THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS

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Suppressive therapy with thyroid hormone (TH) has been used in the management of benign thyroid disorders for over 90 years. Administration of exogenous TH in excess of normal production by the thyroid gland leads to a reduction in the serum level of thyrotropin (TSH), the pituitary hormone which stimulates thyroid gland growth. TSH suppression should lead to shrinkage (or a reduction in further growth) of benign nodules or goiter. Several recent studies have suggested that TH may be ineffective in reducing the size of nodules or preventing the growth of goiters. TH therapy may also have adverse effects on bone; several studies have suggested that prolonged treatment with suppressive or even physiologic doses of TH leads to a significant loss of calcium from bone and would pre.dispose these patients to an increased risk for fractures of the spine, hip and wrist. These issues are especially important to women since they are 7 - 10 times as likely as men to have thyroid nodules or goiters and are at greater risk for the development of osteoporosis and fracture. The goal of this proposed study is to prospectively evaluate both the effectiveness and the detrimental effects of TH suppressive therapy on bone and benign thyroid diseases. The specific aims of this proposal are 1) to evaluate the effectiveness of suppressive TH therapy in the management of benign nodules and goiter, 2) to evaluate whether TH therapy produces a significant loss of bone mass 3) to establish whether shrinkage of benign thyroid tissue or excess bone loss is dependent upon the extent of TSH suppression and 4) to evaluate the effect of TH therapy on the patient's quality of life. This information is needed to determine whether a currently accepted therapy is either inappropriate or needs to be administered in a specific way to be both effective and safe. These results of this study will also have implications for the 8.5 million patients (mostly women) receiving TH for the treatment of primary hypothyroidism or thyroid cancer. The specific aims will be evaluated in a prospective, double-blind, placebo controlled study of suppressive thyroxine (T4) therapy in women with benign nodules or goiters. In patients receiving active T4, doses will be adjusted using a highly sensitive TSH assay and maintaining TSH values at one of two reduced levels. Patients will be followed for 2 years on therapy with baseline and serial measurements of urine and serum markers for bone resorption and formation, evaluations of quality of life, determination of bone mineral density using dual-photon x-ray absorptiometry (a highly sensitive and precise technique) and objective measurements of thyroid gland and nodule size using high resolution, real time ultrasound.