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Guías: enfermedad de Hashimoto y embarazo

24.02.2023
Autores: Joanna Klubo-Gwieździńska (MD, PhD, MHSc), Leonard Wartofsky (MD, MPH)
Hashimoto thyroiditis: an evidence-based guide to etiology, diagnosis and treatment, Polish Archives of Internal Medicine, 2022, 132: 16222. doi: 10.20452/pamw.1622

Enfermedad de Hashimoto y embarazo

Se estima que los niveles de anticuerpos anti-TPO están elevados en un 5-14 % de las embarazadas, mientras que los niveles de anti-Tg en un 3-18 % de ellas.90 La presencia de estos anticuerpos indica la autoinmunidad de la tiroides y se asocia a un riesgo 2-4 veces más alto de abortos habituales91,92 y un riesgo 2-3 veces mayor de parto prematuro.91,93,94 Se desconocen los mecanismos que conducen a estas complicaciones de embarazo en mujeres eutiroideas con anticuerpos anti-TPO, pero algunos autores creen que estos anticuerpos pueden ser marcadores de otro tipo de procesos de autoinmunidad maternofetal.95 No obstante, parece que la tiroiditis autoinmune en las embarazadas con hipotiroidismo subclínico tiene efecto adicional o sinérgico sobre el riesgo de aborto espontáneo93 o parto prematuro.96 En un metaanálisis reciente de 19 estudios de cohorte con 47 045 embarazadas se demostró que el riesgo de parto prematuro es casi 3 veces más alto que en mujeres con hipotiroidismo subclínico y 1,5 veces más alto que en mujeres con hipotiroxinemia aislada.94 Por su parte, otro metaanálisis de 26 ensayos indica una fuerte relación entre el hipotiroidismo subclínico o hipotiroxinemia materna y un IQ más bajo y retraso en el desarrollo lingüístico o general del niño en comparación con los hijos de las mujeres eutiroideas.97

El hipotiroidismo clínico se asoció a una mayor frecuencia de: hipertensión gestacional, incluida la preeclampsia y eclampsia, diabetes gestacional, desprendimiento de la placenta, hemorragia posparto, parto prematuro, bajo peso al nacer, estancia del neonato en la unidad de cuidados intensivos, muerte fetal y retraso del neurodesarrollo en el niño.98,99,100 Esto apunta a la necesidad de tratar el hipotiroidismo clínico para prevenir su efecto desfavorable sobre el curso del embarazo y el desarrollo del niño. El tratamiento debe iniciarse antes de la concepción para lograr el eutiroidismo bioquímico.26 Se ha demostrado que el uso de L-T4 aumenta la eficacia de la fecundación in vitro en mujeres con niveles elevados de anticuerpos anti-TPO y con niveles de TSH >2,5 mUI/l.26 Es importante aumentar la dosis de L-T4 en un 20-30 % de manera precoz en el 1.er trimestre de embarazo en las mujeres tratadas por hipotiroidismo. En general, esto consiste en agregar 2 comprimidos a la semana a la dosis ya utilizada.26 Las causas fisiológicas del requerimiento elevado de las hormonas tiroideas incluyen varios factores, incluido el aumento en la síntesis de la globulina fijadora de tiroxina (TBG) en el hígado y el metabolismo más intenso de las hormonas tiroideas debido a su inactivación por las desyodasas tipo 3 en la placenta.26,101 No se recomienda utilizar preparaciones de L-T3 ni la combinación de L-T4 + L-T3 en embarazadas, puesto que la L-T3 no penetra la barrera hematoencefálica hasta el cerebro del feto.102 Debido al efecto negativo tanto de la corrección excesiva, como insuficiente de la función tiroidea sobre el embarazo, en las mujeres sometidas al tratamiento de sustitución con L-T4 es necesario realizar las pruebas de control mensuales.26 Se sugiere intentar mantener los niveles de TSH en la mitad inferior del rango de referencia para el trimestre de embarazo determinado, o <2,5 mUI/l, si los valores de referencia no están disponibles.26

