Induction of stimulating thyrotropin receptor antibodies after radioiodine therapy for toxic multinodular goitre and Graves' disease measured with a novel bioassay

BackgroundRadioactive iodine therapy (RaI) in toxic multinodular goitre (TMNG) has been associated with the occurrence of Graves'-like hyperthyroidism. It has been postulated that pre-existing autoimmunity may contribute to this phenomenon. ObjectiveTo study whether RaI induces thyrotropin receptor stimulating antibodies (TSAbs) in the short term in TMNG and whether pre-existing autoimmunity is relevant. PatientsThirty-one patients with relapsing Graves' disease and 17 patients with TMNG, all eligible for RaI. MethodsBefore and 6 weeks after RaI, sera were collected and analysed for the presence of thyroglobulin (Tg), thyroid peroxidase antibodies (TPO-Abs) and thyrotropin receptor binding antibodies (TBIIs). TSAbs were analysed with a novel high-sensitive luciferase-based bioassay based on the JP-26-26 cell line, which constitutively expresses the TSH receptor. ResultsIn Graves' disease, RaI did not induce or increase the levels and proportion of patients with measurable levels of any of the antibodies measured, despite a significant increase in Tg. In contrast, in TMNG, RaI induced TBIIs in three TMNG patients, which was accompanied by measurable TSAbs on one occasion. ConclusionsWe conclude from the present study that induction of TBIIs and TSAbs may occur shortly after RaI in TMNG and that pre-existing autoimmunity may not be a requirement for the induction of TBIIs, as evidenced by the lack of effect of RaI on TBIIs in Graves' disease.

[1]  J. Romijn,et al.  A bioluminescence assay for thyrotropin receptor antibodies predicts serum thyroid hormone levels in patients with de novo Graves’ disease , 2006, Clinical endocrinology.

[2]  C. Schuemichen,et al.  Incidence of radiation-induced Graves’ disease in patients treated with radioiodine for thyroid autonomy before and after introduction of a high-sensitivity TSH receptor antibody assay , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[3]  N. Morgenthaler,et al.  A coated tube assay for the detection of blocking thyrotropin receptor autoantibodies. , 2004, The Journal of clinical endocrinology and metabolism.

[4]  A. Syed,et al.  Early Changes in Thyroid-Stimulating Antibody Activity following Radioiodine Therapy , 2003, Medical Principles and Practice.

[5]  R. Paschke,et al.  Induction of TSH-receptor antibodies in patients with toxic multinodular goitre by radioiodine treatment. , 2002, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[6]  N. Takasu,et al.  TSBAb (TSH-stimulation blocking antibody) and TSAb (thyroid stimulating antibody) in TSBAb-positive patients with hypothyroidism and Graves' patients with hyperthyroidism. , 2001, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[7]  N. Morgenthaler,et al.  A luminescent bioassay for thyroid blocking antibodies , 2001, Clinical endocrinology.

[8]  J. Soule,et al.  Graves' disease after 131I therapy for toxic nodule. , 2001, Thyroid : official journal of the American Thyroid Association.

[9]  A. D. de Craen,et al.  Clinical outcome after standardized versus dosimetric radioiodine treatment of hyperthyroidism: an equivalence study , 2000, Nuclear medicine communications.

[10]  Y. Ochi,et al.  Augmentative Effect of Polyethylene Glycol, Polyvinyl Alcohol and Dextran on Thyroid-Stimulating Antibody Stimulated cAMP Production in FRTL-5 Cells and CHO Cells Expressing Human TSH Receptor , 2000, Hormone Research in Paediatrics.

[11]  P. Fergelot,et al.  Use of Chinese hamster ovary cell lines transfected with cloned human thyrotropin receptor for the measurement of thyroid-stimulating antibodies: advantages and difficulties. , 2000, Clinica chimica acta; international journal of clinical chemistry.

[12]  L. Hegedüs,et al.  Graves’ disease and thyroid associated ophthalmopathy triggered by 131I treatment of non-toxic goiter , 1999, Journal of endocrinological investigation.

[13]  L. Hegedüs,et al.  Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131I therapy. , 1999, Thyroid : official journal of the American Thyroid Association.

[14]  R. Paschke,et al.  Detection of thyroid stimulating (TSAB)‐ and thyrotropin stimulation blocking (TSBAB) antibodies with CHO cell lines expressing different TSH‐receptor numbers , 1999, Clinical endocrinology.

