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Autoimmune Hypothyroidism

  • Francesco Latrofa
  • Aldo Pinchera
Part of the Contemporary Endocrinology book series (COE)

Summary

Hypothyroidism is defined as the lack of action of thyroid hormones on target tissues. The term autoimmune hypothyroidism identifies situations with insufficient thyroid function caused by an autoimmune thyroid diseases autoimmune destruction of the thyroid gland. The most common form of autoimmune thyroid diseases is chronic or lymphocytic autoimmune thyroiditis (Hashimoto’s thyroiditis). Prevalence of autoimmune hypothyroidism is high. In its initial stage, chronic autoimmune thyroiditis is characterized by the presence of hallmarks of thyroid autoimmunity and normal thyroid function. As a consequence of the autoimmune attack to the gland, hypothyroidism may develop, usually slowly and insidiously, through a subclinical phase (normal thyroid hormone and slightly elevated thyroid-stimulating hormone [TSH] levels) and an eventual phase of overt insufficiency (low thyroid hormones and frankly elevated TSH levels). Etiology and pathogenesis of chronic autoimmune thyroiditis and mechanisms leading to the hypothyroid phase remain elusive. However, some predisposing genetic factors and some triggering environmental factors have been identified. The role of antigen-presenting cells, of T- and B-cell response, and of effector mechanisms in the immunopathogenesis of chronic autoimmune hypothyroidism has been extensively investigated. Clinical presentation and consequences of autoimmune hypothyroidism vary according to patient’s age and duration and severity of hypothyroidism. The picture is peculiar in the elderly, and the effects are particularly negative in fetuses and newborns. Circulating thyroid autoantibodies and a hypoecogenic pattern at thyroid ultrasound are the two hallmarks of AITD. Treatment of hypothyroidism is based on the administration of synthetic levo-thyroxine (l-T4), whereas the usefulness of combined treatment with liothyronine (l-T3) is uncertain and difficult to manage. Opinions about treatment of subclinical hypothyroidims diverge largely, but it should be supported, or at least not discouraged. Because of the awareness about negative consequences of maternal hypothyroidism on the fetus development, screening or intensive case finding for chronic autoimmune hypothyroidism in women of childbearing aging is unanimously recommended.

Keywords

Thyroid chronic autoimmune thyroiditis Hashimoto’s thyroiditis hypothyroidism thyroid autoantibodies levo-thyroxine liothyronine screening pregnancy 

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References

  1. 1.
    Pinchera A. Subclinical thyroid disease: to treat or not to treat? Thyroid 2005; 15;(1):1–2.PubMedCrossRefGoogle Scholar
  2. 2.
    Williams ED, Doniach I. The post-mortem incidence of focal thyroiditis. J Pathol Bacteriol 1962; 83:255–264.PubMedCrossRefGoogle Scholar
  3. 3.
    Bastenie PA, Bonnyns M, Neve P, Vanhaelst L, Chailly M. Clinical and pathological significance of asymptomatic atrophic thyroiditis. A condition of latent hypothyroidism. Lancet 1967; 1;(7496):915–918.PubMedCrossRefGoogle Scholar
  4. 4.
    Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977; 7;(6):481–493.Google Scholar
  5. 5.
    Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160;(4):526–534.PubMedCrossRefGoogle Scholar
  6. 6.
    Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. 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;(2):489–499.PubMedCrossRefGoogle Scholar
  7. 7.
    Mariotti S, Sansoni P, Barbesino G, Caturegli P, Monti D, Cossarizza A, et al. Thyroid and other organ-specific autoantibodies in healthy centenarians. Lancet 1992; 339;(8808):1506–1508.PubMedCrossRefGoogle Scholar
  8. 8.
    Pinchera A, Mariotti S, Barbesino G, Bechi R, Sansoni P, Fagiolo U, et al. Thyroid autoimmunity and ageing. Horm Res 1995; 43(1–3):64–68.PubMedGoogle Scholar
  9. 9.
    Mariotti S, Franceschi C, Cossarizza A, Pinchera A. The aging thyroid. Endocr Rev 1995; 16;(6):686–715.PubMedCrossRefGoogle Scholar
  10. 10.
    Aghini-Lombardi F, Antonangeli L, Martino E, Vitti P, Maccherini D, Leoli F, et al. The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey. J Clin Endocrinol Metab 1999; 84;(2):561–566.PubMedCrossRefGoogle Scholar
  11. 11.
    Bulow P, I, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Laurberg P. Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey. J Clin Endocrinol Metab 2002; 87;(10):4462–4469.CrossRefGoogle Scholar
  12. 12.
    Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995; 43;(1):55–68.Google Scholar
  13. 13.
    Rallison ML, Dobyns BM, Meikle AW, Bishop M, Lyon JL, Stevens W. Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults. Am J Med 1991; 91;(4):363–370.PubMedCrossRefGoogle Scholar
  14. 14.
    Brix TH, Kyvik KO, Hegedus L. A population-based study of chronic autoimmune hypothyroidism in Danish twins. J Clin Endocrinol Metab 2000; 85;(2):536–539.PubMedCrossRefGoogle Scholar
  15. 15.
    Barbesino G, Chiovato L. The genetics of Hashimoto’s disease. Endocrinol Metab Clin North Am 2000; 29;(2):357–374.PubMedCrossRefGoogle Scholar
  16. 16.
    Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med 1996; 335;(2):99–107.PubMedCrossRefGoogle Scholar
  17. 17.
    Chopra IJ, Solomon DH, Chopra U, Yoshihara E, Terasaki PI, Smith F. Abnormalities in thyroid function in relatives of patients with Graves’ disease and Hashimoto’s thyroiditis: lack of correlation with inheritance of HLA-B8. J Clin Endocrinol Metab 1977; 45;(1):45–54.PubMedGoogle Scholar
  18. 18.
    Phillips D, Prentice L, Upadhyaya M, Lunt P, Chamberlain S, Roberts DF, et al. Autosomal dominant inheritance of autoantibodies to thyroid peroxidase and thyroglobulin–studies in families not selected for autoimmune thyroid disease. J Clin Endocrinol Metab 1991; 72;(5):973–975.PubMedGoogle Scholar
  19. 19.
    Roman SH, Greenberg D, Rubinstein P, Wallenstein S, Davies TF. Genetics of autoimmune thyroid disease: lack of evidence for linkage to HLA within families. J Clin Endocrinol Metab 1992; 74;(3):496–503.PubMedCrossRefGoogle Scholar
  20. 20.
    Tomer Y, Davies TF. Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function. Endocr Rev 2003; 24;(5):694–717.PubMedCrossRefGoogle Scholar
  21. 21.
    Jaume JC, Guo J, Pauls DL, Zakarija M, McKenzie JM, Egeland JA, et al. Evidence for genetic transmission of thyroid peroxidase autoantibody epitopic “fingerprints”. J Clin Endocrinol Metab 1999; 84;(4):1424–1431.PubMedCrossRefGoogle Scholar
  22. 22.
    Pirro MT, De F, V, Di Cerbo A, Scillitani A, Liuzzi A, Tassi V. Thyroperoxidase microsatellite polymorphism in thyroid diseases. Thyroid 1995; 5;(6):461–464.PubMedGoogle Scholar
  23. 23.
