Serum insulin-like growth factor-I (IGF-I) levels during long-term IGF-I treatment of children and adults with primary GH resistance (Laron syndrome)

Serum IQ;F-I levels were measured in 14 patients (9 children and 5 adults) with Laron syndrome (LS) during long-term treatment by IGF-II. Recombinant IGF-I (FK-780, Fujisawa Pharmaceutical Co. Ltd., Japan) was administered on ce daily subcutaneously before breakfast for 3-5 years to the children and for 9 months to the adults. The initial daily dose was 150 mu g/kg for chil dren and 120 mu g/kg for adults. Before initiation of treatment the mean ov ernight fasting levels of serum IGF-I in the children was 3.2 +/- 0.8 nmol/ l (mean +/- SEM), rising to 10 +/- 1.7 nmol/l during long-term treatment ev en on a dose of 120 mu g/kg/day. The serum IGF-I levels 4 hours after injec tion rose from 31.2 +/- 3.5 to 48 +/- 2 nmol/l, In the adult patients, the initial basal IGF-I was 4.1 +/- 0.7 nmol/l, rising to 16.1 +/- 3.84 nmol/l after 8-9 months treatment, Serum IGF-I levels at 4 hours after injection r ose in the adult patients from 24.1 +/- 5.8 up to 66.8 +/- 15.4 nmol/l. A p rogressively increasing half-life during long term exogenous administration of IGF-I to patients with Laron syndrome was demonstrated by following ser um IGF-I dynamics after injection. Based on the fact that no antibodies to IGF-I were detected and on findings in previous studies, it is speculated t hat the increasing serum IGF-I levels during long-term IGF-I treatment are caused by an increase in serum IGFBP-3 induced by chronic IGF-I administrat ion. It is concluded that treatment with IGF-I necessitates regular monitor ing of serum IGF-I levels; in patients in whom the age adjusted maximal lev els are exceeded, a reduction of the daily IGF-I dose is indicated to avoid undesirable effects.