Dataset Information

A randomized pilot trial of growth hormone with anastrozole versus growth hormone alone, starting at the very end of puberty in adolescents with idiopathic short stature.

ABSTRACT:

Background

When given during the course of puberty, anastrozole (A), an aromatase inhibitor, has been shown to increase the predicted adult height (PAH) of GH-deficient (GHD) boys treated with recombinant human growth hormone (rhGH). Our study questioned whether this treatment could retain some of its effects in non-GHD adolescent boys if started only at the very end of puberty, a time when rhGH treatment is denied to short adolescents who have almost reached their final height.

Objective

To explore the effect on adult height of a combination of rhGH and A, compared with rhGH alone, at the end of puberty in boys with idiopatic short stature (ISS).

Methods

A prospective randomized study comparing rhGH + A and rhGH was conducted in 24 healthy adolescent boys aged 15.2 ± 1.2 yrs with serum testosterone at adult levels and a faltering growth velocity <3.5 cm/yr leading to a predicted adult height (PAH) <2.5 SDS. Treatments were stopped when growth velocity became <10 mm in 6 months or when height was close to 170 cm. A historical group of ISS adolescents (N = 17) matched for puberty and growth was used for comparison.

Results

IGF1 levels remained within normal limits in all treated patients. Mean treatment duration was 19 months in the rhGH + A group and 11.5 months in the rhGH group (P = 6.10(-4)). Adult height reached 168.4 ± 2.6 cm in the rhGH + A group and 164.2 ± 5.6 cm in the rhGH group (P < 0.02). Adult height was 160.1 ± 2.8 cm in the historical controls.

Conclusion

A combination of rhGH and A, started at the very end of puberty, seems to allow boys with ISS to reach a greater adult height than rhGH alone. Larger trials are needed to confirm this preliminary observation.

SUBMITTER: Rothenbuhler A

PROVIDER: S-EPMC4429943 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Children 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. OBJECTIVE:The 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. RESULTS:Eighty 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. CONCLUSION:Our 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:Background:Treatment 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. Methods:Data 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. Results:A 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. Conclusions:In 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 registration:This trial was sponsored by Novo Nordisk and is registered with ClinicalTrials.gov (NCT01009905). Registered November 11, 2009; retrospectively registered.