Thyroid dyshormonogenesis (THD) is a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones. Genetic variants in DUOX2 can cause partial to total iodination organification defects and clinical heterogeneity, from transient to permanent congenital hypothyroidism. The aim of this study was to undertake a molecular characterization and genotype–phenotype correlation in patients with THD and candidate variants in DUOX2. A total of 31 (19.38%) patients from the Catalan Neonatal Screening Program presented with variants in DUOX2 that could explain their phenotype. Fifteen (48.39%) patients were compound heterozygous, 10 (32.26%) heterozygous, and 4 (12.90%) homozygous. In addition, 8 (26.67%) of these patients presented variants in other genes. A total of 35 variants were described, 10 (28.57%) of these variants have not been previously reported in literature. The most frequent variant in our cohort was c.2895_2898del/p.(Phe966SerfsTer29), classified as pathogenic according to reported functional studies. The final diagnosis of this cohort was permanent THD in 21 patients and transient THD in 10, according to reevaluation and/or need for treatment with levothyroxine. A clear genotype–phenotype correlation could not be identified; therefore, functional studies are necessary to confirm the pathogenicity of the variants.

Background: The worldwide increase in the prevalence of childhood obesity necessitates effective prevention and treatment strategies. Clinical practice guidelines (CPGs) offer guidance, but significant heterogeneity or lack of practical application exists in their recommendations. The purpose of the present study is to provide an expert, comprehensive, and comparative analysis of gaps in current CPGs for the prevention and treatment of obesity in children and adolescents. Results: A total of 14 CPGs were identified, focusing on childhood obesity prevention (n = 11), treatment (n = 9), or both (n = 6). Prevention CPGs generally recommend body mass index (BMI) assessment, but specific measurement frequency is often absent. While some provide age-specific dietary recommendations, graphical tools are lacking. Recommendations for increased physical activity and reduced screen time are common, but age-stratified guidance is deficient. Furthermore, recommendations regarding mental health and sleep are notably absent. Treatment CPGs utilize BMI for obesity diagnosis, but inconsistencies in cut-off points persist. Comorbidity assessment is generally recommended, yet age-specific guidance remains lacking. Dietary recommendations are present in most CPGs, but many lack detailed specifications (e.g., meal frequency, portion sizes, macronutrient distribution, age-appropriate examples). Most CPGs advocate for 60 min of daily physical activity and limit screen time to 2 h per day. Recommendations concerning sleep are consistently absent. While parental involvement is acknowledged, specific guidance for active participation in prevention and treatment is deficient. Pharmacological treatment options are frequently outdated, and surgical intervention is reserved for exceptional cases of severe obesity. Conclusions: Standardizing BMI cut-off points and defining age groups across CPGs would improve consistency and comparability in the diagnosis, prevention, and treatment of childhood obesity. Tailoring recommendations for diet, physical activity, sedentary behavior, and sleep to specific age groups would ensure developmentally appropriate interventions. A stronger emphasis on early prevention strategies is needed to address the root causes of obesity. Clear guidance for parents and families would facilitate their active engagement in prevention and treatment. Up-to-date information regarding pharmacological and surgical treatments is imperative.

To investigate the incidence of pseudotumor cerebri syndrome in children treated with growth hormone in a paediatric hospital and to identify risk factors of this complication. Prospective pilot study of paediatric patients treated with growth hormone, prescribed by the Paediatric Endocrinology Department, between February 2013 and September 2017. In all these patients, a fundus examination was performed before starting treatment and 3-4 months later. 289 patients were included: 244 had a growth hormone deficiency, 36 had short stature associated with small for gestational age, six had a mutation in the SHOX gene and three had Prader-Willi Syndrome. Five patients developed papilledema, all were asymptomatic and had a growth hormone deficiency: one had a craniopharyngioma, two a polymalformative syndrome associated with hypothalamic-pituitary axis anomalies, one patient a non-specified genetic disease with hippocampal inversion and one patient with normal magnetic resonance imaging who had developed a primary pseudotumor cerebri syndrome years before. Growth hormone treatment is a cause of pseudotumor cerebri syndrome. In our series, at risk patients had growth hormone deficiency and hypothalamic-pituitary anatomic anomalies or genetic or chromosome diseases. Fundus examination should be systematically screened in all patients in this at-risk group irrespective of the presence or not of symptoms.