En las guías de 2017 la ATA recomienda tomar decisiones sobre el tratamiento de hipotiroidismo subclínico en embarazadas (tabla 2) teniendo en cuenta los niveles séricos de anticuerpos anti-TPO y TSH.26

En 2021 se realizó una revisión sistemática y metaanálisis de 6 estudios clínicos aleatorizados que evaluaron el tratamiento con L-T4 en mujeres eutiroideas con tiroiditis autoinmune. No se observaron diferencias significativas en cuanto al riesgo relativo de abortos espontáneos, parto prematuro ni del porcentaje de nacimientos vivos (en comparación con las mujeres no tratadas con L-T4). Por esta razón, no hay fundamentos necesarios para recomendar fuertemente el uso de L-T4 en este grupo. En cada caso, el tratamiento debe considerarse de manera individual (tabla 2).103

Tabla 2. Indicaciones de tratamiento de la enfermedad de Hashimoto en embarazadas
Parámetros de laboratorio Tratamiento
Ausencia de anticuerpos anti-TPO, TSH ≥10 mUI/l Administrar el tratamiento con L-T4
Niveles elevados de anticuerpos anti-TPO, TSH desde 4 mUI/l (o cerca del límite superior del rango de referencia para el trimestre determinado) hasta 10 mUI/l Considerar el tratamiento con L-T4
Niveles elevados de anticuerpos anti-TPO, TSH por encima del límite superior del rango de referencia para el trimestre determinado o >4 mUI/l Administrar el tratamiento con L-T4
Niveles elevados de anticuerpos anti-TPO, TSH 2,5-4 mUI/l (o cerca del límite superior del rango de referencia para el trimestre de embarazo determinado) Considerar el tratamiento con L-T4
Hipotiroxinemia aislada No administrar L-T4

anti-TPO — (anticuerpos) antitiroperoxidasa, L-T4 — levotiroxina, TSH — tirotropina

A partir de Lee y Pearce95 y Alexander y cols.26

Volver al artículo principal: Guías: enfermedad de Hashimoto. Etiología, diagnóstico y tratamiento

Bibliografía:
  1. Hashimoto H., The knowledge of the lymphomatous changes in the thyroid gland (struma lymphomatosa) [en alemán], Archiv für klinische Chirurgie, 1912; 97: 219
  2. Caturegli P., De Remigis A., Chuang K. y cols., Hashimoto’s thyroiditis: celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records, Thyroid, 2013; 23: 142-150
  3. Ralli M., Angeletti D., Fiore M. y cols., Hashimoto’s thyroiditis: an update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation, Autoimmun. Rev., 2020; 19: 102 649
  4. McLeod D.S., Caturegli P., Cooper D.S. y cols., Variation in rates of autoimmune thyroid disease by race/ethnicity in US military personnel, JAMA, 2014; 311: 1563-1565
  5. Song R.H., Yao Q.M., Wang B. y cols., Thyroid disorders in patients with myasthenia gravis: a systematic review and meta analysis, Autoimmun. Rev., 2019; 18: 102 368
  6. Yao Q., Song Z., Wang B. y cols., Thyroid disorders in patients with sys temic sclerosis: a systematic review and meta analysis, Autoimmun. Rev., 2019; 18: 634-636
  7. Nakamura H., Usa T., Motomura M. y cols., Prevalence of interrelated auto antibodies in thyroid diseases and autoimmune disorders, J. Endocrinol. Ivest., 2008; 31: 861-865
  8. Feldt Rasmussen U., Hoier Madsen M., Bech K. y cols., Anti thyroid peroxidase antibodies in thyroid disorders and non thyroid autoimmune diseases, Autoimmunity, 1991; 9: 245-254
