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Risks and Benefits of Insulin-like Growth Factor

TO THE EDITOR: Bondy and colleagues [1] provided an excellent review of available knowledge regarding insulin-like growth factor (IGF). I report additional information concerning IGF-I adverse drug experience reports received by the Food and Drug Administration (FDA) in the last 5 years. Syncopal reactions in the absence of hypoglycemia were reported in 11 patients. Nine received IGF-I intravenously at doses of 100 g/kg of body weight as a bolus or by infusions that exceeded 24 g/kg per hour, whereas another patient received 18 g/kg per hour. One patient received IGF-I subcutaneously. Two patients had concomitant seizure-like activity with tonic muscle movements of the extremities and head, and one of these two had an episode of asystole lasting 11 seconds or longer. Dizziness, bradycardia, and hypotension were accompanying features in most patients. In July 1992, in response to these reports, the FDA recommended that IGF-I not be given in intravenous boluses or infusions in excess of 24 g/kg per hour. We have not received reports of syncope since. The underlying mechanisms of syncope during IGF-I administration remain unknown, but rapid reduction in serum phosphate levels [2] and previously unrecognized direct vasoactive actions have been postulated as causes (Copeland KC. Personal communication). It seems attractive to speculate that when the capacities of IGF-I-binding proteins are exceeded, the high levels of free IGF-I could result in these short-term adverse events. Asymptomatic hypoglycemia has also been reported with both intravenous and subcutaneous administration of IGF-I. In addition, in patients treated for short stature associated with growth hormone resistance, mid- and long-term effects of IGF-I have resulted in symptoms previously associated with growth hormone therapy, such as intracranial hypertension [3], gynecomastia [4], avascular necrosis of the head of the femur, and, more importantly, marked acromegaloid changes with severe coarsening of facial features. Bell palsy, nephrolithiasis (in pediatric patients), and nasal swelling have also been reported. Whether other organ systems are affected by long-term IGF-I therapy remains unknown. Renal and cardiac size and function, as well as changes in acral bones and mandibular characteristics, are being monitored in studies of the long-term effects of this peptide hormone.