CC BY-NC-ND 4.0 · Horm Metab Res 2018; 50(12): 853-862
DOI: 10.1055/a-0723-9023
Review
Eigentümer und Copyright ©Georg Thieme Verlag KG 2018

Thyrotropin Receptor Blocking Antibodies

Tanja Diana
1   Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany
,
Paul D. Olivo
2   Department of Molecular Microbiology, Washington University Medical School, St. Louis, Missouri, USA
,
George J. Kahaly
1   Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany
› Author Affiliations
Further Information

Publication History

received 04 June 2018

accepted 22 August 2018

Publication Date:
04 October 2018 (online)

Abstract

Autoantibodies (Ab) against the thyroid-stimulating hormone receptor (TSHR) are frequently found in autoimmune thyroid disease (AITD). Autoantibodies to the TSHR (anti-TSHR-Ab) may mimic or block the action of TSH or be functionally neutral. Measurement of anti-TSHR-Ab can be done either via competitive-binding immunoassays or with functional cell-based bioassays. Antibody-binding assays do not assess anti-TSHR-Ab functionality, but rather measure the concentration of total anti-TSHR binding activity. In contrast, functional cell-based bioassays indicate whether anti-TSHR-Ab have stimulatory or blocking activity. Historically bioassays for anti-TSHR-Ab were research tools and were used to study the pathophysiology of Graves’ disease and Hashimoto’s thyroiditis. In the past, bioassays for anti-TSHR-Abs were laborious and time-consuming and varied widely in performance from laboratory to laboratory. Recent advances in the development of cell-based assays, including the application of molecular engineering, have led to significant improvements that have enabled bioassays to be employed routinely in clinical laboratories. The prevalence and functional significance of TSHR blocking autoantibodies (TBAb) in autoimmune hypothyroidism has been less well investigated compared to TSHR stimulating Ab. There is an increasing body of data, however, that demonstrate the clinical utility and relevance of TBAb, and thus the importance of TBAb bioassays, in the diagnosis and management of patients with AITD. In the present review, we summarize the different methods used to measure TBAb, and discuss their prevalence and clinical relevance.

 
  • References

  • 1 Dittmar M, Libich C, Brenzel T, Kahaly GJ. Increased familial clustering of autoimmune thyroid diseases. Horm Metab Res 2011; 43: 200-204
  • 2 Dittmar M, Woletz K, Kahaly GJ. Reduced DNASE1 gene expression in thyroid autoimmunity. Horm Metab Res 2013; 45: 257-260
  • 3 Dultz G, Matheis N, Dittmar M, Bender K, Kahaly GJ. CTLA-4 CT60 polymorphism in thyroid and polyglandular autoimmunity. Horm Metab Res 2009; 41: 426-429
  • 4 Barkia Beradhi S, Flesch BK, Hansen MP, Matheis N, Kahaly GJ. HLA Class II Differentiates Between Thyroid and Polyglandular Autoimmunity. Horm Metab Res 2016; 48: 232-237
  • 5 Brent GA. Clinical practice. Graves' disease. N Engl J Med 2008; 358: 2594-2605
  • 6 Weetman AP. Graves’ disease. N Engl J Med 2000; 343: 1236-1248
  • 7 Kahaly GJ, Olivo PD. Graves’ Disease. N Engl J Med 2017; 376: 184
  • 8 Zophel K, Roggenbuck D, Schott M. Clinical review about TRAb assay’s history. Autoimmun Rev 2010; 9: 695-700
  • 9 Kahaly GJ, Diana T. TSH receptor antibody functionality and nomenclature. Front Endocrinol (Lausanne) 2017; 8: 28
  • 10 Lytton SD, Kahaly GJ. Bioassays for TSH-receptor autoantibodies: an update. Autoimmun Rev 2010; 10: 116-122
