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We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.
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Enanismo Hipofisario , Hormona de Crecimiento Humana , Humanos , Niño , Hormona de Crecimiento Humana/efectos adversos , Hormona del Crecimiento/uso terapéutico , Calidad de Vida , Análisis Costo-Beneficio , Enanismo Hipofisario/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/efectos adversos , Terapia de Reemplazo de Hormonas/métodosRESUMEN
AIM: To assess a new formula to improve the screening of isolated impaired glucose tolerance (IGT) in youth with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional study was performed in 1189 Caucasian youths with OW/OB aged 5-17 years, in whom impaired fasting glucose and high glycosylated hemoglobin were excluded. The sample was divided into training set (TS) (n = 883) and validation set (VS) (n = 306). Fasting (FG) and post-load plasma glucose, alanine aminotransferase (ALT), lipids and familial history for type 2 diabetes (FD) were available in all individuals. In the TS youths with IGT (n = 58, 7.0%) showed higher prevalence of female sex (FS), FD, and higher levels of FG, post-load glucose, ALT and lower levels of HDL-cholesterol vs individuals without IGT. The linear formula was obtained by logistic regression analysis in the TS: 0.05∗ALT + 0.07∗FG + 0.87∗FD + (0.06∗HDL∗ - 1) + 1∗FS. The best cut-off was 5.84. The performance of the formula vs IGT was: sensitivity: 0.74 and specificity: 0.71. Similar results were obtained in the VS. CONCLUSIONS: Using metabolic and anamnestic data we obtained a simple formula with a good performance for screening isolated IGT. This formula may support pediatricians to identify youths with OW/OB in whom the OGTT may be useful for detecting IGT.
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Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Femenino , Humanos , Adolescente , Masculino , Sobrepeso/diagnóstico , Sobrepeso/epidemiología , Intolerancia a la Glucosa/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Estudios Transversales , Obesidad/diagnóstico , Obesidad/epidemiología , GlucosaRESUMEN
Critical illness-related corticosteroid insufficiency or CIRCI is characterized by acute and life-threatening disfunction of hypothalamic-pituitary-adrenal (HPA) axis observed among intensive care unit- staying patients.It is associated with increased circulating levels of biological markers of inflammation and coagulation, morbidity, length of ICU stay, and mortality.Several mechanisms are involved in CIRCI pathogenesis: reduced CRH-stimulated ACTH release, peripheral resistance to glucocorticoids, altered cortisol synthesis, impaired cortisol-free fraction and bioavailability.Diagnostic and therapeutic management of this condition in children is still debated, probably because of the lack of agreement among intensive care specialists and endocrinologists regarding diagnostic criteria and prevalence of CIRCI in paediatric age.In the present narrative review, we focused on definition of CIRCI in paediatric age and we advise on how to diagnose and treat this poorly understood condition, based on current literature data.
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Insuficiencia Suprarrenal , Humanos , Niño , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/tratamiento farmacológico , Enfermedad Crítica/terapia , Corticoesteroides/uso terapéutico , Hidrocortisona/uso terapéutico , Glucocorticoides/uso terapéuticoRESUMEN
PURPOSE: Turner syndrome (TS) is the most common sex chromosomal abnormality found in female subjects. It is a result of a partial or complete loss of one of the X chromosomes. Short stature is a hallmark of TS. Attainment of adult height (AH) within the normal range for height within the general female population represents the usual long-term goal of growth hormone (GH) treatment. The aim of this systematic review was to understand the efficacy of GH therapy on AH of patients with TS. METHODS: The literature review yielded for analysis 9 articles published from 2010 to 2021. Using the data from this literature search, the goal was to answer 5 questions: (1) What is the efficacy of GH on AH of girls with TS?; (2) Is AH influenced by the age at initiation of GH treatment?; (3) What is the optimal dose of GH to improve AH?; (4) Can the timing of either spontaneous or induced puberty influence AH?; and (5) Can the karyotype influence AH in patients with TS? FINDINGS: GH therapy and adequate dose could enable patients with TS to achieve appropriate AH compared with the possible final height without therapy. The greatest increase in height during GH therapy occurs in the prepubertal years, and if therapy is continued to AH, there is no further increase. Furthermore, karyotype did not show a predictive value on height prognosis and did not affect the outcome of GH administration or the height gain in girls with TS. IMPLICATIONS: Even if GH therapy is safe, close monitoring is indicated and recommended. Further evidence is needed to understand what other parameters may influence AH in patients undergoing GH therapy.
