PP-29 Growth hormone dosing in obese children

Abstract

Background Obesity has direct effects on dosing any drug by increasing the proportion of the total body weight (TBW) composed of lipid. Validated algorithms exist to convert a child’s actual weight to either an ideal (IBW) or lean body weight (LBW), but these are not widely used within paediatric practice. Pharmacokinetic data in obese patients do not exist for the majority of drugs and there is little direct evidence as to how obesity affects the overall risk-benefit of medications. Recombinant human growth hormone (rhGH) offers a unique opportunity to examine this, as the population receiving it routinely has height and weight measured, and the positive outcome (height gain) and adverse effect (increase in IGF-1) are both routinely measured. rhGH dosing derived by TBW may result in inappropriately high doses in obese children. Methods Retrospective audit of all paediatric patients treated with rhGH at a tertiary paediatric hospital in the UK with a catchment population of 2.7 million. Change in height SDS and IGF-I SDS during the first year of treat-ment was stratified by initial BMI SDS in a mixed cohort, and a subgroup of GH deficient (GHD) patients. Alterna-tive doses for those BMI SDS ≥2.0 (obese) were calculated using body surface area (BSA), IBW and LBW. All patients who commenced treatment with rhGH be-tween 2010 and 2014 were identified. The following data were extracted from the appointment prior to starting rhGH treatment: clinical indication, gender, BMI-SDS, height-SDS, and IGF-1 SDS. IGF-1 SDS 1 year (+/-3 months) and height SDS 1 year (+/-2 months) following the start of treatment was also recorded. Patients were studied in two cohorts: 1 an unselected cohort of patients with multiple diagnoses, and 2 only those with GHD. IGF-1 was measured using a validated solid-phase, enzyme-la-beled chemiluminescent immunometric assay. Results 354 patients (133 female) received rhGH, includ-ing 213 (60.2%) with GHD. Obesity was present in 40 pa-tients (11.3%) of the unselected cohort, and 32 (15.0%) of the GHD cohort. For GHD patients, gain in height SDS was directly related to BMI SDS, except in obese patients (p Conclusion Gain in IGF-I SDS is greater in obese chil-dren, and is likely to be related to relatively higher doses of rhGH. Additional gain in height was not achieved at the higher doses administered to obese children. Alternative dosing strategies in the obese patient population should be examined in rigorous clinical trials.