Comparison of thyroid stimulating activities measured by cyclic AMP production, those by radioiodine uptake in FRTL-5 cells and TSH-binding inhibitory activities in patients with hyperthyroid and euthyroid Graves' diseases

Abstract

Abstract. By using an assay measuring cAMP production in FRTL-5 thyroid cells, thyroid stimulating antibodies (TSab) were detected in all of 15 patients with euthyroid Graves' disease (EG) and of 26 patients with hyperthyroid Graves' disease (HG). There was no significant difference between TSab activities in EG and in HG. In an effort to elucidate why EG patients remain euthyroid in spite of having TSab, we investigated the effect of the patient's crude immunoglobulin fractions on 125I uptake in FRTL-5 thyroid cells, one of the indices of stimulation subsequent to cAMP production. The 125I uptake stimulating (IUS) activity was positive in 46.7% (7/15) of EG patients and 88.5% (23/26) of HG patients, being significantly lower in the former than in the latter (P < 0.02). Although the IUS activities significantly correlated with TSab activities in 41 patients with EG and HG (r = 0.784, P < 0.001), the ratio of IUS to TSab in EG tended to be lower than that in HG. TSH-binding inhibitor immunoglobulins (TBII) activities in EG patients were negative or weakly positive, being significantly lower than those in HG patients (P < 0.001). Thus, the ratios of TBII to both TSab and IUS activities were significantly higher in HG than in EG (P < 0.01, P < 0.001, respectively). The in vitro IUS activities also correlated with TBII activities (r = 0.441, P < 0.001) and in vivo 99mTc thyroid uptake (r = 0.401, P < 0.001) in both EG and HG patients. The EG patients with positive IUS activities displayed smaller goitre size and lower 99m thyroid uptake in comparison to 19 HG patients with a similar range of IUS activities. There was a good correlation between thyroid weight and 99mTc thyroid uptake (r = 0.827, P < 0.001). In conclusion, lower IUS activity and/or smaller goitre size in EG than in HG, which may lead to lower thyroidal uptake of 99mTc and presumably radioiodine in vivo, might be a factor responsible for keeping EG patients euthyroid despite the presence of TSab.