Régis Coutant

Aims: Obesity is a complication of childhood craniopharyngioma that remains difficult to treat. We investigated whether semaglutide was associated with a decrease in BMI among adolescents with craniopharyngioma‐related obesity. Material and Methods: This multicentre retrospective study included 20 patients < 18 years old with craniopharyngioma and obesity (BMI > 2 WHO Z ‐score) from 2019 to 2024 (source population: 139 children with craniopharyngioma, including 36 children with obesity). They received off‐label semaglutide with dose titration (0.25–2 mg/week), tailored to tolerance and clinical response. The primary outcome was the within‐patient comparison of BMI change from −12 months to treatment initiation and from initiation to +12 months. Results: At semaglutide initiation, patients were 14.0 ± 3.9 years old, the interval since craniopharyngioma diagnosis was 6.3 ± 4.7 years, and BMI was 33.4 ± 3.9 kg/m ² (3.2 ± 0.7 Z ‐score). Tumour treatment was surgery alone (8/20), surgery and proton therapy (11/20), or proton therapy alone (1/20). All patients had growth hormone and TSH deficiency; 19/20 had ACTH and AVP deficiency. In the year before treatment, patients gained 3.5 ± 4.4 kg/m ² in BMI and 0.6 ± 1.6 in BMI Z ‐score; after 1 year of semaglutide therapy, they lost 2.5 ± 3.9 kg/m ² in BMI and 0.5 ± 0.5 in BMI Z ‐score (paired comparisons, p < 0.001 and p = 0.004, respectively). During treatment, BMI decreased by 10% or more in 40% of patients (95% CI: 19%–64%). Gastrointestinal side effects occurred in 30% of patients but were mild. No cases of treatment discontinuation, pituitary insufficiency decompensation or tumour recurrence were observed. Conclusions: Semaglutide was associated with reversal of weight gain among adolescents with craniopharyngioma‐related obesity.

Objective: Autosomal dominant hypocalcemia type 1 (ADH1) results from activating CASR variants, causing parathyroid hormone (PTH) suppression and abnormal renal calcium handling. Management is challenging, as hypoparathyroidism is associated with inappropriate renal calcium wasting, leading to hypercalciuria, nephrocalcinosis, and renal impairment. We evaluated long-term outcomes of continuous subcutaneous PTH(1–34) infusion (CSPI) in children with ADH1 refractory to standard of care therapy (SOC). Design: Single-center observational study. Methods: Five children with genetically confirmed ADH1 were treated with CSPI between 2012 and 2017 and followed for up to 11 years. Clinical outcomes, biochemical parameters, and renal findings were assessed under SOC and CSPI. Serum calcium, phosphate (standard deviation score, SDS), magnesium, alkaline phosphatase, eGFR, urinary calcium/creatinine ratio (relative to the age-specific 95th percentile), and fractional calcium excretion (FECa) were analyzed using linear mixed-effects models. Results: Hypocalcemic seizures and emergency visits decreased, growth was appropriate, and no treatment-related adverse events occurred over a median 7-year follow-up. CSPI was associated with higher serum calcium (P < .001) and lower serum phosphate (P < .001). Urinary calcium/creatinine ratios, expressed relative to the age-specific 95th percentile, were lower under CSPI (P < .001). FECa was approximately 8% lower under CSPI (P = .014), suggesting improved renal calcium handling. Renal function remained stable despite progression of nephrocalcinosis in 4/5 patients. Conclusion: SPI appears to be a safe and effective long-term treatment in pediatric ADH1, improving mineral homeostasis and renal calcium handling. Prospective multicenter studies are needed to assess long-term skeletal outcomes and optimize dosing strategies.

Context: Diagnosing SHOX gene variations is important because growth hormone treatment is an approved option for affected children. Subtle clinical and radiological abnormalities were reported in SHOX deficiency associated with idiopathic short stature (ISS). Whether systematic or phenotype-based molecular screening should be performed remains debated. Objective: To determine whether simple radiological features on left-hand radiography could serve as indicators for molecular analysis of the SHOX gene, and to compare these with published clinical/radiological scores. Methods: This retrospective study included 266 patients diagnosed with ISS who underwent SHOX gene analysis without any predefined selection criteria at the Pediatric Endocrinology Unit of Angers University Hospital from 2016 to 2023, aiming to determine the rate of SHOX gene variations. We also included 33 ISS patients diagnosed with a SHOX gene variation between 2005 and 2015 to refine sensitivity analyses. Results: Systematic screening using MLPA identified SHOX gene variations in 9.8% of ISS children and sequencing in MLPA-negative subjects detected an additional 6%. Variations occurred in the coding regions in one-third and in the enhancer regions in two-thirds. A cutoff of 147° for the convexity of the distal radial metaphysis showed sensitivity/specificity of 89%/50%. A cutoff of 128° for pyramidalization of the carpal row yielded sensitivity/specificity of 86%/49%. Combining both criteria yielded 91% sensitivity and 70% specificity. Previous scores proposed by Rappold and Binder had sensitivity/specificity of 36%/51% and 81%/10%, respectively. Conclusion: Systematic molecular screening by MLPA and sequencing is recommended to detect all SHOX gene variants in children with ISS.

