Development of hyperandrogenism during treatment with insulin-like growth factor-I (IGF-I) in female patients with Laron syndrome
Article first published online: 25 DEC 2001
Blackwell Science Ltd, Oxford
Volume 48, Issue 1, pages 81–87, January 1998
How to Cite
Klinger, Anin, Silbergeld, Eshet and Laron (1998), Development of hyperandrogenism during treatment with insulin-like growth factor-I (IGF-I) in female patients with Laron syndrome. Clinical Endocrinology, 48: 81–87. doi: 10.1046/j.1365-2265.1998.00356.x
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
Patients with Laron syndrome (LS) can now be treated with recombinant IGF-I. We describe the development of androgenization during IGF-I treatment of female LS patients.
Six female patients with LS—two clinically prepubertal (11.6 and 13.8 years of age) and four young adults (30 to 39 years old)—underwent long-term replacement treatment with recombinant IGF-I. The daily doses were 150 μg/kg/day by subcutaneous (s.c.) injection in the girls and 120 μg/kg/day in the adult women.
Testosterone, Δ4-androstenedione, LH, FSH, insulin and IGF-I were determined by radioimmunoassay. Blood samples were obtained after an overnight fast before the IGF-I injection. Serum IGF-I was also determined 4 hours after the s.c. injections.
During IGF-I treatment, four out of the six patients (two girls and two adults) developed progressive clinical symptoms and signs of hyperandrogenism (oligo/amenorrhoea and acne). Laboratory determinations showed a significant elevation in serum testosterone, Δ4-androstenedione and LH/FSH ratio. The hyperandrogenism occurred concomitantly with an increase in IGF-I serum and a decrease in serum insulin concentrations. Reduction in IGF-I dose or interruption in IGF-I treatment restored androgen levels to normal values. At the same time, the acne and oligomenorrhoea resolved.
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.