukovic R, Zeljkovic A, Bufan B, Spasojevic-Kalimanovska V, Milenkovic T, Vekic J. Hashimoto Thyroiditis and Dyslipidemia in Childhood: A Review. Front Endocrinol (Lausanne). 2019;10:868. Published 2019 Dec 10. doi:10.3389/fendo.2019.00868.
61. Watemberg N, Greenstein D, Levine A. Encephalopathy associated with Hashimoto thyroiditis: pediatric perspective. J Child Neurol. 2006;21(1):1-5. doi:10.1177/0883073 8060210010201.
62. Rodriguez L, Dinauer C, Francis G. Treatment of hypothyroidism in infants, children and adolescents. Trends Endocrinol Metab. 2022;33(7):522-532. doi:10.1016/j.te m.2022.04.007.
63. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1 670-1751. doi:10.1089/thy.2014.0028.
64. Radetti G, Salerno M, Guzzetti C, et al. Thyroid function in children and adolescents with Hashimoto's thyroiditis after l-thyroxine discontinuation. Endocr Connect. 2017;6(4):2 06-212. doi:10.1530/EC-17-0023.
65. Gopalakrishnan S, Chugh PK, Chhillar M, Ambardar VK, Sahoo M, Sankar R. Goitrous autoimmune thyroiditis in a pediatric population: a longitudinal study. Pediatrics. 2008;122(3):e670-e674. doi:10.1542/peds.2008-0493.
66. Osowiecka K, Myszkowska-Ryciak J. The Influence of Nutritional Intervention in the Treatment of Hashimoto's Thyroiditis-A Systematic Review. Nutrients. 2023;15(4):104 1. doi:10.3390/nu15041041.
67. Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13(4-5):391-397. doi:10.1016/j.autrev.2014.01.007.
68. Vincent A, Bouvattier C, Teinturier C, et al. Evaluation of catch-up growth in severe pediatric Hashimoto's hypothyroidism. Arch Pediatr. 2023;30(3):142-148. doi:10.1016/j.ar cped.2023.01.001.
69. Brain L, Jellinek EH, Ball K. Hashimoto’s disease and encephalopathy. Lancet. 1966;2( 7462):512-514. doi:10.1016/s0140-6736(66)92876-5.
70. Mocellin R, Walterfang M, Velakoulis D. Hashimoto’s encephalopathy: epidemiology, pathogenesis and management. CNS Drugs. 2007;21(10):799-811. doi:10.2165/00023210-200721100-00002.
71. Ruggeri RM, Trimarchi F, Giuffrida G, Certo R, Cama E, Campennì A, Alibrandi A, De Luca F, Wasniewska M. Autoimmune comorbidities in Hashimoto's thyroiditis: different patterns of association in adulthood and childhood/adolescence. Eur J Endocrinol. 2017;176(2):133-141.
72. Penta L, Cofini M, Lanciotti L, Leonardi A, Principi N, Esposito S. Hashimoto's Disease and Thyroid Cancer in Children: Are They Associated?. Front Endocrinol (Lausanne). 2018;9:565. Published 2018 Oct 9. doi:10.338 9/fendo.2018.00565.
73. Keefe G, Culbreath K, Cherella CE, et al. Autoimmune Thyroiditis and Risk of Malignancy in Children with Thyroid Nodules. Thyroid. 2022;32(9):1109-1117. doi:10.1089/ thy.2022.0241.
74. Gallant J-N, Weiss VL, Chen SC, Liang J, Belcher RH, Ye F, Correa H, Wang H. Hashimoto’s Thyroiditis and the Risk of Papillary Thyroid Cancer in Children. Cancers. 2023;15(19):4902. doi:10.3390/cancers15194902.
75. Gallant JN, Weiss VL, Chen SC, et al. Hashimoto's Thyroiditis and the Risk of Papillary Thyroid Cancer in Children. Cancers (Basel). 2023;15(19):4902. Published 2023 Oct 9. doi:10.3390/cancers15194902.