  9. Bliddal S., Nielsen C.H., Feldt Rasmussen U., Recent advances in understanding autoimmune thyroid disease: the tallest tree in the forest of polyautoimmunity, F1000Research, 2017; 6: 1776
  10. Lazúrová I., Benhatchi K., Autoimmune thyroid diseases and nonorgan specific autoimmunity, Pol. Arch. Med. Wewn., 2012; 122, suppl. 1: 55-59
  11. Eisenbarth G.S., Gottlieb P.A., Autoimmune polyendocrine syndromes, N. Engl. J. Med., 2004; 350: 2068-2079
  12. Brix T.H., Hegedüs L., Twin studies as a model for exploring the aetiology of autoimmune thyroid disease, Clin. Endocrinol., 2012; 76: 457-464
  13. Gleicher N., Barad D.H., Gender as risk factor for autoimmune diseases, J. Autoimmun., 2007; 28: 1-6
  14. Brand O., Gough S., Heward J., HLA, CTLA 4 and PTPN22: the shared genetic master key to autoimmunity?, Expert Rev. Mol. Med., 2005; 7: 1-15
  15. Weetman A.P., The immunopathogenesis of chronic autoimmune thyroiditis one century after hashimoto, Eur. Thyroid J., 2013; 1: 243-250
  16. Johar A., Sarmiento Monroy J.C., Rojas Villarraga A. y cols., Definition of mutations in polyautoimmunity, J. Autoimmun., 2016; 72: 65-72
  17. Santos L.R., Duraes C., Mendes A. y cols., A polymorphism in the promoter region of the selenoprotein S gene (SEPS1) contributes to Hashimoto’s thyroiditis susceptibility, J. Clin. Endocrinol. Metab., 2014; 99: E719-723
  18. Jia X., Wang B., Yao Q. y cols., Variations in CD14 gene are associated with autoimmune thyroid diseases in the Chinese population, Front. Endocrinol., 2018; 9: 811
  19. Feil R., Fraga M.F., Epigenetics and the environment: emerging patterns and implications, Nat. Rev. Genet., 2012; 13: 97-109
  20. Lepez T., Vandewoestyne M., Deforce D., Fetal microchimeric cells in autoimmune thyroid diseases: harmful, beneficial or innocent for the thyroid gland?, Chimerism, 2013; 4: 111-118
  21. Mynster Kronborg T., Frohnert Hansen J., Nielsen C.H. y cols., Effects of the commercial flame retardant mixture DE 71 on cytokine production by human immune cells, PloS One, 2016; 11: e0154621
  22. Wiersinga W.M., Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease, Endocrinol. Metab. (Seoul), 2016; 31: 213-222
  23. Gong B., Wang C., Meng F. y cols., Association between gut microbiota and autoimmune thyroid disease: a systematic review and meta analysis, Front. Endocrinol., 2021; 12: 774362
  24. Aghini Lombardi F., Fiore E., Tonacchera M. y cols., The effect of voluntary iodine prophylaxis in a small rural community: the Pescopagano survey 15 years later, J. Clin. Endocrinol. Metab., 2013; 98: 1031-1039
  25. Carayanniotis G., Recognition of thyroglobulin by T cells: the role of iodine, Thyroid, 2007; 17: 963-973
  26. Alexander E.K., Pearce E.N., Brent G.A. y cols., 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum, Thyroid, 2017; 27: 315-389
  27. Toulis K.A., Anastasilakis A.D., Tzellos T.G. y cols., Selenium supplementation in the treatment of Hashimoto’s thyroiditis: a systematic review and a meta analysis, Thyroid, 2010; 20: 1163-1173
  28. Winther K.H., Wichman J.E., Bonnema S.J. y cols., Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta analysis, Endocrine, 2017; 55: 376-385
  29. Metso S., Hyytiä Ilmonen H., Kaukinen K. y cols., Gluten free diet and auto immune thyroiditis in patients with celiac disease. A prospective controlled study, Scand. J. Gastroenterol., 2012; 47: 43-48
