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Background and Objectives: bLH is considered an excellent biochemical predictor of CPP. However, its utilization in clinical practice shows some uncertainties. This study aims to evaluate the diagnostic power of bLH and propose a diagnostic algorithm for CPP. Materials and Methods: We conducted a monocentric cohort retrospective study evaluating all females referred for suspicion of CPP between 1 January 2017 and 31 December 2020 who underwent a GnRH test. Auxological, hormonal, and instrumental data were collected, including pelvic ultrasonography and bone age (BA) assessment. Simple linear regression, t-test, and ROC tests were utilized to study the diagnostic value of basal hormone levels. Two hundred thirteen girls were included in the study. They were subdivided into two groups according to the results of the GnRH test: Group 1, with LH peak > 5 IU/L (pubertal) and 79 patients (37%), and Group 2, with an LH peak ≤ 5 IU/L (prepubertal) and 134 patients (63%). Results: The ROC curve showed that bLH level > 1.5 Ul/L best predicts a pubertal response to the GnRH test (AUC 0.8821, accuracy 82%), with low sensitivity (34%). The multivariate analysis found that bLH > 0.5 IU/L, basal FSH (bFSH) > 3.5 IU/L, bLH/bFSH ratio > 0.16, BA advancement > 1.7 years, uterine volume > 3.6 mL, longitudinal uterine diameter > 41 mm, and the presence of endometrial rhyme were significantly associated with a pubertal response at the GnRH test. An algorithm based on these features was created, and its application would reduce the number of GnRH tests by 34%. Overall, 96.2% of Group 1 patients reached the LH peak at the 30th minute of the GnRH test, supporting the hypothesis that the GnRH test duration could be reduced to 30 min. Conclusions: Morning bLH > 1.5 IU/L could be carefully used as a diagnostic predictor of CPP. The GnRH test, even reduced to 30 min, could be reserved for girls who show low intermediate morning bLH and specific clinical signs of pubertal development.
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Hormona Luteinizante , Pubertad Precoz , Femenino , Humanos , Hormona Folículo Estimulante , Pubertad Precoz/diagnóstico , Estudios Retrospectivos , Hormona Liberadora de GonadotropinaRESUMEN
PURPOSE: We aimed to evaluate the near-final height (nFHt) in a large cohort of pediatricpatients with growth hormone deficiency (GHD) and to elaborate a new predictive method of nFHt. METHODS: We recruited GHD patients diagnosed between 1987 and 2014 and followed-up until nFHt. To predict the values of nFHt, each predictor was run in a univariable spline. RESULTS: We enrolled 1051 patients. Pre-treatment height was -2.43 SDS, lower than parental height (THt) (-1.09 SDS, p < 0.001). The dose of recombinant human GH (rhGH) was 0.21mg/kg/week at start of treatment. nFHt was -1.08 SDS (height gain 1.27 SDS), higher than pre-treatment height (p < 0.001) and comparable to THt. 1.6% of the patients were shorter than -2 SDS from THt. The rhGH dose at nFHt was 0.19 mg/kg/week, lower than at the start (p < 0.001). The polynomial regression showed that nFHt was affected by gender, THt, age at puberty, height at puberty, age at the end of treatment (F = 325.37, p < 0.0001, R2 87.2%). CONCLUSION: This large national study shows that GHD children can reach their THt. The rhGH/kg/day dose significantly decreased from the start to the end of the treatment. Our model suggests the importance of a timely diagnosis, possibly before puberty, the beneficial effect of long-term treatment with rhGH, and the key-role of THt. Our prediction model has a very acceptable error compared to the majority of other published studies.