  • 11 Diana T, Kahaly GJ. Thyroid stimulating hormone receptor antibodies in thyroid eye disease – Methodology and clinical applications. Ophthal Plast Reconstr Surg 2018; 34 4S Suppl S13-S19
  • 12 Diana T, Wuster C, Kanitz M, Kahaly GJ. Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies. J Endocrinol Invest 2016; 39: 1159-1165
  • 13 Diana T, Wuster C, Olivo PD, Unterrainer A, Konig J, Kanitz M, Bossowski A, Decallonne B, Kahaly GJ. Performance and specificity of 6 immunoassays for tsh receptor antibodies: A multicenter study. Eur Thyroid J 2017; 6: 243-249
  • 14 Vitti P, Valente WA, Ambesi-Impiombato FS, Fenzi GF, Pinchera A, Kohn LD. Graves' IgG stimulation of continuously cultured rat thyroid cells: A sensitive and potentially useful clinical assay. J Endocrinol Invest 1982; 5: 179-182
  • 15 Kasagi K, Konishi J, Iida Y, Tokuda Y, Arai K, Endo K, Torizuka K. A sensitive and practical assay for thyroid-stimulating antibodies using FRTL-5 thyroid cells. Acta Endocrinol (Copenh) 1987; 115: 30-36
  • 16 Tokuda Y, Kasagi K, Iida Y, Hatabu H, Misaki T, Arai K, Endo K, Konishi J. 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: 251-258
  • 17 Chiovato L, Vitti P, Bendinelli G, Santini F, Fiore E, Capaccioli A, Tonacchera M, Mammoli C, Ludgate M, Pinchera A. Detection of antibodies blocking thyrotropin effect using Chinese hamster ovary cells transfected with the cloned human TSH receptor. J Endocrinol Invest 1994; 17: 809-816
  • 18 Botero D, Brown RS. Bioassay of thyrotropin receptor antibodies with Chinese hamster ovary cells transfected with recombinant human thyrotropin receptor: clinical utility in children and adolescents with Graves disease. J Pediatr 1998; 132: 612-618
  • 19 Morgenthaler NG, Pampel I, Aust G, Seissler J, Scherbaum WA. Application of a bioassay with CHO cells for the routine detection of stimulating and blocking autoantibodies to the TSH-receptor. Horm Metab Res 1998; 30: 162-168
  • 20 Watson PF, Ajjan RA, Phipps J, Metcalfe R, Weetman AP. A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease. Clin Endocrinol (Oxf) 1998; 49: 577-581
  • 21 Evans C, Morgenthaler NG, Lee S, Llewellyn DH, Clifton-Bligh R, John R, Lazarus JH, Chatterjee VK, Ludgate M. Development of a luminescent bioassay for thyroid stimulating antibodies. J Clin Endocrinol Metab 1999; 84: 374-377
  • 22 Lytton SD, Li Y, Olivo PD, Kohn LD, Kahaly GJ. Novel chimeric thyroid-stimulating hormone-receptor bioassay for thyroid-stimulating immunoglobulins. Clin Exp Immunol 2010; 162: 438-446
  • 23 Li Y, Kim J, Diana T, Klasen R, Olivo PD, Kahaly GJ. A novel bioassay for anti-thyrotrophin receptor autoantibodies detects both thyroid-blocking and stimulating activity. Clin Exp Immunol 2013; 173: 390-397
  • 24 Jordan NJ, Rinderle C, Ashfield J, Morgenthaler NG, Lazarus J, Ludgate M, Evans C. A luminescent bioassay for thyroid blocking antibodies. Clin Endocrinol (Oxf) 2001; 54: 355-364
  • 25 Diana T, Li Y, Olivo PD, Lackner KJ, Kim H, Kanitz M, Kahaly GJ. Analytical performance and validation of a bioassay for thyroid-blocking antibodies. Thyroid 2016; 26: 734-740
  • 26 Diana T, Brown RS, Bossowski A, Segni M, Niedziela M, Konig J, Bossowska A, Ziora K, Hale A, Smith J, Pitz S, Kanitz M, Kahaly GJ. Clinical relevance of thyroid-stimulating autoantibodies in pediatric graves' disease-a multicenter study. J Clin Endocrinol Metab 2014; 99: 1648-1655
  • 27 Ponto KA, Kanitz M, Olivo PD, Pitz S, Pfeiffer N, Kahaly GJ. Clinical relevance of thyroid-stimulating immunoglobulins in graves' ophthalmopathy. Ophthalmology 2011; 118: 2279-2285