  30. Krysiak R., Szkrobka W., Okopień B., The effect of gluten free diet on thyroid autoimmunity in drug naive women with hashimoto’s thyroiditis: a pilot study, Exp. Clin. Endocrinol., 2019; 127: 417-422
  31. Giordano C., Stassi G., De Maria R. y cols., Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto’s thyroiditis, Science, 1997; 275: 960-963
  32. Ahmed R., Al Shaikh S., Akhtar M., Hashimoto thyroiditis: a century later, Adv. Anat. Pathol., 2012; 19: 181-186
  33. Hennessey J.V., Clinical review: Riedel’s thyroiditis: a clinical review, J. Clin. Endocrinol. Metab., 2011; 96: 3031-3041
  34. Stone J.H., Khosroshahi A., Deshpande V. y cols., Recommendations for the nomenclature of IgG4 related disease and its individual organ system manifestations, Arthritis Rheum., 2012; 64: 3061-3067
  35. Zhang Q.Y., Ye X.P., Zhou Z. y cols., Lymphocyte infiltration and thyrocyte destruction are driven by stromal and immune cell components in Hashimoto’s thyroiditis, Nat. Commun., 2022; 13: 775
  36. Pedersen I.B., Knudsen N., Jorgensen T. y cols., Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency, Clin. Endocrinol., 2003; 58: 36-42
  37. Jonklaas J., Bianco A.C., Bauer A.J. y cols., Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement, Thyroid, 2014; 24: 1670-1751
  38. Biondi B., Cappola A.R., Cooper D.S., Subclinical hypothyroidism: a review, JAMA, 2019; 322: 153-160
  39. Boucai L., Hollowell J.G., Surks M.I., An approach for development of age, gender, and ethnicity specific thyrotropin reference limits, Thyroid, 2011; 21: 5-11
  40. Jonklaas J., Optimal thyroid hormone replacement, Endocr. Rev, 2022; 43: 366-404
  41. Caturegli P., De Remigis A., Rose N.R., Hashimoto thyroiditis: clinical and diagnostic criteria, Autoimmun. Rev., 2014; 13: 391-397
  42. Anderson L., Middleton W.D., Teefey S.A. y cols., Hashimoto thyroiditis: part 2, sonographic analysis of benign and malignant nodules in patients with diffuse Hashimoto thyroiditis, AJR Am. J. Roentgenol., 2010; 195: 216-222
  43. McLachlan S.M., Rapoport B., Why measure thyroglobulin autoantibodies rather than thyroid peroxidase autoantibodies?, Thyroid, 2004; 14: 510-520
  44. Jonklaas J., Bianco A.C., Cappola A.R. y cols., Evidence based use of levothyroxine/liothyronine combinations in treating hypothyroidism: a consensus document, Eur. Thyroid J., 2021; 10: 10-38
  45. Fatourechi V., McConahey W.M., Woolner L.B., Hyperthyroidism associated with histologic Hashimoto’s thyroiditis, Mayo Clin. Proc., 1971; 46: 682-689
  46. Rodondi N., den Elzen W.P., Bauer D.C. y cols., Subclinical hypothyroidism and the risk of coronary heart disease and mortality, JAMA, 2010; 304: 1365-1374
  47. Chaker L., Baumgartner C., den Elzen W.P. y cols., Subclinical hypothyroidism and the risk of stroke events and fatal stroke: an individual participant data analysis, J. Clin. Endocrinol. Metab., 2015; 100: 2181-2191
  48. Kabadi U.M., Jackson T., Serum thyrotropin in primary hypothyroidism. A possible predictor of optimal daily levothyroxine dose in primary hypothyroidism, Arch. Intern. Med., 1995; 155: 1046-1048
  49. Lillevang Johansen M., Abrahamsen B., Jorgensen H.L. y cols., Duration of over and under treatment of hypothyroidism is associated with increased cardiovascular risk, Eur. J. Endocrinol., 2019; 180: 407-416
  50. Huang H.K., Wang J.H., Kao S.L., Association of hypothyroidism with all cause mortality: a cohort study in an older adult population, J. Clin. Endocrinol. Metab., 2018; 103: 3310-3318
