A small number of
children with growth failure have severe IGF-I deficiency that is not
responsive to exogenous GH. Causes include mutations in the GH receptor and in
the GH receptor signaling pathway, neutralizing antibodies to GH, and IGF-I
gene defects. In 2005, the FDA approved two forms of recombinant human IGF-I
(rhIGF-I) for treatment of severe IGF-I deficiency that is not responsive to
GH: mecasermin and mecasermin rinfabate. Mecasermin is rhIGF-I alone, while
mecasermin rinfabate is a complex of recombinant human IGF-I (rhIGF-I) and
recombi-nant human insulin-like growth factor-binding protein-3 (rhIGFBP-3).
This binding protein significantly increases the cir-culating half-life of
rhIGF-I. Normally, the great majority of the circulating IGF-I is bound to
IGFBP-3, which is produced prin-cipally by the liver under the control of GH.
Mecasermin rinfa-bate is not currently available in the United States.
Mecasermin is administered subcutaneously twice daily at a recommended
start-ing dosage of 0.04–0.08 mg/kg and increased weekly up to a maximum
twice-daily dosage of 0.12 mg/kg.
The most important
adverse effect observed with mecasermin is hypoglycemia. To avoid hypoglycemia,
the prescribing instruc-tions require consumption of a carbohydrate-containing
meal or snack 20 minutes before or after mecasermin administration. Several
patients have experienced intracranial hypertension and asymptomatic elevation
of liver enzymes.