title: Serum insulin-like growth factor-I, insulin-like growth factor binding proteins, and bone mineral content in hyperthyroidism.
abstract: The mechanism by which thyroid hormones promote bone growth has not yet been elucidated. In vitro, thyroid hormones stimulate insulin-like growth factor-I (IGF-I) production by osteoblasts, which is important for the anabolic effects of the hormone on bone. To determine whether the IGF-I/IGF binding protein (IGFBP) profile is affected when thyroid hormone production is altered in vivo, we studied 36 women who had recently been diagnosed with hyperthyroidism (age: 29-67 years; 19 with Graves' disease, 17 with toxic nodular goiter) and 36 age-matched healthy women as controls. Serum IGF-I, and its binding proteins (IGFBP-3, IGFBP-4, and IGFBP-5), as well as bone mineral density (BMD) at the lumbar spine, femoral neck, and radius midshaft were measured before and 1 year after antithyroid (methimazole) treatment. Serum IGF-I levels were significantly increased in the hyperthyroid patients before treatment (214 +/- 18.2 ng/mL vs. 145 +/- 21.3 ng/mL; p < 0.05). There was no difference in IGF-I levels of patients with Graves' disease and toxic nodular goiter. Serum IGF-I concentrations returned to normal after treatment with methimazole. Serum IGFBP-3 and IGFBP-4 values were significantly elevated in the hyperthyroid group before treatment (3960 +/- 220 ng/mL and 749.7 +/- 53.1 ng/mL vs. 2701 +/- 180 ng/mL and 489.9 +/- 32.4 ng/mL; p < 0.05 and p < 0.01, respectively) and were reduced to those of controls after treatment. Serum IGFBP-5 of hyperthyroid subjects was not different from that of controls either before or after therapy. Serum free thyroxine showed a positive correlation with serum levels of IGF-I (r = 0.73, p < 0.05), IGFBP-3 (r = 0.59, p < 0.05), and IGFBP-4 (r = 0.67, p < 0.05) but not IGFBP-5. BMD at the radius midshaft was significantly lower in hyperthyroid patients at the start of the study and showed a positive correlation with serum IGF-I (r = 0.58; p < 0.001) and a negative correlation with IGFBP-4 (r = -0.61; p < 0.05). Radius BMD showed a 7.2% increase in the hyperthyroid group after 1 year of methimazole treatment, and the correlation between BMD and serum IGF-I disappeared. Our data indicate that thyroid hormones may influence the IGF-I/IGFBP system in vivo in hyperthyroidism. The anabolic effects of increased levels of IGF-I may be limited in hyperthyroidism due to the increases of inhibitory IGFBPs that can counteract the anabolic effects and contribute to the observed net bone loss.
authors.affiliation: 1st Department of Medicine, Semmelweis University Medical School, Budapest, Hungary. lakpet@bell.sote.hu
authors.forename: P
authors.initials: P
authors.lastname: Lakatos
authors.forename: J
authors.initials: J
authors.lastname: Foldes
authors.forename: Z
authors.initials: Z
authors.lastname: Nagy
authors.forename: I
authors.initials: I
authors.lastname: Takacs
authors.forename: G
authors.initials: G
authors.lastname: Speer
authors.forename: C
authors.initials: C
authors.lastname: Horvath
authors.forename: S
authors.initials: S
authors.lastname: Mohan
authors.forename: D J
authors.initials: DJ
authors.lastname: Baylink
authors.forename: P H
authors.initials: PH
authors.lastname: Stern
mesh_terms: D000328:Adult; D000368:Aged; D013956:Antithyroid Agents / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008713:Methimazole / Q000627:therapeutic use; D008875:Middle Aged; D011884:Radius / Q000378:metabolism; D012016:Reference Values
chemical_list: D013956:Antithyroid Agents; D018969:Insulin-Like Growth Factor Binding Proteins; D008713:Methimazole; D007334:Insulin-Like Growth Factor I