Genetic defects in the TSH receptor (TSHR) can cause poor thyroid differentiation (thyroid dysgenesis) and/or thyroid malfunction (thyroid dyshormonogenesis). The phenotype spectrum is wide: from severe congenital hypothyroidism to mild hyperthyrotropinemia. Over 250 TSHR variants have been published, many uncharacterized in vitro. We aimed to genetically characterize patients with thyroid dyshormonogenesis with TSHR defects and to study in vitro the effect of the genetic variants to establish the genotype–phenotype relationship. Pediatric patients with thyroid dyshormonogenesis (160 patients, Catalan CH neonatal screening program, confirmation TSH range: 18.4–100 mIU/L), were analyzed by a high-throughput gene panel. In vitro studies measuring the TSH-dependent cAMP–response–element activation were performed. Five patients with mild or severe thyroid dyshormonogenesis presented six TSHR variants, two unpublished. Each variant showed a different in vitro functional profile that was totally or partially deleterious. Depending on the genotype, some of the variants showed partial deficiency in both genotypes, whereas others presented a different effect. In conclusion, the percentage of patients with thyroid dyshormonogenesis and candidate variants in TSHR is 3.13%. Our in vitro studies contributed to the confirmation of the pathogenicity of the variants and highlighted the importance of studying the effect of the patient’s genotype for a correct diagnostic confirmation.

Summary: Two pediatric patients with different causes of hyperparathyroidism are reported. First patient is a 13-year-old male with severe hypercalcemia due to left upper parathyroid gland adenoma. After successful surgery, calcium and phosphate levels normalized, but parathormone levels remained elevated. Further studies revealed a second adenoma in the right gland. The second patient is a 13-year-old female with uncommon hypercalcemia symptoms. Presence of pathogenic calcium-sensing receptor gene ( CASR ) mutation was found, resulting in diagnosis of symptomatic familial hypocalciuric hypercalcemia. Cinacalcet, a calcium-sensing agent that increases the sensitivity of the CASR, was used in both patients with successful results. Learning points: Hyperparathyroidism is a rare condition in pediatric patients. If not treated, it can cause serious morbidity. Genetic tests searching for CASR or MEN1 gene mutations in pediatric patients with primary hyperparathyroidism should be performed. Cinacalcet has been effective for treating different causes of hyperparathyroidism in our two pediatric patients. Treatment has been well tolerated and no side effects have been detected.

Background: The worldwide increase in the prevalence of childhood obesity necessitates effective prevention and treatment strategies. Clinical practice guidelines (CPGs) offer guidance, but significant heterogeneity or Lack of practical application exists in their recommendations. The purpose of the present to provide an expert, comprehensive and comparative analysis of gaps in current CPGs for the prevention and treatment of obesity in children and adolescents.Results: A total of 13 CPGs were identified, focusing on childhood obesity prevention (n=10), treatment (n=9), or both (n=6). Prevention CPGs recommend incorporating BMI assessment however, specific frequency of measurement is often lacking. Some offer specific dietary recommendations by age, but graphical tools are absent. Increasing physical activity and minimizing screen time is recommended in most CPGs, but age-specific guidance is lacking. Also, recommendations on mental health or sleep are absent. Treatment CPGs recommend BMI for childhood obesity diagnosis but there are inconsistencies in cut-off points among CPGs. Assessment for comorbidities is generally recommended, but age-specific guidance is lacking. Dietary recommendations are present in most CPGs, but some lack details (number of meals per day, portion size, macronutrient percentages, examples according to age). Most CPGs recommended 60 minutes of physical activity/day and limit screen time to 2 hours/day. Recommendations on sleep are absent. Most CPGs acknowledge parental importance but lack specific guidance for their active involvement in childhood obesity prevention and treatment. Pharmacological treatment options are outdated and surgical treatment is recommended in exceptional cases of severe obesity (BMI ≥ 40 kg/m2 or ≥ 35 kg/m2 with severe comorbid disease). Conclusions: Standardizing BMI cut-off points and defining age groups across CPGs would improve consistency and comparability in the diagnosis, prevention and treatment of childhood obesity. Tailoring recommendations for diet, physical activity, sedentary behavior and sleep to specific age groups would ensure that interventions are developmentally appropriate. A stronger emphasis on early prevention strategies is needed to address the root causes of obesity, while providing clear guidance to parents and families would facilitate their active involvement in both prevention and treatment. Up-to-date information regarding pharmacological and surgical treatments is needed.