  • 28 Ponto KA, Diana T, Binder H, Matheis N, Pitz S, Pfeiffer N, Kahaly GJ. Thyroid-stimulating immunoglobulins indicate the onset of dysthyroid optic neuropathy. J Endocrinol Invest 2015; 38: 769-777
  • 29 Konishi J, Iida Y, Endo K, Misaki T, Nohara Y, Matsuura N, Mori T, Torizuka K. Inhibition of thyrotropin-induced adenosine 3'5'-monophosphate increase by immunoglobulins from patients with primary myxedema. J Clin Endocrinol Metab 1983; 57: 544-549
  • 30 Takasu N, Matsushita M. Changes of TSH-Stimulation Blocking Antibody (TSBAb) and Thyroid Stimulating Antibody (TSAb) Over 10 Years in 34 TSBAb-Positive Patients with Hypothyroidism and in 98 TSAb-Positive Graves' Patients with Hyperthyroidism: Reevaluation of TSBAb and TSAb in TSH-Receptor-Antibody (TRAb)-Positive Patients. J Thyroid Res 2012; 2012: 182176
  • 31 Takasu N, Mori T, Koizumi Y, Takeuchi S, Yamada T. Transient neonatal hypothyroidism due to maternal immunoglobulins that inhibit thyrotropin-binding and post-receptor processes. J Clin Endocrinol Metab 1984; 59: 142-146
  • 32 Takasu N, Yamada T, Takasu M, Komiya I, Nagasawa Y, Asawa T, Shinoda T, Aizawa T, Koizumi Y. Disappearance of thyrotropin-blocking antibodies and spontaneous recovery from hypothyroidism in autoimmune thyroiditis. N Engl J Med 1992; 326: 513-518
  • 33 Chiovato L, Vitti P, Lombardi A, Lopez G, Santini F, Macchia E, Fenzi GF, Mammoli C, Battiato S, Pinchera A. Detection and characterization of autoantibodies blocking the TSH-dependent cAMP production using FRTL-5 cells. J Endocrinol Invest 1987; 10: 383-388
  • 34 Vitti P, Chiovato L, Fiore E, Mammoli C, Rocchi R, Pinchera A. Use of cells expressing the human thyrotropin (TSH) receptor for the measurement of thyroid stimulating and TSH-blocking antibodies. Acta Med Austriaca 1996; 23: 52-56
  • 35 Brown RS, Bellisario RL, Botero D, Fournier L, Abrams CA, Cowger ML, David R, Fort P, Richman RA. Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies. J Clin Endocrinol Metab 1996; 81: 1147-1151
  • 36 Evans C, Jordan NJ, Owens G, Bradley D, Ludgate M, John R. Potent thyrotrophin receptor-blocking antibodies: a cause of transient congenital hypothyroidism and delayed thyroid development. Eur J Endocrinol 2004; 150: 265-268
  • 37 Brown RS, Keating P, Mitchell E. Maternal thyroid-blocking immunoglobulins in congenital hypothyroidism. J Clin Endocrinol Metab 1990; 70: 1341-1346
  • 38 Kiefer FW, Klebermass-Schrehof K, Steiner M, Worda C, Kasprian G, Diana T, Kahaly GJ, Gessl A. Fetal/Neonatal Thyrotoxicosis in a newborn from a hypothyroid woman with hashimoto thyroiditis. J Clin Endocrinol Metab 2017; 102: 6-9
  • 39 Sanders J, Evans M, Premawardhana LD, Depraetere H, Jeffreys J, Richards T, Furmaniak J, Rees Smith B. Human monoclonal thyroid stimulating autoantibody. Lancet 2003; 362: 126-128
  • 40 Evans M, Sanders J, Tagami T, Sanders P, Young S, Roberts E, Wilmot J, Hu X, Kabelis K, Clark J, Holl S, Richards T, Collyer A, Furmaniak J, Smith BR. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample. Clin Endocrinol (Oxf) 2010; 73: 404-412
  • 41 Giordano C, Stassi G, De Maria R, Todaro M, Richiusa P, Papoff G, Ruberti G, Bagnasco M, Testi R, Galluzzo A. Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis. Science 1997; 275: 960-963
  • 42 Stassi G, Di Liberto D, Todaro M, Zeuner A, Ricci-Vitiani L, Stoppacciaro A, Ruco L, Farina F, Zummo G, De Maria R. Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins. Nat Immunol 2000; 1: 483-488