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Enanismo Hipofisario , Hormona de Crecimiento Humana , Estatura , Niño , Estudios de Cohortes , Enanismo Hipofisario/diagnóstico , Enanismo Hipofisario/tratamiento farmacológico , Enanismo Hipofisario/epidemiología , Hormona del Crecimiento/uso terapéutico , Humanos , PubertadRESUMEN
BACKGROUND AND AIMS: Phenylketonuria (PKU)-affected women may become pregnant, and dietary phenylalanine (Phe) intake must be adjusted according to Phe tolerance. We report our experience with maternal PKU in relation to genotype PKU heterogeneity. METHODS AND RESULTS: A total of 10 pregnancies in 7 PKU women (7 different genotypes) were followed up as part of personalized care. Phe tolerance during preconception and pregnancy was assessed by strict dietary control and weekly Phe measurement (blood spots) in relation to genotype. Most women had stopped PKU diet during childhood or adolescence and six pregnancies were unplanned; a phenylalanine-restricted diet was reinstituted soon after conception. Women were classified according to their Phe levels at birth screening and genotype. Phe tolerance increased systematically in the course of pregnancy in all cases, but the increase was different in subjects with classic PKU (cPKU) when compared with cases with mild hyperphenylalaninemia (mHPA), both on average (+297 mg/day in cPKU vs. 597 in mHPA; P = 0.017) and as percentage (+107% in cPKU vs. +17% in mHPA). Notably, Phe tolerance also varied in the same women in the course of different pregnancies, when body weight gain was also different. Two newborns from the same cPKU mother (unplanned pregnancies on free diet) were affected by congenital alterations. CONCLUSIONS: Several factors influence metabolic phenotype in maternal PKU, to an unpredictable extent even in the same woman. The number of maternal PKU cases is growing in dedicated Nutrition Units, and the burden associated with careful management of this condition for the health care system should be adequately considered.
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Dieta con Restricción de Proteínas , Fenilalanina Hidroxilasa/genética , Fenilalanina/administración & dosificación , Fenilcetonuria Materna/dietoterapia , Adulto , Femenino , Retardo del Crecimiento Fetal/etiología , Predisposición Genética a la Enfermedad , Ganancia de Peso Gestacional , Cardiopatías Congénitas/etiología , Humanos , Nacimiento Vivo , Fenotipo , Fenilalanina/efectos adversos , Fenilalanina Hidroxilasa/deficiencia , Fenilcetonuria Materna/diagnóstico , Fenilcetonuria Materna/genética , Embarazo , Factores de Riesgo , Riñón Único/etiología , Resultado del Tratamiento , Adulto JovenRESUMEN
Congenital hypothyroidism (CH), the most frequent form of preventable mental retardation, is predicted to have a relevant genetic origin. However, CH is frequently reported to be sporadic and candidate gene variations were found in <10% of the investigated patients. Here, we characterize the involvement of 11 candidate genes through a systematic Next Generation Sequencing (NGS) analysis. The NGS was performed in 177 unrelated CH patients (94 gland-in-situ; 83 dysgenesis) and in 3,538 control subjects. Non-synonymous or splicing rare variants (MAF < 0.01) were accepted, and their functional impact was predicted by a comprehensive bioinformatic approach and co-segregation studies. The frequency of variations in cases and controls was extended to 18 CH-unrelated genes. At least one rare variant was accepted in 103/177 patients. Monogenic recessive forms of the disease were found in five cases, but oligogenic involvement was detected in 39 patients. The 167 variations were found to affect all genes independently of the CH phenotype. These findings were replicated in an independent cohort of additional 145 CH cases. When compared to 3,538 controls, the CH population was significantly enriched with disrupting variants in the candidate genes (P = 5.5 × 10-7), but not with rare variations in CH-unrelated genes. Co-segregation studies of the hypothyroid phenotype with multiple gene variants in several pedigrees confirmed the potential oligogenic origin of CH. The systematic NGS approach reveals the frequent combination of rare variations in morphogenetic or functional candidate genes in CH patients independently of phenotype. The oligogenic origin represents a suitable explanation for the frequent sporadic CH occurrence.
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Hipotiroidismo Congénito/genética , Estudios de Cohortes , Biología Computacional/métodos , Hipotiroidismo Congénito/metabolismo , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Italia , Masculino , Herencia Multifactorial/genética , Mutación , Linaje , FenotipoRESUMEN
BACKGROUND: The aim of this study is to investigate free carnitine (C0) and total acylcarnitine levels (AC) in preterm infants with BW < 1800 g and the relationship with neonatal and perinatal factors. METHODS: Ninety-three thousand two hundred and ninety-three newborns were screened between 2011 and 2013. Dried blood samples (DBS) were collected at 48-72 h, 14, and 30 days of age. We studied 92 consecutive preterm (BW < 1800 g) infants with low carnitine levels at 30 days of life (Group 1). As controls, we included the first 92 cases (BW < 1800 g) with normal carnitine levels (Group 2) and another 92 at or near-term newborns with BW > 1800 g (Group 3). RESULTS: Compared to 48-72 h levels, C0 and AC decreased at 14 and 30 days of life in Groups 1 and 2 (p < 0.001). In Group 2, the percentage of children with carnitine-free parenteral nutrition (PN) and BW < 1000 g was lower than in Group 1 (p < 0.001). Only in Group 2 did C0 increase at 30 days (p < 0.001). The multivariate regression analysis confirmed the influence of body weight and type of nutrition on C0 and AC. CONCLUSION: Body weight and type of nutrition influenced the carnitine longitudinal pattern.
