IGF-I TREATMENT OF ADULT PATIENTS WITH LARON SYNDROME - PRELIMINARY-RESULTS

OBJECTIVE Laron syndrome is a genetic disease due to a defect in the GH receptor or in the post-receptor mechanism which leads to an inability to generate IGF-I. Biosynthetic IGF-I treatment given to dwarfed children with this syndrome, produced a significant acceleration of growth velocity and reduction in obesity. In view of the known metabolic disturbances in untreated adult patients, the present clinical trial was performed to define the usefulness of IGF-I treatment in LS adults. PATIENTS AND DESIGN Five patients (1 male, 4 females) aged 28-40 years were treated during 9 months by daily administration of IGF-I (120 mu g/kg), and followed for 6 months after its discontinuation. METHODS At each visit, a complete physical examination was performed and blood was drawn for biochemical and hormone determinations. Twenty-four-hour urinary samples were collected at various intervals during treatment. Bone densitometry was performed before and after 6-9 months of therapy. RESULTS The main findings were a reduction in skinfold thickness (from 27.5 +/- 1.4 (mean +/- SEM) to 19.5 +/- 1.0 mm; P < 0.002), a decrease in total cholesterol (from 6.78 +/- 0.28 (mean +/- SEM) to 5.80 +/- 0.36 mmol/l) and in LDL cholesterol (from 4.86 +/- 0.23 to 3.76 +/- 0.35 mmol/l), an increase in creatinine clearance (from 71.2 +/- 8.4 to 86.8 +/- 4.3 ml/min/1.73 m(2), P < 0.04), an increase in phosphate reabsorption (from 0.89 +/- 0.06 to 1.14 +/- 0.06 mmol%; P < 0.02) leading to an increase in serum phosphate (from 1.08 +/- 0.06 to 1.27 +/- 0.03 mmol/l; P < 0.03), a rise in alkaline phosphatase (from 80.8 +/- 5.0 to 100.7 +/- 7.0 U/l) and in procollagen I-PICP (from 44.2 +/- 4.0 to 171.0 +/- 19.2 mu g/l; P < 0.0001) and in procollagen III-PIIINP (from 2.68 +/- 0.45 to 10.10 +/- 1.4 mu g/l; P < 0.005). There was a transient retention of water, sodium and chloride. serum IGFBP-3 levels were low, Pretreatment but increased progressively during treatment. This permitted a reduction In the IGF-I dose. There were no adverse effects other than pain and slight erythema at the injection site during the first weeks of treatment. All the anthropometric and metabolic changes reversed upon discontinuation of IGF-I. CONCLUSIONS IGF-I treatment is beneficial in adults, as well as in children, with resistance to GH.