Clinical significance of classification of Graves' disease according to the characteristics of TSH receptor antibodies

BACKGROUND: It has been widely accepted that the epitope(s) and/or functional characteristics of thyrotropin receptor antibodies (TSHRAb) from Graves' patients are heterogenous among patients. However, the clinical significance of such heterogeneity has not been systematically evaluated yet. We were to elucidate and find the clinical significance of heterogeneity for TSH receptor antibodies in Graves' disease. METHODS: We measured stimulating TSHRAb (TSAb) activities using CHO-hTSHR cells, FRTL-5 cells and chimeric receptor expressing cells (Mc1 + 2 and Mc2), specific blocking TSHRAb (TSBAb) activities using Mc2 cells and TBII activities using porcine thyroid membrane in 136 patients with untreated hyperthyroid Graves' disease. RESULTS: Based on various TSHRAb activities from each patient, the patients could be categorized into 7 subgroups by cluster analysis; 1) Group 1 (n = 41) was characterized by moderate TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, typical TSAb epitope, rare blocking antibodies and high TBII activities. 2) Group 2 (n = 16) was characterized by the presence of blocking TSHRAb in most patients, albeit the other characteristics were the same as those in Group 1. 3) Group 3 (n = 19) patients had low TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, seldom had blocking TSHRAb, but they had high TBII activities. 4) Group 4 (n = 30) could be categorized as 'mild disease' group, as they had low activities in all kinds of TSHRAb assay and had low antimicrosomal antibody activities. 5) Group 5 (n = 14) was characterized by moderate TSAb activities with atypical epitope(s), rare blocking TSHRAb and moderate TBII activities. 6) Group 6 (n = 10) patients had very high TSAb activities with typical epitopes, seldom blocking TSHRAb and low TBII activities. 7) Group 7 (n = 6) was characterized by very high TSAb activities with atypical epitopes and high TBII activities. Pretreatment serum thyroid hormone level was low only in group 4 patients compared to the other 6 groups (p < 0.05). The size of goiter was significantly larger in those in group 1 and group 3 (p < 0.05) compared to the other 5 groups. The prevalence of clinically significant ophthalmopathy was higher in group 2 patients than the other 6 groups (50% vs. 27.5%, p = 0.06). Among 6 kinds of TSHRAb activities, only the blocking TSHRAb activity was significantly associated with the presence of ophthalmopathy in multivariate analysis. CONCLUSION: These results suggest that the differences in epitopes for TSAb or the presence of blocking TSHRAb is not a major factor in determining the degree of thyrotoxicosis in Graves' disease. Although the pathogenic mechanism is not clear yet, we suggest that patients with ophthalmopathy have different TSHRAb repertoire from those without ophthalmopathy in Graves' disease.

Hallazgos tomográficos preliminares acerca del efecto de la terapia del iodo radiactivo sobre la oftalmopatía de Graves / Preliminary tomographic of the effect of the radioactive iodine therapy on Grave's ophtalmopathy

Este estudio pretende profundizar la investigación acerca de las modificaciones orbitarias en pacientes con enfermedad de Graves tratados con Iodo radiactivo, objetivada mediante TC y observando su evolución. Se utilizó un protocolo de cortes axiales a menos 10 grados del plano órbitomeatal y coronales perpendiculares al plano órbitomeatal, de 5mm de espesor cada 3 mm de intervalo. Se realizaron treinta tomografías en diez pacientes con enfermedad de Graves, con distinto grado de compromiso ocular. Los mismos recibieron una dosis de Iodo radiactivo. Se tomaron los siguientes parámetros: 1) cambios en los diámetros de la musculatura extrínseca; 2) densitometría de la grasa retroocular y 3) proptosis. En el 80 por ciento de los pacientes hallamos aumento en los diámetros de los músculos extraoculares, no evidencia de cambios cualicuantitativos en la valoración de la grasa retroorbitaria y ausencia de proptosis. Los resultados hasta la fecha no son concluyentes, existiendo escasa literatura referida a estudios prospectivos en este sentido