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

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\p=n-\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\p=n-\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.

Iodine‐131 treatment of hyperthyroidism: current issues

“…The disbelievers should continue as before. Those who suspect that the anecdotes may be true will be reassured that prednisolone started at the same time as the administration of iodine-131 in a dose of some 30 mg daily for 1 month and gradually withdrawn over the next 3 months prevents deterioration in mild ophthalmopathy (Bartalena et al, 1989). However, it can be argued that steroids are indicated only in the small proportion ofpatients destined to develop severe ophthalmopathy.…”

A Case of Pituitary Resistant Free Triiodothyronine Toxicosis Following Hepatitis B Immunization

“…Because the pituitary gland is open to the general circulation, it is possible that HBV triggered the production of anti-TRβ2 autoantibodies with the capability of blocking access of FT3 and FT4 to TRβ2 binding domains. Adults receiving HBV have been reported to have increased odds-ratios of developing autoimmune disease, including systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, multiple sclerosis, and immune thrombocytopenia [9,10], and our patient was particularly predisposed to developing autoimmune thyroid disease, which is associated with HLA-DR3 haplotypes in Caucasians [11]. 112 (normal 14-70) 7.7 (normal >7) Table 2: Hypothalamic-pituitary-thyroid axis.…”

Radioiodine Treatment of Basedow's Disease: Interference and Influence Factors, Risk Estimation

“…Above that, some authors showed a correlation between human leucocyte antigens (HLA) and outcome of J-131 treatment. Althaus et al (1986) speculate that the presence of B8/DR3 represents a genetic pattern protective against the development of overt hypothyroidism whereas the presence of DRw6 is associated with an increased risk for post-irradiation hypothyroidism. Davies et al (1982) found in patients with TSH-receptor binding inhibiting antibodies (TB I) a rate of remmission after I-13 1 of 82% whereas this frequency was as low as 20% in patients without TB!.…”