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Peso al Nacer , Carnitina/sangre , Recien Nacido Prematuro/sangre , Estudios de Casos y Controles , Pruebas con Sangre Seca , Humanos , Recién Nacido , Estudios LongitudinalesRESUMEN
The term 'differences of sex development' (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, or anatomical sex. Disorders of steroidogenesis comprise autosomal recessive conditions that affect adrenal and gonadal enzymes and are responsible for some conditions of 46,XX DSD where hyperandrogenism interferes with chromosomal and gonadal sex development. Congenital adrenal hyperplasias (CAHs) are disorders of steroidogenesis that mainly involve the adrenals (21-hydroxylase and 11-hydroxylase deficiencies) and sometimes the gonads (3-beta-hydroxysteroidodehydrogenase and P450-oxidoreductase); in contrast, aromatase deficiency mainly involves the steroidogenetic activity of the gonads. This review describes the main genetic, biochemical, and clinical features that apply to the abovementioned conditions. The activities of the steroidogenetic enzymes are modulated by post-translational modifications and cofactors, particularly electron-donating redox partners. The incidences of the rare forms of CAH vary with ethnicity and geography. The elucidation of the precise roles of these enzymes and cofactors has been significantly facilitated by the identification of the genetic bases of rare disorders of steroidogenesis. Understanding steroidogenesis is important to our comprehension of differences in sexual development and other processes that are related to human reproduction and fertility, particularly those that involve androgen excess as consequence of their impairment.
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Trastornos del Desarrollo Sexual 46, XX/genética , Trastornos del Desarrollo Sexual 46, XX/metabolismo , Andrógenos/metabolismo , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Trastornos del Desarrollo Sexual 46, XX/diagnóstico , Alelos , Biomarcadores , Regulación Enzimológica de la Expresión Génica , Pruebas Genéticas , Humanos , Patrón de Herencia , Redes y Vías Metabólicas , Fenotipo , Esteroides/metabolismoRESUMEN
Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.
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Disruptores Endocrinos/farmacología , Sistema Endocrino/efectos de los fármacos , Animales , Carcinogénesis , Disruptores Endocrinos/efectos adversos , Epigénesis Genética , Femenino , Glucosa/metabolismo , Humanos , Obesidad , EmbarazoRESUMEN
Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.
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Endocrinología , Raquitismo , Humanos , Raquitismo/diagnóstico , Raquitismo/terapia , Raquitismo/metabolismo , Endocrinología/métodos , Endocrinología/normas , Italia , Vitamina D/metabolismo , Vitamina D/uso terapéutico , Niño , Sociedades Médicas/normas , Manejo de la EnfermedadRESUMEN
CONTEXT: There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000. OBJECTIVE: We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones. METHODS: We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities. RESULTS: The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis <â¯7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started. CONCLUSION: In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature.
