Persistent increase in bone turnover in Graves' patients with subclinical hyperthyroidism

Hyperthyroid patients exhibit accelerated bone loss by increased bone turno ver, and normalization of thyroid function is associated with a significant attenuation of increased bone turnover, followed by an increase in bone mi neral density. However, of patients with Graves' disease (GD) maintained on antithyroid drug (ATD) treatment, some exhibit persistent suppression of T SH long after normalization of their serum free T-3 (FT3) and free T-4 (FT4 ) levels. The aim of this study was to examine whether bone metabolism is s till enhanced in TSH-suppressed premenopausal GD patients with normal FT3 a nd FT4 levels after ATD therapy (n = 19) compared with that in TSH-normal p remenopausal GD patients (n = 30), and to evaluate the relationship between serum TSH receptor antibody (TRAb), an indicator of disease activity of GD , and various biochemical markers of bone metabolism. No difference was fou nd between the two groups in serum Ca, phosphorus, or intact PTH, or in uri nary Ca excretion. Serum bone alkaline phosphatase (B-ALP), bone formation markers, and urinary excretions of pyridinoline (U-PYD) and deoxypyridinoli ne (U-DPD), which are bone resorption markers, were significantly higher in the TSH-suppression group than in the TSH-normal group (B-ALP, P < 0.05; U -PYD, P < 0.001; U-DPD, P < 0.001). For the group of all GD patients enroll ed in this study, TSH, but neither FT3 nor FT4, exhibited a significant neg ative correlation with B-ALB (r = -0.300; P < 0.05), U-PYD (r = -0.389; P < 0.05), and U-DPD (r = -0.446; P < 0.05), whereas TRAb exhibited a highly p ositive and significant correlation with B-ALP (r = 0.566; P < 0.0001), U-P YD (r = 0.491; P < 0.001), and U-DPD (r = 0.549; P < 0.0001). Even in GD pa tients with normal TSH, serum TRAb was positively correlated with B-ALP (r = 0.638; P < 0.001), U-PYD (r = 0.638; P < 0.001), and U-DPD (r = 0.641; P < 0.001). In conclusion, it is important to achieve normal TSH levels durin g ATD therapy to normalize bone turnover. TRAb was not only a useful marker for GD activity, but was also a very sensitive marker for bone metabolism in GD patients during ATD treatment.