Abstract

BackgroundRecombinant human growth hormone (rhGH) treatment in children is usually prescribed using actual body weight. This may result in inappropriately high doses in obese children.MethodsRetrospective audit of all paediatric patients treated with rhGH 2010–14 at a tertiary paediatric hospital in the UK. Change in height SDS and IGF-I SDS during the first year of treatment was stratified by initial BMI SDS in a mixed cohort, and a subgroup of GH deficient (GHD) patients. Alternative doses for those BMI SDS ≥2.0 (Obese) were calculated using BSA, IBW and LBW.Results354 patients (133 female) received rhGH, including 213 (60.2%) with GHD. Obesity was present in 40 patients (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<0.05). For both the entire cohort, and GHD patients only, IGF-1 SDS was significantly higher in obese patients (p<0.0001 for both groups). Cross sectional data identified 265 children receiving rhGH, 81 (30.5%) with a BMI-SDS ≥1.75. Alternate prescribing strategies for rhGH prescribing in obese patients suggest a saving of 27% - 38% annually.ConclusionsGain in IGF-I SDS is greater in obese children, 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.

Highlights

  • In many paediatric populations worldwide the proportion of children who are overweight and obese is increasing, but there is wide geographical variation [1, 2].Obesity has direct effects on dosing any drug, increasing the proportion of the total body weight (TBW) composed of lipid, thereby providing a reservoir for lipophilic medications, while risking overdose of drugs contained within the intravascular compartment as this does not increase in proportion with the increase in weight [3]

  • For GH deficient (GHD) patients, gain in height SDS was directly related to BMI SDS, except in obese patients (p

  • For both the entire cohort, and GHD patients only, IGF-1 SDS was significantly higher in obese patients (p

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Summary

Introduction

Obesity has direct effects on dosing any drug, increasing the proportion of the total body weight (TBW) composed of lipid, thereby providing a reservoir for lipophilic medications, while risking overdose of drugs contained within the intravascular compartment as this does not increase in proportion with the increase in weight [3]. In non-obese adults, the volume of distribution of rhGH delivered exogenously has been calculated at approximately 78L [6], which is consistent with the majority of the drug being distributed in the total body water compartment (with the intravascular proportion predominantly bound to growth hormone binding protein [7]). Recombinant human growth hormone (rhGH) treatment in children is usually prescribed using actual body weight. This may result in inappropriately high doses in obese children

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