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Noonan syndrome and Turner syndrome patients respond similarly to 4 years' growth-hormone therapy: longitudinal analysis of growth-hormone-naive patients enrolled in the NordiNet® International Outcome Study and the ANSWER Program.

ABSTRACT: BACKGROUND:Turner syndrome (TS) and Noonan syndrome (NS) are distinct syndromes associated with short stature and other similar phenotypic features. We compared the responses to growth hormone (GH) therapy of TS and NS patients enrolled in the NordiNet® International Outcome Study (IOS) or the American Norditropin Studies: Web-Enabled Research (ANSWER) Program, which collect information on GH therapy in clinical practice. METHODS:Repeated-measures regression analysis was performed on change in height standard deviation score (HSDS) and target-height-corrected HSDS, based on national normal references and treatment-naïve disease-specific references. Models were adjusted for baseline age and HSDS, and average GH dose. The study population was paediatric patients with TS and NS in the NordiNet® IOS and ANSWER Program. Longitudinal growth responses over 4 years were evaluated. RESULTS:In 30 NS patients (24 males; baseline age 8.39?±?3.45 years) and 294 TS patients (7.81?±?3.22 years), 4-year adjusted ?HSDS were +1.14?±?0.13 and +1.03?±?0.04, respectively (national references). Based on untreated, disease-specific references, 4-year adjusted ?HSDS for NS and TS were +1.48?±?0.10 and +1.79?±?0.04. The analyses showed a significant increase in HSDS over time for both NS and TS (P?

SUBMITTER: Lee PA

PROVIDER: S-EPMC4562101 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Noonan syndrome and Turner syndrome patients respond similarly to 4 years' growth-hormone therapy: longitudinal analysis of growth-hormone-naïve patients enrolled in the NordiNet® International Outcome Study and the ANSWER Program.

Lee Peter A PA Ross Judith L JL Pedersen Birgitte Tønnes BT Kotnik Primoz P Germak John A JA Christesen Henrik T HT

International journal of pediatric endocrinology 20150908 1

<h4>Background</h4>Turner syndrome (TS) and Noonan syndrome (NS) are distinct syndromes associated with short stature and other similar phenotypic features. We compared the responses to growth hormone (GH) therapy of TS and NS patients enrolled in the NordiNet® International Outcome Study (IOS) or the American Norditropin Studies: Web-Enabled Research (ANSWER) Program, which collect information on GH therapy in clinical practice.<h4>Methods</h4>Repeated-measures regression analysis was performed ...[more]

PMID: 26351466

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Project description:BackgroundNoonan syndrome (NS) is a genetic disorder characterized by phenotypic features, including facial dysmorphology, cardiovascular anomalies, and short stature. Growth hormone (GH) has been approved by the United States Food and Drug Administration for short stature in children with NS. The objective of this analysis was to assess the height standard deviation score (HSDS) and change in HSDS (ΔHSDS) for up to 4 years (Y4) of GH therapy in children with NS.MethodsThe American Norditropin Studies: Web-Enabled Research (ANSWER) Program®, a US-based registry, collects long-term efficacy and safety information on patients treated with Norditropin® (somatropin rDNA origin, Novo Nordisk A/S) at the discretion of participating physicians. A total of 120 children (90 boys, 30 girls) with NS, naïve to previous GH treatment, were included in this analysis.ResultsThe mean (SD) baseline age of subjects (n = 120) was 9.2 (3.8) years. Mean (SD) HSDS increased from -2.65 (0.73) at baseline to -1.32 (1.11) at Y4 (n = 17). Subjects showed continued increase in HSDS from baseline to Y4 without significant differences between genders at Y1 or Y2. The mean (SD) GH dose was 47 (11) mcg/kg/day at baseline and 59 (16) mcg/kg/day at Y4. There was a negative correlation between baseline age and ΔHSDS at Y1 (R = -0.3156; P = 0.0055) and Y2 (R = -0.3394; P = 0.017). ΔHSDS at Y1 was significantly correlated with ΔHSDS at Y2 (n = 37; R = 0.8527, P < 0.0001) and Y3 (n = 20; R = 0.5145; P = 0.0203), but not Y4 (n = 12; R = 0.4066, P = 0.1896).ConclusionsGH treatment-naïve patients with NS showed continued increases in HSDS during 4 years of treatment with GH with no significant differences between genders up to 2 years. Baseline age was negatively correlated with ΔHSDS at Y1 and Y2. Whether long-term therapy in NS results in continued increase in HSDS to adult height remains to be investigated.Trial registrationClinicalTrials.gov NCT01009905.

