RESUMEN
PURPOSE: MKNR3 is a paternally expressed gene whose mutations are the main cause of central precocious puberty (CPP). Protein circulating levels can be easily measured, as demonstrated in idiopathic CPP and healthy controls. No data are available for patients harboring an MKRN3 mutation. Our aim was to perform MKRN3 mutation screening and to investigate if circulating protein levels could be a screening tool to identify MKRN3 mutation in CPP patients. METHODS: We enrolled 140 CPP girls and performed MKRN3 mutation analysis. Patients were stratified into two groups: idiopathic CPP (iCPP) and MKRN3 mutation-related CPP (MKRN3-CPP). Clinical characteristics were collected. Serum MKRN3 values were measured by a commercially available ELISA assay kit in MKRN3-CPP and a subgroup of 15 iCPP patients. RESULTS: We identified 5 patients with MKRN3 mutations: one was a novel mutation (p.Gln352Arg) while the others were previously reported (p.Arg328Cys, p.Arg345Cys, p.Pro160Cysfs*14, p.Cys410Ter). There was a significant difference in circulating MKRN3 values in MKRN3-CPP compared to iCPP (p < 0.001). In MKRN3-CPP, the subject harboring Pro160Cysfs*14 presented undetectable levels. Subjects carrying the missense mutations p.Arg328Cys and p.Gln352Arg showed divergent circulating protein levels, respectively 40.56 pg/mL and undetectable. The patient with the non-sense mutation reported low but measurable MKRN3 levels (12.72 pg/mL). CONCLUSIONS: MKRN3 defect in patients with CPP cannot be predicted by MKRN3 circulating levels, although those patients presented lower protein levels than iCPP. Due to the great inter-individual variability of the assay and the lack of reference values, no precise cut-off can be identified to suspect MKRN3 defect.
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Mutación , Pubertad Precoz , Ubiquitina-Proteína Ligasas , Humanos , Pubertad Precoz/genética , Pubertad Precoz/sangre , Pubertad Precoz/diagnóstico , Femenino , Ubiquitina-Proteína Ligasas/genética , Niño , Ribonucleoproteínas/genética , Ribonucleoproteínas/sangre , Preescolar , Análisis Mutacional de ADN , Estudios de Casos y Controles , Biomarcadores/sangreRESUMEN
PURPOSE: Transition from pediatric to adult care is associated with significant challenges in patients with Turner syndrome (TS). The objective of the TRansition Age Management In Turner syndrome in Italy (TRAMITI) project was to improve the care provided to patients with TS by harnessing the knowledge and expertise of various Italian centers through a Delphi-like consensus process. METHODS: A panel of 15 physicians and 1 psychologist discussed 4 key domains: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders. RESULTS: A total of 41 consensus statements were drafted. The transition from pediatric to adult care is a critical period for patients with TS, necessitating tailored approaches and early disclosure of the diagnosis to promote self-reliance and healthcare autonomy. Fertility preservation and bone health strategies are recommended to mitigate long-term complications, and psychiatric evaluations are recommended to address the increased prevalence of anxiety and depression. The consensus also addresses the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS; regular screenings and interventions are advised to manage these conditions effectively. In addition, cardiac abnormalities, including aortic dissections, require regular monitoring and early surgical intervention if certain criteria are met. CONCLUSIONS: The TRAMITI consensus statement provides valuable insights and evidence-based recommendations to guide healthcare practitioners in delivering comprehensive and patient-centered care for patients with TS. By addressing the complex medical and psychosocial aspects of the condition, this consensus aims to enhance TS management and improve the overall well-being and long-term outcomes of these individuals.
