Endocrine Abstracts

JOINT3473

Aim: Serum IGF-I is widely advocated as a tool for monitoring adherence, safety and effectiveness of recombinant human growth hormone (rhGH). However, there is a need to understand the real-world variations in IGF-I levels in children on rhGH and the management of abnormal levels in clinical practice.

Method: Centres participating in the Global Registry for Novel Therapies in Rare Bone and Endocrine Conditions (www. GloBE-Reg. net) were invited to complete the minimum dataset for rhGH therapy. Information on the indications for rhGH therapy, gender, age at diagnosis and rhGH initiation, rhGH doses and serum IGF-I on therapy were collected for analysis. Based on available reference data for 6 different assays, IGF-I SDS were calculated. IGF-I values more than 2SDS below and above the mean were classed as low and high, respectively. Results are shown in median (range).

Results: A total of 2, 697 IGF-I values from 690 children (475 daily/215 LAGH; 429M/261F) were available from 17 centres in 12 countries. The main indications for daily rhGH treatment included growth hormone deficiency (GHD) in 239/475 (50%), small for gestational age (SGA) in 58/475 (12%) and Prader-Willi syndrome (PWS) in 41/475 (9%). The majority were on long-acting GH (LAGH) for GHD 192/215 (89%), with 17/215 for idiopathic short stature (ISS, 8%) and 5/215 for SGA (2%). In those on daily GH, IGF-I SDS were low –2. 4 (-3. 4, -2. 1) in 6% (126/2182) and high +3. 1 (+2. 1, +21. 6) in 10% (218/2182). Noticeably, 73/218 (33%) high IGF-I SDS were within the normal for the centres’ laboratory reference range. A quarter of children (49/203) with PWS have high IGF-I with median +3. 15 (2. 2, 21. 6), with variation in the 3 contributing centres. Children with PWS and SGA (both P<0. 001) were more likely to have high IGF-I, +0. 3 (-3. 4, +21. 6) and +0. 03 (-3. 4, +9. 2) respectively compared to GHD -0. 4 (-3. 4, +6. 2). In those on LAGH, IGF-I SDS were low –2. 2 (-3. 0, -2. 1) in 1. 6% (8/515) and high +2. 7 (+2. 1, +6. 4) in 12% (60/515). Those with high IGF-I were on the recommended LAGH doses 0. 15 (0. 07, 0. 19) mg/kg or 0. 50 (0. 45, 0. 50) mg/kg for the respective brands. Adherence data were only available in 20%.

Conclusion: Based on this study, 15% (412/2697) of IGF-I values are outwith the recommended +/- 2SDS range. IGF-SDS, as recommended in international guidelines, is underused in routine clinical practice, which often rely on laboratory reference range. Further studies into the implication of high IGF-I in children with PWS and SGA is needed.