Height outcomes in children with growth hormone deficiency and idiopathic short stature treated concomitantly with growth hormone and aromatase inhibitor therapy: data from the ANSWER program

Bradley S Miller,Vlady Ostrow,Judith Ross

doi:10.1186/s13633-020-00089-z

Abstract

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

Highlights

Idiopathic short stature (ISS) is a clinical condition defined as non-growth hormone (GH)-deficient short stature characterized by a height below 2 SD of the mean for age in the absence of any endocrine, metabolic, or other known condition that explains the short stature [1,2,3].Recombinant GH was first introduced in 1985 and is effective in increasing short-term growth rates and attainment of adult height in patients with various growth disorders [4,5,6,7,8,9]
Patients with growth hormone deficiency (GHD) or idiopathic short stature (ISS) who had initiated GH therapy but had not yet initiated Aromatase inhibitor therapy (AIT) showed increases in height standard deviation score (HSDS) compared with baseline
Among patients with GHD, HSDS improved from a baseline value of − 1.97 ± 0.78 to − 0.99 ± 0.88 at AIT initiation, while patients with ISS showed an improvement from − 2.15 ± 0.72 at baseline to − 1.04 ± 0.79 at AIT initiation

Summary

Introduction

Recombinant GH was first introduced in 1985 and is effective in increasing short-term growth rates and attainment of adult height in patients with various growth disorders [4,5,6,7,8,9]. Recombinant GH was approved as a therapy in the United States in 2003 for children with ISS whose HSDS was ≥2.25 SD below the mean for age and sex who demonstrate growth rates unlikely to permit attainment of normal adult height [10]. Aromatase inhibitor therapy (AIT) is a suggested form of treatment, and functions by blocking the conversion of androgens to estrogens, thereby delaying epiphyseal fusion and bone age advancement [1, 12]. 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.

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Conclusion