Growth and metabolic effects of long-term recombinant human growth hormone (rhGH) treatment in short children born small for gestational age: GH-RAST study

Abstract

<jats:title>Abstract</jats:title><jats:sec id="j_jpem-2019-0438_abs_001_w2aab3b7b3b1b6b1aab1c12b2Aa"><jats:title>Objectives</jats:title><jats:p>To study the efficacy and influence on metabolism of recombinant human growth hormone (rhGH) treatment in short children born small for gestational age (SGA).</jats:p></jats:sec><jats:sec id="j_jpem-2019-0438_abs_002_w2aab3b7b3b1b6b1aab1c12b3Aa"><jats:title>Methods</jats:title><jats:p>Retrospective, observational, multicenter study in 305 short children born SGA, treated with rhGH during a mean ± SD of 5.03 ± 1.73 years at a mean ± SD dose of 37 ± 8 μg/kg/day. Auxological and metabolic assessment including glucose and lipids profile were collected.</jats:p></jats:sec><jats:sec id="j_jpem-2019-0438_abs_003_w2aab3b7b3b1b6b1aab1c12b4Aa"><jats:title>Results</jats:title><jats:p>Mean ± SD age at the start of treatment was 7.11 ± 2.78 years. Height and weight improved significantly until the end of treatment from mean −2.72 (CI<jats:sub>95%</jats:sub>: −2.81 to −2.63) standard deviation score (SDS) to −1.16 (CI<jats:sub>95%</jats:sub>: −1.44 to −0.88) SDS and from −1.62 (CI<jats:sub>95%</jats:sub>: −1.69 to −1.55) SDS to −0.94 (CI<jats:sub>95%</jats:sub>: −1.14 to −0.74) SDS respectively. Mean height gain was 1.27 (CI<jats:sub>95%</jats:sub>: 0.99–1.54) SDS. Prepubertal patients showed higher height gain than pubertal children (mean [CI<jats:sub>95%</jats:sub>] = 1.44 [CI<jats:sub>95%</jats:sub>: 1.14–1.74] vs. 0.73 [CI<jats:sub>95%</jats:sub>: 0.22–1.24], p=0.02). Height gain SDS during treatment negatively correlated with chronological age (CA) and bone age (BA) delay and positively correlated with duration of treatment, height gain during first year of treatment, years on prepubertal treatment and height SDS from target height (TH). Glucose, insulin, and triglycerides increased significantly but remained within the normal range. Total and LDL-cholesterol decreased significantly, and HDL-cholesterol remained unchanged.</jats:p></jats:sec><jats:sec id="j_jpem-2019-0438_abs_004_w2aab3b7b3b1b6b1aab1c12b5Aa"><jats:title>Conclusions</jats:title><jats:p>rhGH treatment in short SGA children effectively normalized height in most of the patients and showed a safe metabolic profile. Children who benefit the most are those with greater height SDS distance from TH, BA delay, longer duration of treatment and prepubertal treatment initiation.</jats:p></jats:sec>

Growth hormone treatment does not to lead to insulin resistance nor excessive rise in IGF‐1 levels, while improving height in patients small for gestational age A long‐term observational study

“…Accordingly, Rhie et al 28 showed similar results, with the highest increase being observed during the first year of rhGH treatment, and then it gradually decreased, although it remained above 5 cm. Moreover, height was found to be normal with rhGH treatment in short SGA children with a safe metabolic profile as described Labarta et al 29 Regarding the children's growth, the mean BA-CA ratio increased significantly during rhGH treatment from baseline to Visit 4 and then stabilized until the end of the study. BA increases over time, as suggested by the increase in the BA-CA ratio (close to 1 after 6 years of treatment).…”

“…Accordingly, Rhie et al 28 showed similar results, with the highest increase being observed during the first year of rhGH treatment, and then it gradually decreased, although it remained above 5 cm. Moreover, height was found to be normal with rhGH treatment in short SGA children with a safe metabolic profile as described Labarta et al 29 …”

“…In this respect, Zhao et al 31 showed that following GH therapy in small children, there was a positive association between IGF‐1 (SDS) and the BA–CA ratio when the IGF‐1 level was lower than 2 SDS, as observed in our study, suggesting that a low level of IGF‐1 could contribute to BA delay in short children and adolescents. Moreover, a moderate but significant BA acceleration during rhGH treatment as the BA–CA ratio increased in SGA children who experienced an increase in IGF‐1 levels, although it remained within the normal range 29 . Taken together, the increase in IGF‐I levels due to rhGH treatment could potentiate catch‐up growth and normal BA maturation in SGA children.…”

“…Moreover, a moderate but significant BA acceleration during rhGH treatment as the BA–CA ratio increased in SGA children who experienced an increase in IGF‐1 levels, although it remained within the normal range. 29 Taken together, the increase in IGF‐I levels due to rhGH treatment could potentiate catch‐up growth and normal BA maturation in SGA children.…”

Twenty-five years of growth hormone treatment in non-dialyzed children with chronic kidney disease in Poland – efficacy, safety, metabolic effects, and factors influencing response

“…Labarta et al showed that in children with SGA (small for gestational age) treated with rhGH, tyreo globulina levels increased significantly but remained within the normal range. On the other hand, total and LDL cholesterol decreased in the study period [28].…”