title: Characteristics and clinical correlates of a novel thyroid-stimulating autoantibody.
abstract: We reported a patient who gave birth to 3 children with transient neonatal hypothyroidism. She had 3 different antibodies (Ab) to the thyrotropin receptor (TSHR) in her serum, viz., TSH binding-inhibiting (TBIAb), 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 data now obtained with Chinese hamster ovary (CHO) cells transfected with cloned human TSHR]. Because of symptomatic goiter enlargement the patient underwent subtotal thyroidectomy. About 50% of the gland was infiltrated with lymphocytes; thyroid follicles had columnar epithelium, despite suppression of TSH by thyroxine and the presence of the potent TBIAb. Fifteen months later, when all 3 Ab showed a decline of approximately 3 fold, she gave birth to hypothyroid twins. These data support the following conclusions: 1) thyroidectomy and immunosuppression of pregnancy 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 share binding epitopes on the TSHR with either TSH or TBIAb; 4) SAb was the probable cause of thyroid growth in this patient.
authors.affiliation: Department of Medicine, University of Miami School of Medicine, FL 33101, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zakarija
authors.forename: R
authors.initials: R
authors.lastname: De Forteza
authors.forename: J M
authors.initials: JM
authors.lastname: McKenzie
authors.forename: L
authors.initials: L
authors.lastname: Ghandur-Mnaymneh
mesh_terms: D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016466:CHO Cells; D003409:Congenital Hypothyroidism; D006224:Cricetinae; D000242:Cyclic AMP / Q000032:analysis; D004200:Diseases in Twins; D005260:Female; D005500:Follow-Up Studies; D006111:Graves Disease / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology; D007112:Immunity, Maternally-Acquired; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood / Q000276:immunology / Q000302:isolation & purification*; D007231:Infant, Newborn; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology; D051381:Rats; D011989:Receptors, Thyrotropin / Q000276:immunology*; D013961:Thyroid Gland / Q000473:pathology; D013965:Thyroidectomy; D013967:Thyroiditis, Autoimmune / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013972:Thyrotropin / Q000494:pharmacology; D013974:Thyroxine / Q000627:therapeutic use
chemical_list: D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D000242:Cyclic AMP; D013974:Thyroxine