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Effect of growth hormone treatment on children with idiopathic short stature and idiopathic growth hormone deficiency.

ABSTRACT: There are inconsistencies in the results reported in a small number of previous studies into growth hormone (GH) treatment in Korean children with idiopathic short stature (ISS) and idiopathic growth hormone deficiency (IGHD). Thus, the authors retrospectively compared the effects of GH in ISS and IGHD.From the medical records of 26 ISS and 30 IGHD children, auxological and biochemical changes including chronologic age (CA), bone age (BA), height standard deviation score (HT-SDS), predicted adult height (PAH), midparental height (MPH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) were compared.Before treatment, IGHD group had younger BA, lower BA/CA ratio, and lower IGF-1 level than those in the ISS group. During GH treatment, the levels of IGF-1 and IGFBP-3 were not different. Although annual BA increment was higher in IGHD group, and annual PAH-SDS increment was higher in ISS group, annual HT-SDS increments were not different. Both HT-SDS and PAH-SDS in the ISS group increased significantly until the end of the second year, and then those were not significantly different from MPH-SDS. In the IGHD group, the HT-SDS showed a significant increase till the end of the second year, and the PAH-SDS was not significantly changed at each year, but both HT-SDS and PAH-SDS were not significantly different from MPH-SDS at the end of the third year.During GH treatment, both HT-SDS and PAH-SDS approached the genetic target range of MPH-SDS after 2 years in ISS children and 3 years in IGHD children.

SUBMITTER: Im M

PROVIDER: S-EPMC5495978 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Project description:BackgroundTreatment of children with growth hormone deficiency (GHD) or idiopathic short stature (ISS) using GH is only effective for bone growth prior to epiphyseal fusion. Aromatase inhibitor therapy (AIT) blocks estrogen production, thereby delaying epiphyseal fusion. The current study analyzed baseline characteristics and longitudinal data of male patients with GHD or ISS who were treated with GH and concomitant AIT.MethodsData were obtained from the observational American Norditropin® Studies: Web-Enabled Research (ANSWER) Program, which collected efficacy and safety data of patients treated with Norditropin®. A longitudinal cohort approach compared patient characteristics, including chronologic age, bone age, and height standard deviation score (HSDS), in GH-treated males before and after AIT initiation.ResultsA total of 142 GH-naïve patients with GHD (n = 115) or ISS (n = 27) with mean (± SD) baseline chronological ages of 12.10 ± 3.00 and 10.76 ± 3.07 years, respectively, were analyzed. The majority were classified at advanced Tanner stages II to V. Patients with GHD had mean HSDS of - 1.97 ± 0.78 at baseline and - 0.99 ± 0.88 prior to AIT initiation, while corresponding values for patients with ISS were - 2.15 ± 0.72 and - 1.04 ± 0.79, respectively. In patients evaluated after 2 years of concomitant AIT, mean HSDS had decreased to - 0.40 ± 1.16 and - 0.65 ± 0.52 for patients with GHD and ISS, respectively. Patients with GHD had a mean bone age/chronological age ratio (BA/CA) of 0.91 ± 0.11 at baseline and 0.97 ± 0.10 prior to AIT initiation, while corresponding values for patients with ISS were 0.85 ± 0.16 and 0.99 ± 0.10, respectively. In patients evaluated after 2 years of concomitant AIT, mean BA/CA values were 0.95 ± 0.10 and 0.96 ± 0.06 for patients with GHD and ISS, respectively.ConclusionsIn this real-world analysis, use of AIT with GH in males appeared to be associated with ongoing growth over 2 years, and AIT likely augmented growth potential as indicated by continued HSDS increase with decreased BA/CA after AIT initiation.Trial registrationThis trial was sponsored by Novo Nordisk and is registered with ClinicalTrials.gov (NCT01009905). Registered November 11, 2009; retrospectively registered.