  51. Lillevang Johansen M., Abrahamsen B., Jorgensen H.L. y cols., Over and under treatment of hypothyroidism is associated with excess mortality: a register based cohort study, Thyroid, 2018; 28: 566-574
  52. Thayakaran R., Adderley N.J., Sainsbury C. y cols., Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study, BMJ, 2019; 366: 4892
  53. Okosieme O.E., Belludi G., Spittle K. y cols., Adequacy of thyroid hormone replacement in a general population, QJM – Mon. J. Assoc. Physicians, 2011; 104: 395-401
  54. Ettleson M.D., Bianco A.C., Zhu M. y cols., Sociodemographic disparities in the treatment of hypothyroidism: NHANES 2007–2012, J. Endocr. Soc., 2021; 5: bvab041
  55. Santini F., Pinchera A., Marsili A. y cols., Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases, J. Clin. Endocrinol. Metab., 2005; 90: 124-127
  56. Pilo A., Iervasi G., Vitek F. y cols., Thyroidal and peripheral production of 3,5,3’ triiodothyronine in humans by multicompartmental analysis, Am. J. Physiol., 1990; 258: E715 726
  57. Devdhar M., Drooger R., Pehlivanova M. y cols., Levothyroxine replacement doses are affected by gender and weight, but not age, Thyroid, 2011; 21: 821-827
  58. Jonklaas J., Sex and age differences in levothyroxine dosage requirement, Endocr. Pract., 2010; 16: 71-79
  59. Hollowell J.G., Staehling N.W., Flanders W.D. y cols., Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III), J. Clin. Endocrinol. Metab., 2002; 87: 489-499
  60. Taylor P.N., Razvi S., Pearce S.H. y cols., Clinical review: a review of the clinical consequences of variation in thyroid function within the reference range, J. Clin. Endocrinol. Metab., 2013; 98: 3562-3571
  61. Samuels M.H., Kolobova I., Niederhausen M. y cols., Effects of altering levothyroxine (LT4) doses on quality of life, mood, and cognition in LT4 treated subjects, J. Clin. Endocrinol. Metab., 2018; 103: 1997-2008
  62. Samuels M.H., Kolobova I., Niederhausen M. y cols., Effects of altering levothyroxine dose on energy expenditure and body composition in subjects treated with LT4, J. Clin. Endocrinol. Metab., 2018; 103: 4163-4175
  63. Walsh J.P., Ward L.C., Burke V. y cols., Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well being, or quality of life: results of a double blind, randomized clinical trial, J. Clin. Endocrinol. Metab., 2006; 91: 2624-2630
  64. Boeving A., Paz Filho G., Radominski R.B. y cols., Low normal or high normal thyrotropin target levels during treatment of hypothyroidism: a prospective, comparative study, Thyroid, 2011; 21: 355-360
  65. Sturgess I., Thomas S.H., Pennell D.J. y cols., Diurnal variation in TSH and free thyroid hormones in patients on thyroxine replacement, Acta Endocrinol., 1989; 121: 674-676
  66. Massolt E.T., Meima M.E., Swagemakers S.M.A. y cols., Thyroid state regulates gene expression in human whole blood, J. Clin. Endocrinol. Metab., 2018; 103: 169-178
  67. Nygaard B., Jensen E.W., Kvetny J. y cols., Effect of combination therapy with thyroxine (T4) and 3,5,3’-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study, Eur. J. Endocrinol., 2009; 161: 895-902
  68. Bunevicius R., Kazanavicius G., Zalinkevicius R. y cols., Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism, N. Eng. J. Med., 1999; 340: 424-429
  69. Escobar Morreale H.F., Botella Carretero J.I., Gomez Bueno M. y cols., Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L thyroxine plus liothyronine with L thyroxine alone, Ann. Intern. Med., 2005; 142: 412-424