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Hormona de Crecimiento Humana , Síndrome de Turner , Adulto , Humanos , Femenino , Hormona de Crecimiento Humana/uso terapéutico , Síndrome de Turner/tratamiento farmacológico , Estatura , Cuidados PaliativosRESUMEN
BACKGROUND: Fever is one of the most frequent symptoms highlighted during medical assistance. Due to this great impact, our study has the purpose of analyzing the demographic and laboratory characteristics of patients hospitalized in our center and identifying predictive markers to make the differential diagnosis between infectious and non-infectious fever. METHODS: Our population included 220 children, collected from January 2017 to August 2022, hospitalized for continuous fever (4 days or more in duration with at least one temperature peak ≥37.5 °C) and excluded cases of discharge against medical advice and/or transfer to other operating units. Demographic (mean age at the time of admission, frequency of hospitalization, and mean days of hospitalization), laboratory, and instrumental variables were analyzed in order to find correlation with fever etiology. RESULTS: Older age at the time of hospitalization, family history of periodic fever, fever lasting more than 8 days, and longer hospitalization are strongly associated with non-infectious fever, together with anemia, high platelet count, high CRP and ferritin, and hyponatremia at the time of admission. Paracetamol is the preferred antipyretic treatment. Echocardiogram has shown anomalies in patients with infectious fever, while ECG anomalies were detected in non-infectious fever. CONCLUSIONS: Our data underline the importance of predictive markers, such as clinical and laboratory parameters, to differentiate infectious from non-infectious fevers, but further studies are necessary.
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INTRODUCTION: ACTH-independent Cushing's Syndrome (CS) is very rare condition in children. Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of CS, which in most cases occurs in the context of Carney complex (CNC). CNC is an autosomal-dominantly inherited genetic syndrome, usually due to pathogenic variants of the PRKAR1A (regulatory subunit R1A of the protein kinase A) gene. The clinical picture is characterized by spotty skin pigmentation, cardiac, cutaneous and mammary myxomas, melanocytic schwannomas, endocrinopathies and tumours of the endocrine glands (mostly adrenal, pituitary and thyroid). CASE PRESENTATION: A 10-year-old boy first came to our Outpatient clinic due to severe obesity. During the first three months of follow-up the height growth rate was normal, but the response to dietary-behavioural indications was poor in term of weight loss. Later, 10 months after the last evaluation, there was evidence of significant worsening of obesity, growth failure, arterial hypertension and the occurrence of red skin striae at the trunk and root of the limbs. Endocrinological causes of obesity associated with growth failure were investigated. The circadian rhythm of cortisol, ACTH and cortisoluria were suggestive of ACTH-independent hypercortisolaemia. Iatrogenic causes were ruled out. Adrenal ultrasound and computer tomography initially indicated the presence of a nodule or hyperplasia of the medial arm of the left adrenal gland. Conversely, magnetic resonance imaging showed a significant increase in the global dimensions of the adrenals with a bilateral micronodular appearance. Considering the association between ACTH-independent hypercortisolism and PPNAD, a genetic investigation was performed, which found a pathogenic variant of the PRKAR1A gene. Patient started, and well tolerated, therapy with metyrapone during a two-year follow-up. The clinical picture has slightly improved, cortisoluria returned and remains within normal limits, but ACTH suppression persists. CONCLUSION: This is the first report on the clinical and biochemical effects of 2-year medical treatment with metyrapone of PPNAD-related hypercortisolaemia in a paediatric patient with CNC. Currently, there are no established protocols for the management of hypercortisolism in PPNAD and data are scarce especially in the paediatric field. Medical therapies may play a role in reducing the need, at least initially, for bilateral adrenalectomy. However, further studies are needed to clarify this aspect. In cases of CS due to PPNAD in which medical therapy was the initial approach, in the absence of clear clinical, auxological and biochemical improvements, metyrapone may have to be discontinued in favour of another approach, including surgery.
