Naoki Hattori1, Takashi Ishihara2, Naoki Matsuoka2, Takanori Saito3, Akira Shimatsu4. 1. 1 Department of Pharmaceutical Sciences, Ritsumeikan University , Shiga, Japan . 2. 2 Department of Endocrinology, Kobe City General Hospital , Kobe, Japan . 3. 3 Department of Orthopedic Surgery, Kansai Medical University , Osaka, Japan . 4. 4 Clinical Research Institute , National Hospital Organization Kyoto Medical Center, Kyoto, Japan .
Abstract
BACKGROUND: 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. METHODS: 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 using 125I-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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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 using 125I-humanTSH, 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. RESULTS: 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-humanTSH-β autoantibodies that were partially cross-reactive to bovine and/or ratTSH-β. There were also autoantibodies against human glycoprotein α, a common subunit among humanTSH, 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. CONCLUSIONS: It is concluded that anti-humanTSH autoantibodies are a major cause of macro-TSH and that macro-TSH may persist for a long time.