A pilot study of discontinuous, insulin-like growth factor 1-dosing growth hormone treatment in young children with FGFR3 N540K-mutated hypochondroplasia.

OBJECTIVE: To assess the growth promoting effect of a recombinant growth hormone (rGH) treatment protocol adjusted on insulin-like growth factor 1 (IGF-1) dosing in children affected by the most severe forms of FGFR3 N540K-mutated hypochondroplasia. STUDY DESIGN: Midterm results of an open-label, single-center, nonrandomized, 2003-2020 pilot trial to final stature, including 6 children (mean age, 2.6 ± 0.7 years; mean height SDS, -3.0 ± 0.5) with the N540K mutation of FGFR3 gene who received an rGH dosage titrated to an IGF-1 level close to 1.5 SDS of the normal range. rGH therapy was interrupted 1 day per week, 1 month per year, and 6 months every 2 years. RESULTS: The mean height SDS increased by 1.9 during the 6.1 ± 0.9-year study period, reaching -0.8 to -1.3 at age 8.7 ± 1 years. The mean±SDS baseline IGF-1 value was -1.6 ± 0.5 before rGH treatment and 1.4±0.3 during the last year of observation. The average cumulative rGH dose was 0.075 ± 0.018 mg/kg/day (range, 0.059-0.100 mg/kg/day). Trunk/leg disproportion was improved. CONCLUSION: IGF-1-dosing rGH treatment durably improves growth and reduces body disproportion in children with severe forms of hypochondroplasia.

Short-term results of single-port sleeve gastrectomy in adolescents with severe obesity.

BACKGROUND: Dietary and lifestyle modifications, which are commonly proposed to overweight or obese youth, lack efficacy in individuals who are severely obese. Early results with bariatric procedures in obese adolescents suggest that weight loss and safety are comparable or better than seen in adults. One of these procedures, laparoscopic sleeve gastrectomy, is commonly performed using multiple ports. METHODS: We selected single-port sleeve gastrectomy (SPSG) as a minimally invasive surgery to be tested in severely obese adolescents. Prospective clinical and biochemical data were collected from 16 young severely obese patients who underwent SPSG. The setting was a university hospital. RESULTS: The mean age of the cohort was 17.8 years (12 girls, 4 boys). The individuals' average weight was 125.5 kg and their average body mass index was 45.3 kg/m(2). All patients were insulin-resistant and 6 showed hypertriglyceridemia. The median operating time was 66 minutes, and there were no intraoperative complications. No conversion to open surgery was required. No patient required additional trocars and no patient had postoperative complications. The median hospital stay was 3 days. After a one-year follow-up, the average weight decrease was 40.3 kg, resulting in a decrease in excess weight loss by 70.61%. Insulin-resistance decreased in 16/16 patients and hypertriglyceridemia decreased in 5/6 patients. CONCLUSION: SPSG seems safe and effective in the short term in severely obese adolescents.

Near normalization of adult height and body proportions by growth hormone in pycnodysostosis.

CONTEXT: Mutations in the cathepsin K gene (CTSK) cause a very rare form of short-limb dwarfism called pyknodysostosis (online inheritance in man 265800) that reduces adult height to 130-150 cm. OBJECTIVE: To study the effects of GH in children with pyknodysostosis. DESIGN AND METHODS: This was a pilot open study of three children with pyknodysostosis (P1, P2, P3) and 16 age-matched children with idiopathic short stature (ISS) treated with a similar IGF-I-based dosing of GH therapy. P1, P2, and P3 received a mean GH dose of 29, 67, and 120 microg/kg x d, respectively, during 12, 6.5, and 5 yr, whereas the ISS group received a mean dose of 62 +/- 21 microg/kg x d during 5.4 +/- 2 yr. RESULTS: P1, P2, and P3 had the typical clinical and radiological features of pyknodysostosis. They were shown to carry three different homozygous missense mutations of the CTSK gene. After onset of GH at 4.5, 5.4, and 10.9 yr of age, respectively, height increased from -2, -4.2, and -3 SD score to -1, -0.5, and -1 SD score after a 12, 6.5, and 5 yr GH treatment. Remarkably, body disproportion was largely corrected by GH treatment. IGF-I levels in P1, P2, and P3 were within the range of the ISS group. CONCLUSIONS: Pyknodysostotic patients can reach near-normal stature and skeletal proportions with a personalized GH treatment targeted at appropriate IGF-I levels. Given the severity of this rare dwarfism, we propose that GH should be offered to affected children.