Project description:BackgroundThe final adult height of untreated girls aged up to 18 years with Turner syndrome (TS) is approximately 20 cm shorter compared with healthy females. Treatment with growth hormone (GH) increases the adult height of people with TS. The effects of adding the androgen, oxandrolone, in addition to GH are unclear. Therefore, we conducted this systematic review to investigate the benefits and harms of oxandrolone as an adjuvant therapy for people with TS treated with GH.ObjectivesTo assess the effects of oxandrolone on growth hormone-treated girls aged up to 18 years with Turner syndrome.Search methodsWe searched CENTRAL, MEDLINE, Embase, the ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was October 2018. We applied no language restrictions.Selection criteriaWe included randomised controlled clinical trials (RCTs) that enrolled girls aged up to 18 years with TS who were treated with GH and oxandrolone compared with GH only treatment.Data collection and analysisThree review authors independently screened titles and abstracts for relevance, selected trials, extracted data and assessed risk of bias. We resolved disagreements by consensus, or by consultation with a fourth review author. We assessed trials for overall certainty of the evidence using the GRADE instrument.Main resultsWe included six trials with 498 participants with TS, 267 participants were randomised to oxandrolone plus GH treatment and 231 participants were randomised to GH only treatment. The individual trial sample size ranged between 22 and 133 participants. The included trials were conducted in 65 different paediatric endocrinology healthcare facilities including clinics, centres, hospitals and academia in the USA and Europe. The duration of interventions ranged between 3 and 7.6 years. The mean age of participants at start of therapy ranged from 9 to 12 years. Overall, we judged only one trial at low risk of bias in all domains and another trial at high risk of bias in most domains. We downgraded the level of evidence mainly because of imprecision (low number of trials, low number of participants or both). Comparing oxandrolone plus GH with GH only for final adult height showed a mean difference (MD) of 2.7 cm in favour of oxandrolone plus GH treatment (95% confidence interval (CI) 1.3 to 4.1; P < 0.001; 5 trials, 270 participants; moderate-quality evidence). The 95% prediction interval ranged between 0.3 cm and 5.1 cm. For adverse events, we based our main analysis on reliable date from two trials with overall low risk of bias. There was no evidence of a difference between oxandrolone plus GH and GH for adverse events (RR 1.81, 95% CI 0.83 to 3.96; P = 0.14; 2 trials, 170 participants; low-quality evidence). Six out of 86 (18.6%) participants receiving oxandrolone plus GH compared with 8/84 (9.5%) participants receiving GH only reported adverse events, mainly signs of virilisation (e.g. deepening of the voice). One trial each investigated the effects of treatments on speech (voice frequency; 88 participants), cognition (51 participants) and psychological status (106 participants). The overall results for these comparisons were inconclusive (very low-quality evidence). No trial reported on health-related quality of life or all-cause mortality.Authors' conclusionsAddition of oxandrolone to the GH therapy led to a modest increase in the final adult height of girls aged up to 18 years with TS. Adverse effects identified included virilising effects such as deepening of the voice, but reporting was inadequate in some trials.

Dataset Information

Noonan syndrome and Turner syndrome patients respond similarly to 4 years' growth-hormone therapy: longitudinal analysis of growth-hormone-naive patients enrolled in the NordiNet® International Outcome Study and the ANSWER Program.

Publications

Noonan syndrome and Turner syndrome patients respond similarly to 4 years' growth-hormone therapy: longitudinal analysis of growth-hormone-naïve patients enrolled in the NordiNet® International Outcome Study and the ANSWER Program.

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