Effects of Hypothyroidism and Hyperthyroidism on Insulin-like Growth Factors and IGF-Binding Proteins

Background: 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.Subjects and Method: We have studied the effects of hyperthyroidism (n=22, aged 33.14±5.41 years) and hypothy-roidism (n=22, clinical =10 and subclinical =12, aged 34.5± 5.26 years) on levels of serum immunoreactive (IR) IGF-I and IGF-binding protein 3 (IGFBP-3) measured by IRMA kit. Twenty persons were also included as a normal control group. Eight hyperthyroid and 8 hypothyroid patients were followed up 3 months after specific treatment.Results: The mean IGF-I and IGFBP-3 Z-values were not significantly higher in hyperthyroid patients (-0.40±0.90 and -0.53±0.72 respectively) than in the control group (-1.07±1.05 and -0.99+0.63 respectively) but they were significantly higher than clinical hypothyroid cases (-1.92±0.62 and -1.50±0.76 respectively, p 0.05). After 3 months of Antithyroid therapy, TSH level increased to 0.01±0.02|iIU/ml but is still signifi¬cantly suppressed. There was significant lowering in their thyroid hormones levels (11.19+6.69pg/ml to 3.16+0.87pg/ml for T3 and 3.90±1.62ng/dl to 1.39±0.27ng/dl for T4, p 0.01). Their mean IGF-I Z-value was significantly lowered (-0.40± 0.90 changed to -0.98±0.55, p 0.05) under treatment but the lowered IGFBP-3 Z-value was not significant (-0.53±0.72 lowered to -0.73±0.88, /?=0.4). In clinical cases of hypothy¬roidism, the mean serum IGF-I Z value was significantly lower (-1.92±0.62) than the control group (-1.07±1.0, p=0.03). This difference is not significant in subclinical cases (-1.55± 0.58). After 3 months therapy in the clinical hypothyroid group, the serum TSH level dropped significantly from 25.94± 22.82 to 16.40± 12. 19jiIU/ml, p 0.05. The rise of both IGF- I Z-values and IGFBP-3 Z values under therapy with thyroxin were not significant (-1.92±0.62 rose to -1.10±0.97 for IGF- 1 and -1.50±0.76 rose to -1.25±1.51 for IGFBP-3). In all studied cases as well as in control subjects, serum fT4 and fT3 values were positively correlated (r=0.627, /? 0.01) and serum TSH levels were inversely correlated (r=0.312, /? 0.01) with circulating IGF-I concentrations.Conclusion: our data suggest that even subclinical alter¬ation in thyroid functions correlated with IGF-I concentrations.We have confirmed that IR IGF-I and IGFBP-3 level are low in hypothyroidism and high in hyperthyroidism reflecting a direct relationship between circulating levels of thyroid hormones and IGF-I. Their response to specific therapy suggests their possible use in monitoring the response to treatment in cases of thyroid dysfunction.