THYROID AUTOANTIBODIES

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Hashimoto56 described dense lymphoid infiltration causing goiter and hypothyroidism in 1912; however, it was not until 1956 that autoantibodies, that is, antithyroglobulin antibodies (anti-Tg), were detected in this condition,115 leading to the novel concept that diseases could be caused by an autoimmune process. Evidence for a serum thyroid-stimulating factor was presented in the same year,1 a substance later shown to be antibodies to the thyroid-stimulating hormone (TSH) receptor.73 The discovery of antibodies to the thyroid microsomal antigen followed in 1964,116 a substance later recognized as thyroid peroxidase (TPO). Since then, several other antigenic targets in the thyroid have been proposed, the most consistent of which have been the rare finding of anti–thyroid hormone autoantibodies114 and the recent recognition of the sodium-iodide symporter (NIS) as an autoantigenic target.37

Commercial assays to measure anti-Tg, anti-TPO, and anti–TSH receptor antibodies are now available. Widespread application of these tests has identified autoimmune thyroid disease as the most common autoimmune condition, with approximately 2% of women and 0.2% of men affected at the clinical level.134 The prevalence of subclinical disease is now known to be tenfold higher.139 This article reviews the immunobiology of thyroid autoantibodies and the available detection techniques and discusses current indications for thyroid autoantibody testing in clinical practice.

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IMMUNOBIOLOGY OF THYROID AUTOANTIBODIES

Table 1 summarizes the properties of the four best-defined protein antigenic targets of thyroid autoantibodies. Antibodies to other antigens have also been described, including a second colloid component and growth-stimulating or inhibiting antibodies, but their clinical significance is either controversial or not proved.11, 35, 36, 88, 89, 135 Autoantibodies to the thyroid hormones (T4 and T3) also spontaneously occur, usually in association with anti-Tg antibodies, and can cause important

Antithyroglobulin and Antimicrosomal/Thyroid Peroxidase Assays

Early techniques to measure thyroid autoantibodies included precipitation and diffusion techniques for anti-Tg and the complement fixation test for antimicrosomal antibodies. These tests gave way to immunofluorescence using human or primate thyroid tissue or passive (tanned) erythrocyte hemagglutination assays; however, these assays were only semiquantitative and required experienced interpretative skills. Immunoassays using purified Tg or recombinant TPO (as the microsomal antigen) are now in

Diagnosing the Cause of Thyrotoxicosis

At diagnosis, anti-Tg antibodies are present in as many as 30% and anti-TPO antibodies in as many as 80% of patients with clinical Graves' disease (see Table 2). TSH receptor antibody assays are more sensitive, and TSAb measurements tend to be more sensitive (85% to 100%) than TBII measurements (75% to 96%) in untreated Graves' disease.27, 130, 150 TBII positivity alone still correlates remarkably well with disease, supporting the widespread use of this simpler assay method. As discussed

Differentiated Thyroid Cancer

Serial measurements of serum Tg levels are valuable in identifying recurrences of differentiated thyroid cancer76; however, when anti-Tg antibodies are present, Tg assay results become unreliable owing to immunointerference, even when recovery of added Tg is simultaneously estimated.125 Anti–Tg antibody testing is mandatory in patients in whom serial Tg measurements are planned and is the only indication for antithyroid antibody testing in differentiated thyroid cancer. This indication remains

SUMMARY AND FUTURE PROSPECTS

The prevalence of and predictive value of testing for thyroid autoantibody have been studied in a wide variety of conditions. Table 7 summarizes the authors' view on the current clinical indications for the use of these tests. Anti–TPO antibody testing by immunoassay has replaced anti-Tg and antimicrosomal antibody testing in routine practice because of its improved sensitivity and specificity and should be easily available to all physicians who manage thyroid disease. Currently, the only clear

References (150)

  • S. Mariotti et al.

    Thyroid autoimmunity and aging

    Exp Gerontol

    (1998)
  • S. Mariotti et al.

    Thyroid and other organ-specific autoantibodies in healthy centenarians

    Lancet

    (1992)
  • N. Matsuura et al.

    TSH-receptor antibodies in mothers with Graves' disease and outcome in their offspring

    Lancet

    (1988)
  • J. Orgiazzi

    Anti-TSH receptor antibodies in clinical practice

    Endocrinol Metab Clin North Am

    (2000)
  • D.D. Adams et al.

    Abnormal responses in the assay of thyrotropin

    Proc Univ Otago Med Sch

    (1956)
  • K. Aho et al.

    Development of thyroid autoimmunity

    Acta Endocrinol (Copenh)

    (1985)
  • R.A. Ajjan et al.

    Detection of binding and blocking autoantibodies to the human sodium-iodide symporter in patients with autoimmune thyroid disease

    J Clin Endocrinol Metab

    (2000)
  • T. Akamizu et al.

    Molecular studies on thyrotropin (TSH) receptor and anti-TSH receptor antibodies

    Endocr J

    (1995)
  • T. Akamizu et al.

    Pathogenesis of Graves' disease: Molecular analysis of anti-thyrotropin receptor antibodies

    Endocr J

    (1997)
  • M. Alvarez-Marfany et al.

    Long-term prospective study of postpartum thyroid dysfunction in women with insulin-dependent diabetes mellitus

    J Clin Endocrinol Metab

    (1994)
  • N. Amino et al.

