Horm Metab Res 2016; 48(10): 623-629
DOI: 10.1055/s-0042-112815
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Anti-Thyroperoxidase Antibody Levels >500 IU/ml Indicate a Moderately Increased Risk for Developing Hypothyroidism in Autoimmune Thyroiditis

M. Ehlers*
1   Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany
,
A-L. Jordan*
1   Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany
,
J. Feldkamp
2   Department for Endocrinology and Diabetes, Municipal Hospital Bielefeld, Bielefeld, Germany
,
R. Fritzen
3   Outpatient Clinic for Endocrinology, Aachener Platz, Duesseldorf, Germany
,
B. Quadbeck
4   Outpatient Clinic for Endocrinology, Duesseldorf, Germany
,
M. Haase
1   Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany
,
S. Allelein
1   Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany
,
C. Schmid
1   Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany
,
M. Schott
1   Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany
› Author Affiliations
Further Information

Publication History

received 12 October 2015

accepted 08 July 2016

Publication Date:
08 September 2016 (online)

Abstract

Autoimmune Thyroiditis (AIT) is the most common autoimmune disease, which is characterized by cellular and humoral immunity leading to thyroid destruction. The impact of the humoral immunity on the risk to develop hypothyroidism has not exactly been defined yet. The aim of the present study was to investigate the association between thyroid antibody levels and the risk for developing hypothyroidism. In this retrospective study, 335 untreated AIT patients were enrolled. Anti-thyroperoxidase (TPO) antibodies, anti-thyroglobulin (Tg) antibodies (Abs), and the TSH level were measured. Patients with TPO-Ab levels>500 IU/ml showed a moderately increased risk of having elevated TSH levels [p=0.0023; relative risk (95% confidence interval): 1.343 (1.108–1.627)] compared to those below this threshold. AIT patients with TPO- or Tg-Abs<100 IU/ml and between 100–500 IU/ml had no significantly different TSH levels. Presence of Tg-Abs alone or in combination with TPO-Abs did not help to increase the sensitivity to identify patients at risk. Long term follow-up of AIT patients with high TPO-Abs level (>500 IU/ml) showed an increase of TSH levels (mean: 0.5 mIU/l; range: 2.52±2.73 to 3.02±3.05 mIU/l; p=0.0420). Still, these patients remained euthyroid. Our data indicate largely elevated levels of TPO-Abs being associated with a moderately increased risk of developing hypothyroidism.