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OBJECTIVE: Growth hormone deficiency (GHD) is the most common pituitary hormone deficiency and is one of the main causes of short stature in children and adolescents. The aim of this study is to evaluate the epidemiology of pediatric GHD worldwide, since no other systematic review has been published so far. METHODS: We searched PubMed, Embase, and Web of Science up to July 2023 to find epidemiological studies involving children with GHD. Two review authors independently screened articles, extracted data and performed the quality assessment. RESULTS: We selected 9 epidemiological studies published from 1974 to 2022. The range of prevalence was 1/1107-1/8,646. A study based on a registry of GH users in the Piedmont region (Italy) reported the highest mean prevalence. In the included studies, the mean incidence ranged from 1/28,800 to 1/46,700 cases per year. One study reported a 20-year cumulative incidence of 127/100,000 for boys and 93/100,000 for girls. Studies were heterogeneous in terms of population (age and GHD etiology) and diagnostic criteria. As for the methodological quality of included studies, all but one study satisfied the majority of the checklist items. CONCLUSIONS: The included studies are mostly European, so the provided estimates cannot be considered global. International multicentre studies are needed to compare epidemiological estimates of GHD among different ethnical groups. Considering the considerable cost of human recombinant GH, the only available therapy to treat GHD, understanding accurate epidemiological estimates of GHD in each country is fundamental for resource allocation.
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Hormona de Crecimiento Humana , Humanos , Adolescente , Niño , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Prevalencia , Masculino , Femenino , Trastornos del Crecimiento/epidemiología , Incidencia , Enanismo Hipofisario/epidemiologíaRESUMEN
BACKGROUND: The increase in childhood obesity rates represents a serious public health problem. The project "EpPOI: Education to prevent childhood obesity" is aimed at a multidisciplinary approach to raise awareness of the importance of preventing childhood obesity through lifestyle education. METHODS: Two actions by experts were performed: an intervention with children in schools and a meeting for both parents and school staff. Participants completed a questionnaire structured as a Likert scale. RESULTS: The sample size was 96 people, and awareness of the childhood obesity problem as well as the need for obesity prevention was high among respondents. We also found great interest among participants in having more information on pediatric nutrition and physical activity, with a positive correlation with age. Furthermore, the multivariate regression model configured interest in having more information on nutrition and physical activity as an independent and statistically significant predictor of awareness of childhood obesity as a current issue. CONCLUSIONS: The results highlight the need to act on childhood obesity through lifestyle prevention strategies early in life.
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Ejercicio Físico , Obesidad Infantil , Humanos , Obesidad Infantil/prevención & control , Obesidad Infantil/epidemiología , Femenino , Masculino , Niño , Encuestas y Cuestionarios , Conocimientos, Actitudes y Práctica en Salud , Educación en Salud/métodos , Estilo de Vida , Adulto , Adolescente , Padres , Instituciones AcadémicasRESUMEN
Background: Despite the optimization of replacement therapy, adrenal crises still represent life-threatening emergencies in many children with adrenal insufficiency. Objective: We summarized current standards of clinical practice for adrenal crisis and investigated the prevalence of suspected/incipient adrenal crisis, in relation to different treatment modalities, in a group of children with adrenal insufficiency. Results: Fifty-one children were investigated. Forty-one patients (32 patients <4 yrs and 9 patients >4 yrs) used quartered non-diluted 10 mg tablets. Two patients <4 yrs used a micronized weighted formulation obtained from 10 mg tablets. Two patients <4 yrs used a liquid formulation. Six patients >4 yrs used crushed non-diluted 10 mg tablets. The overall number of episodes of adrenal crisis was 7.3/patient/yr in patients <4yrs and 4.9/patient/yr in patients >4 yrs. The mean number of hospital admissions was 0.5/patient/yr in children <4 yrs and 0.53/patient/yr in children >4 yrs. There was a wide variability in the individual number of events reported. Both children on therapy with a micronized weighted formulation reported no episode of suspected adrenal crisis during the 6-month observation period. Conclusion: Parental education on oral stress dosing and switching to parenteral hydrocortisone when necessary are the essential approaches to prevent adrenal crisis in children.
