title: Anti-Thyrotropin Autoantibodies in Patients with Macro-Thyrotropin and Long-Term Changes in Macro-Thyrotropin and Serum Thyrotropin Levels.
abstract: Macro-thyrotropin (TSH) is a high-molecular-weight form of TSH. Most cases of macro-TSH are TSH complexed with immunoglobulin G. This study was undertaken to characterize macro-TSH.
  
  
  
  Blood samples taken from patients with subclinical hypothyroidism were screened for the presence of macro-TSH with the polyethylene glycol method and confirmed with gel filtration chromatography. TSH receptor antibody was quantified with an electrochemiluminescence immunoassay. Binding studies were performed using125I-human TSH, and the specificity of anti-TSH autoantibodies was tested by displacement experiments using excess amounts of the unlabeled related peptides. Macro-TSH and serum TSH levels were evaluated twice over a one- to four-year interval.
  
  
  
  Sixteen patients (11 females and 5 males; aged 8-82 years) were diagnosed as having macro-TSH. None of the patients with macro-TSH tested positive for TSH receptor antibody. Judging from the affinity and the binding capacity of anti-TSH autoantibodies, two classes of binding sites were identified. Regarding specificity, there were anti-human TSH-β autoantibodies that were partially cross-reactive to bovine and/or rat TSH-β. There were also autoantibodies against human glycoprotein α, a common subunit among human TSH, luteinizing hormone, and follicle stimulating hormone. Macro-TSH persisted in 11/13 patients who could be reevaluated over a one- to four-year interval after the first evaluation. Serum TSH levels returned to normal in the remaining two patients whose macro-TSH disappeared.
  
  
  
  It is concluded that anti-human TSH autoantibodies are a major cause of macro-TSH and that macro-TSH may persist for a long time.
authors: 1 Department of Pharmaceutical Sciences, Ritsumeikan University , Shiga, Japan .
authors: Naoki
authors: N
authors: Hattori
authors: 2 Department of Endocrinology, Kobe City General Hospital , Kobe, Japan .
authors: Takashi
authors: T
authors: Ishihara
authors: 2 Department of Endocrinology, Kobe City General Hospital , Kobe, Japan .
authors: Naoki
authors: N
authors: Matsuoka
authors: 3 Department of Orthopedic Surgery, Kansai Medical University , Osaka, Japan .
authors: Takanori
authors: T
authors: Saito
authors: 4 Clinical Research Institute , National Hospital Organization Kyoto Medical Center, Kyoto, Japan .
authors: Akira
authors: A
authors: Shimatsu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058070:Asymptomatic Diseases; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D002850:Chromatography, Gel; D005260:Female; D050031:Hashimoto Disease / Q000097:blood / Q000276:immunology*; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000276:immunology*; D018828:Immunoglobulins, Thyroid-Stimulating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013972:Thyrotropin / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D013974:Thyroxine / Q000097:blood
chemical_list: D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; C094372:thyrotropin-binding inhibitory immunoglobulin; D013972:Thyrotropin; D013974:Thyroxine
keywords: TSH; TSH receptor; autoimmunity; thyroid autoimmunity—clinical