title: Frequency and characteristics of TBII-seronegative patients in a population with untreated Graves' hyperthyroidism: a prospective study.
abstract: OBJECTIVE
  It is claimed that second generation thyrotropin-binding inhibitory immunoglobulin (TBII) assays have a very high sensitivity for the diagnosis of Graves' hyperthyroidism (GH). However, studies evaluating the accuracy of TBII have been retrospective in nature and/or GH had not been diagnosed independently of TBII. The aim of the present study, therefore, was to prospectively evaluate the frequency and characteristics of TBII-seronegative patients in a population of untreated GH diagnosed independent of serum TBII.
  
  
  METHODS
  Prospective multicentre observational study.
  
  
  METHODS
  A total of 259 consecutive untreated patients with a first episode of GH, diagnosed independent of serum TBII. TBII levels were measured by second generation assay and correlated to thyroid function, clinical characteristics and exposure to environmental factors.
  
  
  RESULTS
  Serum TBII was positive in 245 (94.6%) patients and negative (< 2 IU/l) in 14 (5.4%) patients. TBII-seronegative patients had lower fT4 (median 42.5 vs. 53.9 pmol/l, P = 0.02), T3 (median 3.55 vs. 4.90 nmol/l, P < 0.01) and fT3-index (median 4.30 vs. 6.27, P < 0.01) compared to TBII-seropositive patients. None of the TBII-seronegative patients had TSH-receptor activating mutations, Graves' orbitopathy or pretibial myxedema. Serum TBII was positively correlated to free T3 (fT3)-index and free T4 (fT4)-index (P < 0.01), goitre size (P < 0.01) and the prevalence of Graves' orbitopathy (P < 0.01). There were no significant differences between TBII-seropositive and TBII-seronegative patients in environmental factors.
  
  
  CONCLUSIONS
  The prevalence of TBII-seronegativity in untreated patients with GH is 5.4% using a second generation assay. TBII-seronegative patients have biochemically less severe thyrotoxicosis and no Graves' orbitopathy. TBII-seronegative and TBII-seropositive patients apparently belong to the same population of GH, albeit the severity of the autoimmune attack is less in TBII-seronegative patients.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdamn, Amsterdam, The Netherlands. x.g.vos@amc.nl
authors.forename: Xander G
authors.initials: XG
authors.lastname: Vos
authors.forename: Natalie
authors.initials: N
authors.lastname: Smit
authors.forename: Erik
authors.initials: E
authors.lastname: Endert
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
mesh_terms: D000328:Adult; D005260:Female; D006111:Graves Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D018828:Immunoglobulins, Thyroid-Stimulating / Q000032:analysis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016036:Seroepidemiologic Studies; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D018828:Immunoglobulins, Thyroid-Stimulating; D013963:Thyroid Hormones; C094372:thyrotropin-binding inhibitory immunoglobulin