[15]  N. Morgenthaler,et al.  Development of a luminescent bioassay for thyroid stimulating antibodies. , 1999, The Journal of clinical endocrinology and metabolism.

[16]  B. Rapoport,et al.  The Thyrotropin (TSH)-Releasing Hormone Receptor: Interaction with TSH and Autoantibodies , 1998 .

[17]  Watson,et al.  A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease , 1998, Clinical endocrinology.

[18]  T. Satoh,et al.  Preserved activation of thyrotropin receptor antibody to stimulate thyroid function despite long-term treatment in euthyroid patients with Graves' disease. , 1998, European journal of endocrinology.

[19]  Y. Kiso,et al.  Role of thyroid‐stimulating blocking antibody in patients who developed hypothyroidism within one year after 131I treatment for Graves' disease , 1998, Clinical endocrinology.

[20]  B. Rapoport,et al.  The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. , 1998, Endocrine reviews.

[21]  A. Pinchera,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. , 1998, The Journal of clinical endocrinology and metabolism.

[22]  R. Paschke,et al.  The thyrotropin receptor in thyroid diseases. , 1997, The New England journal of medicine.

[23]  L. Hegedüs,et al.  Thyrotropin Receptor Antibodies and Graves’ Disease, a Side-Effect of 131I Treatment in Patients with Nontoxic Goiter , 1997 .

[24]  R. Rittmaster,et al.  Effect of methimazole with or without exogenous L-thyroxine on serum concentrations of thyrotropin (TSH) receptor antibodies in patients with Graves' disease. , 1996, The Journal of clinical endocrinology and metabolism.

[25]  H. Escobar-Morreale,et al.  Methimazole has no dose-related effect on the serum concentrations of soluble class I major histocompatibility complex antigens, soluble interleukin-2 receptor, and beta 2-microglobulin in patients with Graves' disease. , 1996, Thyroid : official journal of the American Thyroid Association.

[26]  R. Paschke,et al.  Methimazole has no dose-related effect on the intensity of the intrathyroidal autoimmune process in relapsing Graves' disease. , 1995, The Journal of clinical endocrinology and metabolism.

[27]  B. Nygaard,et al.  Appearance of Graves'‐like disease after radioiodine therapy for toxic as well as non‐toxic multinodular goitre , 1995, Clinical Endocrinology.

[28]  P. Colman,et al.  Specific effects of radioiodine treatment on TSAb and TBAb levels in patients with Graves' disease. , 1995, Thyroid : official journal of the American Thyroid Association.

[29]  A. Pinchera,et al.  Appearance of thyroid stimulating antibody and Graves' disease after radioiodine therapy for toxic nodular goitre , 1994, Clinical endocrinology.

[30]  T. Akamizu,et al.  Use of thyrotropin receptor (TSHR) mutants to detect stimulating TSHR antibodies in hypothyroid patients with idiopathic myxedema, who have blocking TSHR antibodies. , 1993, The Journal of clinical endocrinology and metabolism.

[31]  A. Pinchera,et al.  Detection of thyroid-stimulating antibody using Chinese hamster ovary cells transfected with cloned human thyrotropin receptor. , 1993, The Journal of clinical endocrinology and metabolism.

[32]  M. Parmentier,et al.  Stable expression of the human TSH receptor in CHO cells and characterization of differentially expressing clones. , 1990, Biochemical and biophysical research communications.

[33]  J. Mckillop,et al.  THE EFFECT OF ANTITHYROID DRUGS ON B AND T CELL ACTIVITY IN VITRO , 1988, Clinical endocrinology.

[34]  A. Weetman,et al.  Antithyroid drugs ameliorate thymectomy-induced experimental autoimmune thyroiditis. , 1988, Autoimmunity.

[35]  L. Braverman,et al.  The Effect of Methimazole on the Development of Spontaneous Lymphocytic Thyroiditis in the Diabetes‐Prone BB/W Rat , 1986, The American journal of the medical sciences.

[36]  C. Balázs,et al.  THE IMMUNOSUPPRESSIVE EFFECT OF METHIMAZOLE ON CELL‐MEDIATED IMMUNITY IS MEDIATED BY ITS CAPACITY TO INHIBIT PEROXIDASE AND TO SCAVENGE FREE OXYGEN RADICALS , 1986, Clinical endocrinology.