  • 43 Marinkovic T, Garin A, Yokota Y, Fu YX, Ruddle NH, Furtado GC, Lira SA. Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid. J Clin Invest 2006; 116: 2622-2632
  • 44 Chiovato L, Bassi P, Santini F, Mammoli C, Lapi P, Carayon P, Pinchera A. Antibodies producing complement-mediated thyroid cytotoxicity in patients with atrophic or goitrous autoimmune thyroiditis. J Clin Endocrinol Metab 1993; 77: 1700-1705
  • 45 Liblau RS, Singer SM, McDevitt HO. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol Today 1995; 16: 34-38
  • 46 Grubeck-Loebenstein B, Buchan G, Chantry D, Kassal H, Londei M, Pirich K, Barrett K, Turner M, Waldhausl W, Feldmann M. Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6. Clin Exp Immunol 1989; 77: 324-330
  • 47 Fisfalen ME, Palmer EM, Van Seventer GA, Soltani K, Sawai Y, Kaplan E, Hidaka Y, Ober C, DeGroot LJ. Thyrotropin-receptor and thyroid peroxidase-specific T cell clones and their cytokine profile in autoimmune thyroid disease. J Clin Endocrinol Metab 1997; 82: 3655-3663
  • 48 Mackenzie WA, Davies TF. An intrathyroidal T-cell clone specifically cytotoxic for human thyroid cells. Immunology 1987; 61: 101-103
  • 49 Chiovato L, Vitti P, Santini F, Lopez G, Mammoli C, Bassi P, Giusti L, Tonacchera M, Fenzi G, Pinchera A. Incidence of antibodies blocking thyrotropin effect in vitro in patients with euthyroid or hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab 1990; 71: 40-45
  • 50 Furmaniak J, Sanders J, Rees Smith B. Blocking type TSH receptor antibodies. Auto Immun Highlights 2012; 4: 11-26
  • 51 Endo K, Kasagi K, Konishi J, Ikekubo K, Okuno T, Takeda Y, Mori T, Torizuka K. Detection and properties of TSH-binding inhibitor immunoglobulins in patients with Graves' disease and Hashimoto's thyroiditis. J Clin Endocrinol Metab 1978; 46: 734-739
  • 52 Matsuura N, Yamada Y, Nohara Y, Konishi J, Kasagi K, Endo K, Kojima H, Wataya K. Familial neonatal transient hypothyroidism due to maternal TSH-binding inhibitor immunoglobulins. N Engl J Med 1980; 303: 738-741
  • 53 Arikawa K, Ichikawa Y, Yoshida T, Shinozawa T, Homma M, Momotani N, Ito K. Blocking type antithyrotropin receptor antibody in patients with nongoitrous hypothyroidism: its incidence and characteristics of action. J Clin Endocrinol Metab 1985; 60: 953-959
  • 54 Ambesi-Impiombato FS. Living, fast-growing thyroid cell strain, FRTL-5. In: Google Patents; US4608341A US Grant; 1986
  • 55 Massart C, Gibassier J, Verite F, Fergelot P, Maugendre D. Use of Chinese hamster ovary cell lines transfected with cloned human thyrotropin receptor for the measurement of thyroid-stimulating antibodies: advantages and difficulties. Clin Chim Acta 2000; 291: 67-81
  • 56 Grasso YZ, Kim MR, Faiman C, Kohn LD, Tahara K, Gupta MK. Epitope heterogeneity of thyrotropin receptor-blocking antibodies in Graves' patients as detected with wild-type versus chimeric thyrotropin receptors. Thyroid 1999; 9: 531-537
  • 57 Tahara K, Ishikawa N, Yamamoto K, Hirai A, Ito K, Tamura Y, Yoshida S, Saito Y, Kohn LD. Epitopes for thyroid stimulating and blocking autoantibodies on the extracellular domain of the human thyrotropin receptor. Thyroid 1997; 7: 867-877
  • 58 Minich WB, Lenzner C, Bergmann A, Morgenthaler NG. A coated tube assay for the detection of blocking thyrotropin receptor autoantibodies. J Clin Endocrinol Metab 2004; 89: 352-356
  • 59 Kamijo K, Nagata A, Sato Y. Clinical significance of a sensitive assay for thyroid-stimulating antibodies in Graves' disease using polyethylene glycol at high concentrations and porcine thyroid cells. Endocr J 1999; 46: 397-403
