INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 (IGFBP-3) BUT NOT INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) REMAINS ELEVATED IN EUTHYROID TSH-SUPPRESSED GRAVES-DISEASE

Thyroid hormones have been shown to be involved in the regulation of i nsulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3 ) expression. This is a cross-sectional study to look at the effects o f thyroid hormone status on the circulating levels of IGF-I and IGFBP- 3 in a group of 127 patients, aged 20-80 years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay, wh ile radioimmunoassays for total T3 and T4 were performed using kits fr om ICN, USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 us ing kits from Nichols Institute Diagnostics B.V., Netherlands. Differe nces in the levels of IGF-l between the 4 groups of patients were sign ificant only in the patients aged 20-40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was significantly lower than hyp erthyroid (315+/-26ng/ml, p = 0.003), euthyroid patients (241+/-19ng/m l, p = 0.002) and patients with suppressed TSH (308+/-29ng/ml, p = 0.0 2). The IGF-I levels of the hyperthyroid and suppressed TSH patients w ere, however, comparable to age-matched normal subjects (281+/-86ng/ml ). Although there was no difference in mean IGFBP-3 levels between the 4 groups of patients, the levels in the patients aged 20-40 with hype rthyroidism (3.7+/-0.9 mu g/ml) and suppressed TSH (3.9+/-1.2 mu g/ml) were significantly higher (p=0.02) than age-matched normal subjects ( 3.1+/-0.8 mu g/ml). The IGF-I levels of the thyroid patients aged 20-4 0 showed significant negative correlation to TSH and positive correlat ions to the thyroid hormones. Hence, whilst low IGF-I is associated wi th hypothyroidism, high IGFBP-3 is associated with hyperthyroidism. Ou r finding that IGFBP-3 remained significantly elevated in patients wit h suppressed TSH but normalised fT4 and fT3 is important as it suggest s a prolonged tissue effect of thyroid hormones on IFGBP-3. As such pa tients have been shown to have higher risk for atrial fibrillation, th e significance and possible role of IGFBP-3 in these conditions should be further elucidated in future studies.