EFFECTS OF HYPOTHYROIDISM AND HYPERTHYROIDISM ON INSULIN-LIKE GROWTH-FACTORS (IGFS) AND GROWTH HORMONE-BINDING AND IGF-BINDING PROTEINS

Normal thyroid status is a prerequisite for the normal growth and development of many tissues. The interrelationships between the thyroid and pituitary-GH-insulin-like growth factor (IGF) axes are complex and not yet fully understood. We have studied the effects of hypothyroidism (n = 22) and hyperthyroidism (n = 17) on levels of serum immunoreactive IGF-I and II, IGF-binding proteins (IGFBP-1 and -3), and IGF bioactivity before and during treatment. We have also assessed changes in GH-binding activity (GHBP). Mean immunoreactive (IR) IGF-I levels in the hypothyroid group rose from 106.6 +/- 10.6 mug/L at diagnosis to 139.9 +/- 12.7 mug/L (P = 0.009) on normalization of thyroid function. In hyperthyroidism, mean IGF-I levels (258.9 +/- 33.9 mug/L) were high initially and fell to 188.7 +/- 14.8 mug/L (P = 0.04) after treatment. IR IGF-I levels correlated positively with free T3 and free T4 and negatively with TSH levels. Mean serum IGF-II levels were low in hypothyroid patients (375.2 +/- 37.3) and rose during treatment (516.9 +/- 59.4 mug/L; P = 0.04). In the hyperthyroid subjects, however, there was no significant change during therapy (625.0 +/- 66.9 vs. 621.9 +/- 120.8 mug/L; P = 0.98). IGF bioactivity potency ratios were low in the hypothyroid group (0.26 +/- 0.03 U/mL) and rose to 0.71 +/- 0.10 U/mL (P = 0.01) during treatment. IGF bioactivity in the hyperthyroid group was also low (0.38 +/- 0.05 U/mL) and rose significantly during treatment (0.81 +/-0.06 U/mL; P = 0.003). Mean IGFBP-1 levels (29.8 +/- 5.7 mug/L) were unaltered by treatment of hypothyroid subjects (28.4 +/- 4.8 mug/L). In contrast, IGFBP-1 levels in the hyperthyroid subjects were high at diagnosis (134.6 +/- 26.6 mug/L) and fell significantly (71.3 +/- 14.3 mug/L; P = 0.04) during treatment. In the hypothyroid group, IGFBP-3 levels rose from an initial mean of 1.98 +/- 0.17 to 2.67 +/- 0.27 mg/L (P = 0.04) during treatment. The higher mean pretreatment levels in the thyrotoxic group (3.46 +/- 0.32 mg/L) were unaltered by treatment (3.20 +/- 0.51 mg/L; P = 0.71). GHBP was low in the hypothyroid group at diagnosis (28.5 2.5%) and rose during treatment to 40.6 +/- 3.9% (P = 0.02). We have confirmed that IR IGF-I levels are low in hypothyroidism and have demonstrated a reduction in IGF bioactivity and IGF-II and IGFBP-3 levels, and low GH-binding activity, which may reflect a reduction in the processing of GH receptors. In hyperthyroidism, despite normal or high IR IGF-I levels, IGF bioactivity is reduced, which may be a result of the induction of specific inhibitors of somatomedin activity. IGFBP-1 levels were high in hyperthyroidism, and this peptide is known to inhibit IGF actions in a number of bioassay systems. The majority of the abnormalities of the GH/IGF axis are reversed on normalization of thyroid function.