The TRansition Age Management in Turner syndrome in Italy (TRAMITI) project aims to improve care for individuals with Turner Syndrome (TS) during their transition from pediatric to adult care. A team of 15 physicians and 1 psychologist collaborated to create a comprehensive set of 41 consensus statements, covering four key areas: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders. The consensus statements highlight the importance of patient-centered care, early intervention and long-term monitoring. They emphasize a multidisciplinary approach to address the complex medical and psychosocial aspects of TS. During the critical transition period, tailored approaches and early disclosure of the diagnosis are recommended to promote self-reliance and healthcare autonomy. To mitigate long-term complications, the consensus addresses fertility preservation and bone health strategies. It also recommends psychological or psychiatric evaluations to tackle the increased prevalence of anxiety and depression in patients with TS. In addition, strategies for addressing the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS are proposed. Regular screenings and interventions are advised to effectively manage these conditions. Furthermore, cardiac abnormalities, including aortic dissections, require close monitoring and early surgical intervention if specific criteria are met. Overall, the TRAMITI consensus statement provides valuable insights and evidence-based recommendations. It offers guidance for healthcare practitioners in delivering comprehensive and patient-centered care for individuals with TS. By addressing both medical and psychosocial aspects, the consensus aims to enhance TS management and improve the well-being and long-term outcomes of those affected by this genetic disorder.
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Consenso , Transición a la Atención de Adultos , Síndrome de Turner , Humanos , Síndrome de Turner/terapia , Síndrome de Turner/psicología , Italia/epidemiología , Transición a la Atención de Adultos/normas , Transición a la Atención de Adultos/organización & administración , Adulto , Femenino , Niño , Adolescente , Técnica DelphiRESUMEN
PURPOSE: The hormonal thyroid changes related to obesity, even when in the euthyroid state, may contribute to the unfavorable cardio-metabolic profile of obese patients. In this retrospective study, we aim to investigate the biochemical thyroid changes and the association between serum TSH, FT4, FT3 and cardio-metabolic risk factors in euthyroid obese youths. METHODS: Four hundred ninety-one Caucasian euthyroid obese children and adolescents aged 9.93 ± 2.90 years were recruited. Each patient underwent clinical and auxological examination and laboratory workup including an OGTT and the measurement of thyroid function and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride to high-density lipoprotein cholesterol ratio, total cholesterol to HDL ratio, atherogenic index of plasma, insulinogenic index, area under the glucose and insulin curves were calculated. RESULTS: We found that TSH was positively correlated with BMI-SDS values and significantly associated with hypercholesterolemia and hyperinsulinemia; FT4 resulted negatively correlated with BMI-SDS; FT3 was positively correlated with BMI-SDS and the area under the curve of insulin and negatively correlated with HDL. FT3 and FT4 resulted significantly associated with severe obesity. In addition, children with high-normal TSH values showed higher triglyceride to high-density lipoprotein cholesterol ratio values than those with normal TSH levels. CONCLUSIONS: Our data showed that thyroid hormones could influence obesity, lipid and glycemic parameters in euthyroid youths. These findings could carry implications regarding optimal TSH levels in obese children and confirm the importance of evaluating the thyroid function as possible adjunctive cardio-metabolic risk factor related to obesity.
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Resistencia a la Insulina , Obesidad Infantil , Adolescente , Humanos , Niño , Estudios Retrospectivos , Obesidad Infantil/complicaciones , Insulina , Triglicéridos , HDL-Colesterol , Tirotropina , Tiroxina , TriyodotironinaRESUMEN
PURPOSE/METHODS: Prader-Willi syndrome (PWS) is a rare genetic disorder displaying different clinical features, including obesity and bone impairment. LIGHT/TNFSF14 is a cytokine produced by immune cells affecting both fat and bone metabolism. The present study aimed to evaluate LIGHT serum levels in 28 children and 52 adult PWS patients compared to age and sex-matched controls, as well as correlations with parameters of bone and fat metabolism. RESULTS: Median serum LIGHT levels were significantly increased in pediatric PWS with respect to controls [255.82 (284.43) pg/ml vs 168.11 (76.23) pg/ml, p ≤ 0.02] as well as in adult PWS compared to controls [296.85 (895.95) pg/ml vs 134.18 (141.18) pg/ml, p ≤ 0.001]. In pediatric PWS, LIGHT levels were positively correlated with weight-SDS, height-SDS, and glucose levels, and negatively with total 25 (OH) vitamin D, cholesterol, LDL cholesterol and triglycerides. Additionally, LIGHT levels were negatively correlated with total BMD and fat mass. In adult PWS, LIGHT levels were positively correlated with weight, HDL cholesterol and PTH, and negatively with glucose, insulin, HOMA-IR, total cholesterol, LDL cholesterol, triglycerides, calcium, phosphorus, 25(OH)Vitamin D as well as with instrumental parameters of bone and fat quality. Consistently, multiple regression analysis showed that LIGHT serum levels in pediatric and adult PWS were predicted by different parameters including 25 (OH) Vitamin D as well as DXA parameters of bone and fat quality. CONCLUSIONS: In PWS children and adults the high levels of LIGHT could represent a marker of the altered bone and fat metabolism.
