Abnormalities in Thyroid Function in Relatives of Patients with Graves' Disease and Hashimoto's Thyroiditis: Lack of Correlation with Inheritance of HLA-B8

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Abstract
Thyroid function, antithyroid antibodies and human major histocompatibility locus (HLA) antigens were studied in first-degree relatives (parents, siblings and children) of patients with Graves' disease and Hashimoto's thyroiditis. The particularly common abnormalities in Graves' relatives were positive antithyroid antibodies (25 of 74 cases, 34%) and supranormal thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) (12 of 44 cases, 27%). Less common abnormalities were goiter (10 of 92 cases, 11%), ophthalmopathy (1 of 92 cases, 1.1%), non-suppressibility of 24 h thyroid radioiodine uptake (2 of 48 cases, 4.2%), elevated baseline serum TSH (4 of 80 cases, 5.0%), subnormal TSH response to TRH (2 of 44 cases, 4.5%) and detectable LATS-protector (3 of 47 cases, 6.4%). Thyroid uptake was non-suppressible in two of the three cases with LATS-protector; the remaining one had ophthalmopathy and normally suppressible thyroid uptake. Of the 14 relatives of patients with Hashimoto's thyroiditis included in the study, three were hypothyroid with antithyroid antibodies and goiter. The thyroid-related abnormalities, similar to those noted above for Graves' relatives, occurred frequently in the remaining euthyroid cases. Although frequency of HLA-B8 in 73 patients with Graves' disease was significantly higher than in control subjects (37% vs. 21%, P < 0.05), no significant abnormality was detected in HLA patterns of relatives of patients with Graves' disease. Furthermore, the incidence of thyroid-related abnormalities (vide supra) in Graves' relatives with HLA-B8 did not differ significantly from that in relatives without HLA-B8. HLA patterns of patients with Hashimoto's thyroiditis were normal except for increased uncorrected frequency of B8 (42%, P < 0.01); this was not significantly different from normal when the probability was corrected for the number of antigens studied (P = 0.24, N = 31). Conclusions: 1) thyroid functional abnormalities occur very frequently in relatives of patients with Graves' disease and Hashimoto's thyroiditis; 2) since thyroid functional abnormalities occur so often even when HLApatterns are normal, mechanism(s) responsible for abnormalities must include factor(s) other than inheritance of B8 or other HLA antigens.

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