Backgound: The purpose of this study is to compare the effect of long-acting growth hormone (LAGH) to daily GH on body mass index (BMI) in children with growth hormone deficiency (GHD). Methods: We searched the PubMed database from its inception to July 2025 and identified three relevant randomized controlled trials lasting over 6 months, with extension phases providing longitudinal BMI data. Longitudinal BMI data were available for lonapegsomatropin, somatrogon, and somapacitan, but not for polyethylene glycol LAGH. Results: A total of 585 patients were included in the present analysis, of which 346 were in the LAGH group, and 239 were in the daily rhGH group, derived from seven original articles and two abstracts/ePosters. At 12 months, there was a significant difference in BMI SD scores between LAGH and daily GH groups (Mean difference [MD] 0.66 SDS [95% confidence interval [CI] 0.04–1.29]). BMI SDS significantly increased in the LAGH group (MD + 0.41 SDS [95% CI 0.04–0.77] from 0 to 12 months), whereas it did not change in the daily GH group (MD −0.35 SDS [95% CI −0.76 to +0.07] from 0 to 12 months). Between 12 and 24 months, after switching from daily GH to LAGH (daily GH/LAGH), or pursuing LAGH (LAGH/LAGH) in the extension phases of the studies, BMI SDS significantly increased in the daily GH/LAGH switching group (MD + 0.75 SDS [95% CI 0.24–1.27] from 12 to 24 months), whereas it remained steady in the LAGH/LAGH group. Omitting one study at a time from the meta-analysis did not materially affect the results. Conclusion: An increase in body mass index SD score is associated with the first year of LAGH use.

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Introduction: Recombinant human growth hormone (rhGH) treatment for short children born small for gestational age (SGA) is effective in improving height outcomes. Determinants of height response to rhGH treatment have been identified using multiple regression analyses. Although adverse events (AEs) associated with treatment have been described, determinants of AE occurrence are not well known. Methods: This analysis used safety data collected between 2007 and 2018 in an observational, prospective registry study (NCT01578135) including children born SGA across 126 sites in France. AEs were reported by patients or recorded by treating physicians. Univariate and multivariate analyses were performed to identify determinants of occurrence of AEs and serious AEs (SAEs). Results: Of 291 patients from the registry, 287 AEs were reported in 149 (51.2%) patients. Each patient experienced a mean of 0.205 AEs per patient-year (range 0–4.3) and a mean of 0.054 SAEs (range 0–1.8). The most frequently reported AEs were headache (9.3%) and arthralgia (4.5%). Using multiple regression analyses, longer registry participation (p=0.0146, odds ratio [OR]=1.98), presence of chronic disease (p=0.0004, OR = 2.56), and concomitant treatment (p=0.0162, OR = 1.79) were associated with increased risk of experiencing AEs. GH dose at inclusion or cumulative GH dose during first 2 years of treatment were not associated with AE risk, while higher GH dose at last visit was associated with reduced risk (p=0.0412, OR = 0.58). Conclusions: In short children born SGA, underlying conditions and associated treatments seem to be the main factors associated with AE occurrence, while GH dose was inversely related to AE occurrence.

Context: Congenital hypogonadotropic hypogonadism (CHH) in infant boys is a rare disorder that can manifest as micropenis and/or cryptorchidism. Mini-puberty is considered a window of opportunity for CHH diagnosis and treatment. The lack of testosterone (T) elevation during this period is the gold standard for CHH diagnosis, but hormonal evaluation is not always available at this time. Objectives: The aim was to compare inhibin B (INHB), anti-Müllerian hormone (AMH), T, LH, and FSH between infant boys (1 to 365 days) with micropenis and/or cryptorchidism due to isolated CHH (iCHH), CHH as part of combined pituitary hormone deficiency (CPHD), or of idiopathic origin (controls) and to determine discriminating cutoffs for CHH diagnosis based on sensitivity (Se) and specificity (Sp). Methods: This multicenter study from 7 University Hospitals in France included 138 boys aged 0 to 12 months (58 with iCHH, including 28 with a positive molecular diagnosis, 32 with CPHD, and 48 controls). Four periods of interest were studied: between 1 to 4 days, 15 to 65 days (early mini-puberty, corresponding to the T peak), 66 to 179 days (late mini-puberty), and 180 to 365 days (post mini-puberty). Results: Out of mini-puberty, the best-discriminating hormones were INHB between 1 to 4 days (Se/Sp 100%/75% at 150 pg/mL and 89%/100% at 85 pg/mL) and INHB and AMH after 180 days (INHB: Se/Sp 100%/100% at 100 pg/mL; AMH: Se/Sp 100%/92% at 600 pmol/L, and 75%/100% at 370 pmol/L). INHB and/or AMH discriminating performances were good (area under the receiver operating characteristic curve ≥ 0.95) across all 4 periods. Conclusion: Inhibin B and/or AMH can be used to diagnose CHH in boys < 1 year of age.