    Ban Y, Greenberg DA, Concepcion ES, Tomer Y. A germline single nucleotide polymorphism at the intracellular domain of the human thyrotropin receptor does not have a major effect on the development of Graves’ disease. Thyroid 2002; 12:1079–1083.PubMedCrossRefGoogle Scholar
  24. 24.
    Ban Y, Greenberg DA, Concepcion E, Skrabanek L, Villanueva R, Tomer Y. Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease. Proc Natl Acad Sci USA 2003; 100;(25):15119–15124.PubMedCrossRefGoogle Scholar
  25. 25.
    Vallotton MB, Forbes AP. Autoimmunity in gonadal dysgenesis and Klinefelter’s syndrome. Lancet 1967; 1;(7491):648–651.PubMedCrossRefGoogle Scholar
  26. 26.
    McHardy-Young S, Doniach D, Polani PE. Thyroid function in Turner’s syndrome and allied conditions. Lancet 1970; 2:1161–1164.PubMedCrossRefGoogle Scholar
  27. 27.
    Friedman DL, Kastner T, Pond WS, O’Brien DR. Thyroid dysfunction in individuals with Down syndrome. Arch Intern Med 1989; 149;(9):1990–1993.PubMedCrossRefGoogle Scholar
  28. 28.
    Kennedy RL, Jones TH, Cuckle HS. Down’s syndrome and the thyroid. Clin Endocrinol (Oxf) 1992; 37;(6):471–476.Google Scholar
  29. 29.
    Loudon MM, Day RE, Duke EM. Thyroid dysfunction in Down’s syndrome. Arch Dis Child 1985; 60;(12):1149–1151.PubMedGoogle Scholar
  30. 30.
    Bottazzo GF, Mirakian R, Drexhage HA. Adrenalitis, oophoritis and autoimmune polyglandular disease. In: Rich RR, Fleischer TA, Schwartz DB, Shearer WT, Strober W, editors. Clinical immunology, principles and practice. St.Louis: Mosby, 1996: 1523–1536.Google Scholar
  31. 31.
    Olsen NJ, Kovacs WJ. Gonadal steroids and immunity. Endocr Rev 1996; 17;(4):369–384.PubMedCrossRefGoogle Scholar
  32. 32.
    Chiovato L, Lapi P, Fiore E, Tonacchera M, Pinchera A. Thyroid autoimmunity and female gender. J Endocrinol Invest 1993; 16;(5):384–391.PubMedGoogle Scholar
  33. 33.
    Nalbandian G, Kovats S. Understanding sex biases in immunity: effects of estrogen on the differentiation and function of antigen-presenting cells. Immunol Res 2005; 31;(2):91–106.PubMedCrossRefGoogle Scholar
  34. 34.
    Chiovato L, Vitti P, Cucchi P, Mammoli C, Carajon P, Pinchera A. The expression of the microsomal/peroxidase autoantigen in human thyroid cells is thyrotrophin-dependent. Clin Exp Immunol 1989; 76;(1):47–53.PubMedGoogle Scholar
  35. 35.
    Wick G, Brezinschek HP, Hala K, Dietrich H, Wolf H, Kroemer G. The obese strain of chickens: an animal model with spontaneous autoimmune thyroiditis. In Advances in immunology. Academic Press, Inc., Burlington, MA 1989: 433–500.Google Scholar
  36. 36.
    Phillips DI, Osmond C, Baird J, Huckle A, Rees-Smith B. Is birthweight associated with thyroid autoimmunity? A study in twins. Thyroid 2002; 12;(5):377–380.PubMedCrossRefGoogle Scholar
  37. 37.
    Clarke WL, Shaver KA, Bright GM, Rogol AD, Nance WE. Autoimmunity in congenital rubella syndrome.J Pediatr 1984; 104;(3):370–373.PubMedCrossRefGoogle Scholar
  38. 38.
    Metcalfe RA, Ball G, Kudesia G, Weetman AP. Failure to find an association between hepatitis C virus and thyroid autoimmunity. Thyroid 1997; 7;(3):421–424.PubMedGoogle Scholar
  39. 39.
    Harach HR, Escalante DA, Onativia A, Lederer OJ, Saravia DE, Williams ED. Thyroid carcinoma and thyroiditis in an endemic goitre region before and after iodine prophylaxis. Acta Endocrinol (Copenh) 1985; 108;(1):55–60.Google Scholar
  40. 40.
    Braverman LE, Ingbar SH, Vagenakis AG, Adams L, Maalof F. Enhanced susceptibility to iodide myxedema in patients with Hashimoto’s disease. J Clin Endocrinol Metab 1971; 32:515–521.PubMedGoogle Scholar
  41. 41.
    Martino E, Safran M, Aghini-Lombardi F, Rajatanavin R, Lenziardi M, Fay M, et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med 1984; 101;(1):28–34.PubMedGoogle Scholar
  42. 42.
    Trip MD, Wiersinga W, Plomp TA. Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism. Am J Med 1991; 91;(5):507–511.PubMedCrossRefGoogle Scholar
  43. Martino E, Aghini-Lombardi F, Mariotti S, Bartalena L, Lenziardi M, Ceccarelli C, et al. Amiodarone iodine-induced hypothyroidism: risk factors and follow-up in 28 cases. Clin Endocrinol (Oxf) 1987; 26;(2):227–237.Google Scholar
  44. 44.
    Martino E, Bartalena L, Bogazzi F, Braverman LE. The effects of amiodarone on the thyroid. Endocr Rev 2001; 22;(2):240–254.PubMedCrossRefGoogle Scholar
  45. 45.
    Bocchetta A, Mossa P, Velluzzi F, Mariotti S, Zompo MD, Loviselli A. Ten-year follow-up of thyroid function in lithium patients. J Clin Psychopharmacol 2001; 21;(6):594–598.PubMedCrossRefGoogle Scholar
  46. 46.
    Imagawa A, Itoh N, Hanafusa T, Oda Y, Waguri M, Miyagawa J, et al. Autoimmune endocrine disease induced by recombinant interferon-alpha therapy for chronic active type C hepatitis. J Clin Endocrinol Metab 1995; 80;(3):922–926.PubMedCrossRefGoogle Scholar
  47. 47.
    Atkins MB, Mier JW, Parkinson DR, Gould JA, Berkman EM, Kaplan MM. Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells. N Engl J Med 1988; 318;(24):1557–1563.PubMedGoogle Scholar
  48. 48.
    van Liessum PA, de Mulder PH, Mattijssen EJ, Corstens FH, Wagener DJ. Hypothyroidism and goitre during interleukin-2 therapy without LAK cells. Lancet 1989; 1;(8631):224.Google Scholar
  49. 49.
    Hoekman K, von Blomberg-van der Flier BM, Wagstaff J, Drexhage HA, Pinedo HM. Reversible thyroid dysfunction during treatment with GM-CSF. Lancet 1991; 338;(8766):541–542.PubMedCrossRefGoogle Scholar
  50. 50.
    Marazuela M, Garcia-Buey L, Gonzalez-Fernandez B, Garcia-Monzon C, Arranz A, Borque MJ, et al. Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-alpha therapy. Clin Endocrinol (Oxf) 1996; 44;(6):635–642.CrossRefGoogle Scholar
  51. 51.
    Eheman CR, Garbe P, Tuttle RM. Autoimmune thyroid disease associated with environmental thyroidal irradiation. Thyroid 2003; 13;(5):453–464.PubMedCrossRefGoogle Scholar
  52. 52.
