Endocrine Abstracts

Introduction: Growth hormone (GH) insensitivity, also known as severe primary IGF-1 deficiency (SPIGFD) is a rare condition that causes significant growth impairment in children. The classical form of SPIGFD is Laron syndrome, where a genetic defect of the GH receptor gene leads to GH resistance with high GH and low or undetectable IGF-1 levels. Twice daily injections of recombinant IGF-1 (rhIGF-1) therapy are used for the treatment of SPIGFD (height <-3 SD, serum IGF-1 <2.5th centile and normal GH)

Aim: To report final height in seven children with SPIGFD due to a confirmed GH receptor mutation (Laron syndrome) who were treated with rhIGF-1 (Mecasermin)

Methods: A retrospective review of all patients diagnosed with SPIGFD who received rhIGF-1 treatment

Results: Seven patients (5 male, 2 female) received treatment with rhIGF-1, at mean age of initiation of 9.1 years (range: 6.7–15.1 years) for a mean duration of 8.51 years (range: 1.5 to 12 years). The mean baseline height at the initiation treatment was -4.75 SD with a mean final height of -3.6 SD, reflecting a mean gain of 1.1 SDS. Final heights ranged from -5.44 to -2.24 SD. Height velocity increased from a baseline of 3.19 cm/year to 6.23 cm/year in the first year and 3.66 cm/year in the second year of treatment. The mean BMI increased from -1.2 SD to -0.2 SD. All children had lipohypertrophy at the injection sites. Two had lymphoid hyperplasia and snoring, one experienced hypoglycaemia. One child who started treatment at age 15.1 years had a reduction in height SDS probably reflecting that he was reaching final height prior to initiation of treatment.

Conclusion: This single-centre study, representing one of the largest reported cohorts of children with Laron syndrome in the UK, demonstrates that rhIGF-1 therapy enhances height velocity, with an increase in height velocity in the first year. There is a modest gain in final height for most patients. Suboptimal height gains may be associated with late initiation of therapy and issues with treatment adherence.