Influence of the HLA-DR4 antigen and iodine status on the development of autoimmune postpartum thyroiditis

HLA-A, -B, and -DR antigens were determined in all 50 women with a serum thyroid microsomal hemagglutination antibody (MsAb) titer equal to or greater than 1:100 in the first trimester of pregnancy in a population of 733 pregnant women. The DR4 antigen was found in 58.0% of the women compared to 33.7% in control subjects, which corresponds to a relative risk of 2.71 (P less than 0.01 by X2 test). The MsAb-positive women were examined regularly during the year after delivery for the development of thyroid dysfunction. The DR4 antigen frequency was found to be even higher, 69.0% (relative risk = 4.36; P less than 0.001), among the 29 women who developed hypothyroidism in the postpartum period. No other HLA antigen deviations were found among those 15 hypothyroid women in whom an initial thyrotoxic phase occurred before hypothyroidism. The B8, DR3 haplotype was found in 3 of 5 women who developed Graves' thyrotoxicosis alone. Urinary iodine excretion measured in some MsAb-positive women 3 (n = 19) or 6 months (n = 29) postpartum, respectively, was compatible with leakage of thyroid iodine during the initial destruction-induced thyrotoxic phase of postpartum thyroiditis, followed by low iodine excretion during the subsequent hypothyroid phase. We conclude that genes coding for the DR4 antigen may have a regulatory influence on MsAb production, which in turn affects the development of postpartum hypothyroidism. Thyroid iodine content and iodine intake also may have an impact on the severity of the thyrotoxic and the hypothyroid phases of autoimmune postpartum thyroiditis.