    Larsen PR, Conard RA, Knudsen KD, Robbins J, Wolff J, Rall JE, et al. Thyroid hypofunction after exposure to fallout from a hydrogen bomb explosion. JAMA 1982; 247;(11):1571–1575.PubMedCrossRefGoogle Scholar
  53. 53.
    Pacini F, Vorontsova T, Molinaro E, Kuchinskaya E, Agate L, Shavrova E, et al. Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout. Lancet 1998; 352;(9130):763–766.PubMedCrossRefGoogle Scholar
  54. 54.
    Davis S, Kopecky KJ, Hamilton TE, Onstad L. Thyroid neoplasia, autoimmune thyroiditis, and hypothyroidism in persons exposed to iodine 131 from the hanford nuclear site. JAMA 2004; 292;(21):2600–2613.PubMedCrossRefGoogle Scholar
  55. 55.
    Nagataki S, Shibata Y, Inoue S, Yokoyama N, Izumi M, Shimaoka K. Thyroid diseases among atomic bomb survivors in Nagasaki. JAMA 1994; 272;(5):364–370.PubMedCrossRefGoogle Scholar
  56. 56.
    Imaizumi M, Usa T, Tominaga T, Neriishi K, Akahoshi M, Nakashima E, et al. Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55-58 years after radiation exposure. JAMA 2006; 295;(9):1011–1022.PubMedCrossRefGoogle Scholar
  57. 57.
    Volzke H, Werner A, Wallaschofski H, Friedrich N, Robinson DM, Kindler S, et al. Occupational exposure to ionizing radiation is associated with autoimmune thyroid disease. J Clin Endocrinol Metab 2005; 90;(8):4587–4592.PubMedCrossRefGoogle Scholar
  58. 58.
    Spitalnik PF, Straus FH. Patterns of human thyroid parenchymal reaction following low-dose childhood irradiation. Cancer 1978; 41;(3):1098–1105.PubMedCrossRefGoogle Scholar
  59. 59.
    Kaplan MM, Boice JD, Jr., Ames DB, Rosenstein M. Thyroid, parathyroid, and salivary gland evaluations in patients exposed to multiple fluoroscopic examinations during tuberculosis therapy: a pilot study. J Clin Endocrinol Metab 1988; 66;(2):376–382.PubMedGoogle Scholar
  60. 60.
    Hancock SL, Cox RS, McDougall IR. Thyroid diseases after treatment of Hodgkin’s disease. N Engl J Med 1991; 325;(9):599–605.PubMedCrossRefGoogle Scholar
  61. 61.
    Pinchera A, Liberti P, Martino E, Fenzi GF, Grasso L, Rovis L, et al. Effects of antithyroid therapy on the long-acting thyroid stimulator and the antithyroglobulin antibodies. J Clin Endocrinol Metab 1969; 29;(2):231–238.PubMedGoogle Scholar
  62. 62.
    Chiovato L, Santini F, Vitti P, Bendinelli G, Pinchera A. Appearance of thyroid stimulating antibody and Graves’ disease after radioiodine therapy for toxic nodular goitre. Clin Endocrinol (Oxf) 1994; 40;(6):803–806.Google Scholar
  63. 63.
    Nygaard B, Knudsen JH, Hegedus L, Scient AVC, Molholm Hansen JE. Thyrotropin receptor antibodies and Graves’ disease, a side-effect of 131I treatment in patients with nontoxic goiter. J Clin Endocrinol Metab 1997; 82;(9):2926–2930.PubMedCrossRefGoogle Scholar
  64. 64.
    Fukata S, Kuma K, Sugawara M. Relationship between cigarette smoking and hypothyroidism in patients with Hashimoto’s thyroiditis. J Endocrinol Invest 1996; 19;(9):607–612.PubMedGoogle Scholar
  65. 65.
    Pujo-Borrell R, Hanafusa T, Chiovato L, Bottazzo GF. Lectin-induced expression of DR antigen on human cultured follicular thyroid cells. Nature 1983; 304;(5921):71–73.PubMedCrossRefGoogle Scholar
  66. 66.
    Hanafusa T, Pujol-Borrell R, Chiovato L, Russell RC, Doniach D, Bottazzo GF. Aberrant expression of HLA-DR antigen on thyrocytes in Graves’ disease: relevance for autoimmunity. Lancet 1983; 2;(8359):1111–1115.PubMedCrossRefGoogle Scholar
  67. 67.
    Chiovato L, Lapi P, Mariotti S, Del Prete G, De Carli M, Pinchera A. Simultaneous expression of thyroid peroxidase and human leukocyte antigen-DR by human thyroid cells: modulation by thyrotropin, thyroid-stimulating antibody, and interferon-gamma. J Clin Endocrinol Metab 1994; 79;(2):653–656.PubMedCrossRefGoogle Scholar
  68. 68.
    Zheng RQ, Abney ER, Grubeck-Loebenstein B, Dayan C, Maini RN, Feldmann M. Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3 on human thyroid epithelial cells in Graves’ and Hashimoto’s diseases. J Autoimmun 1990; 3;(6):727–736.PubMedCrossRefGoogle Scholar
  69. 69.
    Faure GC, Bensoussan-Lejzerowicz D, Bene MC, Aubert V, Leclere J. Coexpression of CD40 and class II antigen HLA-DR in Graves’ disease thyroid epithelial cells. Clin Immunol Immunopathol 1997; 84;(2):212–215.PubMedCrossRefGoogle Scholar
  70. 70.
    Metcalfe RA, McIntosh RS, Marelli-Berg F, Lombardi G, Lechler R, Weetman AP. Detection of CD40 on human thyroid follicular cells: analysis of expression and function. J Clin Endocrinol Metab 1998; 83;(4):1268–1274.PubMedCrossRefGoogle Scholar
  71. 71.
    Battifora M, Pesce G, Paolieri F, Fiorino N, Giordano C, Riccio AM, et al. B7.1 costimulatory molecule is expressed on thyroid follicular cells in Hashimoto’s thyroiditis, but not in Graves’ disease. J Clin Endocrinol Metab 1998; 83;(11):4130–4139.PubMedCrossRefGoogle Scholar
  72. 72.
    Weetman AP. Chronic autoimmune thyroiditis. In: Braverman LE, Utiger RD, editors. Werner & Ingbar’s The Thyroid: a fundamental and clinical text. Philadelphia: Lippincott Williams & Wilkins, 2005: 701–713.Google Scholar
  73. 73.
    Quaratino S, Feldmann M, Dayan CM, Acuto O, Londei M. Human self-reactive T cell clones expressing identical T cell receptor beta chains differ in their ability to recognize a cryptic self-epitope. J Exp Med 1996; 183;(2):349–358.PubMedCrossRefGoogle Scholar
  74. 74.
    Quaratino S, Duddy LP, Londei M. Fully competent dendritic cells as inducers of T cell anergy in autoimmunity. Proc Natl Acad Sci USA 2000; 97;(20):10911–10916.PubMedCrossRefGoogle Scholar
  75. 75.
    Quaratino S, Badami E, Pang YY, Bartok I, Dyson J, Kioussis D, et al. Degenerate self-reactive human T-cell receptor causes spontaneous autoimmune disease in mice. Nat Med 2004; 10;(9):920–926.PubMedCrossRefGoogle Scholar
  76. 76.