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Síndrome de Prader-Willi , Adulto , Humanos , Niño , LDL-Colesterol , Vitamina D , Vitaminas , Glucosa , Triglicéridos , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis TumoralRESUMEN
PURPOSE: We aimed to investigate a cohort of female and male patients with idiopathic central precocious puberty (CPP), negative for Makorin Ring Finger Protein 3 (MKRN3) defect, by molecular screening for Delta-like 1 homolog (DLK1) defects. DLK1 is an imprinted gene, whose mutations have been described as a rare cause of CPP in girls and adult women with precocious menarche, obesity and metabolic derangement. METHODS: We enrolled 14 girls with familial CPP and 13 boys with familial or sporadic CPP from multiple academic hospital centers. Gene sequencing of DLK1 gene was performed. Circulating levels of DLK1 were measured and clinical and biochemical characteristics were described in those with DLK1 defects. RESULTS: A novel heterozygous mutation in DLK1, c.288_289insC (p.Cys97Leufs*16), was identified in a male proband, his sister and their father. Age at onset of puberty was in line with previous reports in the girl and 8 years in the boy. The father with untreated CPP showed short stature. No metabolic derangement was present in the father except hypercholesterolemia. Undetectable Dlk1 serum levels indicated the complete lack of protein production in the three affected patients. CONCLUSION: A DLK1 defect has been identified for the first time in a boy, underscoring the importance of genetic testing in males with idiopathic or sporadic CPP. The short stature reported by his untreated father suggests the need for timely diagnosis and treatment of subjects with DLK1 defects.
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Enanismo , Maduración Sexual , Masculino , Femenino , Humanos , Ubiquitina-Proteína Ligasas/genética , Mutación , Proteínas de la Membrana/genética , Fenotipo , Proteínas de Unión al Calcio/genéticaRESUMEN
BACKGROUND AND AIM: Screening for pediatric hypertension (HTN) is based on several measurements of blood pressure (BP) in different visits. We aimed to assess its feasibility in outpatient youths with overweight/obesity (OW/OB) in terms of adherence to two-repeated measurements of BP and to show the features of youths who missed the follow-up and the predictive role of clinical and/or anamnestic features on confirmed HTN. METHODS AND RESULTS: Six hundred, eighty-eight youths (9-17 years) with OW/OB, consecutively recruited, underwent a first measurement of BP. Those exhibiting BP levels within the hypertensive range were invited to repeat a second measurement within 1-2 weeks. Confirmed HTN was diagnosed when BP in the hypertensive range was confirmed at the second measurement. At entry, 174 youths (25.1%) were classified as hypertensive. At the second visit, 66 youths (37.9%) were lost to follow-up. In the remaining 108 participants, HTN was confirmed in 59, so that the prevalence of confirmed HTN was 9.5% in the overall sample; it was higher in adolescents than children (15.9% vs 6.8%, P = 0.001). HTN at first visit showed the best sensitivity (100%) and a good specificity (91%) for confirmed HTN. The association of HTN at first visit plus familial HTN showed high specificity (98%) and positive predictive value of 70%. CONCLUSION: The high drop-out rate confirms the real difficulty to obtain a complete diagnostic follow up in the obese population. Information about family history of HTN may assist pediatricians in identifying those children who are at higher risk of confirmed HTN.