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Insuficiencia Suprarrenal , Hidrocortisona , Humanos , Niño , Lactante , Preescolar , Hidrocortisona/uso terapéutico , Enfermedad Aguda , Escolaridad , Terapia de Reemplazo de Hormonas , Insuficiencia Suprarrenal/tratamiento farmacológico , Insuficiencia Suprarrenal/epidemiología , Insuficiencia Suprarrenal/prevención & controlRESUMEN
PURPOSE: Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory disease characterized by chronic synovitis, sometimes associated with fever, rash, pericarditis and uveitis. Limited data are available concerning autoimmune diseases associated with JIA in childhood. THE AIMS OF OUR STUDY WERE: (a) evaluating the thyroid function in a group of Italian children affected by JIA; (b) identifying which Autoimmune Thyroid Diseases (ATDs) are related to JIA in this population. METHODS: A population of 51 patients with JIA was investigated. Each patient enrolled was evaluated clinically (family history for Autoimmune Diseases (ADs), personal history and physical examination). In the sample were evaluated thyroid function, inflammation's index and anti-thyroid antibodies. RESULTS: The 68.6% (35) of our patients had the oligoarticular form, 27.5% (14) had the polyarticular one, 2% (1) had systemic onset and 2% (1) had undifferentiated arthritis. We focused our attention on the differences between the first two forms. We did not find any difference on the gender prevalence (p > 0.05). A higher presence of anti-TPO antibodies was found in the polyarticular form, with a significant difference with the oligoarticular one (p = 0.032). We researched the anti-hTG antibodies (p > 0.05) and ANA for each group (p > 0.05). We found a significant prevalence of family history for ADs in the polyarticular form (p < 0.05). CONCLUSION: Our findings show the necessity to focus on thyroid function in patients with JIA. Although the oligoarticular form is the most frequent, the polyarticular form shows a higher frequency of thyroid function's alteration. This suggests the need for specific attention in polyarticular form.
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Congenital hypothyroidism (CH) is a relatively frequent congenital endocrine disorder, caused by defective production of thyroid hormones (THs) at birth. Because THs are essential for the development of normal neuronal networks, CH is also a common preventable cause of irreversible intellectual disability (ID) in children. Prolonged hypothyroidism, particularly during the THs-dependent processes of brain development in the first years of life, due to delays in diagnosis, inadequate timing and dosing of levothyroxine (l-thyroxine or l-T4), the non-compliance of families, incorrect follow-up and the interference of foods, drugs and medications affecting the absorption of l-T4, may be responsible for more severe ID. In this review we evaluate the main factors influencing levels of THs and the absorption of l-T4 in order to provide a practical guide, based on the existing literature, to allow optimal follow-up for these patients.
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Hipotiroidismo Congénito , Tiroxina , Niño , Hipotiroidismo Congénito/tratamiento farmacológico , Composición de Medicamentos , Humanos , Recién Nacido , Hormonas Tiroideas/uso terapéutico , Tiroxina/uso terapéuticoRESUMEN
Osteogenesis imperfecta/Ehlers−Danlos (OI/EDS) overlap syndrome is a recently described disorder of connective tissue, characterized by mutation of COL1A1 (17q21.33) or COL1A2 (7q21.3) genes, that are involved in α-1 and α-2 chains of type 1 collagen synthesis. The clinical spectrum of this new clinical entity is broad: patients could present a mixed phenotype that includes features of both osteogenesis imperfecta (bone fragility, long bone fractures, blue sclerae, short stature) and Ehlers−Danlos syndrome (joint hyperextensibility, soft and hyperextensible skin, abnormal wound healing, easy bruising, vascular fragility). We reported the case of a young Caucasian girl with severe short stature and a previous history of neuroblastoma, who displayed the compound phenotype of OI/EDS. Next generation sequencing was applied to the proband and her parent genome. Our patient presented a de novo heterozygous COL1A1 variant (c.3235G>A, p.Gly1079Ser), whose presence might be indicative of diagnosis of OI/EDS overlap syndrome. We also hypothesize that the association with the previous history of neuroblastoma could be influenced by the presence of COL1A1 mutation, whose role has been already described in the behavior and progression of some cancers.
