CHARACTERISTICS AND CLINICAL CORRELATES OF A NOVEL THYROID-STIMULATING AUTOANTIBODY

We reported a patient who gave birth to 3 children with transient neon atal hypothyroidism. She had 3 different antibodies (Ab) to the thyrot ropin receptor (TSHR) in her serum, viz., TSH binding-inhibiting (TBIA b), thyroid-stimulating (TSAb) and an additional stimulating Ab (SAb). The SAb differed from TSAb in that its in vitro stimulating effect in human thyroid and FRTL5 cells was not inhibited by TBIAb [similar dat a now obtained with Chinese hamster ovary (CHO)cells transfected with cloned human TSHR]. Because of symptomatic goiter enlargement the pati ent underwent subtotal thyroidectomy. About 50% of the gland was infil trated with lymphocytes; thyroid follicles had columnar epithelium, de spite suppression of TSH by thyroxine and the presence of the potent T BIAb. Fifteen months later, when all 3 Ab showed a decline of similar to 3 ford, she gave birth to hypothyroid twins. These data support the following conclusions: I)thyroidectomy and immunosuppression of pregn ancy do not prevent neonatal thyroid disease if TSHR Ab (TRAb) are of high titer; 2) the thyroid is not a major site of TRAb production; 3) SAb is a thyroid stimulator, distinct from TSAb in that it does not sh are binding epitopes on the TSHR with either TSH or TBIAb; 4) SAb was the probable cause of thyroid growth in this patient.