Effects of Suppressive Doses of Levothyroxine Treatment on Sex-Hormone-Binding Globulin and Bone Metabolism

The adverse effects of suppressive thyroxine treatment have previously been investigated and conflicting results have been published. This study aimed at evaluating the effects of subclinical hyperthyroidism on the liver and bones. We investigated the action of thyroxine on the liver by measuring sex-hormone-binding globulin (SHBG) levels and on bone turnover by evaluating osteocalcin (BGP) in both pre- and postmenopausal women. We compared the levels of both proteins to those of untreated subjects matched for age, menopausal status, and weight. Bone mineral density (BMD) was evaluated by biphotonic absorptiometry only in postmenopausal women with estrogen replacement therapy (ERT) and compared to two postmenopausal estrogen-treated controls. Forty-five women with multinodular goiter (38) or postsurgical thyroid carcinoma (7) were studied. They had received LT₄ for 3 to 5 years (150 ± 34 µg/day for nontoxic multinodular goiter, 184 ± 46 µg/day for thyroid carcinoma). All patients had normal free T₃ concentrations. No significant difference was found in SHBG values between patients and controls whatever the menopausal status and the BMI; a significant increase in BGP was noted in premenopausal women (9.6 ± 2.2 vs 6.7 ± 2.3 ng/ml;p < 0.0006). No significant BGP and BMD variations were observed in treated postmenopausal women. In summary, the study of carefully matched patients and controls revealed that thyroxine treatment has no effect on SHBG levels. The increase in BGP observed in premenopausal women might suggest a high turnover bone loss. A deleterious effect on spine BMD was not observed in this small group of postmenopausal women, but ERT might be a confounding factor and could also explain the absence of variation of BGP in postmenopausal women. However, the long-term impact of this treatment upon bone density has to be thoroughly evaluated.