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Hipertensión , Adolescente , Presión Sanguínea , Determinación de la Presión Sanguínea , Niño , Estudios de Factibilidad , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Obesidad/diagnóstico , Obesidad/epidemiología , Sobrepeso/diagnósticoRESUMEN
PURPOSE: Girls affected with Turner syndrome (TS) present with low bone mineral density (BMD) and osteopenia/osteoporosis. Thus, they have an increased risk to develop fractures compared to normal population. The aim of this study was to deepen the pathophysiology of skeletal fragility in TS subjects by evaluating the serum levels of Dickkopf-1 (DKK-1) and sclerostin, main regulators of bone mass, as well as the percentage of circulating osteoblast precursors (OCPs). METHODS: Thirty-four TS girls and 24 controls were recruited. All subjects underwent anthropometric measures (height, weight, body mass index-BMI). A peripheral venous blood sample was collected to determine serum levels of active intact parathyroid hormone (PTH), 25-OH vitamin D, calcium, phosphorus, bone alkaline phosphatase (bALP), osteocalcin, sclerostin, DKK-1, RANKL and OPG. OCPs were detected by flow cytometry. In TS subjects bone mineralization was measured at lumbar spine by dual energy X-ray absorptiometry (DXA). RESULTS: bALP, 25-OH Vitamin D, and osteocalcin levels were significant lower in TS subjects than in the controls. Statistically significant higher levels of sclerostin, DKK-1 and RANKL were measured in patients compared with the controls. The percentage of OCPs did not show significant differences between patients and controls. Sclerostin and DKK-1 levels were related with anthropometric parameters, bone metabolism markers, HRT, rhGH therapy, RANKL and lumbar BMAD-Z-score. CONCLUSION: TS patients showed higher levels of sclerostin and DKK-1 than controls which can be related to HRT, and to reduced bone formation markers as well as the increased bone resorption activity.
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Proteínas Adaptadoras Transductoras de Señales , Péptidos y Proteínas de Señalización Intercelular , Osteoporosis , Síndrome de Turner , Vía de Señalización Wnt , Proteínas Adaptadoras Transductoras de Señales/sangre , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/metabolismo , Biomarcadores/metabolismo , Densidad Ósea , Femenino , Marcadores Genéticos , Humanos , Péptidos y Proteínas de Señalización Intercelular/sangre , Masculino , Osteocalcina/metabolismo , Osteoporosis/sangre , Osteoporosis/metabolismo , Osteoporosis/patología , Síndrome de Turner/sangre , Síndrome de Turner/metabolismo , Síndrome de Turner/patología , Vitamina D/sangreRESUMEN
PURPOSE: To assess the prevalence of pre-diabetes phenotypes, i.e., impaired fasting glucose (IFG), impaired glucose tolerance (IGT), increased HbA1c (IA1c), and their association with metabolic profile and atherogenic lipid profile in youths with overweight/obesity (OW/OB). METHODS: This cross-sectional study analyzed data of 1549 youths (5-18 years) with OW/OB followed in nine Italian centers between 2016 and 2020. Fasting and post-load measurements of glucose, insulin, and HbA1c were available. Insulin resistance (IR) was estimated by HOMA-IR and insulin sensitivity (IS) by reciprocal of fasting insulin. The atherogenic lipid profile was assessed by triglycerides-to-HDL ratio or cholesterol-to-HDL ratio. Insulinogenic index was available in 939 youths, in whom the disposition index was calculated. RESULTS: The prevalence of overall pre-diabetes, IFG, IGT and IA1c was 27.6%, 10.2%, 8% and 16.3%, respectively. Analyzing each isolated phenotype, IGT exhibited two- to three-fold higher odds ratio of family history of diabetes, and worse metabolic and atherogenic lipid profile vs normoglycemic youths; IFG was associated only with IR, while IA1c showed a metabolic and atherogenic lipid profile intermediate between IGT and IFG. CONCLUSION: Prevalence of pre-diabetes was high and IA1c was the most prevalent phenotype in Italian youths with OW/OB. The IGT phenotype showed the worst metabolic and atherogenic lipid profile, followed by IA1c. More studies are needed to assess whether HbA1c may help improving the prediction of diabetes.