    Davies TF, Martin A, Concepcion ES, Graves P, Lahat N, Cohen WL, et al. Evidence for selective accumulation of intrathyroidal T lymphocytes in human autoimmune thyroid disease based on T cell receptor V gene usage. J Clin Invest 1992; 89;(1):157–162.PubMedGoogle Scholar
  77. 77.
    McIntosh RS, Tandon N, Pickerill AP, Davies R, Barnett D, Weetman AP. IL-2 receptor-positive intrathyroidal lymphocytes in Graves’ disease. Analysis of V alpha transcript microheterogeneity. J Immunol 1993; 151;(7):3884–3893.PubMedGoogle Scholar
  78. 78.
    Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003; 423;(6939):506–511.PubMedCrossRefGoogle Scholar
  79. 79.
    Marcocci C, Marino M. Thyroid-directed antibodies. In: Braverman LE, Utiger RD, editors. Werner & Ingbar’s The Thyroid: a fundamental and clinical text. Philadelphia: Lippincott Williams & Wilkins, 2005: 360–372.Google Scholar
  80. 80.
    Mariotti S, Pisani S, Russova A, Pinchera A. A new solid-phase immunoradiometric assay for anti-thyroglobulin autoantibody. J Endocrinol Invest 1982; 5;(4):227–233.PubMedGoogle Scholar
  81. 81.
    Mariotti S, Caturegli P, Piccolo P, Barbesino G, Pinchera A. Antithyroid peroxidase autoantibodies in thyroid diseases. J Clin Endocrinol Metab 1990; 71;(3):661–669.PubMedGoogle Scholar
  82. 82.
    Mariotti S, Barbesino G, Caturegli P, Atzeni F, Manetti L, Marino M, et al. False negative results observed in anti-thyroid peroxidase autoantibody determination by competitive radioimmunoassays using monoclonal antibodies. Eur J Endocrinol 1994; 130;(6):552–558.PubMedGoogle Scholar
  83. 83.
    Latrofa F, Pichurin P, Guo J, Rapoport B, McLachlan SM. Thyroglobulin-thyroperoxidase autoantibodies are polyreactive, not bispecific: analysis using human monoclonal autoantibodies. J Clin Endocrinol Metab 2003; 88;(1):371–378.PubMedCrossRefGoogle Scholar
  84. 84.
    Caturegli P, Kuppers RC, Mariotti S, Burek CL, Pinchera A, Ladenson PW, et al. IgG subclass distribution of thyroglobulin antibodies in patients with thyroid disease. Clin Exp Immunol 1994; 98;(3):464–469.PubMedCrossRefGoogle Scholar
  85. 85.
    McLachlan SM, Rapoport B. Why measure thyroglobulin autoantibodies rather than thyroid peroxidase autoantibodies? Thyroid 2004; 14;(7):510–520.PubMedCrossRefGoogle Scholar
  86. 86.
    McLachlan SM, Rapoport B. Autoimmune response to the thyroid in humans: thyroid peroxidase–the common autoantigenic denominator. Int Rev Immunol 2000; 19;(6):587–618.PubMedGoogle Scholar
  87. 87.
    Saboori AM, Rose NR, Burek CL. Iodination of human thyroglobulin (Tg) alters its immunoreactivity. II. Fine specificity of a monoclonal antibody that recognizes iodinated Tg. Clin Exp Immunol 1998; 113;(2):303–308.PubMedCrossRefGoogle Scholar
  88. 88.
    Dai YD, Rao VP, Carayanniotis G. Enhanced iodination of thyroglobulin facilitates processing and presentation of a cryptic pathogenic peptide. J Immunol 2002; 168;(11):5907–5911.PubMedGoogle Scholar
  89. 89.
    Latrofa F, Phillips M, Rapoport B, McLachlan SM. Human monoclonal thyroglobulin autoantibodies: epitopes and immunoglobulin genes. J Clin Endocrinol Metab 2004; 89;(10):5116–5123.PubMedCrossRefGoogle Scholar
  90. 90.
    Prentice L, Kiso Y, Fukuma N, Horimoto M, Petersen V, Grennan F, et al. Monoclonal thyroglobulin autoantibodies: variable region analysis and epitope recognition. J Clin Endocrinol Metab 1995; 80;(3):977–986.PubMedCrossRefGoogle Scholar
  91. 91.
    Caturegli P, Mariotti S, Kuppers RC, Burek CL, Pinchera A, Rose NR. Epitopes on thyroglobulin: a study of patients with thyroid disease. Autoimmunity 1994; 18;(1):41–49.PubMedCrossRefGoogle Scholar
  92. 92.
    Kohno Y, Naito N, Hiyama Y, Shimojo N, Suzuki N, Tarutani O, et al. Thyroglobulin and thyroid peroxidase share common epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis. J Clin Endocrinol Metab 1988; 67;(5):899–907.PubMedGoogle Scholar
  93. 93.
    Ruf J, Ferrand M, Durand-Gorde JM, Carayon P. Immunopurification and characterization of thyroid autoantibodies with dual specificity for thyroglobulin and thyroperoxidase. Autoimmunity 1992; 11;(3):179–188.PubMedCrossRefGoogle Scholar
  94. 94.
    Ruf J, Carayon P. The molecular recognition theory applied to bispecific antibodies. Nat Med 1995; 1;(12):1222.PubMedCrossRefGoogle Scholar
  95. 95.
    Vitti P, Elisei R, Tonacchera M, Chiovato L, Mancusi F, Rago T, et al. Detection of thyroid-stimulating antibody using Chinese hamster ovary cells transfected with cloned human thyrotropin receptor. J Clin Endocrinol Metab 1993; 76;(2):499–503.PubMedCrossRefGoogle Scholar
  96. 96.
    Costagliola S, Morgenthaler NG, Hoermann R, Badenhoop K, Struck J, Freitag D, et al. Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves’ disease. J Clin Endocrinol Metab 1999; 84;(1):90–97.PubMedCrossRefGoogle Scholar
  97. 97.
    Chiovato L, Vitti P, Santini F, Lopez G, Mammoli C, Bassi P, et al. Incidence of antibodies blocking thyrotropin effect in vitro in patients with euthyroid or hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab 1990; 71;(1):40–45.PubMedGoogle Scholar
  98. 98.
    Tamaki H, Amino N, Kimura M, Hidaka Y, Takeoka K, Miyai K. Low prevalence of thyrotropin receptor antibody in primary hypothyroidism in Japan. J Clin Endocrinol Metab 1990; 71;(5):1382–1386.PubMedGoogle Scholar
  99. 99.
    Weetman AP, Yateman ME, Ealey PA, Black CM, Reimer CB, Williams RC, Jr., et al. Thyroid-stimulating antibody activity between different immunoglobulin G subclasses. J Clin Invest 1990; 86;(3):723–727.PubMedGoogle Scholar
  100. 100.
    Latrofa F, Chazenbalk GD, Pichurin P, Chen CR, McLachlan SM, Rapoport B. Affinity-enrichment of thyrotropin receptor autoantibodies from Graves’ patients and normal individuals provides insight into their properties and possible origin from natural antibodies. J Clin Endocrinol Metab 2004; 89;(9):4734–4745.PubMedCrossRefGoogle Scholar
  101. 101.
