ESPE Abstracts (2014) 82 P-D-1-2-151

Sequential Measurements of IGFI Serum Concentrations in Patients With Severe Primary IGFI Deficiency (SPIGFD) and Growth Failure Treated With Recombinant IGFI (Increlex[reg])

Markus Bettendorfa, Klaus Kapelarib, Carolin Kneppoa, Hermann L Müllerc, Dirk Schnabeld & Joachim Wölflee

aUniversity Children’s Hospital, Heidelberg, Germany; bUniversity Children’s Hospital, Innsbruck, Austria; cUniversity Children’s Hospital, Oldenburg, Germany; dUniversity Children’s Hospital, Berlin, Germany; eUniversity Children’s Hospital, Bonn, Germany

Introduction: Increlex® was approved as an orphan drug for treatment of growth failure in children and adolescents with SPIGFD in 2007 with relatively little data available. Therefore sequential measurements of serum IGFI, glucose, insulin and potassium were performed in SPIGFD patients treated with Increlex® to evaluate their significance in safety and efficacy.

Design: Blood samples were taken after meals before and 30, 60, 120, 180 and 360 min after s.c. Increlex® injections in seven patients (six male, one female) with idiopathic SPIGFD (n=5) or Laron syndrome (n=2). 23 sequences were performed at treatment start, dose escalation or dose adjustment. Serum IGFI was measured centrally by RIA (Mediagnost, Reutlingen). Written informed consent was obtained for all patients and the study approved by the ethics committee of Heidelberg University.

Results: Median IGFI concentrations were 248 (n=37), 442 (n=138) and 410 (n=46) ng/ml for patients receiving 0.04–0.08, 0.08–0.12 or >0.12 mg/kg Increlex® respectively. Maximal IGFI concentrations were reached 2–3 h after injections and values were still higher 6 h after injections than at baseline. 21.3% of all and 48% of maximal IGFI concentrations were greater than +2 SDS (adjusted for bone age, retarded by 2.5 years). Height velocity correlated poorly with Increlex® dose but significantly with individual maximum serum IGFI (cm/year, P<0.01; SDS P<0.002). Insulin and glucose did not correlate to IGFI concentrations but serum K+ declined after injections (3.1–4.7 mmol/l) and showed a significant negative correlation with IGFI concentrations (n=203, P<0.0001).

Conclusions: Sequential measurements of serum IGFI and serum glucose, insulin and potassium in SPIGFD patients may add to optimize and individualize Increlex® treatment. IGFI concentrations should be referenced using bone ages which better reflect biological ages. The inverse correlation of IGFI and serum K+ concentrations after injections of IGFI has not been reported before and warrants further consideration.

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