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Intolerancia a la Glucosa , Resistencia a la Insulina , Estado Prediabético , Glucemia/metabolismo , Estudios Transversales , Ayuno , Intolerancia a la Glucosa/epidemiología , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Insulina , Obesidad/epidemiología , Sobrepeso/epidemiología , Fenotipo , Estado Prediabético/epidemiologíaRESUMEN
AIMS: To evaluate the prevalence of diabetes and impaired fasting glucose in Poland in 2013-2014 and to determine the temporal trends between 2003-2005 and 2013-2014. METHODS: A questionnaire survey was conducted in a representative sample of Polish adults, complemented by anthropometric and fasting plasma glucose measurements. The research was part of the national cross-sectional WOBASZ study. Diabetes was assessed as self-reported or screened (fasting plasma glucose level ≥ 7 mmol/l, based on one blood sample). RESULTS: In the years 2013-2014 among 5694 participants aged 20-74 years, 6.0% (95% CI 5.4-6.6) reported a previous diagnosis of diabetes (5.8% in women and 6.2% in men). In addition, 2.4% of the participants (95% CI 2.0-2.8) without a previous diagnosis of diabetes (1.8% of women and 3.1% of men) had a fasting blood glucose level ≥7.0 mmol/l in a single measurement. In a single measurement, 18.4% of the participants (95% CI 17.4-19.4; 13.2% of women and 23.8% of men) had impaired fasting glucose. The prevalence of dysglycaemia in the WOBASZ II study was significantly higher compared to the WOBASZ I study findings from 2003-2005, increased from 6.6% to 8.4% for diabetes and from 9.3% to 18.4% for impaired fasting glucose (after age and sex standardization to the 2013 Polish population). CONCLUSIONS: The prevalence of diabetes in Poland is similar to that observed in other European populations and has increased significantly over the last decade.
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Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Estado Prediabético/epidemiología , Adulto , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ayuno , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Estado Prediabético/metabolismo , Prevalencia , Enfermedades no Diagnosticadas/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Due to the lack of specific pediatric studies, no data are available about natural history of endogenous subclinical hyperthyroidism (SH) in childhood. AIMS: (a) To investigate for the first time the natural history of SH [suppressed thyrotropin (TSH) and normal free thyroxine free thyroxine (FT4) levels] when presenting as initial manifestation of Hashimoto's thyroiditis (HT) in childhood (group A); (b) to compare spontaneous evolution of HT-related SH with that observed in age-matched patients with HT-related frank hyperthyroidism (suppressed TSH and elevated FT4 levels), i.e., Hashitoxicosis Htx (group B). RESULTS: In the 11 patients of group A, TSH normalization spontaneously occurred 1-24 months after diagnosis, while in the 10 patients of group B it occurred 3-9 months after diagnosis, with no differences between the 2 groups in terms of time interval from entry to TSH normalization. In group A, this time interval was related to baseline thyroid peroxidase antibodies (r=0.78, p = 0.04). During follow-up, eight patients of each group remained euthyroid, whereas two became hypothyroid (in both groups) and one developed Graves' disease (in group A). CONCLUSION: (a) HT should be included among the causes of endogenous SH in pediatric age; (b) in children with HT-related SH, spontaneous normalization of TSH levels occurs within the first 24 months after diagnosis, as well as in age-matched patients with Htx; (c) in both these conditions, a further deterioration of thyroid function might re-present in some patients during follow-up; (d) Ht-related SH and Htx might be possibly seen as different biochemical stages along the same continuum.
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Enfermedad de Hashimoto/complicaciones , Hipertiroidismo/diagnóstico , Adolescente , Autoanticuerpos/sangre , Niño , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Hipertiroidismo/etiología , Masculino , Pronóstico , Estudios Prospectivos , Hormonas Tiroideas/sangreRESUMEN
BACKGROUND: Numerous studies have shown that GH, in addition to promoting linear growth, exerts a key role in many metabolic processes. However, there are only few studies aiming at evaluating the metabolic panel of children with GH deficiency (GHD). The aims of the study were: to verify the presence of metabolic alterations in GHD children in comparison with age-matched controls and to check the possible effects of two year GH therapy on the metabolic parameters in GHD. STUDY DESIGN: cross-sectional and prospective; one center experience POPULATION AND METHODS: We enrolled 32 pediatric GHD patients (group A) and 33 sex- and age-matched healthy controls (group B). Baseline serum assays (lipid, insulin, glucose) were performed in both groups. GHD children underwent replacement therapy with GH. The same assays were repeated after 12 and 24 months of GH treatment. RESULTS: No differences, in basal assays were found between the two groups. In group A, after initiation of GH, there was a significant increase of basal insulin and HOMA- insulin resistance (IR) index (p <0.001). In children with severe GHD (peak GH <3 ng / ml), after beginning of GH therapy a significant improvement in the lipid profile was found (p < 0.05). CONCLUSIONS: a) At the time of diagnosis GHD children had a metabolic picture that was not different from non- GHD group; b) in children with severe GHD, the metabolic profile showed a trend towards at improvement after the initiation of replacement therapy with GH, with beneficial effects in terms of total cholesterol, LDL cholesterol and cardiovascular risk indices; c) GHD patients with unfavorable metabolic profile (high BMI and hypercholestorolemia) need a monitoring of glucose metabolism by periodical evaluations of insulin and HOMA - IR.
