Increased frequency of HLA-DR3 and 5 in the syndromes of painless thyroiditis with transient thyrotoxicosis: evidence for an autoimmune aetiology.

We studied fifty patients with painless thyroiditis with transient thyrotoxicosis (PTTT) and a low radioiodine thyroidal uptake. In 25 PTTT occurred post-partum (P) and in the remainder was unrelated to pregnancy (U). Seventeen patients with classical subacute thyroiditis were studied for comparison. All patients were typed for HLA-A, B, C, DR antigens. Four of the P patients had recurrences with each pregnancy; two had one previous attack of U; three had a maternal history of Graves' disease; 76% of the P patients had small to moderate goitres and 76% antimicrosomal antibody titres at greater than 1:400. HLA-B35 was found in 24% of P patients compared to 17% of controls; 71% of patients with subacute thyroiditis were, by contrast, B35. Two of P were HLA-B8 positive (versus 25% of controls); 11 patients were HLA-DR3 positive and 15 (60%) HLA-DR5 positive compared to 23% and 27% of controls yielding a relative risk (RR) = 2.50 (P less than 0.05) and 3.83 (P less than 0.005), respectively. All four P patients with recurrences carried HLA-DR5. Thirteen of 25 patients in the U subgroup were HLA-DR3, yielding a RR = 3.38 (P less than 0.01); seven were HLA-DR5, with a non-significant RR = 1.12; four of U had first degree relatives with either autoimmune thyroid disorders or Type 1 diabetes mellitus. Thus, both P and U are associated with HLA-DR3, the P subgroup had in addition an increased frequency of DR5. The observed HLA associations for the PTTT syndromes favours an autoimmune rather than viral aetiology.