    Tokuda Y, Kasagi K, Iida Y, Hatabu H, Misaki T, Arai K, et al. Inhibition of thyrotropin-stimulated iodide uptake in FRTL-5 thyroid cells by crude immunoglobulin fractions from patients with goitrous and atrophic autoimmune thyroiditis. J Clin Endocrinol Metab 1988; 67;(2):251–258.PubMedGoogle Scholar
  102. 102.
    Rapoport B, Chazenbalk GD, Jaume JC, McLachlan SM. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr Rev 1998; 19;(6):673–716.PubMedCrossRefGoogle Scholar
  103. 103.
    Schwarz-Lauer L, Chazenbalk GD, McLachlan SM, Ochi Y, Nagayama Y, Rapoport B. Evidence for a simplified view of autoantibody interactions with the thyrotropin receptor. Thyroid 2002; 12;(2):115–120.PubMedCrossRefGoogle Scholar
  104. 104.
    Chen CR, Pichurin P, Nagayama Y, Latrofa F, Rapoport B, McLachlan SM. The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim. J Clin Invest 2003; 111;(12):1897–1904.PubMedCrossRefGoogle Scholar
  105. 105.
    Chazenbalk GD, Pichurin P, Chen CR, Latrofa F, Johnstone AP, McLachlan SM, et al. Thyroid-stimulating autoantibodies in Graves disease preferentially recognize the free A subunit, not the thyrotropin holoreceptor. J Clin Invest 2002; 110;(2):209–217.PubMedCrossRefGoogle Scholar
  106. 106.
    Chiovato L, Latrofa F, Braverman LE, Pacini F, Capezzone M, Masserini L, et al. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens. Ann Intern Med 2003; 139(5 Pt 1):346–351.PubMedGoogle Scholar
  107. 107.
    Lisi S, Pinchera A, McCluskey RT, Willnow TE, Refetoff S, Marcocci C, et al. Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: a control mechanism for thyroid hormone release. Proc Natl Acad Sci USA 2003; 100;(25):14858–14863.PubMedCrossRefGoogle Scholar
  108. 108.
    Marino M, Chiovato L, Friedlander JA, Latrofa F, Pinchera A, McCluskey RT. Serum antibodies against megalin (GP330) in patients with autoimmune thyroiditis. J Clin Endocrinol Metab 1999; 84;(7):2468–2474.PubMedCrossRefGoogle Scholar
  109. 109.
    Sakata S, Nakamura S, Miura K. Autoantibodies against thyroid hormones or iodothyronine. Implications in diagnosis, thyroid function, treatment, and pathogenesis. Ann Intern Med 1985; 103;(4):579–589.PubMedGoogle Scholar
  110. 110.
    Raspe E, Costagliola S, Ruf J, Mariotti S, Dumont JE, Ludgate M. Identification of the thyroid Na+/I- cotransporter as a potential autoantigen in thyroid autoimmune disease. Eur J Endocrinol 1995; 132;(4):399–405.PubMedGoogle Scholar
  111. 111.
    Endo T, Kogai T, Nakazato M, Saito T, Kaneshige M, Onaya T. Autoantibody against Na+/I-Symporter in the Sera of Patients with Autoimmune Thyroid Disease. Biochem Biophys Res Commun 1996; 224;(1):92–95.PubMedCrossRefGoogle Scholar
  112. 112.
    Chin HS, Chin DK, Morgenthaler NG, Vassart G, Costagliola S. Rarity of anti-Na+/I- symporter (NIS) antibody with iodide uptake inhibiting activity in autoimmune thyroid diseases (AITD). J Clin Endocrinol Metab 2000; 85;(10):3937–3940.PubMedCrossRefGoogle Scholar
  113. 113.
    Tonacchera M, Agretti P, Ceccarini G, Lenza R, Refetoff S, Santini F, et al. Autoantibodies from patients with autoimmune thyroid disease do not interfere with the activity of the human iodide symporter gene stably transfected in CHO cells. Eur J Endocrinol 2001; 144;(6):611–618.PubMedCrossRefGoogle Scholar
  114. 114.
    Seissler J, Wagner S, Schott M, Lettmann M, Feldkamp J, Scherbaum WA, et al. Low frequency of autoantibodies to the human Na(+)/I(-) symporter in patients with autoimmune thyroid disease. J Clin Endocrinol Metab 2000; 85;(12):4630–4634.PubMedCrossRefGoogle Scholar
  115. 115.
    Giordano C, Stassi G, De Maria R, Todaro M, Richiusa P, Papoff G, et al. Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto’s thyroiditis. Science 1997; 275;(5302):960–963.PubMedGoogle Scholar
  116. 116.
    Stokes TA, Rymaszewski M, Arscott PL, Wang SH, Bretz JD, Bartron J, et al. Constitutive expression of FasL in thyrocytes. Science 1998; 279:2015a.CrossRefGoogle Scholar
  117. 117.
    Fiedler P, Schaetzlein CE, Eibel H. Constitutive expression of FasL in thyrocytes. Science 1998; 279:2015a.CrossRefGoogle Scholar
  118. 118.
    Chiovato L, Bassi P, Santini F, Mammoli C, Lapi P, Carayon P, et al. Antibodies producing complement-mediated thyroid cytotoxicity in patients with atrophic or goitrous autoimmune thyroiditis. J Clin Endocrinol Metab 1993; 77;(6):1700–1705.PubMedCrossRefGoogle Scholar
  119. 119.
    Zimmer KP, Scheumann GF, Bramswig J, Bocker W, Harms E, Schmid KW. Ultrastructural localization of IgG and TPO in autoimmune thyrocytes referring to the transcytosis of IgG and the antigen presentation of TPO. Histochem Cell Biol 1997; 107;(2):115–120.PubMedCrossRefGoogle Scholar
  120. 120.
    Guo J, Jaume JC, Rapoport B, McLachlan SM. Recombinant thyroid peroxidase-specific Fab converted to immunoglobulin G (IgG) molecules: evidence for thyroid cell damage by IgG1, but not IgG4, autoantibodies. J Clin Endocrinol Metab 1997; 82;(3):925–931.PubMedCrossRefGoogle Scholar
  121. 121.
    Brostoff SW, Howell MD. T cell receptors, immunoregulation, and autoimmunity. Clin Immunol Immunopathol 1992; 62(1 Pt 1):1–7.PubMedCrossRefGoogle Scholar
  122. 122.
    Wenzel BE, Chow A, Baur R, Schleusener H, Wall JR. Natural killer cell activity in patients with Graves’ disease and Hashimoto’s thyroiditis. Thyroid 1998; 8;(11):1019–1022.PubMedGoogle Scholar
  123. 123.
    Okamoto Y, Hamada N, Saito H, Ohno M, Noh J, Ito K, et al. Thyroid peroxidase activity-inhibiting immunoglobulins in patients with autoimmune thyroid disease. J Clin Endocrinol Metab 1989; 68;(4):730–734.PubMedGoogle Scholar
  124. 124.
    Saller B, Hormann R, Mann K. Heterogeneity of autoantibodies against thyroid peroxidase in autoimmune thyroid disease: evidence against antibodies directly inhibiting peroxidase activity as regulatory factors in thyroid hormone metabolism. J Clin Endocrinol Metab 1991; 72;(1):188–195.PubMedGoogle Scholar
  125. 125.