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Síndrome de Ehlers-Danlos , Neuroblastoma , Osteogénesis Imperfecta , Cadena alfa 1 del Colágeno Tipo I , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Femenino , Heterocigoto , Humanos , Neuroblastoma/genética , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/genéticaRESUMEN
Objectives: We designed a multicentre open prospective randomized trial to evaluate the risk-benefit profile of two different initial treatment schemes with levothyroxine (L-T4), 10-12.5 µg/kg/day vs 12.6-15 µg/kg/day, on growth and neurodevelopmental outcomes in children with congenital hypothyroidism (CH) detected by neonatal screening to identify the best range dose to achieve optimal neurocognitive development. Design patients and methods: Children detected by neonatal screening were randomly assigned to receive an initial L-T4 dose of 10-12.5 µg/kg/day (Low) or 12.6-15 µg/kg/day (High). All patients underwent periodical clinical examination with measurement of growth parameters and measurement of TSH and FT4. Neurocognitive development was evaluated at the age of 24 months using Griffiths Mental Development Scales (GMDS) and cognitive and behavioral assessment was performed at 48 months of age using Wechsler Preschool and Primary scale of Intelligence (WIPPSI-III). The study was registered with clinicaltrials.gov (NCT05371262). Results: Treatment schemes below or above 12.5 µg/kg/day were both associated with rapid normalization of TSH and thyroid hormone levels in most patients with no differences in the risk of over- and under-treatment episodes in the first months of life. Growth parameters were normal and comparable between the two groups. Developmental quotients at 24 months of age were normal in both groups (Low 100.6 ± 15.5 vs High 96.9 ± 16.6). Likewise, at 4 years of age IQ and subtest scores were comparable between patients from Low and High (Total IQ 104.2 ± 11.4 vs 101.0 ± 20.3, Verbal IQ 103.9 ± 11.5 vs 98.7 ± 15.1, Performance IQ 105.3 ± 10.4 vs 100.3 ± 19.8). 6/45 CH patients (13.3%) showed a total IQ below 85 (73.7 ± 5.9) regardless of age at diagnosis, L-T4 starting dose, time of FT4 and TSH normalization and episodes of over and undertreatment. Worse socioeconomic status and delayed bone age at diagnosis were the only predictors of an increased risk of having suboptimal IQ at 24 and IQ at 48 months. Conclusions: Our results indicate that initial treatment with L-T4, 10-12.5 µg/kg/day vs 12.6-15 µg/kg/day, are both associated with normal growth and neurodevelopmental outcomes in children with CH detected by neonatal screening. Further studies with a long-term follow-up on a larger number of patients are needed to confirm these results. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT05371262?term=NCT05371262&draw=2&rank=1 identifer NCT05371262.