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Trastornos del Crecimiento/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/métodos , Hormona de Crecimiento Humana/uso terapéutico , Adolescente , Enfermedades Cardiovasculares/etiología , Estudios de Casos y Controles , Niño , Preescolar , Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Femenino , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/farmacología , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Increased artery intima-media thickness (IMT) was found in adults with classical congenital adrenal hyperplasia (CAH). No data are available in patients with non-classical (NC) CAH. AIMS: To evaluate IMT in adolescents with classical and NC CAH and to compare the results with those recorded in a control population. PATIENTS AND METHODS: Eighteen adolescents with either classical (Subgroup A1) or NC CAH (Subgroup A2) were compared with 16 controls (Group B). All subjects underwent IMT ultrasonography measurement at different sites; results were correlated with clinical, metabolic, and insulin resistance (IR) data. RESULTS: When compared with Group B, both subgroups exhibited higher IMT values at all sites. No differences were found between classical and NC CAH. Univariate analysis of factors impacting on IMT of CAH patients demonstrated that: a) abdominal aorta (AA) IMT was positively correlated with cumulative glucocorticoid doses, triglyceride serum levels, and diastolic blood pressure SD score and negatively with androstenendione and ACTH levels; b) common carotid (CC) IMT was positively associated with triglycerides and triglyceride/HDL ratio. At multiple regression analysis, the independent positive predictors of AA and CC IMT were respectively triglyceride levels and triglyceride/HDL ratio. CONCLUSIONS: a) Even adolescents with NC CAH and not only those with classical form may be at higher risk of artery alterations; b) this risk is not necessarily associated with either obesity or waist/height ratio or dyslipidemia; c) an important role in the pathogenesis of artery alterations in CAH may be played by intermittent iatrogenic hypercortisolism and secondary IR.
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Hiperplasia Suprarrenal Congénita/complicaciones , Grosor Intima-Media Carotídeo , Adolescente , Hiperplasia Suprarrenal Congénita/sangre , Hiperplasia Suprarrenal Congénita/patología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Pronóstico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
A prepubescent 11 year-old girl came to our attention for short stature. Auxological evaluation showed peculiar phenotype. In order to exclude Turner syndrome standard karyotype was performed with normal result. Because of anemia and selective deficiency of the erythroid lineage further investigations were performed and a diagnosis of Blackfan-Diamond anemia was made.
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Anemia de Diamond-Blackfan/diagnóstico , Síndrome de Turner/diagnóstico , Anomalías Múltiples/etiología , Anomalías Múltiples/fisiopatología , Estatura , Niño , Femenino , Humanos , CariotipoRESUMEN
UNLABELLED: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Children typically show ROHHAD after the first years of life with rapid weight gain and subsequently autonomic nervous system dysregulation (altered pain perception, pupillary dysfunction, hypothermia and bradycardia); alveolar hypoventilation with risk of cardiorespiratory arrest and hypothalamic dysfunction (central diabetes insipidus, hypothyroidism, growth hormone and corticotrophin deficiency). Tumours of neural crest origin, such as ganglioneuroblastoma and ganglioneuronoma, are reported in 33% of the patients and may be found in the chest or abdomen. Here we describe two girls who presented with rapid weight gain, at the age of 5 and 9 years respectively. The first was admitted due to obesity and central hypothyroidism. After two months she rapidly developed a clinical picture characterized by thermal dysregulation, hypodipsia and severe hypernatriemia, hypertrigliceridemia, alveolar hypoventilation supported by mechanical ventilation. The second presented with rapid-onset obesity and a mild hyperprolactinemia. After three months of follow-up she was admitted due to a clinical picture of hypothermia, seizures and hyponatremia. Subsequentely she developed altered water balance (severe hypernatremia) and severe hypoventilation. Chest CT and MR imaging showed a posterior mediastinal mass. Endocrinological investigation showed corticotrophin deficiency and central hypothyroidism treated with specific replacement therapies. CONCLUSIONS: On the basis of our experiences we can infer that it is necessary perform specific further investigations of hypothalamic function in all the children with rapid onset obesity in order to early prevent the catastrophic consequences that may occur in this syndrome.
