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Background/Aims: Growth Hormone (GH) dosage in childhood is adjusted for body size, but there is no consensus whether body weight (BW) or body surface area (BSA) should be used. We aimed at comparing the biological effect and cost-effectiveness of GH treatment dosed per m(2) BSA in comparison with dosing per kg BW in girls with Turner syndrome (TS). Methods: Serum IGF-I, GH dose, and adult height gain (AHG) from girls participating in two Dutch and five Swedish studies on the efficacy of GH were analyzed, and the cumulative GH dose and costs were calculated for both dose adjustment methods. Additional medication included estrogens (if no spontaneous puberty occurred) and oxandrolone in some studies. Results: At each GH dose, the serum IGF-I standard deviation score remained stable over time after an initial increase after the start of treatment. On a high dose (at 1 m(2) equivalent to 0.056-0.067 mg/kg/day), AHG was at least equal on GH dosed per m(2) BSA compared with dosing per kg BW. The cumulative dose and cost were significantly lower if the GH dose was adjusted for m(2) BSA. Conclusion: Dosing GH per m(2) BSA is at least as efficacious as dosing per kg BW, and is more cost-effective. (c) 2014 S. Karger AG, Basel

Models predicting the growth response to growth hormone treatment in short children independent of GH status, birth size and gestational age

<p>Abstract</p> <p>Background</p> <p>Mathematical models can be used to predict individual growth responses to growth hormone (GH) therapy. The aim of this study was to construct and validate high-precision models to predict the growth response to GH treatment of short children, independent of their GH status, birth size and gestational age. As the GH doses are included, these models can be used to individualize treatment.</p> <p>Methods</p> <p>Growth data from 415 short prepubertal children were used to construct models for predicting the growth response during the first years of GH therapy. The performance of the models was validated with data from a separate cohort of 112 children using the same inclusion criteria.</p> <p>Results</p> <p>Using only auxological data, the model had a standard error of the residuals (SD_res), of 0.23 SDS. The model was improved when endocrine data (GH_maxprofile, IGF-I and leptin) collected before starting GH treatment were included. Inclusion of these data resulted in a decrease of the SD_resto 0.15 SDS (corresponding to 1.1 cm in a 3-year-old child and 1.6 cm in a 7-year old). Validation of these models with a separate cohort, showed similar SD_resfor both types of models. Preterm children were not included in the Model group, but predictions for this group were within the expected range.</p> <p>Conclusion</p> <p>These prediction models can with high accuracy be used to identify short children who will benefit from GH treatment. They are clinically useful as they are constructed using data from short children with a broad range of GH secretory status, birth size and gestational age.</p

The first-year growth response to growth hormone treatment predicts the long-term prepubertal growth response in children

<p>Abstract</p> <p>Background</p> <p>Pretreatment auxological variables, such as birth size and parental heights, are important predictors of the growth response to GH treatment. For children with missing pretreatment data, published prediction models cannot be used.</p> <p>The objective was to construct and validate a prediction model for children with missing background data based on the observed first-year growth response to GH. The accuracy and reliability of the model should be comparable with our previously published prediction model relying on pretreatment data. The design used was mathematical curve fitting on observed growth response data from children treated with a GH dose of 33 μg/kg/d.</p> <p>Methods</p> <p>Growth response data from 162 prepubertal children born at term were used to construct the model; the group comprised of 19% girls, 80% GH-deficient and 23% born SGA. For validation, data from 205 other children fulfilling the same inclusion and treatment criteria as the model group were used. The model was also tested on data from children born prematurely, children from other continents and children receiving a GH dose of 67 μg/kg/d.</p> <p>Results</p> <p>The GH response curve was similar for all children, but with an individual amplitude. The curve SD score depends on an individual factor combining the effect of dose and growth, the 'Response Score', and time on treatment, making prediction possible when the first-year growth response is known. The prediction interval (± 2 SD_res) was ± 0.34 SDS for the second treatment year growth response, corresponding to ± 1.2 cm for a 3-year-old child and ± 1.8 cm for a 7-year-old child. For the 1–4-year prediction, the SD_reswas 0.13 SDS/year and for the 1–7-year prediction it was 0.57 SDS (i.e. < 0.1 SDS/year).</p> <p>Conclusion</p> <p>The model based on the observed first-year growth response on GH is valid worldwide for the prediction of up to 7 years of prepubertal growth in children with GHD/ISS, born AGA/SGA and born preterm/term, and can be used as an aid in medical decision making.</p

Prediction of the growth response of short prepubertal children treated with growth hormone

The aim of this study was to identify predictors of the growth response to growth hormone (GH) during the first 2 years of GH treatment, using auxological data and the maximum GH response (GH(max)) to provocation tests. The patients were 169 prepubertal short children (27F, 142M), with G(max) values ranging from 0 to 65 mU/l. Their mean age (± SD) was 8.3 ± 2.4 years (range 3-13 years), mean height SDS -3.0 ± 0.7 (range -1.5 to -6.0 SDS) and mean pretreatment height velocity was normal (± 0.0 SDS) (range 1.6 to ± 0.9 SDS). The increase in height SDS during the first 2 years of GH treatment (0.1 U/kg/day) varied from 0.10 to 3.75 SDS, with younger children having a better growth response. Individual growth responses correlated (p < 0.001) with GH(max) (r =- 0.37), age (r = -0.35), 1-year pretreatment delta SDS (r = -0.25), mid-parental height SDS (r = 0.34), height SDS at start of treatment (r = -0.22) and difference between height SDS of an individual child at the onset of GH treatment and mid-parental height expressed in SDS (diff SDS) (r = -0.43). In a multiple stepwise linear regression model, diff SDS and log GH(max) were found to be the strongest predictors of the magnitude of the growth response. In the short children in this study who exhibited a broad range of GH(max) values, 33% of the growth response during the first 2 years of treatment could be predicted.link_to_subscribed_fulltex