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Hipotiroidismo Congénito , Tiroxina , Preescolar , Hipotiroidismo Congénito/tratamiento farmacológico , Humanos , Estudios Prospectivos , Hormonas Tiroideas/uso terapéutico , Tirotropina , Tiroxina/uso terapéuticoRESUMEN
Background: Growth hormone deficiency (GHD) is the first and most common endocrine complication in pediatric brain tumor survivors (BTS). GHD can occur due to the presence of the tumor itself, surgery, or cranial radiotherapy (CRT). Aims: This study aimed to evaluate management and adherence to current guidelines of the Italian centers engaged in the diagnosis and follow-up of GHD patients with BTS. Methods: A multidisciplinary scientific board of pediatric endocrinologists, oncologists and radiologists with neuroimaging expertise discussed and reviewed the main issues relating to the management of GHD in pediatric BTS and developed a survey. The survey included questions relating to organizational aspects, risk factors, diagnosis, definition of stable disease, and treatment. The online survey was sent to an expanded panel of specialists dedicated to the care of pediatric BTS, distributed among the three specialty areas and throughout the country (23 Italian cities and 37 Centers). Results: The online questionnaire was completed by 86.5% (32 out of 37) of the Centers involved. Most had experience in treating these patients, reporting that they follow more than 50 BTS patients per year. Responses were analyzed descriptively and aggregated by physician specialty. Overall, the results of the survey showed some important controversies in real life adherence to the current guidelines, with discrepancies between endocrinologists and oncologists in the definition of risk factors, diagnostic work-up, decision-making processes and safety. Furthermore, there was no agreement on the neuroimaging definition of stable oncological disease and how to manage growth hormone therapy in patients with residual tumor and GHD. Conclusions: The results of the first Italian national survey on the management of GHD in BTS highlighted the difference in management on some important issues. The time to start and stop rhGH treatment represent areas of major uncertainty. The definition of stable disease remains critical and represents a gap in knowledge that must be addressed within the international guidelines in order to increase height and to improve metabolic and quality of life outcomes in cancer survivors with GHD.
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Neoplasias Encefálicas , Enanismo Hipofisario , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Niño , Testimonio de Experto , Hormona del Crecimiento , Humanos , Italia/epidemiología , Calidad de Vida , Encuestas y Cuestionarios , SobrevivientesRESUMEN
BACKGROUND/OBJECTIVES: The present study aimed to validate the Italian version of the Hyperphagia Questionnaire (HQ), a 11-items questionnaire developed to assess hyperphagia in individuals with Prader-Willi syndrome (PWS). This is a complex neurodevelopmental disorder characterized by endocrine dysfunction, hypotonia, intellectual disability, psychiatric disorders and obesity. METHODS: Parents of 219 individuals with PWS (age range 3-54 years; Mage = 17.90; 108 Males), recruited in 12 hospitals in Italy responded to HQ during routine visits. In function of the level of analyses the sample was divided into two subgroups (<18> years) or into four age-subgroups (2.5-4.5; 4.5-8; 8-18; >18 years) corresponding to different clinical stages. RESULTS: Confirmatory factor analysis (CFA) confirmed the three hyperphagic subdimensions of the original structure (behavior, drive, and severity), but one item was dropped out, reducing the final version to 10 items. Using multi-group CFA, HQ showed satisfactory indexes of measurement invariance by age. Good indexes of internal consistency (Cronbach's alpha and McDonald's Omega coefficients) were found for each subdimension. The three hyperphagia subdimensions positively converged with other food-related measures: emotional overeating, food enjoyment, food responsiveness, and satiety responsiveness. A significant increase of all hyperphagic subdimensions was found across age groups. Higher hyperphagic levels were found in participants with higher body mass index. Hyperphagic drive differently increased in function of the interaction between age and underlying genetic mechanisms. CONCLUSION: The Italian version of the HQ is a psychometrically valid and reliable instrument for assessing hyperphagia in individuals with PWS. This tool may prove useful to evaluate the efficacy of pharmacologic and rehabilitative treatments.
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Autoimmune diseases (ADs) are characterized by a multifactorial etiology, in which genetic and environmental factors are responsible for the loss of immunological tolerance [...].