    Nishikawa T, Jaume JC, McLachlan SM, Rapoport B. Human monoclonal autoantibodies against the immunodominant region on thyroid peroxidase: lack of cross-reactivity with related peroxidases or thyroglobulin and inability to inhibit thyroid peroxidase enzymatic activity. J Clin Endocrinol Metab 1995; 80;(4):1461–1466.PubMedCrossRefGoogle Scholar
  126. 126.
    Matsuura N, Yamada Y, Nohara Y, Konishi J, Kasagi K, Endo K, et al. Familial neonatal transient hypothyroidism due to maternal TSH-binding inhibitor immunoglobulins. N Engl J Med 1980; 303;(13):738–741.PubMedCrossRefGoogle Scholar
  127. 127.
    Zakarija M, McKenzie JM, Eidson MS. Transient neonatal hypothyroidism: characterization of maternal antibodies to the thyrotropin receptor. J Clin Endocrinol Metab 1990; 70;(5):1239–1246.PubMedCrossRefGoogle Scholar
  128. 128.
    Boyages SC, Halpern JP, Maberly GF, Eastman CJ, Chen J, Wang ZH, et al. Endemic cretinism: possible role for thyroid autoimmunity. Lancet 1989; 2;(8662):529–532.PubMedCrossRefGoogle Scholar
  129. 129.
    Chiovato L, Vitti P, Bendinelli G, Santini F, Fiore E, Tonacchera M, et al. Humoral thyroid autoimmunity is not involved in the pathogenesis of myxedematous endemic cretinism. J Clin Endocrinol Metab 1995; 80;(5):1509–1514.PubMedCrossRefGoogle Scholar
  130. 130.
    Michelangeli VP, Poon C, Topliss DJ, Colman PG. Specific effects of radioiodine treatment on TSAb and TBAb levels in patients with Graves’ disease. Thyroid 1995; 5;(3):171–176.PubMedGoogle Scholar
  131. 131.
    Chiovato L, Fiore E, Vitti P, Rocchi R, Rago T, Dokic D, et al. Outcome of thyroid function in Graves’ patients treated with radioiodine: role of thyroid-stimulating and thyrotropin-blocking antibodies and of radioiodine-induced thyroid damage. J Clin Endocrinol Metab 1998; 83;(1):40–46.PubMedCrossRefGoogle Scholar
  132. 132.
    Baloch ZW, Livolsi VA. Pathology. In: Braverman LE, Utiger RD, editors. Werner & Ingbar’s The Thyroid: a fundamental and clinical text. Philadelphia: Lippincott Williams & Wilkins, 2005.Google Scholar
  133. 133.
    Muller AF, Drexhage HA, Berghout A. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care. Endocr Rev 2001; 22;(5):605–630.PubMedCrossRefGoogle Scholar
  134. 134.
    Klintschar M, Schwaiger P, Mannweiler S, Regauer S, Kleiber M. Evidence of fetal microchimerism in Hashimoto’s thyroiditis. J Clin Endocrinol Metab 2001; 86;(6):2494–2498.PubMedCrossRefGoogle Scholar
  135. 135.
    Srivatsa B, Srivatsa S, Jhonson KL, Samura O, Lee SL, Bianchi DW. Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study. Lancet 2001; 358:2034–2038.PubMedCrossRefGoogle Scholar
  136. 136.
    Billewicz WZ, Chapman RS, Crooks J, Day ME, Gossage J, Wayne E, et al. Statistical methods applied to the diagnosis of hypothyroidism. Q J Med 1969; 38;(150):255–266.PubMedGoogle Scholar
  137. 137.
    Zulewski H, Muller B, Exer P, Miserez AR, Staub JJ. Estimation of tissue hypothyroidism by a new clinical score: evaluation of patients with various grades of hypothyroidism and controls. J Clin Endocrinol Metab 1997; 82;(3):771–776.PubMedCrossRefGoogle Scholar
  138. 138.
    Huber G, Staub JJ, Meier C, Mitrache C, Guglielmetti M, Huber P, et al. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab 2002; 87;(7):3221–3226.PubMedCrossRefGoogle Scholar
  139. 139.
    Tonacchera M, Chiovato L, Pinchera A. Clinical Assessment and systemic manifestations of hypothyroidism. In: Wass JAH, Shale SM, editors. Oxford Textbook of Endocrinology and Diabetes. Oxford, New York: Oxford University Press Inc., 2002: 491–502.Google Scholar
  140. 140.
    Krassas GE, Pontikides N, Kaltsas T, Papadopoulou P, Paunkovic J, Paunkovic N, et al. Disturbances of menstruation in hypothyroidism 2. Clin Endocrinol (Oxf) 1999; 50;(5):655–659.CrossRefGoogle Scholar
  141. 141.
    Sutherland JM, Esselborn VM, Burket RL, Skillman TB, Benson JT. Familial nongoitrous cretinism apparently due to maternal antithyroid antibody. Report of a family. N Engl J Med 1960; 263:336–341.PubMedCrossRefGoogle Scholar
  142. 142.
    Brown RS, Bellisario RL, Botero D, Fournier L, Abrams CA, Cowger ML, et al. Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies. J Clin Endocrinol Metab 1996; 81;(3):1147–1151.PubMedCrossRefGoogle Scholar
  143. 143.
    Foley TP, 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.PubMedCrossRefGoogle Scholar
  144. 144.
    Latrofa F, Pinchera A. Aging and the thyroid. Hot thyroidology (www hotthyroidology com) 2005; July(1).Google Scholar
  145. 145.
    Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, et al. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol (Oxf) 1999; 50;(2):149–155.CrossRefGoogle Scholar
  146. 146.
    Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999; 341;(8):549–555.PubMedCrossRefGoogle Scholar
  147. 147.
    Burrow GN, Fisher DA, Larsen PR. Maternal and fetal thyroid function. N Engl J Med 1994; 331;(16):1072–1078.PubMedCrossRefGoogle Scholar
  148. 148.
    Monzani F, Caraccio N, Del Guerra P, Casolaro A, Ferrannini E. Neuromuscular symptoms and dysfunction in subclinical hypothyroid patients: beneficial effect of L-T4 replacement therapy. Clin Endocrinol (Oxf) 1999; 51;(2):237–242.CrossRefGoogle Scholar
  149. 149.
    Bindels AJ, Westendorp RG, Frolich M, Seidell JC, Blokstra A, Smelt AH. The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding? Clin Endocrinol (Oxf) 1999; 50;(2):217–220.CrossRefGoogle Scholar
  150. 150.
    Kanaya AM, Harris F, Volpato S, Perez-Stable EJ, Harris T, Bauer DC. Association between thyroid dysfunction and total cholesterol level in an older biracial population: the health, aging and body composition study. Arch Intern Med 2002; 162;(7):773–779.PubMedCrossRefGoogle Scholar
  151. 151.
    Vitale G, Galderisi M, Lupoli GA, Celentano A, Pietropaolo I, Parenti N, et al. Left ventricular myocardial impairment in subclinical hypothyroidism assessed by a new ultrasound tool: pulsed tissue Doppler. J Clin Endocrinol Metab 2002; 87;(9):4350–4355.PubMedCrossRefGoogle Scholar
  152. 152.
    Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med 2002; 137;(11):904–914.PubMedGoogle Scholar
  153. 153.
    Faber J, Petersen L, Wiinberg N, Schifter S, Mehlsen J. Hemodynamic changes after levothyroxine treatment in subclinical hypothyroidism. Thyroid 2002; 12;(4):319–324.PubMedCrossRefGoogle Scholar
  154. 154.
    Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, et al. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab 2003; 88;(8):3731–3737.PubMedCrossRefGoogle Scholar
  155. 155.
    Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 2000; 132;(4):270–278.PubMedGoogle Scholar
  156. 156.
    Imaizumi M, Akahoshi M, Ichimaru S, Nakashima E, Hida A, Soda M, et al. Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J Clin Endocrinol Metab 2004; 89;(7):3365–3370.PubMedCrossRefGoogle Scholar
  157. 157.
    Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 2001; 358;(9285):861–865.PubMedCrossRefGoogle Scholar
  158. 158.
    Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004; 291;(2):228–238.PubMedCrossRefGoogle Scholar
  159. 159.
    Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab 2002; 87;(3):1068–1072.PubMedCrossRefGoogle Scholar
  160. 160.
    Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab 2005; 90;(9):5483–5488.PubMedCrossRefGoogle Scholar
  161. 161.
    Surks MI, Goswami G, Daniels GH. The thyrotropin reference range should remain unchanged. J Clin Endocrinol Metab 2005; 90;(9):5489–5496.PubMedCrossRefGoogle Scholar
  162. 162.
    Diez JJ, Iglesias P, Burman KD. Spontaneous normalization of thyrotropin concentrations in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 2005; 90;(7):4124–4127.PubMedCrossRefGoogle Scholar
  163. 163.
    Stagnaro-Green A, Roman SH, Cobin RH, el Harazy E, Alvarez-Marfany M, Davies TF. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA 1990; 264;(11):1422–1425.PubMedCrossRefGoogle Scholar
  164. 164.
    Glinoer D, Soto MF, Bourdoux P, Lejeune B, Delange F, Lemone M, et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J Clin Endocrinol Metab 1991; 73;(2):421–427.PubMedGoogle Scholar
  165. 165.
    Poppe K, Velkeniers B. Female infertility and the thyroid. Best Pract Res Clin Endocrinol Metab 2004; 18;(2):153–165.PubMedCrossRefGoogle Scholar
  166. 166.
    Poppe K, Glinoer D, Tournaye H, Devroey P, van Steirteghem A, Kaufman L, et al. Assisted reproduction and thyroid autoimmunity: an unfortunate combination? J Clin Endocrinol Metab 2003; 88;(9):4149–4152.PubMedCrossRefGoogle Scholar
  167. 167.
    Betterle C, Volpato M, Rees SB, Furmaniak J, Chen S, Zanchetta R, et al. II. Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison’s disease. J Clin Endocrinol Metab 1997; 82;(3):939–942.PubMedCrossRefGoogle Scholar
  168. 168.
    Kato I, Tajima K, Suchi T, Aozasa K, Matsuzuka F, Kuma K, et al. Chronic thyroiditis as a risk factor of B-cell lymphoma in the thyroid gland. Jpn J Cancer Res 1985; 76;(11):1085–1090.PubMedGoogle Scholar
  169. 169.
    Santini F, Pinchera A. Causes and laboratory investigation of hypothyroidism. In: Wass JAH, Shale SM, editors. Oxford textbook of endocrinology and diabetes. Oxford, New York: Oxford University Press Inc., 2006: 502–510.Google Scholar
  170. 170.
    Yoshida H, Amino N, Yagawa K, Uemura K, Satoh M, Miyai K, et al. Association of serum antithyroid antibodies with lymphocytic infiltration of the thyroid gland: studies of seventy autopsied cases. J Clin Endocrinol Metab 1978; 46:859–862.PubMedGoogle Scholar
  171. 171.
    McKenzie JM, Zakarija M. Clinical review 3: The clinical use of thyrotropin receptor antibody measurements. J Clin Endocrinol Metab 1989; 69;(6):1093–1096.PubMedGoogle Scholar
  172. 172.
    Set PA, Oleszczuk-Raschke K, von Lengerke JH, Bramswig J. Sonographic features of Hashimoto thyroiditis in childhood. Clin Radiol 1996; 51;(3):167–169.PubMedCrossRefGoogle Scholar
  173. 173.
    Jansson R, Karlsson A, Dahlberg PA. Thyroxine, methimazole, and thyroid microsomal autoantibody titres in hypothyroid Hashimoto’s thyroiditis. Br Med J (Clin Res Ed) 1985; 290;(6461):11–12.Google Scholar
  174. 174.
    Hayashi Y, Tamai H, Fukata S, Hirota Y, Katayama S, Kuma K, et al. A long term clinical, immunological, and histological follow-up study of patients with goitrous chronic lymphocytic thyroiditis. J Clin Endocrinol Metab 1985; 61;(6):1172–1178.PubMedCrossRefGoogle Scholar
  175. 175.
    Papapetrou PD, Lazarus JM, McSween RNM, Harden RM. Long-term treatment of Hashimoto’s thyroiditis with thyroxine. Lancet 1972; 2;(7786):1045–1048.PubMedCrossRefGoogle Scholar
  176. 176.
    Chiovato L, Marcocci C, Mariotti S, Mori A, Pinchera A. L-thyroxine therapy induces a fall of thyroid microsomal and thyroglobulin antibodies in idiopathic myxedema and in hypothyroid, but not in euthyroid Hashimoto’s thyroiditis. J Endocrinol Invest 1986; 9;(4):299–305.PubMedGoogle Scholar
  177. 177.
    Marcocci C, Vitti P, Cetani F, Catalano F, Concetti R, Pinchera A. Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism. J Clin Endocrinol Metab 1991; 72;(1):209–213.PubMedGoogle Scholar
  178. 178.
    Surks MI, Chopra IJ, Mariash CN, Nicoloff JT, Solomon DH. American Thyroid Association guidelines for use of laboratory tests in thyroid disorders. JAMA 1990; 263;(11):1529–1532.PubMedCrossRefGoogle Scholar
  179. 179.
    Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994; 331;(19):1249–1252.PubMedCrossRefGoogle Scholar
  180. 180.
    Bauer DC, Ettinger B, Nevitt MC, Stone KL. Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med 2001; 134;(7):561–568.PubMedGoogle Scholar
  181. 181.
    Santini F, Pinchera A, Marsili A, Ceccarini G, Castagna MG, Valeriano R, et al. Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases. J Clin Endocrinol Metab 2005; 90;(1):124–127.PubMedCrossRefGoogle Scholar
  182. 182.
    Zindrou D, Taylor KM, Bagger JP. Excess coronary artery bypass graft mortality among women with hypothyroidism. Ann Thorac Surg 2002; 74;(6):2121–2125.PubMedCrossRefGoogle Scholar
  183. 183.
    Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med 2001; 344;(23):1743–1749.PubMedCrossRefGoogle Scholar
  184. 184.
    Centanni M, Gargano L, Canettieri G, Viceconti N, Franchi A, Delle FG, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med 2006; 354;(17):1787–1795.PubMedCrossRefGoogle Scholar
  185. 185.
    Pinchera A, Santini F. Is combined therapy with levothyroxine and liothyronine effective in patients with primary hypothyroidism? Nat Clin Pract Endocrinol Metab 2005; 1;(1):19.CrossRefGoogle Scholar
  186. 186.
    Escobar-Morreale HF, Botella-Carretero JI, del Rey FE, de Escobar GM. Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine. J Clin Endocrinol Metab 2005; 90;(8):4946–4954.PubMedCrossRefGoogle Scholar
  187. 187.
