Not required for Letter to the Editor

Context: In children with idiopathic isolated growth hormone deficiency (IIGHD), GH secretion often normalizes by near adult height (NAH). Whether recombinant human GH (rhGH) treatment can be safely discontinued earlier remains unclear. Objective: This work aimed to investigate if withdrawing rhGH treatment from mid-puberty onward had no negative effect on attained NAH in adolescents who, after retesting, were no longer GH deficient. Methods: A prospective multicenter patient preference study was conducted at pediatric endocrinology departments in multiple centers (2017-2024) with follow-up until NAH (SEENEZ GH Study). Participants included 127 adolescents (95 male, 75%) with childhood IIGHD (GH peak 1.7-10 µg/L) who tested GH sufficient (GH peak >6.7 µg/L) at mid-puberty. Forty-four continued rhGH (GHcont), 83 discontinued (GHstop). A total of 99% of patients completed the study. Intervention included rhGH treatment continuation vs discontinuation from mid-puberty until NAH. The primary outcome measure was NAH-SDS minus target height (TH)-SDS. The secondary outcome was NAH-SDS, total pubertal growth (TPG), and predicted vs attained height gain. Results: Mean (SD) NAH-SDS minus TH-SDS was −0.17 (0.60) in the GHcont and −0.18 (0.62) in the GHstop group (P = .96). Mean NAH-SDS was −0.91 (0.76) (GHcont) vs −0.78 (0.76) (GHstop) (P = .35). Mean (SD) TPG (from start of puberty) in males was 27.5 cm (7.0; GHcont) vs 25.9 cm (6.2; GHstop) (P = .25) and in females 20.5 cm (5.7; GHcont) vs 20.9 cm (7.6; GHstop) (P = .90). Predicted vs attained height gain based on the prediction model did not differ between groups. Conclusions: In adolescents with transient IIGHD, rhGH treatment can be stopped at mid-puberty. These findings support reducing rhGH treatment duration, lowering patient burden and health-care costs.

Context: Idiopathic isolated growth hormone deficiency (IIGHD) is difficult to diagnose due to the day-to-day variation in growth hormone (GH) secretion and limitations of GH stimulation testing (GHST). Although recombinant human GH (rhGH) is typically continued until near adult height (NAH), many patients no longer show deficiency at that point. The optimal timing and method for retesting GH secretion remain unclear. Objective: To summarize the currently available GHSTs in children with IIGHD, with particular focus on diagnostic strategies in the peripubertal period, timing of retesting, and the role of sex steroid priming. Methods: A systematic literature search was conducted in 4 databases up to June 2025. Studies were included if they reported on GH retesting in children with IIGHD. Data were extracted on patient characteristics, GHST protocols, priming strategies, cutoff values, and reversal rates. Risk of bias was assessed using the ROBINS-I tool. Results: Thirty-one studies involving 2057 patients were included. Retesting occurred after 1–2 years of rhGH treatment, during mid-puberty, or at (N)AH, with mean reversal rates of 46.4%, 46.3%, and 69.6%, respectively. Priming with sex steroids was inconsistently applied, using testosterone in boys and ethinyl estradiol in girls. A GH peak cutoff of 7 μg/L was most commonly used, though values varied. Mid-pubertal retesting may reduce false-positive diagnoses and treatment burden. Conclusion: Retesting strategies for IIGHD should be individualized based on treatment response and pubertal development. Early retesting is advised for poor responders, while mid-puberty retesting suits most patients with normal development. Priming is recommended in older prepubertal children. Standardization of GHST protocols and long-term outcome studies are needed to optimize care and reduce overtreatment.

Introduction: Recombinant human growth hormone (rhGH) treatment of children with idiopathic isolated growth hormone deficiency (IIGHD) typically results in catch-up growth for several years followed by a period of normal growth. The effect of rhGH treatment on late pubertal height gain in adolescents with IIGHD has remained unclear. This study aimed to develop and validate a prediction model for height gain from mid-puberty to near adult height (NAH) in patients with IIGHD, treated with rhGH. Methods: Data from the Dutch National Registry of Growth Hormone Treatment in Children were used, focusing on 151 patients who received rhGH treatment until NAH. Predictors included age, bone age, Tanner stage, and target height SDS minus height SDS at mid-puberty. Validation was performed in 33 males and 7 females who had a normal GH response in a GH stimulation test at mid-puberty and continued rhGH until NAH. Results: The model explained 48% of the variance for males (residual SD 4.16 cm) and 18% for females (residual SD 3.64 cm). Validation showed a mean (SD) difference of 1.48 (2.36) cm for males and 3.57 (2.66) cm for females between predicted and attained NAH. Conclusion: For females, explained variance was insufficient to reliably predict height gain. For GH sufficient males, the model can be used to assess efficacy of continuing or discontinuing rhGH treatment at mid-puberty in future studies.