HLA-DR3 and DRw6: prognostic factors for the incidence of hypothyroidism in Graves' disease after radioiodine treatment

Abstract

Abstract. Several studies demonstrated a relationship between HLA-B8 and -DR3 and the early course of thyroid function after treatment of thyrotoxicosis. However, the association between certain DR antigens and the outcome of thyroid function years after radioiodine treatment for Graves' disease remains unclear. We therefore determined the HLA pattern in 2 groups of female patients with different severity of hypothyroidism. From a total of 45 patients, 27 had developed pre-clinical hypothyroidism (normal serum levels of T4, FT4 and T3, normal or elevated basal TSH levels, but an exaggerated TSH response to TRH, Group A). Mean follow-up was 111 months (range 36–360 months) for this group. Eighteen patients had become overtly hypothyroid (T4 and FT4 levels in the hypothyroid range and an elevated basal TSH concentration, group B) after a mean interval of 51 months (range: 4–132 months) following treatment. Eighty-seven healthy blood donors served a controls. Positive plasma antibody titres (tanned red cell haemagglutination technique) were observed in 67% of all patients with a preponderance in group B (83% versus 56% in group A, n.s.). The whole group of Graves' disease patients showed the antigens B8, DR3 and Drw6 in 37.8%, 33.3% and 35.6%, respectively (P < 0.02, < 0.05, and < 0.04 vs controls). In patients with pre-clinical hypothyroidism there was a significantly increased prevalence of antigen B8 (P < 0.01) and DR3 (P < 0.05) compared to the control group. In contrast, the overt hypothyroid group showed an augmented frequency of HLA-DRw6 (P < 0.04). Antibody positivity was related to the antigens B8 and DR3 (P < 0.005, < 0.03, respectively). Thus, the presence of B8/DR3 represents a genetic pattern possibly protecting against the development of overt hypothyroidism, at least over several years after 131I-treatment. The presence of DRw6 and the absence of DR3 were associated with an increased risk for overt post-irradiation hypothyroidism.