Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency

Abstract

Background: Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.Methods: This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.Results: Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.Conclusion: GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

Impact of non-weight-dependent low-dose somatropin on bone accrual in childhood-onset GH deficient in the transition: an 18-month randomized controlled trial

“…This sample size was equal to that of the multicenter study by Mauras et al [27]. In a Korean study that recruited 187 patients from 6 hospitals, only 40 patients CO-DGH performed DXA after 1 year of treatment [22]. Another positive aspect of our trial was the joint analysis of the BMD Z-score and its percentage change that made the DXA more sensitive for the diagnosis of bone loss.…”

“…Most studies that showed bone mineral accrual used higher weight-based doses [17][18][19][20], some were retrospective [21,22], and not all had a GH-su cient group [22,23]. The originality of the present study consists of prospectively verifying whether the rhGH discontinuation compromised the bone mineral gain in CO-DGH adolescents, who were compared with GH-insu cient patients, users of xed and smaller doses, and GH-su cient individuals.…”

“…They only found a Z-score increase in femur BMD. The lack of response in LS and the nonexistence of a control group consisting of insu cient patients without rhGH made it di cult for the authors to attribute the improvement in the femur to the reinstitution of the treatment [22].…”

Relationship between the Stimulated Peak Growth Hormone Level and Metabolic Parameters in Children with Growth Hormone Deficiency

“…The PGH level was negatively associated with the TC and TG levels in children with short stature, regardless of the presence or absence of GHD [33]. The discontinuation of GH therapy increased the serum TC, LDL-C, and non-HDL-C levels in GHD adolescents [19].…”

“…Children with GHD have increased insulin sensitivity, which manifests as low glucose and insulin levels, and low HOMA-IR [28][29][30]. In adolescents with GHD who have reached their final height, withdrawal of GH therapy decreased the fasting glucose and insulin levels, and HOMA-IR [19,21]. However, a study of obese children and adolescents showed that PGH level was negatively correlated with HOMA-IR [24].…”