RESUMO
Objectives: Growth impairment is a common manifestation in Noonan syndrome (NS). Recombinant human GH (rhGH) treatment has been shown to increase growth and adult height (AH) in a few studies. We aimed to evaluate the growth trajectory towards the AH, and the effects of rhGH treatment in a large cohort of NS children. Methods: Retrospective, multicenter, cohort study including subjects with genetic diagnosis of NS. A total of 228 NS patients, 154 with PTPN11 mutations, 94 who reached AH, were recruited. Auxological data were collected at 2, 5, and 10 years, at pubertal onset, at AH. Sixty-eight NS subjects affected with GH deficiency (GHD) were treated with rhGH at a mean dose of 0.24 mg/kg per week until AH achievement. Results: ANOVA analysis showed a significant difference between birth length and height standard deviation scores (HSDS) at the different key ages (p<0.001), while no significant differences were found between HSDS measurements at 2, 5, and 10 years, at pubertal onset, and at AH. HSDS increased from -3.10 ± 0.84 to -2.31 ± 0.99 during rhGH treatment, with a total height gain of 0.79 ± 0.74, and no significant difference between untreated and treated NS at AH. Conclusions: rhGH treatment at the standard dose used for children with GH idiopathic deficiency is effective in improving growth and AH in NS with GHD. Further studies are needed to assess genotype-specific response to rhGH treatment in the different pathogenic variants of PTPN11 gene and in the less common genotypes.
Assuntos
Estatura/efeitos dos fármacos , Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Noonan/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Children with nonclassical congenital adrenal hyperplasia (NCCAH) often present increased growth velocity secondary to elevation of adrenal androgens that accelerates bone maturation and might compromise adult height (AH). OBJECTIVE: The aim of the study was to analyze prognostic factors affecting growth trajectory (GT) and AH in children with NCCAH. METHODS: The study was a retrospective, multicentric study. The study population consisted of 192 children with a confirmed molecular diagnosis of NCCAH, followed by pediatric endocrinology centers from diagnosis up to AH. Clinical records were collected and analyzed. AH (standard deviation score; SDS), pubertal growth (PG) (cm), GT from diagnosis to AH (SDS), and AH adjusted to target height (TH) (AH-TH SDS) were evaluated as outcome indicators using stepwise linear regression models. RESULTS: The stepwise linear regression analysis showed that AH and AH-TH were significantly related to chronological age (CA) (p = 0.008 and 0.016), bone age (BA)/CA ratio (p = 0.004 and 0.001), height (H) (p < 0.001 for both parameters) at NCCAH diagnosis, and TH (p = 0.013 and <0.001). PG was higher in males than in females (22.59 ± 5.74 vs. 20.72 ± 17.4 cm, p = 0.002), as physiologically observed, and was positively related to height (p = 0.027), negatively to BMI (p = 0.001) and BA/CA ratio (p = 0.001) at NCCAH diagnosis. Gender, genotype, biochemical data, and hydrocortisone treatment did not significantly impair height outcomes of these NCCAH children. CONCLUSIONS: The results of this study suggest that AH and GT of NCCAH patients are mainly affected by the severity of phenotype (CA, BA/CA ratio, and H) at the time of diagnosis.
Assuntos
Hiperplasia Suprarrenal Congênita/fisiopatologia , Estatura , Modelos Biológicos , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/patologia , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Hidrocortisona/administração & dosagem , Masculino , Estudos RetrospectivosRESUMO
Omalizumab is a monoclonal antibody, targeting Fc receptor of IgE, approved for the treatment of allergic asthma and chronic spontaneous urticaria. Its utility in atopic dermatitis appears controversial from data in literature since the molecule is well tolerated but it seems less effective than other medications used in adult patients (eg, Dupilumab). At present, the use of Dupilumab is not approved in pediatric patients therefore there are no second level treatments available in this age group. Here we report two clinical cases of patients (15 and 16 years old) suffering from both atopic dermatitis and asthma, treated with Omalizumab. Our experience suggests that atopic eczema of young patients with allergic comorbidities can benefit from asthma treatment with Omalizumab observing improvement on both conditions.
Assuntos
Asma , Dermatite Atópica , Adolescente , Adulto , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Asma/diagnóstico , Asma/tratamento farmacológico , Criança , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Humanos , Omalizumab/efeitos adversosRESUMO
BACKGROUND: High mobility group box 1 (HMGB1) is abnormally expressed in serum and sputum of patients with allergic asthma. OBJECTIVE: The aim of this study was to investigate the role of HMGB1 as guidance for treatment management of children with asthma. METHODS: Thirty children with asthma and 44 healthy children were enrolled. The patients were classified according to Global Initiative for Asthma Guideline disease severity criteria. Sputum HMGB1 levels and lung function index (percentage forced expiratory volume in 1 second [FEV1%]) were recorded in the cohort study at baseline (T0) and after 3 (T3) and 6 (T6) months of inhaled corticosteroids (ICS) treatment. RESULTS: Sputum HMGB1 levels were significantly higher in all the patients with asthma (p < 0.001). An inverse correlation between sputum HMGB1 levels and pulmonary function parameters was observed only in the children with moderate asthma (T0: FEV1%, r = -0.9891, p < 0.001; T3: FEV1%, r = -0.6763, p < 0.001; T6: FEV1%, r = -0.5419, p < 0.05) and in the children with severe asthma (T0: FEV1%, r = -0.8696, p < 0.001; T3: FEV1%, r = -0.6477, p < 0.05; T6: FEV1%, r = -0.8627, p < 0.001). After ICS treatment, a significant decrease of sputum HMGB1 levels was noted in moderate (T0 [93.44 ± 20.65 ng/mL] versus T3 [77.96 ± 1.81 ng/mL] versus T6 [67.75 ± 3.01 ng/mL]; p < 0.0001) and in the children with severe asthma (T0 [130.3 ± 7.48 ng/mL] versus T3 [156.9 ± 1.09 ng/mL] versus T6 [116.08 ± 4.77 ng/mL]; p < 0.0001) data are mean ± standard deviation, respectively. The area under the receiver operating characteristic curve, performed to define the diagnostic profile of sputum HMGB1 levels in identifying the children with asthma, was 0.713. CONCLUSION: In addition to the findings that HMGB1 is a sensitive biomarker of allergic asthma in children, our data demonstrated a significant correlation between the decrease of HMGB1 levels and a successful treatment response.