Thyrotrophin receptor antibody characteristics in a woman with long‐standing Hashimoto's who developed Graves' disease and pretibial myxoedema

摘要: Context Sequential conversion of Hashimoto's thyroiditis (HT) to Graves' disease (GD) is uncommon. Distinct immune paradigms, paucity functioning tissue in long-standing HT, and infrequent blocking (TBAb) stimulating (TSAb) thyrotrophin receptor antibody (TRAb) may account for this. Molecular crystal structure analysis helps delineate TSH (TSHR)/TRAb interactions detail. Such ‘fingerprinting’ determine the behaviour characteristics TRAb longitudinal studies. Patient An 80-year-old woman taking thyroxine HT became hyperthyroid. This persisted despite withdrawal – free T3 was 7·3 pmol/l (2·6–5·7) TSH < 0·01 mU/l (0·2–4·5) highly positive. She had a goitre (ultrasound HT), pretibial myxoedema, with mild inactive orbitopathy. RAI treatment on replacement. Measurements Results Blood samples at presentation (A) 1 year (B) showed high TSAb TPOAb activity but no TBAb. Experiments involving TSHR mutations confirmed that (i) stable over 1 year; (ii) mutation R255D caused complete inhibition (iii) R109A marked reduction cAMP production by M22 (TSHR-stimulating human monoclonal antibody) A B; (iv) R80A, E107A K129A while affecting little effect B. Conclusions The reasons an immunological paradigm shift this elderly remain speculative. We believe de-novo synthesis occurred converting her GD although mechanisms responsible unexplained. autoantibody variable effects function.