Background: During childhood, growth hormone (GH) doses are usually calculated using total body weight (TBW). This may result in inappropriately high doses in obese children where the intravascular compartment does not increase in proportion with the increase in weight, as the volume of distribution of GH is consistent with the majority of the drug being distributed in the total body water compartment.
Methods: Single centre, retrospective cohort study of patients treated with GH between 201013. Patients were stratified according to BMI SDS, and changes in height SDS and IGF-I SDS during the first year of treatment was compared between groups (1) in a mixed cohort of patients, and (2) a subgroup of GH deficient (GHD) patients.
Results: 354 patients (133 female) received GH, of whom 213 (60.2%) had GHD. 52 patients (14.7%) were obese (BMI SDS >1.75). The children within the lowest BMI-SDS category (≤−1.75) were shorter at the initiation of treatment than those children with higher BMI-SDS scores, in both the unselected and GHD cohorts (P<0.0001 for both). Baseline IGF-1 SDS did not differ between any of the BMI-SDS categories in either cohort. For both the unselected and GHD cohorts, gain in height SDS increased with increasing BMI SDS, until BMI exceeded 1.75SD (P<0.05 for both groups), and IGF-1 SDS increased significantly across all weight categories, with the highest values seen in the obese patients (P<0.0001 for both cohorts). IGF-1 SDS was >2 at the end of the first year of treatment in in 31/354 (8.6%) patients overall, including 11/20 (55%) obese patients with GHD.
Conclusions: To our knowledge, these are the first data to link changes in height and IGF-I SDS in the first year of GH treatment with BMI. We speculate that our data illustrate a dose dependent effect of GH, as the most overweight children receive the highest doses, relative to the total body water compartment in which GH is distributed. The clinical significance of this observation is unknown, and robust clinical studies examining alternative dosing strategies using ideal or lean body weight should now be considered.
23 - 25 Nov 2016
British Society for Paediatric Endocrinology and Diabetes