C H A N G E I N T O T A L B O D Y W A T E R A S A P R E D I C T I V E T O O L F O R G R O W T H H O R M O N E T R E A T M E N T R E S P O N S E Study design The study design was a prospective cohort study with duration of follow-‐up of 12 months. End points: Primary end points were growth and body composition. Growth was assessed by the evaluation of height during one year. Body composi-‐ tion was assessed by measuring the total body water (TBW) by the Deuterium dilu-‐ tion method (doubly labeled water (DLW) method). Measurements Height Height and weight were measured at the start of therapy and at 3 months intervals during at least one year. Height was measured using a Harpenden stadiometer. Subject’s shoes and socks were removed. A 0.5 kg weight was placed on the head-‐ board to flatten hair. The patient was kept in the correct upright position, the ‘Frankfurt plane’, while a gentle upward pressure was exerted on the mastoid pro-‐ cesses so that the patient was fully extended. Height was expressed in standard deviation score (SDS). The difference in SDS over one year (SDSt1-‐SDSt0) was used to divide the patient group into adequate and inadequate responders. Weight was measured with an electronic scale with digital readings, accurate to 5 gram. Empty body weight was measured without clothing, directly after waking up and voiding. Deuterium dilution method (DLW method) Body composition was determined by measuring the TBW with the stable isotope of hydrogen (Deuterium), according to the Maastricht protocol16 at t = 0 and t = 6 weeks. A baseline urine sample was collected before the labeled water was con-‐ sumed to determine the natural abundance of Deuterium in the urine. The child drank a known amount of the doubly labeled water in the evening, before it went to bed. Instructions were given to drink all the water and to rinse the bottle to be sure all the water is consumed. A second urine sample was collected after an overnight equilibration after the first voiding. TBW was calculated by the formula: C1 x V1 = C2 x V2 (C1 = concentration of label in ingested fluid, V1 = volume ingested fluid, C2 = concentration tracer in second urine sample, V2 = distribution volume). The distri-‐ bution volume was divided by 1.04, because of the exchange of tracer with nonaqueous substances in the body, to calculate the TBW. Because patients with a different height were compared, the changes in TBW after 6 weeks were corrected for height in accordance with the Body Mass Index (TBW/height2). The difference of this value between t0 and t6 is plotted against the change in height SDS after one year of therapy. Based on the mean response found by Ranke et al.17 a cut off value for good re-‐ sponders was determined as a change of more than 0.7 SDS over one year. In this study it was observed that during the first year on rhGH therapy the magnitude of 47
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