Margita Zakarija

Characteristics and Clinical Correlates of a Novel Thyroid-Stimulating Autoantibody

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.

The Effect of Thyroxine on Spontaneous Thyroiditis in BB/W Rats

The effect of T4 on the incidence of lymphocytic thyroiditis and on titers of antibodies to thyroglobulin and thyroid microsomal antigen was studied in BB/W rats that are prone to develop spontaneously autoimmune thyroiditis and diabetes. Thirty-three animals were separated in two groups. Rats in one group had 1 mg T4 per liter of drinking water, and the other group was given no T4. After 3-4 months of therapy the T4-treated group had a reduced production of antibody to thyroglobulin (p less than 0.05) and to microsomal antigen (p less than 0.005) and a significantly lower frequency of lymphocytic thyroiditis (p less than 0.05). Our data are consistent with previous findings in experimentally induced thyroiditis in rats and suggest that T4 has an immunosuppressive effect.

Transplacental Antibody-Induced Neonatal Syndromes

This review will be divided into the following segments: 1. Overview of what is known regarding the effects on the fetus of the transplacental passage of circulating antibodies that occur in autoimmune thyroid disease. 2. Description of what is known about the progression of development of the fetal thyroid-pituitary axis; relevant comparison will be made of the time frame for fetal and maternal contributions to the concentration of IgG in the fetal circulation. 3. Descriptions, with references to the above reviews, of fetal and neonatal thyroid disorders based on maternal autoimmune thyroid disease, collating published reports with experience garnered in this laboratory.