    Measurement of circulating thyroid microsomal antibodies by the tanned red cell haemagglutination technique: Its usefulness in the diagnosis of autoimmune thyroid diseases

    Clin Endocrinol (Oxf)

    (1976)
  • R.S. Bahn et al.

    Thyrotropin receptor expression in cultured Graves' orbital preadipocyte fibroblasts is stimulated by thyrotropin

    Thyroid

    (1998)
  • R.S. Bahn et al.

    Thyrotropin receptor expression in Graves' orbital adipose/connective tissues: Potential autoantigen in Graves' ophthalmopathy

    J Clin Endocrinol Metab

    (1998)
  • B.M. Balfour et al.

    Fluorescent antibody studies in human thyroiditis: Auto-antibodies to an antigen of the thyroid colloid distinct from thyroglobulin

    Br J Exp Pathol

    (1961)
  • M.P. Barbato

    Thyroid autoantibodies in an Australian community

    Med J Aust

    (1978)
  • K. Bech et al.

    Thyroid function and autoimmune manifestations in insulin-dependent diabetes mellitus during and after pregnancy

    Acta Endocrinol (Copenh)

    (1991)
  • T. Bednarczuk et al.

    Autoantibodies reactive with extracellular matrix proteins in patients with thyroid-associated ophthalmopathy

    Thyroid

    (1999)
  • K. Beever et al.

    Highly sensitive assays of autoantibodies to thyroglobulin and to thyroid peroxidase

    Clin Chem

    (1989)
  • G. Benker et al.

    Response to methimazole in Graves' disease: The European Multicenter Study Group

    Clin Endocrinol (Oxf)

    (1995)
  • H. Brochmann et al.

    Prevalence of thyroid dysfunction in elderly subjects: A randomized study in a Norwegian rural community (Naeroy)

    Acta Endocrinol (Copenh)

    (1988)
  • B. Bryhni et al.

    Thyroid antibodies in northern Norway: Prevalence, persistence and relevance

    J Intern Med

    (1996)
  • H.B. Burch et al.

    Graves' ophthalmopathy: Current concepts regarding pathogenesis and management

    Endocr Rev

    (1993)
  • S. Bussen et al.

    Thyroid autoantibodies in euthyroid non-pregnant women with recurrent spontaneous abortions

    Hum Reprod

    (1995)
  • B. Caillou et al.

    Na+/I− symporter distribution in human thyroid tissues: An immunohistochemical study

    J Clin Endocrinol Metab

    (1998)
  • G.D. Chazenbalk et al.

    A mouse monoclonal antibody to a thyrotropin receptor ectodomain variant provides insight into the exquisite antigenic conformational requirement, epitopes and in vivo concentration of human autoantibodies

    J Clin Endocrinol Metab

    (1999)
  • L. Chiovato 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 [published erratum appears in J Clin Endocrinol Metab 1998 Jun;83(6):2155]

    J Clin Endocrinol Metab

    (1998)
  • B.Y. Cho et al.

    High prevalence and little change in TSH receptor blocking antibody titres with thyroxine and antithyroid drug therapy in patients with nongoitrous autoimmune thyroiditis

    Clin Endocrinol (Oxf)

    (1995)
  • I.J. Chopra et al.

    Specific and nonspecific response in the bioassay of the long-acting thyroid stimulator (LATS)

    J Clin Endocrinol Metab

    (1970)
  • D.A. Clark

    Controversies in reproductive immunology

    Crit Rev Immunol

    (1991)
  • S. Costagliola et al.

    Second-generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves' disease

    J Clin Endocrinol Metab

    (1999)
  • G. Dai et al.

    Cloning and characterization of the thyroid iodide transporter

    Nature

    (1996)
  • T.F. Davies et al.

    Thyroid controversy—stimulating antibodies

    J Clin Endocrinol Metab

    (1998)
  • C.M. Dayan

    The natural history of autoimmune thyroiditis: How normal is autoimmunity?

    Proc R Coll Physicians Edinb

    (1996)
  • C.M. Dayan et al.

    Chronic autoimmune thyroiditis

    N Engl J Med

    (1996)
  • R.K. Desai et al.

    Autoantibodies to thyroxin and triiodothyronine

    Clin Chem

    (1988)
  • H.A. Drexhage et al.

    The involvement of the pentose shunt in thyroid metabolism after stimulation with TSH or with immunoglobulins from patients with thyroid disease: 1. The generation of NADPH in relation to stimulation of thyroid growth

    Clin Endocrinol (Oxf)

    (1982)
  • C. Evans et al.

    Development of a luminescent bioassay for thyroid stimulating antibodies

    J Clin Endocrinol Metab

    (1999)
  • U. Feldt-Rasmussen

    Analytical and clinical performance goals for testing autoantibodies to thyroperoxidase, thyroglobulin, and thyrotropin receptor

    Clin Chem

    (1996)
  • M. Garcia et al.

    AACE clinical practice guidelines for the evaluation and treatment of hyperthyroidism and hypothyroidism

    Endocr Pract

    (1995)
  • M.N. Gerding et al.

    Association of thyrotrophin receptor antibodies with the clinical features of Graves' ophthalmopathy

    Clin Endocrinol (Oxf)

    (2000)
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    Address reprint requests to Colin M. Dayan, MB, FRCP, PhD, University Division of Medicine Laboratories, Bristol Royal Infirmary, Bristol, United Kingdom BS2 8HW, e-mail: [email protected]

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    Division of Medicine, University of Bristol, Bristol, United Kingdom

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