* Both authors contributed equally to this study


Supporting Information

 
  • References

  • 1 McLachlan SM, Rapoport B. Breaking tolerance to thyroid antigens: changing concepts in thyroid autoimmunity. Endocr Rev 2014; 35: 59-105
  • 2 Kong YM, Brown NK, Morris GP, Flynn JC. The Essential Role of Circulating Thyroglobulin in Maintaining Dominance of Natural Regulatory T Cell Function to Prevent Autoimmune Thyroiditis. Horm Metab Res 2015; 47: 711-720
  • 3 Jacobson EM, Tomer Y. The genetic basis of thyroid autoimmunity. Thyroid 2007; 17: 949-961
  • 4 Bernecker C, Ostapczuk M, Vordenbaumen S, Ehlers M, Thiel A, Schinner S, Willenberg H, Scherbaum WA, Schott M. HLA-A2 phenotype may be protective against Graves’ disease but not against Hashimoto’s thyroiditis in Caucasians. Horm Metab Res 2013; 45: 74-77
  • 5 Tomer Y, Davies TF. Infection, thyroid disease, and autoimmunity. Endocr Rev 1993; 14: 107-120
  • 6 Rose NR, Bonita R, Burek CL. Iodine: an environmental trigger of thyroiditis. Autoimmun Rev 2002; 1: 97-103
  • 7 Duntas LH. The Role of Iodine and Selenium in Autoimmune Thyroiditis. Horm Metab Res 2015; 47: 721-726
  • 8 Wimmer I, Hartmann T, Brustbauer R, Minear G, Dam K. Selenium levels in patients with autoimmune thyroiditis and controls in lower Austria. Horm Metab Res 2014; 46: 707-709
  • 9 Furmaniak J, Sanders J, Nunez Miguel R, Rees Smith B. Mechanisms of Action of TSHR Autoantibodies. Horm Metab Res 2015; 47: 735-752
  • 10 Bahn RS. Current Insights into the Pathogenesis of Graves’ Ophthalmopathy. Horm Metab Res 2015; 47: 773-778
  • 11 Banga JP, Moshkelgosha S, Berchner-Pfannschmidt U, Eckstein A. Modeling Graves’ Orbitopathy in Experimental Graves’ Disease. Horm Metab Res 2015; 47: 797-803
  • 12 Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003; 348: 2646-2655
  • 13 Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers H, Tunbridge F, Young ET. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995; 43: 55-68
  • 14 Ehlers M, Thiel A, Bernecker C, Porwol D, Papewalis C, Willenberg HS, Schinner S, Hautzel H, Scherbaum WA, Schott M. Evidence of a combined cytotoxic thyroglobulin and thyroperoxidase epitope-specific cellular immunity in Hashimoto’s thyroiditis. J Clin Endocrinol Metab 2012; 97: 1347-1354
  • 15 Drugarin D, Negru S, Koreck A, Zosin I, Cristea C. The pattern of a T(H)1 cytokine in autoimmune thyroiditis. Immunol Lett 2000; 71: 73-77
  • 16 Kemp EH, Metcalfe RA, Smith KA, Woodroofe MN, Watson PF, Weetman AP. Detection and localization of chemokine gene expression in autoimmune thyroid disease. Clin Endocrinol 2003; 59: 207-213
  • 17 Ruffilli I, Ferrari SM, Colaci M, Ferri C, Fallahi P, Antonelli A. IP-10 in autoimmune thyroiditis. Horm Metab Res 2014; 46: 597-602
  • 18 Ahmed R, Al-Shaikh S, Akhtar M. Hashimoto thyroiditis: a century later. AdvAnatPathol 2012; 19: 181-186
  • 19 Latina A, Gullo D, Trimarchi F, Benvenga S. Hashimoto’s thyroiditis: similar and dissimilar characteristics in neighboring areas. Possible implications for the epidemiology of thyroid cancer. PLoS One 2013; 8: e55450
  • 20 Ajjan RA, Weetman AP. The Pathogenesis of Hashimoto’s Thyroiditis: Further Developments in our Understanding. Horm Metab Res 2015; 47: 702-710
  • 21 Bjoro T, Holmen J, Kruger O, Midthjell K, Hunstad K, Schreiner T, Sandnes L, Brochmann H. Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT). Eur J Endocrinol 2000; 143: 639-647
  • 22 Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. 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
  • 23 Pedersen IB, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Laurberg P. Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency. Clin Endocrinol 2003; 58: 36-42
  • 24 Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol 1977; 7: 481-493
  • 25 Diez JJ. Hypothyroidism in patients older than 55 years: an analysis of the etiology and assessment of the effectiveness of therapy. J Gerontol Series A Biol Sci Med Sci 2002; 57: M315-M320
  • 26 Engler H, Riesen WF, Keller B. Anti-thyroid peroxidase (anti-TPO) antibodies in thyroid diseases, non-thyroidal illness and controls. Clinical validity of a new commercial method for detection of anti-TPO (thyroid microsomal) autoantibodies. Clin Chim Acta 1994; 225: 123-136
  • 27 Mariotti S, Caturegli P, Piccolo P, Barbesino G, Pinchera A. Antithyroid peroxidase autoantibodies in thyroid diseases. J Clin Endocrinol Metab 1990; 71: 661-669
  • 28 Tamaki H, Amino N, Iwatani Y, Matsuzuka F, Kuma K, Miyai K. Detection of thyroid microsomal and thyroglobulin antibodies by new sensitive radioimmunoassay in Hashimoto’s disease; comparison with conventional hemagglutination assay. Endocrinol Japon 1991; 38: 97-101
  • 29 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: 1382-1386
  • 30 Carle A, Laurberg P, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, Jorgensen T, Pedersen IB. Thyroid peroxidase and thyroglobulin auto-antibodies in patients with newly diagnosed overt hypothyroidism. Autoimmunity 2006; 39: 497-503
  • 31 Spencer CA, Hollowell JG, Kazarosyan M, Braverman LE. National Health and Nutrition Examination Survey III thyroid-stimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction. J Clin Endocrinol Metab 2007; 92: 4236-4240
  • 32 Sell MA, Schott M, Tharandt L, Cissewski K, Scherbaum WA, Willenberg HS. Functional central hypothyroidism in the elderly. Aging Clin Exp Res 2008; 20: 207-210
  • 33 Strieder TG, Prummel MF, Tijssen JG, Endert E, Wiersinga WM. Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease. Clin Endocrinol 2003; 59: 396-401
  • 34 Watanabe M, Yamamoto N, Maruoka H, Tamai H, Matsuzuka F, Miyauchi A, Iwatani Y. Independent involvement of CD8+ CD25+ cells and thyroid autoantibodies in disease severity of Hashimoto’s disease. Thyroid 2002; 12: 801-808
  • 35 Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 2010; 464: 1293-1300
  • 36 Rotondi M, de Martinis L, Coperchini F, Pignatti P, Pirali B, Ghilotti S, Fonte R, Magri F, Chiovato L. Serum negative autoimmune thyroiditis displays a milder clinical picture compared with classic Hashimoto’s thyroiditis. Eur J Endocrinol 2014; 171: 31-36