Usefulness of Functional Thyroid-Stimulating and Thyroid-Blocking Immunoglobulin Bioassays in an Atypical Presentation of Graves' Disease.

Background/Objective: Thyroid-stimulating hormone (TSH) receptor antibody (TRAb) is well recognized as the pathogenic antibody that causes the clinical manifestation of Graves' disease (GD). Although the majority of TRAb measured in GD is due to thyroid-stimulating immunoglobulin (TSI), there are other functional classes of TRAb, ie, thyroid-blocking immunoglobulin (TBI) and neutral antibodies, which can alter the clinical course of the disease. We present a case of a patient who demonstrated interesting coexistence of both the forms using Thyretain TSI and TBI Reporter BioAssays. Case Report: A 38-year-old woman presented with thyrotoxicosis (TSH level, 0.01 mIU/L, free thyroxine level, >7.8 ng/mL [>100 pmol/L], and free triiodothyronine level, >32.6 pg/mL [>50 pmol/L]) to her general practitioner. She was treated with 15-mg carbimazole twice daily before the dose was reduced to 10 mg. Four weeks later, she developed severe hypothyroidism, with a TSH level of 57.5 mIU/L, free thyroxine level of 0.5 ng/mL (6.7 pmol/L), and free triiodothyronine level of 2.6 pg/mL (4.0 pmol/L). Carbimazole was ceased; however, she remained severely hypothyroid, with a TRAb level of 35 IU/L. Both TSI (304% signal-to-reference ratio) and TBI (56% inhibition) were present, with predominance of the blocking form of thyroid receptor antibodies (54% inhibition). Thyroxine was commenced, and her thyroid functions remained steady and TSI became undetectable. Discussion: The results of the bioassays confirmed that both TSI and TBI can coexist in a patient and that its action changes within a short period of time. Conclusion: Clinicians and laboratory scientists should be aware of the usefulness of TSI and TBI bioassays in the interpretation of atypical presentations of GD.