    Taylor S, Kapur M, Adie R. Combined thyroxine and triiodothyronine for thyroid replacement therapy. Br Med J 1970; 1;(704):270–271.Google Scholar
  188. 188.
    Smith RN, Taylor SA, Massey JC. Controlled clinical trial of combined triiodothyronine and thyroxine in the treatment of hypothyroidism. Br Med J 1970; 4;(728):145–148.PubMedGoogle Scholar
  189. 189.
    Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 1999; 340;(6):424–429.PubMedCrossRefGoogle Scholar
  190. 190.
    Walsh JP, Shiels L, Lim EM, Bhagat CI, Ward LC, Stuckey BGA, et al. Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism. J Clin Endocrinol Metab 2003; 88;(10):4543–4550.PubMedCrossRefGoogle Scholar
  191. 191.
    Sawka AM, Gerstein HC, Marriott MJ, MacQueen GM, Joffe RT. Does a combination regimen of thyroxine (t4) and 3,5,3’-triiodothyronine improve depressive symptoms better than t4 alone in patients with hypothyroidism? Results of a Double-Blind, Randomized, Controlled Trial. J Clin Endocrinol Metab 2003; 88;(10):4551–4555.PubMedCrossRefGoogle Scholar
  192. 192.
    Clyde PW, Harari AE, Getka EJ, Shakir KM. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. JAMA 2003; 290;(22):2952–2958.PubMedCrossRefGoogle Scholar
  193. 193.
    Saravanan P, Simmons DJ, Greenwood R, Peters TJ, Dayan CM. Partial substitution of thyroxine (T4) with tri-iodothyronine in patients on T4 replacement therapy: results of a large community-based randomized controlled trial. J Clin Endocrinol Metab 2005; 90;(2):805–812.PubMedCrossRefGoogle Scholar
  194. 194.
    Appelhof BC, Fliers E, Wekking EM, Schene AH, Huyser J, Tijssen JGP, et al. 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;(5):2666–2674.PubMedCrossRefGoogle Scholar
  195. 195.
    Mandel SJ, Larsen PR, Seely EW, Brent GA. Increased need for thyroxine during pregnancy in women with primary hypothyroidism. N Engl J Med 1990; 323;(2):91–96.PubMedCrossRefGoogle Scholar
  196. 196.
    Mandel SJ. Hypothyroidism and chronic autoimmune thyroiditis in the pregnant state: maternal aspects. Best Pract Res Clin Endocrinol Metab 2004; 18;(2):213–224.PubMedCrossRefGoogle Scholar
  197. 197.
    Escobar GMd, Obregon MJ, del Rey FEd. Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract Res Clin Endocrinol Metab 2004; 18;(2):225–248.PubMedCrossRefGoogle Scholar
  198. 198.
    Caixas A, Albareda M, Garcia-Patterson A, Rodriguez-Espinosa J, de Leiva A, Corcoy R. Postpartum thyroiditis in women with hypothyroidism antedating pregnancy? J Clin Endocrinol Metab 1999; 84;(11):4000–4005.PubMedCrossRefGoogle Scholar
  199. 199.
    Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT. Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the american thyroid association, and the endocrine society. Thyroid 2005; 15;(1):24–28.PubMedCrossRefGoogle Scholar
  200. 200.
    Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT. Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. J Clin Endocrinol Metab 2005; 90;(1):581–585.PubMedCrossRefGoogle Scholar
  201. 201.
    Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab 2002; 87;(4):1533–1538.PubMedCrossRefGoogle Scholar
  202. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285;(19):2486–2497.Google Scholar
  203. 203.
    O’Keefe JH, Jr., Cordain L, Harris WH, Moe RM, Vogel R. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol 2004; 43;(11):2142–2146.PubMedCrossRefGoogle Scholar
  204. 204.
    Tanis BC, Westendorp GJ, Smelt HM. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies. Clin Endocrinol (Oxf) 1996; 44;(6):643–649.CrossRefGoogle Scholar
  205. 205.
    Danese MD, Ladenson PW, Meinert CL, Powe NR. Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab 2000; 85;(9):2993–3001.PubMedCrossRefGoogle Scholar
  206. 206.
    Meier C, Staub JJ, Roth CB, Guglielmetti M, Kunz M, Miserez AR, et al. TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study). J Clin Endocrinol Metab 2001; 86;(10):4860–4866.PubMedCrossRefGoogle Scholar
  207. 207.
    Efstathiadou Z, Bitsis S, Milionis HJ, Kukuvitis A, Bairaktari ET, Elisaf MS, et al. Lipid profile in subclinical hypothyroidism: is L-thyroxine substitution beneficial? Eur J Endocrinol 2001; 145;(6):705–710.PubMedCrossRefGoogle Scholar
  208. 208.
    Kong WM, Sheikh MH, Lumb PJ, Naoumova RP, Freedman DB, Crook M, et al. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Am J Med 2002; 112;(5):348–354.PubMedCrossRefGoogle Scholar
  209. 209.
    Biondi B, Fazio S, Palmieri EA, Carella C, Panza N, Cittadini A, et al. Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 1999; 84;(6):2064–2067.PubMedCrossRefGoogle Scholar
  210. 210.
    Aghini-Lombardi F, Di Bello V, Talini E, Di Cori A, Monzani F, Antonangeli L, et al. Early textural and functional alterations of left ventricula myocardium in mild hypothyroidism. Eur J Endocrinol 2006; 155:3–9.PubMedCrossRefGoogle Scholar
  211. 211.
    Vanderpump M. Subclinical hypothyroidism: the case against treatment. Trends Endocrinol Metab 2003; 14;(6):262–266.PubMedCrossRefGoogle Scholar
  212. 212.
    McDermott MT, Ridgway EC. Subclinical hypothyroidism is mild thyroid failure and should be treated. J Clin Endocrinol Metab 2001; 86;(10):4585–4590.PubMedCrossRefGoogle Scholar
  213. 213.
    Owen PJ, Lazarus JH. Subclinical hypothyroidism: the case for treatment. Trends Endocrinol Metab 2003; 14;(6):257–261.PubMedCrossRefGoogle Scholar
  214. 214.
    Stagnaro-Green A, Glinoer D. Thyroid autoimmunity and the risk of miscarriage. Best Pract Res Clin Endocrinol Metab 2004; 18;(2):167–181.PubMedCrossRefGoogle Scholar
  215. 215.
    Ladenson PW, Singer PA, Ain KB, Bagchi N, Bigos ST, Levy EG, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med 2000; 160;(11):1573–1575.PubMedCrossRefGoogle Scholar
  216. 216.
    AACE Thyroid Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002; 8:457–469.Google Scholar
  217. 217.
    U.S.Preventive Service Task Force. Screening for thyroid disease: recommendation statement. Ann Intern Med 2004; 140;(2):125–127.Google Scholar
  218. 218.
    Vanderpump MP, Tunbridge WM. Epidemiology and prevention of clinical and subclinical hypothyroidism. Thyroid 2002; 12;(10):839–847.PubMedCrossRefGoogle Scholar
  219. 219.
    Morreale de Escobar G, Jesus Obregon M, Escobar del Rey F. Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab 2000; 85;(11):3975–3987.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Francesco Latrofa
  • Aldo Pinchera

There are no affiliations available

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