Project description:BackgroundChildren with Idiopathic Short Stature do not attain a normal adult height. The improvement of adult height with treatment with recombinant human growth hormone (rhGH), at doses of 0.16 to 0.28 mg/kg/week is modest, usually less that 4 cm, and they remain short as adults. The benefit obtained seems dose dependent and benefits of 7.0 to 8.0 cm have been reported with higher doses of 0.32 to 0.4 mg/kg/week, but the number of studies is limited. The topic has remained controversial.ObjectiveThe objective was to conduct a retrospective analysis of our experience with 123 children with ISS treated with 0.32 ± 0.03 mg/kg/week of rhGH, with the aim of comparing the different subgroups of non-familial short stature, familial short stature, normal puberty, and delayed puberty and to assess the benefit by comparison with 305 untreated historical controls, from nine different randomized and nonrandomized controlled studies.ResultsEighty eight of our children (68 males and 20 females) attained an adult height or near adult height of -0.71 SDS (0.74 SD) (95% CI, -0.87 to -0.55) with a benefit over untreated controls of 9.5 cm (7.4 to 11.6 cm) for males and 8.6 cm (6.7 to 10.5 cm) for females. In the analysis of the subgroups, the adult height and adult height gain of children with non-familial short stature were significantly higher than of familial short stature. No difference was found in the cohorts with normal or delayed puberty in any of the subgroups, except between the non-familial short stature and familial short stature puberty cohorts. This has implications for the interpretation of the benefit of treatment in studies where the number of children with familial short stature in the controls or treated subjects is not known. The treatment was safe. There were no significant adverse events. The IGF-1 values were essentially within the levels expected for the stages of puberty.ConclusionOur experience was quite positive with normalization of the heights and growth of the children during childhood and the attainment of normal adult heights, the main two aims of treatment.

Project description:IntroductionThe growth hormone deficiency (GHD) diagnosis is controversial especially due to low specificity of growth hormone (GH) stimulation tests. It is therefore believed that children diagnosed with GHD form a heterogeneous group with growth disorder frequently independent on GH function. No study evaluating the complex etiology of growth failure in children with diagnosed GHD has been performed thus far.AimsTo discover genetic etiology of short stature in children with diagnosed GHD from families with short stature.MethodsFifty-two children diagnosed with primary GHD and vertically transmitted short stature (height SDS in the child and his/her shorter parent <-2 SD) were included to our study. The GHD diagnosis was based on growth data suggestive of GHD, absence of substantial disproportionality (sitting height to total height ratio <-2 SD or >+2 SD), IGF-1 levels <0 for age and sex specific SD and peak GH concentration <10 ug/L in two stimulation tests. All children were examined using next-generation sequencing methods, and the genetic variants were subsequently evaluated by American College of Medical Genetics standards and guidelines.ResultsThe age of children at enrollment into the study was 11 years (median, IQR 9-14 years), their height prior to GH treatment was -3.0 SD (-3.6 to -2.8 SD), IGF-1 concentration -1.4 SD (-2.0 to -1.1 SD), and maximal stimulated GH 6.3 ug/L (4.8-7.6 ug/L). No child had multiple pituitary hormone deficiency or a midbrain region pathology. Causative variant in a gene that affects growth was discovered in 15/52 (29%) children. Of them, only 2 (13%) had a genetic variant affecting GH secretion or function (GHSR and OTX2). Interestingly, in 10 (67%) children we discovered a primary growth plate disorder (ACAN, COL1A2, COL11A1, COL2A1, EXT2, FGFR3, NF1, NPR2, PTPN11 [2x]), in one (7%) a genetic variant impairing IGF-1 action (IGFALS) and in two (12%) a variant in miscellaneous genes (SALL4, MBTPS2).ConclusionsIn children with vertically transmitted short stature, genetic results frequently did not correspond with the clinical diagnosis of GH deficiency. These results underline the doubtful reliability of methods standardly used to diagnose GH deficiency.

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Effect of growth hormone treatment on children with idiopathic short stature and idiopathic growth hormone deficiency.

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