Genistein Aglycone Does Not Affect Thyroid Function: Results from a Three-Year, Randomized, Double-Blind, Placebo-Controlled Trial

Context and Objective: Genistein aglycone positively affects postmenopausal symptoms. However, questions about its long-term safety on the thyroid gland still remain. Design: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24 months. A subcohort (138 patients) continued therapy for an additional year. Setting: Patients received ambulatory care. Patients and Interventions: Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67), plus calcium and vitamin D3 at therapeutic doses. Circulating thyroid hormones (TSH, free T3, free T4) and autoantibodies (thyroid peroxidase, thyroglobulin, and thyroid microsomal antigen) were assessed in 40 genistein and 37 placebo subjects who completed 3 yr. Thyroid hormone receptor (THRα and THRβ) and retinoid receptor (RARα, RARγ, and RXRα) expression from peripheral blood monocytes was also evaluated at baseline, 12, 24, and 36 months in all 3-yr completers. Results: Genistein administration over 3 yr did not affect serum thyroid hormones or autoantibodies. In addition, there were no differences in THRα, THRβ, RARα, RARγ, or RXRα mRNA expression between groups. Conclusion: These data suggest that genistein aglycone intake does not significantly increase the risk of clinical or subclinical hypothyroidism at the dose of 54 mg/d.

Novel routine assay of thyroperoxidase autoantibodies.

This radioimmunoassay was developed for specific and large-scale routine measurement of autoantibodies to thyroperoxidase (TPO), an enzyme recently identified as the thyroid microsomal antigen. Because of the scarcity of purified thyroperoxidase, we did not base the assay on the antigen-coated method but rather on autoantibody inhibition of the binding of labeled TPO to a solid-phase-bound monoclonal antibody to TPO. This assay design ensured highly specific measurements without interference from irrelevant thyroid antigens and autoantibodies. When we used affinity-purified autoantibodies to TPO as standards, the range of the curve extended over 10(3)-fold differences in the autoantibodies' concentrations, which allowed us to assay most sera without dilution. Within- and between-assay coefficients of variation (CVs) ranged from 6.1% to 11.5% and from 6.6% to 12.0%, respectively. The correlation between anti-TPO and antimicrosomal autoantibodies, as assessed by hemagglutination test, was highly significant (r = 0.90, P less than 0.0001). This assay is sensitive, easy to perform, and requires only trace amounts of purified TPO.

Prevalence of thyroid dysfunction in elderly subjects

The prevalence of thyroid dysfunction was investigated in a small, rural community located at the coast in Middle Norway. Two hundred persons (114 women and 86 men) of the total 802 persons over 70 years of age in the community were examined regarding thyroid dysfunction. Blood samples were drawn from 197 (113 women and 84 men). In women previously diagnosed hypothyroidism was found in 3.5% and previously diagnosed hyperthyroidism in 0.9%. In men no previously diagnosed thyroid disease was found. Undiagnosed primary hypothyroidism (TT4 < 70 nmol/l and TSH > 6 mU/l) was found in 1.8% and 1.2% of women and men, respectively. Latent hypothyroidism (TT4 70–150 nmol/l and TSH > 6 mU/l) was found in 3.5% and 2.4%, and borderline hypothyroidism (TSH 4.5–6.0 mU/l) in 3.5% and 2.4%, respectively. Undiagnosed hyperthyroidism was not found in women but in 1.2% of men. Antibody to the thyroid microsomal antigen (TMA) ≥ 400 was detected in 17.5% of women and 9.6% of men. Clearly elevated serum thyrotropin (TSH) concentrations or previously diagnosed thyroid disease were found in 21.7% and 37.5% of the TMA positive women and men, respectively.