Insulin-like growth factor-I treatment in primary growth hormone insensitivity: effect of recombinant human IGF-I (rhIGF-I) and rhIGF-I/rhIGF-binding protein-3 complex

Abstract

Background/aims: Growth hormone insensitivity syndrome (GHIS) is a rare cause of growth retardation characterized by high serum GH levels, and low serum insulin-like growth factor I (IGF-I) levels associated with a genetic defect of the GH receptor (GHR) as well post-GHR signaling pathway. Based on clinical, as well as biochemical characteristics, GHIS can be genetically classified as classical/Laron's syndrome and nonclassical/atypical GHIS. Recombinant human IGF-I (rhIGF-I) treatment is effective in promoting growth in subjects who have GHIS. Further, pharmacological studies of a IGF-I compound containing a 1:1 molar complex of rhIGF-I and rhIGF-binding protein-3 (BP-3) demonstrated that the complex was effective in increasing levels of circulating total and free IGF-I and that the administration in patients with GHIS should be safe, well-tolerated and more effective than rhIGF-I on its own.

Patient/methods: We describe the long-term effect of various IGF-I preparations (rhIGF; rhIGF-I/rhIGFBP-3) in a single subject treated for more than 14 years while focusing on height, height velocity as well as on additional auxological and laboratory data.

Results: This study confirms that rhIGF-I is effective in promoting growth in children with GHIS. However, on the combined rhIGF-I/rhIGFBP-3 treatment as well as off rhIGF-I therapy the height velocity decreased drastically (2 and 1.8 cm vs. overall 6.5 cm/year on rhIGF-I, respectively). On rhIGF-I treatment, serum IGF-I was found to be well within the normal range, whereas serum IGFBP-3 remained low. On the rhIGF-I/rhIGFBP-3 compound therapy, however, serum IGFBP-3 increased into the normal range, which was not the case for serum IGF-I. Importantly, the increase of the serum IGFBP-3 level excludes noncompliance. In addition, body mass index as well as dual-energy X-ray absorptiometry analysis underlined the positive effect of rhIGF-I treatment on body composition.

Conclusions: The rhIGF-I/rhIGFBP-3 compound therapy seems to be not efficient in treating this individual patient with GHIS when compared with rhIGF-I alone.