Changes of thyroid function during long-term hGH therapy in GHD children. A possible relationship with catch-up growth?

Background: Growth hormone (GH) treatment in patients with GH deficiency (GHD) can determine changes in the thyroid function. The clinical significance of these changes remains controversial, and all studies have so far covered rather a short period - usually no longer than one year. Objective: To determine the effect of long-term recombinant hGH treatment in children with idiopathic GHD on the thyroid function. Patients and methods: Nineteen prepubertal children (12 boys and 7 girls, mean age 9.2 +/- 3.1 years) with idiopathic GHD were studied and followed for twenty-four months. None of the patients showed multiple pituitary hormone deficiencies. Nineteen healthy children matched for age and sex acted as controls. Results: Patients with GHD showed a significant increase in TT3 at twelve months and in FT3 at six and twelve months after starting GH treatment, with a significant decrease at eighteen and twenty-four months. TT4 level decreased significantly at twelve months and increased significantly at eighteen and twenty-four months. FT4 also decreased, but only slightly, after twelve months of hGH treatment, and then increased significantly at twenty-four months. TSH levels did not vary significantly during the course of therapy. TT3/TT4 and FT3/FT4 ratios increased significantly after six and twelve months of therapy and significantly decreased later, approaching pre-therapy values. The SDS of Growth Velocity (SDS-GV) increased remarkably during the first year of therapy and then decreased significantly during the second year, although it remained significantly higher than the pre-therapy values. TT3 and TT3/TT4 ratio displayed a significant correlation with SDS-GV at twelve months of therapy. In a multiple regression analysis with age, bone age, parental height, GH dose, TT3, TT3/TT4, and the SDS of IGF-1, only the TT3/TT4 ratio at twelve months of therapy (p < 0.001) was identified as a significant predictor of SDS-GV. Conclusion: Our data confirm that changes in thyroid function are present in GHD children during long-term hGH therapy. These changes probably resulted from the effect of hGH on the peripheral metabolism of thyroid hormones and appear to be transitory, disappearing during the second year of hGH treatment. We speculate on the functional significance of these changes, and in particular, on their role in catch-up growth after hGH therapy.