  • 60 Yamasa https://www.yamasa.com/shindan/english/shindan/tsab.htm
  • 61 FIRS Laboratories. RSR, Ltd. Assay Service. Thyroid blocking (TSBAb) bioassay. Available at www.rsrltd.com/assay_service.html
  • 62 Smith BR, Bolton J, Young S, Collyer A, Weeden A, Bradbury J, Weightman D, Perros P, Sanders J, Furmaniak J. A new assay for thyrotropin receptor autoantibodies. Thyroid 2004; 14: 830-835
  • 63 Araki N, Iida M, Amino N, Morita S, Ide A, Nishihara E, Ito M, Saito J, Nishikawa T, Katsuragi K, Miyauchi A. Rapid bioassay for detection of thyroid-stimulating antibodies using cyclic adenosine monophosphate-gated calcium channel and aequorin. Eur Thyroid J 2015; 4: 14-19
  • 64 Takasu N, Yamada T, Katakura M, Yamauchi K, Shimizu Y, Ishizuki Y. Evidence for thyrotropin (TSH)-blocking activity in goitrous Hashimoto's thyroiditis with assays measuring inhibition of TSH receptor binding and TSH-stimulated thyroid adenosine 3',5'-monophosphate responses/cell growth by immunoglobulins. J Clin Endocrinol Metab 1987; 64: 239-245
  • 65 Kawahara K, Tsukimoto I, Yokoya S. Atrophic autoimmune thyroiditis with positive thyroid stimulation blocking antibody in a prepubertal boy. Clin Pediatr Endocrinol 2000; 9: 105-111
  • 66 Cho BY, Shong YK, Lee HK, Koh CS, Min HK. Inhibition of thyrotropin-stimulated adenylate cyclase activation and growth of rat thyroid cells, FRTL-5, by immunoglobulin G from patients with primary myxedema: Comparison with activities of thyrotropin-binding inhibitor immunoglobulins. Acta Endocrinol (Copenh) 1989; 120: 99-106
  • 67 Cho BY, Shong YK, Lee HK, Koh CS, Min HK, Sohn I. Role of blocking TSH receptor antibodies on the development of hypothyroidism and thyroid atrophy in primary myxedema. Korean J Intern Med 1989; 4: 108-117
  • 68 Yoshikawa N, Nishikawa M, Horimoto M, Uno C, Taniguchi N, Inada M. Activity of thyroid stimulating antibody and thyroid stimulation blocking antibody determined by radioiodine uptake into FRTL-5 cells. Endocrinol Jpn 1989; 36: 55-63
  • 69 Chiovato L, Vitti P, Bendinelli G, Santini F, Fiore E, Tonacchera M, Mammoli C, Capaccioli A, Venturi S, Pretell E. Humoral thyroid autoimmunity is not involved in the pathogenesis of myxedematous endemic cretinism. J Clin Endocrinol Metab 1995; 80: 1509-1514
  • 70 Kraiem Z, Cho BY, Sadeh O, Shong MH, Pickerill P, Weetman AP. The IgG subclass distribution of TSH receptor blocking antibodies in primary hypothyroidism. Clin Endocrinol (Oxf) 1992; 37: 135-140
  • 71 Kraiem Z, Baron E, Kahana L, Sadeh O, Sheinfeld M. Changes in stimulating and blocking TSH receptor antibodies in a patient undergoing three cycles of transition from hypo to hyper-thyroidism and back to hypothyroidism. Clin Endocrinol (Oxf) 1992; 36: 211-214
  • 72 Kung AW, Jones BM. A change from stimulatory to blocking antibody activity in Graves' disease during pregnancy. J Clin Endocrinol Metab 1998; 83: 514-518
  • 73 Wallaschofski H, Paschke R. Detection of thyroid stimulating (TSAB)- and thyrotropin stimulation blocking (TSBAB) antibodies with CHO cell lines expressing different TSH-receptor numbers. Clin Endocrinol (Oxf) 1999; 50: 365-372
  • 74 Wallaschofski H, Kaczmarek M, Miehle K, Hentschel B, Paschke R. Differences between thyrotropin receptor antibody bioactivity and inhibition of 125I-bovine thyrotropin binding. Thyroid 2000; 10: 897-907