  70. Saravanan P., Simmons D.J., Greenwood R. y cols., Partial substitution of thyroxine (T4) with triiodothyronine in patients on T4 replacement therapy: results of a large community based randomized controlled trial, J. Clin. Endocrinol. Metab., 2005; 90: 805-812
  71. Valizadeh M., Seyyed Majidi M.R., Hajibeigloo H. y cols., Efficacy of combined levothyroxine and liothyronine as compared with levothyroxine monotherapy in primary hypothyroidism: a randomized controlled trial, Endocr. Res., 2009; 34: 80-89
  72. Ma C., Xie J., Huang X. y cols., Thyroxine alone or thyroxine plus triiodothyronine replacement therapy for hypothyroidism, Nucl. Med. Commun., 2009; 30: 586-593
  73. Escobar Morreale H.F., Botella Carretero J.I., Morreale de Escobar G.: Treatment of hypothyroidism with levothyroxine or a combination of levo thyroxine plus L triiodothyronine, Best. Pract. Res. Clin. Endocrinol. Metab., 2015; 29: 57-75
  74. Joffe R.T., Brimacombe M., Levitt A.J. y cols., Treatment of clinical hypothyroidism with thyroxine and triiodothyronine: a literature review and meta analysis, Psychosomatics, 2007; 48: 379-384
  75. Grozinsky Glasberg S., Fraser A., Nahshoni E. y cols., Thyroxine triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta analysis of randomized controlled trials, J. Clin. Endocrinol. Metab., 2006; 91: 2592-2599
  76. Celi F.S., Zemskova M., Linderman J.D. y cols., The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross over study in thyroidectomized patients, Clin. Endocrinol., 2010; 72: 709-715
  77. Shakir M.K.M., Brooks D.I., McAninch E.A. y cols., Comparative effectiveness of levothyroxine, desiccated thyroid extract, and levothyroxine + liothyronine in hypothyroidism, J. Clin. Endocrinol. Metab., 2021; 106: e4400-e4413
  78. Castagna M.G., Dentice M., Cantara S. y cols., DIO2 Thr92Ala reduces deiodinase 2 activity and serum T3 levels in thyroid deficient patients, J. Clin. Endocrinol. Metab., 2017; 102: 1623-1630
  79. Panicker V., Saravanan P., Vaidya B. y cols., Common variation in the DIO2 gene predicts baseline psychological well being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients, J. Clin. Endocrinol. Metab., 2009; 94: 1623-1629
  80. Carle A., Faber J., Steffensen R. y cols., Hypothyroid patients encoding combined MCT10 and DIO2 gene polymorphisms may prefer L T3 + L T4 combination treatment – data using a blind, randomized, clinical study, Eur. Thyroid J., 2017; 6: 143-151
  81. Wouters H.J., van Loon H.C., van der Klauw M.M. y cols., No effect of the Thr92Ala polymorphism of deiodinase 2 on thyroid hormone parameters, health related quality of life, and cognitive functioning in a large population based cohort study. Thyroid, 2017; 27: 147–155
  82. Young Cho Y., Jeong Kim H., Won Jang H. y cols., The relationship of 19 functional polymorphisms in iodothyronine deiodinase and psychological well being in hypothyroid patients, Endocrine, 2017; 57: 115-124
  83. Appelhof B.C., Fliers E., Wekking E.M. y cols., Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double blind, randomized, controlled clinical trial, J. Clin. Endocrinol. Metab., 2005; 90: 2666-2674
  84. Gan T., Randle R.W.: The role of surgery in autoimmune conditions of the thyroid, Surg. Clin. North Am., 2019; 99: 633-648