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Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades Hipotalámicas/diagnóstico , Hipoventilación/diagnóstico , Obesidad/diagnóstico , Niño , Preescolar , Femenino , Humanos , SíndromeRESUMEN
Introduction: Central precocious puberty (CPP) results from premature activation of hypothalamic-pituitary-gonadal axis, with the consequent increase of gonadotropin-releasing hormone (GnRH); GnRH agonists (GnRHa) represent the gold-standard therapy in children with CPP although their use might be responsible for pituitary GnRH receptors down-regulation, that in turn suppresses luteinizing hormone (LH) and follicle stimulating hormone (FSH) and blocks of gonadal sex hormones release. The most prescribed GnRHa in the clinical practice are leuprolide and triptorelin, whose use is generally safe and well tolerated; however, mild menopausal-like side effects could appear. The aim of the present study was to investigate and compare the efficacy and tolerability profile of leuprolide and triptorelin in CPP patients. Methods: 110 girls affected by CPP were enrolled in this retrospective study, carried out from 2018 to 2020. The enrolled patients received leuprolide (n = 48) or triptorelin (n = 62). Efficacy was investigated by the means of clinical parameters and radiological changes and side effects were also recorded to evaluate the possible relationship between the two GnRHa treatments and side effects appearance. Results: At baseline triptorelin patients had significantly higher LH and LH peak levels than leuprolide patients, whereas no significant difference in other patient characteristics was observed between the two groups. The leuprolide treatment lasted 971 days [790-1,171 days] while the duration of triptorelin administration was 792 days [760-1,003 days] (p < 0.001). Overall 46 (41.8%) of the studied patients reported mild menopausal-like symptoms: among these 27 were treated with triptorelin and 19 with leuprolide (p = 0.558). Patients treated with triptorelin, or leuprolide showed headache (27.4% vs. 16.7%), mood swings (12.9% vs. 16.7%), increased appetite (12.9% vs. 18.8%) and nausea (1.6% vs. 10.4%) respectively. Moreover, the onset of side effects appearance related to GnRHa therapy significantly reduces with the increase of the initial bone age (p = 0.038). Conclusion: Leuprolide and triptorelin treatment appear to be effective and safe without significant difference between the two drugs in term of efficacy and tolerability, making both good options for treating CPP.
RESUMEN
BACKGROUND: Allopregnanolone, a neuroactive steroid mainly secreted by adrenals and gonads, is a hormone that seems to play a role in precocious puberty, as demonstrated by its high baseline levels found in girls with central precocious puberty (CPP). Allopregnanolone concentrations significantly increase after GnRH and ACTH stimulation test suggesting both its ovarian and adrenal production. AIM: Aim of this study was to evaluate allopregnanolone concentrations after GnRH and GnRH agonist analog stimulation test in girls with CPP to better establish its secretion source. SUBJECTS AND METHODS: Gonadotropins and steroid hormones were evaluated in different days after GnRH and triptorelin stimulation test in 15 CPP girls. RESULTS: After GnRH stimulation, LH, FSH, and allopregnanolone concentrations significantly increased (p<0.05). After triptorelin administration LH, FSH, estradiol and DHEAS levels significantly increased (p<0.05), while allopregnanolone concentrations significantly decreased (1.08±0.24 vs 0.87±0.28 nmol/l; p=0.003). CONCLUSIONS: The different response of allopregnanolone to GnRH and GnRH agonist analog might reflect the agonist and antagonist action exerted by these secretagogues. Our data suggest the prevalent gonadal allopregnanolone production in CPP subjects and the usefulness of its measurement in the diagnosis of CPP.
