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 recombinant IGF-I. We describe the development of androgenization during IGF-I treatment of female LS patients.


METHODS
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 micrograms/kg/day by subcutaneous (s.c.) injection in the girls and 120 micrograms/kg/day in the 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. Serum 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 two adults) developed progressive clinical symptoms and signs of hyperandrogenism (oligo/amenorrhoea and acne). Laboratory determinations showed a significant elevation in serum testosterone, delta 4-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.


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.
Klinger
B
B
Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center of Israel, Tel Aviv.
Anin
S
S
Silbergeld
A
A
Eshet
R
R
Laron
Z
Z
D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000097:blood; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006130:Growth Disorders / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D017588:Hyperandrogenism / Q000209:etiology*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects* / Q000172:deficiency*; D007986:Luteinizing Hormone / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013739:Testosterone / Q000097:blood
D007328:Insulin; D011994:Recombinant Proteins; D013739:Testosterone; D000735:Androstenedione; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone