Effect of Weekly Long-Acting Growth Hormone Replacement Therapy Compared to Daily Growth Hormone on Children With Short Stature: A Meta-Analysis

BackgroundWe performed a meta-analysis to evaluate the efficacy and safety of weekly long-acting growth hormone replacement therapy compared to daily growth hormone in children with short stature.MethodsA systematic literature search up to April 2021 was performed and 11 studies included 1,232 children with short stature treated with growth hormone replacement therapy at the start of the study; 737 of them were using weekly long-acting growth hormone replacement therapy and 495 were using daily growth hormone. They were reporting relationships between the efficacy and safety of long-acting growth hormone replacement therapy and daily growth hormone in children with short stature. We calculated the odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CIs) to assess the efficacy and safety of weekly long-acting growth hormone replacement therapy compared to daily growth hormone in children with short stature using the dichotomous or continuous method with a random or fixed-effect model.ResultsLong-acting growth hormone replacement therapy had significantly lower height standard deviation scores chronological age (MD, −0.10; 95% CI, −0.13 to −0.08, p <0.001), and insulin-like growth factor binding protein-3 (MD, −0.69; 95% CI, −1.09 to −0.30, p <0.001) compared to daily growth hormone in children with short stature.However, growth hormone replacement therapy had no significantly difference in height velocity (MD, −0.09; 95% CI, −0.69–0.5, p = 0.76), height standard deviation scores bone age (MD, −0.04; 95% CI, −0.10–0.02, p = 0.16), insulin-like growth factor 1 standard deviation scores (MD, 0.26; 95% CI, −0.26–0.79, p = 0.33), and incidence of adverse events (OR, 1.16; 95% CI, 0.90–1.50, p = 0.25) compared to daily growth hormone in children with short stature.ConclusionsLong-acting growth hormone replacement therapy had significantly lower height standard deviation scores chronological age, and insulin-like growth factor binding protein-3 compared to daily growth hormone in children with short stature. However, growth hormone replacement therapy had no significant difference in height velocity, height standard deviation scores bone age, insulin-like growth factor 1 standard deviation scores, and incidence of adverse events compared to daily growth hormone in children with short stature. Further studies are required to validate these findings.

Cardiovascular risk profile in Growth Hormone treated adults with a craniopharyngioma compared to a non-functioning pituitary adenoma: a national cohort study

Context: Cardiovascular risk profile might differ between growth hormone treated patients with a craniopharyngioma and a non-functioning pituitary adenoma (NFPA), since patients with craniopharyngioma more frequently suffer from hypothalamic metabolic disruption. Objective: The aim of this study is to investigate cardiovascular risk profile in adult patients with a craniopharyngioma compared to NFPA before and after treatment with growth hormone replacement therapy due to severe GH deficiency. Design: A sub-analysis of the Dutch National Registry of Growth Hormone Treatment in Adults was performed, in which we compared 291 patients with craniopharyngioma to 778 patients with NFPA. Cardiovascular risk profile and morbidity was evaluated at baseline and during long-term follow-up within and between both groups. Results: At baseline, patients with craniopharyngioma demonstrated higher BMI than patients with NFPA and men with craniopharyngioma showed greater waist circumference and lower HDL compared to men with a NFPA. During follow-up, BMI, as well as diastolic blood pressure among patients using antihypertensive drugs, deteriorated in the craniopharyngioma group compared to the NFPA group. Lipid profile improved similarly in both groups over time. No differences were found between groups in the occurrence of diabetes mellitus, cerebrovascular accidents, cardiovascular disease, or in overall mortality. Conclusion: This study suggests that overall cardiovascular risk profile is worse in craniopharyngioma patients with growth hormone deficiency compared to patients with NFPA. During growth hormone replacement therapy, patients with craniopharyngioma demonstrated an increase in BMI over time, where BMI remained stable in patients with NFPA. Also, diastolic blood pressure did not improve with antihypertensive drugs in craniopharyngioma as seen in patients with NFPA.

Growth hormone replacement therapy: is it safe to use in children with asymptomatic pituitary lesions?

Objectives Small pituitary cysts are commonly discovered on pediatric brain magnetic resonance imagings (MRIs), particularly in patients with growth hormone deficiency (GHD). We examined the need for operative management in children with these masses as well as the effect of growth hormone replacement (GHR) on these lesions. Methods This was a retrospective review of pituitary protocol MRIs conducted in children 0–19 at a single center between April 2010–November 2020. Sex, indication for initial MRI, volume, and whether surgery was performed was determined. Records were reviewed to determine whether GHD was present and treatment with GHR documented. For patients with subsequent MRIs, volume on most recent scan was calculated. Results Of the 101 children with cysts, 25 had laboratory-confirmed GHD and 76 did not. GHD patients had a higher mean age compared to no growth hormone deficiency (NGHD) cohort (11.2 and 8.4 years, respectively; p=0.02) and a larger proportion of males (p<0.001). The mean cyst volume on initial MRI was not significantly smaller in patients with GHD (0.063 ± 0.012 cm3) vs. those without GHD (0.171 ± 0.039 cm3, p=0.11). Of the 21 GHD patients who received GHR and had follow-up MRIs, 10 had no change in pituitary cyst size, two had cysts that shrank, and seven disappeared. The remaining two cysts enlarged an average of 0.061 ± 0.033 cm3. Zero GHR recipients required surgical intervention. Conclusions Small sellar cysts discovered incidentally on imaging in children are unlikely to require surgical intervention. GHR does not appear to significantly enlarge these pediatric pituitary lesions and is safe for use.

Pregnancy outcomes in women receiving growth hormone replacement therapy enrolled in the NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program

Purpose Data on the safety of growth hormone (GH) replacement therapy during pregnancy are limited. We report a combined analysis of data from pregnant women treated with GH while enrolled in two non-interventional, multicenter studies: NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program. Methods Pregnancy data were pooled from NordiNet® IOS and the ANSWER Program. Data were collected during routine clinic visits by participating physicians using a web-based system. Patients exposed to GH replacement therapy during pregnancy were included in the analysis. Results The study population included 40 female patients with typical causes of adult GH deficiency (GHD). Overall, there were 54 pregnancies. Of these, 47 were exposed to GH between conception and delivery. In 48.9% of pregnancies exposed to GH, the dose was > 0.6 mg/day. GH was continued past conception and then stopped during the first, second, and third trimester, in 27.7%, 17.0%, and 2.1% of pregnancies, respectively. In 29.8%, GH was continued throughout pregnancy, with an unchanged dose in most cases. Of the 47 GH-exposed pregnancies, 37 (78.7%) progressed to normal delivery. There were three adverse events reported in two pregnancies. Conclusion These real-world data suggest that there were no new safety signals related to GH exposure in women with GHD during pregnancy. These results are consistent with findings from previous studies reporting data in pregnancies exposed to GH at conception or throughout pregnancy. This observational study in additional pregnancies provides further evidence that GH exposure does not adversely affect pregnancy outcome. Clinical trial registration: ClinicalTrials.gov NCT00960128 (date of registration: August 13, 2009) and NCT01009905 (date of registration: November 5, 2009).