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Imagen por Resonancia Magnética , Pubertad Precoz , Humanos , Masculino , Pubertad Precoz/epidemiología , Pubertad Precoz/diagnóstico , Italia/epidemiología , Niño , Estudios Retrospectivos , Preescolar , Estudios de Cohortes , Hormona Liberadora de Gonadotropina/análogos & derivadosRESUMEN
OBJECTIVE: To evaluate the effects of liquid (drops) and tablet formulations of levothyroxine in homogeneous groups of infants with congenital hypothyroidism (CH) as diagnosed through neonatal screening. STUDY DESIGN: Forty-two consecutive infants with CH were subdivided into 2 groups consisting of infants with the severe or the moderate/mild form. For each form, the infants with CH were randomly assigned to receive liquid (group 1) or tablet (group 2) formulation. In all patients, thyroid function tests were performed before the beginning of therapy and at 15 and 30 days and at 3 and 6 months after the beginning of therapy. RESULTS: In the severe form, after 15 days of treatment, serum thyrotropin (TSH) levels became normal in 8 of 9 patients in group 1 and in 5 of 9 patients in group 2; serum free triiodothyronine (fT3) levels were significantly higher in group 1 than in group 2; and serum fT4 levels were higher than the upper limit of the normal range in all patients in both groups. During the follow-up, there were significantly more patients with suppressed TSH concentrations in group 1 than in group 2. In the moderate/mild form, the patients of group 1 and group 2 showed median values of TSH, fT3, and fT4 that were not significantly different. No clinical or electrocardiographic signs of heart disease were found. There were no significant differences in the developmental quotient between group 1 and group 2 patients with severe and moderate/mild CH. CONCLUSIONS: Our data seem to indicate that there is not complete bioequivalence between drops and tablets, especially in infants with severe CH.
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Hipotiroidismo Congénito/tratamiento farmacológico , Tirotropina/sangre , Tiroxina/administración & dosificación , Triyodotironina/sangre , Química Farmacéutica , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Tamizaje Neonatal , Comprimidos , Pruebas de Función de la Tiroides , Tiroxina/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the correlation between serum thyroid-stimulating hormone (TSH) concentration and nodule nature in pediatric patients with thyroid nodules, with the aim of identifying a marker able to differentiate benign and malignant nodules. STUDY DESIGN: This was a retrospective analysis of serum TSH concentrations in a multicentric case series of 125 pediatric patients with benign and malignant thyroid nodules. RESULTS: Of the 125 patients, 99 had benign thyroid nodules and 26 had differentiated thyroid cancer (24 papillary and 2 follicular). Final diagnosis was based on surgery in 57 cases and on a benign cytology plus clinical follow-up in 68 cases. Serum TSH concentration was significantly higher in patients with thyroid cancer compared with those with benign nodules (3.23 ± 1.59 mU/L vs 1.64 ± 0.99 mU/L; P < .001). Binary logistic regression analysis revealed that serum TSH was the sole predictor of malignancy (P < .001). Dividing the patient cohort into 5 groups based on serum TSH quintiles (TSH cutoffs 0.40, 1.00, 1.50, 1.80, and 2.80 mU/L), we observed that cancer prevalence increased in parallel with serum TSH (P < .001), with respective rates of 0%, 4%, 16%, 32%, and 52% in the 5 quintile groups. CONCLUSION: Because cases with malignant nodules are most likely seen in the upper normal serum TSH range (ie, >2.8 mU/L), serum TSH concentration can serve as a predictor of thyroid cancer in pediatric patients with thyroid nodules and can inform the decision of when to submit patients to further investigation by cytology.
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Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/sangre , Nódulo Tiroideo/diagnóstico , Tirotropina/sangre , Adolescente , Biopsia con Aguja Fina , Índice de Masa Corporal , Proliferación Celular , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Prevalencia , Análisis de Regresión , Estudios Retrospectivos , Neoplasias de la Tiroides/epidemiología , Nódulo Tiroideo/epidemiologíaRESUMEN
Introduction: Narcolepsy Type 1 (NT1) is a rare hypersomnia of central origin linked to hypocretin deficiency, most frequently arising at pediatric age. NT1 could be associated with endocrine comorbidities involving the neuroendocrine axis, predominantly obesity, and Central Precocious Puberty (CPP). The primary aim of this study is the evaluation of endocrine and auxological parameters at diagnosis and during follow-up in patients with NT1, treated with Sodium Oxybate (SO) or not. Methods: We retrospectively evaluated the auxological, biochemical, and radiological parameters of 112 patients referred to our Center between 2004-2022. The design of our study is cross-sectional at the time of diagnosis followed by a longitudinal follow-up. Results: Our study confirms an increased frequency of CPP and obesity in patients with NT1. At first evaluation, obesity was found in 31.3% of patients, while overweight was found in 25.0%. A diagnosis of CPP was made in 19.6% of patients. Interestingly, this group showed a significantly lower level of CSF-hypocretin (hrct-1) at diagnosis compared to others. We found an improvement in BMI SDS in the SO-treated group compared to untreated patients, and this trend persisted also at 36 months of follow-up (0.0 ± 1.3 vs 1.3 ± 0.4; p<0.03). Sixty-three patients reached their final height, with a median SDS of 0.6 ± 1.1 in boys and 0.2 ± 1.2 in girls. Discussion: To our knowledge, these are the first results regarding the final height in a large series of pediatric patients with NT1, with a normal range of IGF1-SDS levels and stature SDS.