Asunto(s)
Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/uso terapéutico , Pruebas de Función Hipofisaria/métodos , Pregnanolona/sangre , Pubertad Precoz/diagnóstico , Pamoato de Triptorelina/uso terapéutico , Determinación de la Edad por el Esqueleto , Niño , Preescolar , Regulación hacia Abajo , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Genitales Femeninos/diagnóstico por imagen , Humanos , Hormona Luteinizante/sangre , Pregnanolona/metabolismo , Pubertad Precoz/sangre , Pubertad Precoz/metabolismoRESUMEN
BACKGROUND: The social consequences of COVID-19 pandemic are universally known. In particular, the pediatric population is dealing with a radical lifestyle change. For some risk categories, such as overweight or obese children, the impact of home confinement has been greater than for others. The increased sedentary life, the wrong diet and social distancing have stopped the chance of losing weight. The aims of this study were to analyse the impact of COVID-19 lockdown on the behavior changes in a obese pediatric population and to explore the correlation between the new lifestyle and the level of parental instruction. METHODS: Data show features of 40 obese and overweight pediatric patients of our Clinic in Messina (Italy). We evaluated weight, height, BMI and other biochemical parameters: total cholesterol, HDL, LDL, triglyceride, transaminases, glycemia and insulinemia. After the lockdown, we contacted all patients in order to get some information about diet, physical activity and sedentary lifestyle changes in correlation to the level of their parents' instruction. Additionally, we also evaluated 20 children twice from a clinical and laboratory perspective. RESULTS: The study showed an increase of daily meals during COVID-19 lockdown (3.2 ± 0.4 vs 5 ± 1, P < 0.001). In particular, children whose parents have primary school diploma ate a greater significant number of meals during the lockdown, compared to those who have parents with secondary school diploma (P = 0.0019). In addition, the 95% of patients did low physical activity during the lockdown and the 97.5% spent more time in sedentary activity. Even if BMI's values don't show significant differences, they have increased after the lockdown. We didn't find any correlation between biochemical parameters before and after the lockdown. CONCLUSION: The lockdown has had bad consequences on good style of life's maintenance in overweight and obese children. The absence of a significant correlation between the worsening of biochemical parameters and the lockdown doesn't allow to exclude any long-term consequences. It's safe to assume that, if the hours spent in sedentary activity and the number of meals don't diminish, there will probably repercussion on the biochemical parameters.
Asunto(s)
COVID-19/epidemiología , Control de Enfermedades Transmisibles/métodos , Ejercicio Físico/fisiología , Estilo de Vida , Sobrepeso/epidemiología , Obesidad Infantil/epidemiología , Cuarentena/métodos , Adolescente , Índice de Masa Corporal , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Italia/epidemiología , Masculino , Pandemias , Obesidad Infantil/fisiopatología , Obesidad Infantil/psicología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
UNLABELLED: The aim of the present study was to retrospectively re-evaluate a population of selected infants with congenital hypothyroidism (CH), in order to investigate whether sexual dimorphism affects: a) CH etiology; b) its biochemical severity at the time of screening and recall; c) patients' biochemical response to replacement treatment during the 1st yr of life; d) their bone maturation (BM) at birth; e) their psychomotor status at 1 yr. This retrospective study covers 192 infants (116 females) with persistent CH who were selected from a larger population of CH patients identified during a 10-yr period (1990-1999) by the screening programs of 5 northern, central, and southern regions of Italy. Thirty boys (39.5%) and 66 girls (56.9%) were found to have ectopia, whereas the remaining 46 boys and 50 girls exhibited the other causes of CH. When compared with the prevalence of the remaining causes that of ectopia was significantly higher in girls than in boys (66/116 vs 30/76; chi2=5.57, p<0.025), and sex ratio in ectopia was significantly different also compared with the orthotopic gland group only (66/84 vs 30/51; chi2=6.02, p<0.025). No differences between males and females were detected in the groups with either athyreosis or orthotopic gland. In no groups were there differences between sexes for gestational age, birth auxological data, percentage of newborns with bone retardation or developmental quotient at 1 yr. Thyroid tests at birth, age at TSH normalization and average thyroid tests under L-T4 treatment during the 1st yr did not differ between sexes in any of the groups. CONCLUSIONS: a) in the Italian population sexual dimorphism affects pre-natal thyroid migration but neither biochemical severity of ectopia, nor pre-natal bone maturation and psychomotor development; b) girls with CH do not require higher doses of initial therapy in order to achieve TSH normalization; c) future developmental and molecular studies on ectopia etiology in CH need to take into account the effect of sexual dimorphism.