DEVELOPMENT OF HYPERANDROGENISM DURING TREATMENT WITH INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) IN FEMALE-PATIENTS WITH LARON-SYNDROME

OBJECTIVE Patients with Laron syndrome (LS) can now be treated with re combinant IGF-I. We describe the development of androgenization during IGF-I treatment of female LS patients. PATIENTS Six female patients w ith LS-two clinically prepubertal (11.6 and 13.8 years of age) and fou r young adults (30 to 39 years old)-underwent long-term replacement tr eatment with recombinant IGF-I. The daily doses were 150 mu g/kg/day b y subcutaneous (s.c.) injection in the girls and 120 mu g/kg/day in th e adult women. METHODS Testosterone, Delta 4-androstenedione, LH, FSH, insulin and IGF-I were determined by radioimmunoassay. Blood samples were obtained after an overnight fast before the IGF-I injection. Seru m IGF-I was also determined 4 hours after the s.c. injections. RESULTS During IGF-I treatment, four out of the six patients (two girls and t wo adults) developed progressive clinical symptoms and signs of hypera ndrogenism (oligo/amenorrhoea and acne). Laboratory determinations sho wed a significant elevation in serum testosterone, Delta 4-androstened ione and LH/FSH ratio. The hyperandrogenism occurred concomitantly wit h an increase in IGF-I serum and a decrease in serum insulin concentra tions. Reduction in IGF-I dose or interruption in IGF-I treatment rest ored androgen levels to normal values. At the same time, the acne and oligomenorrhoea resolved. CONCLUSIONS Overdosage of IGF-I can lead to androgenization, a previously undescribed undesirable effect of IGF-I. Long-term IGF-I treatment necessitates progressive adjustment of the IGF-I dose to avoid overtreatment.