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.


METHODS
Five patients (1 male, 4 females) aged 28-40 years were treated during 9 months by daily administration of IGF-I (120 micrograms/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 subscapular 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 m2, 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 micrograms/l; P < 0.0001) and in procollagen III-PIIINP (from 2.68 +/- 0.45 to 10.10 +/- 1.4 micrograms/l; P < 0.005). There was a transient retention of water, sodium and chloride. Pretreatment serum IGFBP-3 levels were low, 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.
Laron
Z
Z
Endocrine and Diabetes Research Unit, Children's Medical Center of Israel, Tel Aviv.
Klinger
B
B
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D002352:Carrier Proteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000097:blood / Q000628:therapy*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D010710:Phosphates / Q000378:metabolism; D011347:Procollagen / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use
D002352:Carrier Proteins; D008078:Cholesterol, LDL; D018969:Insulin-Like Growth Factor Binding Proteins; D010446:Peptide Fragments; D010710:Phosphates; D011347:Procollagen; D011994:Recombinant Proteins; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol; D003404:Creatinine; D000469:Alkaline Phosphatase