76. Seppälä LK, Madanat-Harjuoja LM, Leinonen MK, Lääperi M, Vettenranta K. Maternal Thyroid Disease and the Risk of Childhood Cancer in the Offspring. Cancers (Basel). 2021;13(21):5409. Published 2021 Oct 28. doi:10.3390/cancers13215409.
77. Sur ML, Gaga R, Lazăr C, Lazea C, Aldea C, Sur D. Papillary thyroid carcinoma in children with Hashimoto's thyroiditis - a review of the literature between 2000 and 2020. J Pediatr Endocrinol Metab. 2020;33(12 ):1511-1517. Published 2020 Nov 12. doi:10.1515/jpem-2020-0383.
78. Penta L, Cofini M, Lanciotti L, Leonardi A, Principi N, Esposito S. Hashimoto's Disease and Thyroid Cancer in Children: Are They Associated?. Front Endocrinol (Lausanne). 2018;9:565. Published 2018 Oct 9. doi:10.3389/fendo.2018.00565.
79. Gallant JN, Weiss VL, Chen SC, et al. Hashimoto's Thyroiditis and the Risk of Papillary Thyroid Cancer in Children. Cancers (Basel). 2023;15(19):4902. Published 2023 Oct 9. doi:10.3390/cancers15194902.
80. 80. Lee JH, Kim Y, Choi JW, Kim YS. The association between papillary thyroid carcinoma and histologically proven Hashimoto's thyroiditis: a meta-analysis. Eur J Endocrinol. 2013;168(3):343-349. Published 2013 Feb 15. doi:10.1530/EJE-12-0903.
81. Erbaş İ, Erbaş İ, Evliyaoğlu O. Clinical, biochemical, and radiological follow-up results of children and adolescents with Hashimoto’s thyroiditis: a single-center experience. J Pediatr Endocrinol Metab. 2021;34(8):987-994. doi:10.1515/jpem-2021-0035.
82. Lai X, Xia Y, Zhang B, Li J, Jiang Y. A meta-analysis of Hashimoto's thyroiditis and papillary thyroid carcinoma risk. Oncotarget. 2017;8:62414-62424. doi:10.18632/oncotarget.18620.
83. Iliadou PK, Effraimidis G, Konstantinos M, et al. Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents. Eur J Endocrinol. 2015;173( 6):827-833. doi:10.1530/EJE-14-1046.
84. Ren PY, Liu J, Xue S, Chen G. Pediatric differentiated thyroid carcinoma: The clinicopathological features and the coexistence of Hashimoto's thyroiditis. Asian J Surg. 2019;42(1):112-119. doi:10.1016/j.asjs ur.2017.10.006.
85. Golbert L, de Cristo AP, Faccin CS, et al. Serum TSH levels as a predictor of malignancy in thyroid nodules: A prospective study. PLoS One. 2017;12(11):e0188123. Published 2017 Nov 16. doi:10.1371/journal.pone.0188123.
86. Boi F, Minerba L, Lai ML, Marziani B, Figus B, Spanu F, et al. Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules. J Endocrinol Invest. 2013;36:313-320. doi:103275/8579.
87. Su X, He C, Ma J, Tang T, Zhang X, Ye Z, et al. RET/PTC Rearrangements are associated with elevated postoperative TSH levels and multifocal lesions in papillary thyroid cancer without concomitant thyroid benign disease. PLoS ONE. 2016;11:e016559 6. doi:10.1371/journal.pone.0165596.
88. Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumour microenvironment. J Immunol Res. 2014;2014 :149185. doi:10.1155/2014/149185.
89. Karavanaki K, Karayianni C, Vassiliou I, Tzanela M, Sdogou T, Kakleas K, et al. Multiple autoimmunity, type 1 diabetes (T1DM), autoimmune thyroiditis and thyroid cancer: is there an association? A case report and literature review. J Pediatr Endocrinol Metab. 2014;27:1011-1016. doi:10.1515/jpe m-2013-0370.
90. Mussa A, Matarazzo P, Corrias A. Papillary thyroid cancer and autoimmune polyglandular syndrome. J Pediatr Endocrinol Metab. 2015; 28:793-795. doi:10.1515/jpem-2014-0268.