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Enfermedades Autoinmunes/genética , HumanosRESUMEN
OBJECTIVE: No data are available on advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in pediatric patients with Hashimoto's thyroiditis (HT). The present study was aimed to simultaneously evaluate serum levels of sRAGE, AGEs, and advanced oxidation protein products (AOPPs) and investigate the relationships between these oxidative stress markers and clinical and biochemical parameters of thyroid function in euthyroid children with HT. DESIGN: This is a case-control study carried out in a single university hospital center. METHODS: We enrolled 19 newly diagnosed euthyroid HT pediatric patients (3 M, 16 F; median age 12.44 years, range 6.54-15.81 years) and 16 age-, sex-, and BMI-matched healthy controls (5 M, 11 F; median age 12.83 years, range 5.68-15.07 years). None was on levothyroxine treatment. The exclusion criteria were autoimmune, inflammatory, and infection comorbidities. Patients did not differ significantly from controls with regard to lipid or for anthropometric parameters. RESULTS: sRAGE levels were significantly lower in HT patients (median 414.30 pg/mL, range 307.30-850.30 pg/mL) than in controls (561.30, 273.20-1121.60 pg/mL; p = 0.034). No differences emerged between patients and controls with regard to serum AGEs (124.25 AU/g prot, 71.98-186.72 vs. 133.90, 94.06-200.78 AU/g prot, p = 0.707) and AOPPs (1.13 nmol/mL, 0.62-1.83 vs. 1.17, 0.76-1.42 nmol/mL, p = 0.545). CONCLUSIONS: sRAGE levels were decreased in euthyroid children/adolescents at the onset of HT, suggesting that autoimmunity per se seems to play an important role in such a reduction of sRAGE, irrespective of any functional alteration. Children and adolescents suffering from HT may exhibit increased susceptibility to oxidative damage, even when in euthyroid status.
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Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/diagnóstico , Receptor para Productos Finales de Glicación Avanzada/sangre , Adolescente , Niño , Femenino , Humanos , Masculino , Proyectos PilotoRESUMEN
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.
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Estatura/efectos de los fármacos , Hormona de Crecimiento Humana/uso terapéutico , Síndrome de Noonan/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
CONTEXT: Primary adrenal insufficiency (PAI) is a rare and potentially life-threatening condition that is poorly characterized in children. OBJECTIVE: To describe causes, presentation, auxological outcome, frequency of adrenal crisis and mortality of a large cohort of children with PAI. PATIENTS AND METHODS: Data from 803 patients from 8 centers of Pediatric Endocrinology were retrospectively collected. RESULTS: The following etiologies were reported: 85% (n = 682) congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD); 3.1% (n = 25) X-linked adrenoleukodystrophy; 3.1% (n = 25) autoimmune polyglandular syndrome type 1; 2.5% (n = 20) autoimmune adrenal insufficiency; 2% (n = 16) adrenal hypoplasia congenital; 1.2% (n = 10) non-21-OHD CAH; 1% (n = 8) rare syndromes; 0.6% (n = 5) familial glucocorticoid deficiency; 0.4% (n = 3) acquired adrenal insufficiency; 9 patients (1%) did not receive diagnosis. Since 21-OHD CAH has been extensively characterized, it was not further reviewed. In 121 patients with a diagnosis other than 21-OHD CAH, the most frequent symptoms at diagnosis were fatigue (67%), hyperpigmentation (50.4%), dehydration (33%), and hypotension (31%). Elevated adrenocorticotropic hormone (96.4%) was the most common laboratory finding followed by hyponatremia (55%), hyperkalemia (32.7%), and hypoglycemia (33.7%). The median age at presentation was 6.5 ± 5.1 years (0.1-17.8 years) and the mean duration of symptoms before diagnosis was 5.6 ± 11.6 months (0-56 months) depending on etiology. Rate of adrenal crisis was 2.7 per 100 patient-years. Three patients died from the underlying disease. Adult height, evaluated in 70 patients, was -0.70 ± 1.20 standard deviation score. CONCLUSIONS: We characterized one of the largest cohorts of children with PAI aiming to improve the knowledge on diagnosis of this rare condition.
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Insuficiencia Suprarrenal/epidemiología , Adolescente , Insuficiencia Suprarrenal/congénito , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/genética , Edad de Inicio , Niño , Preescolar , Estudios de Cohortes , Comorbilidad , Diagnóstico Tardío/estadística & datos numéricos , Femenino , Humanos , Lactante , Italia/epidemiología , Masculino , Mutación , Prevalencia , Estudios RetrospectivosRESUMEN
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.