  • 75 Tada H, Izumi Y, Watanabe Y, Takano T, Fukata S, Kuma K, Hidaka Y, Amino N. Blocking type anti-tSH receptor antibodies detected by radioreceptor assay in Graves' disease. Endocr J 2001; 48: 703-710
  • 76 Diana T, Krause J, Olivo PD, Konig J, Kanitz M, Decallonne B, Kahaly GJ. Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease. Clin Exp Immunol 2017; 189: 304-309
  • 77 Tada H, Mizuta I, Takano T, Tatsumi KI, Izumi Y, Hidaka Y, Amino N. Blocking-type anti-TSH receptor antibodies and relation to responsiveness to antithyroid drug therapy and remission in Graves' disease. Clin Endocrinol (Oxf) 2003; 58: 403-408
  • 78 Iseki M, Shimizu M, Oikawa T, Hojo H, Arikawa K, Ichikawa Y, Momotani N, Ito K. Sequential serum measurements of thyrotropin binding inhibitor immunoglobulin G in transient familial neonatal hypothyroidism. J Clin Endocrinol Metab 1983; 57: 384-387
  • 79 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: 171-176
  • 80 Valente WA, Vitti P, Yavin Z, Yavin E, Rotella CM, Grollman EF, Toccafondi RS, Kohn LD. Monoclonal antibodies to the thyrotropin receptor: Stimulating and blocking antibodies derived from the lymphocytes of patients with Graves disease. Proc Natl Acad Sci U S A 1982; 79: 6680-6684
  • 81 Sanders J, Evans M, Betterle C, Sanders P, Bhardwaja A, Young S, Roberts E, Wilmot J, Richards T, Kiddie A, Small K, Platt H, Summerhayes S, Harris R, Reeve M, Coco G, Zanchetta R, Chen S, Furmaniak J, Smith BR. A human monoclonal autoantibody to the thyrotropin receptor with thyroid-stimulating blocking activity. Thyroid 2008; 18: 735-746
  • 82 Furmaniak J, Sanders J, Rees Smith B. Blocking type TSH receptor antibodies. Auto Immun Highlights 2012; 4: 11-26
  • 83 Rees Smith B, Sanders J, Evans M, Tagami T, Furmaniak J. TSH receptor - Autoantibody interactions. Horm Metab Res 2009; 41: 448-455
  • 84 Furmaniak J. In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70). Auto Immun Highlights 2012; 3: 19-25
  • 85 Kahaly GJ, Kanitz M, Kolbe E, Matheis N, Diana T. Thyroid stimulating autoantibodies are clinically useful and predictive in graves’ disease – A prospective trial. Eur Thyroid J 2014; 3 (Suppl. 01) 91
  • 86 Cove DH, Johnston P. Fetal hyperthyroidism: experience of treatment in four siblings. Lancet 1985; 1: 430-432
  • 87 Kung AW, Yeung SS. Prevention of bone loss induced by thyroxine suppressive therapy in postmenopausal women: The effect of calcium and calcitonin. J Clin Endocrinol Metab 1996; 81: 1232-1236
  • 88 McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: Potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid 2013; 23: 14-24
  • 89 Bossowski A, Moniuszko M, Idzkowska E, Grubczak K, Singh P, Bossowska A, Diana T, Kahaly GJ. Decreased proportions of CD4 + IL17+/CD4 + CD25 + CD127- and CD4 + IL17+/CD4 + CD25 + CD127 - FoxP3+ T cells in children with autoimmune thyroid diseases. Autoimmunity 2016; 49: 320-328
  • 90 McKenzie JM, Zakarija M. Fetal and neonatal hyperthyroidism and hypothyroidism due to maternal TSH receptor antibodies. Thyroid 1992; 2: 155-159
  • 91 Abeillon-du Payrat J, Chikh K, Bossard N, Bretones P, Gaucherand P, Claris O, Charrie A, Raverot V, Orgiazzi J, Borson-Chazot F, Bournaud C. Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism. Eur J Endocrinol 2014; 171: 451-460
  • 92 Feingold SB, Smith J, Houtz J, Popovsky E, Brown RS. Prevalence and functional significance of thyrotropin receptor blocking antibodies in children and adolescents with chronic lymphocytic thyroiditis. J Clin Endocrinol Metab 2009; 94: 4742-4748