  85. Guldvog I., Reitsma L.C., Johnsen L. y cols., Thyroidectomy versus medical management for euthyroid patients with hashimoto disease and persisting symptoms: a randomized trial, Ann. Intern. Med., 2019; 170: 453-464
  86. Jankovic B., Le K.T., Hershman J.M.: Clinical Review: Hashimoto’s thyroiditis and papillary thyroid carcinoma: is there a correlation?, J. Clin. Endocrinol. Metab., 2013; 98: 474-482
  87. Sulaieva O., Selezniov O., Shapochka D. y cols., Hashimoto’s thyroiditis attenuates progression of papillary thyroid carcinoma: deciphering immunological links, Heliyon, 2020; 6: e03 077
  88. Abbasgholizadeh P., Naseri A., Nasiri E. y cols., Is Hashimoto thyroiditis associated with increasing risk of thyroid malignancies? A systematic review and meta analysis, Thyroid Res., 2021; 14: 26
  89. Haugen B.R., Alexander E.K., Bible K.C. y cols., 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer, Thyroid, 2
  90. De Leo S., Pearce E.N.: Autoimmune thyroid disease during pregnancy, Lancet Diabetes Endocrinol., 2018; 6: 575-586
  91. Thangaratinam S., Tan A., Knox E. y cols., Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence, BMJ, 2011; 342: d2616
  92. Xie J., Jiang L., Sadhukhan A. y cols., Effect of antithyroid antibodies on women with recurrent miscarriage: a metaanalysis, Am. J. Reprod. Immunol, 2020; 83: e13 238
  93. Liu H., Shan Z., Li C. y cols., Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study, Thyroid, 2014; 24: 1642-1649
  94. Korevaar T.I.M., Derakhshan A., Taylor P.N. y cols., Association of thyroid function test abnormalities and thyroid autoimmunity with preterm birth: a systematic review and meta-analysis, JAMA, 2019; 322: 632-641
  95. Lee S.Y., Pearce E.N., Assessment and treatment of thyroid disorders in pregnancy and the postpartum period, Nat. Rev. Endocrinol., 2022; 18: 158-171
  96. Korevaar T.I., Schalekamp Timmermans S., de Rijke Y.B. y cols., Hypothyroxinemia and TPO antibody positivity are risk factors for premature delivery: the generation R study, J. Clin. Endocrinol. Metab., 2013; 98: 4382-4390
  97. Thompson W., Russell G., Baragwanath G. y cols., Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: a systematic review and meta analysis, Clin. Endocrinol., 2018; 88: 575-584
  98. Davis L.E., Leveno K.J., Cunningham F.G.: Hypothyroidism complicating pregnancy, Obstet. Gynecol., 1988; 72: 108-112
  99. Leung A.S., Millar L.K., Koonings P.P. y cols., Perinatal outcome in hypothyroid pregnancies, Obstet. Gynecol., 1993; 81: 349-353
  100. Mannisto T., Mendola P., Grewal J. y cols., Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort, J. Clin. Endocrinol. Metab., 2013; 98: 2725-2733
  101. Okosieme O.E., Khan I., Taylor P.N.: Preconception management of thyroid dysfunction, Clin. Endocrinol., 2018; 89: 269-279
  102. Calvo R., Obregon M.J., Ruiz de Ona C. y cols., Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3’ tri iodothyronine in the protection of the fetal brain, J. Clin. Invest., 1990; 86: 889-899
  103. Lau L., Benham J.L., Lemieux P. y cols., Impact of levothyroxine in women with positive thyroid antibodies on pregnancy outcomes: a systematic review and meta analysis of randomised controlled trials, BMJ Open, 2021; 11: e043 751
  104. Ma R., Morshed S.A., Latif R. y cols., Thyroid cell differentiation from murine induced pluripotent stem cells, Front. Endocrinol., 2015; 6: 56
  105. Antonica F., Kasprzyk D.F., Opitz R. y cols., Generation of functional thyroid from embryonic stem cells, Nature, 2012; 491: 66-71