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Narcolepsia , Oxibato de Sodio , Masculino , Femenino , Humanos , Niño , Orexinas , Estudios Retrospectivos , Estudios de Seguimiento , Estudios Transversales , Narcolepsia/tratamiento farmacológico , Narcolepsia/epidemiología , Narcolepsia/complicaciones , Obesidad/complicacionesRESUMEN
Cysthiatonine beta-synthase (CBS) deficiency (CBSD) is an autosomal recessive rare disorder caused by variations on CBS that leads to impaired conversion of homocysteine (Hcy) to cystathionine. Marked hyperhomocysteinemia is the hallmark of the disease. The administration of pyridoxine, the natural cofactor of CBS, may reduce total plasma Hcy. Patient phenotype is classified on pyridoxine responsivity in two groups: pyridoxine-responsive and non-responsive patients. Ectopia lentis, bone deformities, developmental delay, and thromboembolism are the classic signs and symptoms of the disease. Early diagnosis and treatment impact patients' natural history. Therapy aims to lower promptly and maintain Hcy concentrations below 100 µmol/L. Depending on the patient's phenotype, the treatment goals could be obtained by the administration of pyridoxine and/or betaine associated with a methionine-restricted diet. CBSD could be diagnosed in the early days of life by expanded newborn screening (ENS), however, the risk of false negative results is not negligible. In Emilia-Romagna (Italy), during the first 10 years of screening experience, only three cases of CBSD identified have been diagnosed, all in the last two years (incidence 1:118,000 live births). We present the cases and a comprehensive review of the literature to emphasize the role of ENS for early diagnosis of CBSD and its potential pitfalls, reiterating the need for a more effective method to screen for CBSD.
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An infant with a prenatal diagnosis of citrullinemia, who started standard treatment at birth (L-arginine; sodium benzoate and a personalized diet characterized by a low protein intake and supplementation of essential nutrients and amino acids), presented at 4 months of age with extended, progressive, and severe skin lesions consistent with acrodermatitis dysmetabolica. Guidelines for the diagnosis and management of urea cycle disorders underline that a low-protein diet places patients at risk of essential fatty acids, trace elements, and vitamin deficiency. At hospital admission, our patient had normal levels of zinc and alkaline phosphatases. The plasmatic amino acid profile revealed a severe and generalized deficiency. In particular, the serum levels of arginine, valine, and isoleucine were very low and the dermatitis did not improve until the blood levels of these amino acids increased. In our patient, skin lesions happened despite an early diagnosis of citrullinemia and timely treatment due to compliance issues as a consequence of linguistic barriers.
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Premature pubarche (PP) could represent the first manifestation of non-classic congenital adrenal hyperplasia caused by 21 hydroxylase deficiency (NC21OHD) (10-30% of cases). In the last 20 years, the necessity of performing an ACTH test to diagnose NC21OHD in all cases with PP has been questioned, with conflicting results. This study aims to retrospectively evaluate the predictive value of the basal androgens, 17-OHP levels, and auxological features in suggesting the presence of NC21OHD and, thus, the need for a standard ACTH test to confirm the diagnosis. In all, 111 consecutive patients (87 females) with PP and advanced bone age underwent an ACTH test. Of these, 6/111 cases (1 male) were diagnosed with NC21OHD. The mean baseline 17 hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), delta 4 androstenedione (Δ4A), and testosterone serum levels were higher in NC21OHD patients than in the others (p < 0.05). We found three predictive features for NC21OHD: basal 17 OHP of >200 ng/mL, bone age advance of >2 years, and DHEA-S levels of >228 ng/mL with sensitivity and specificity of 83.3% and 97.1%, 83.3% and 65.7%, and 83.3% and 96.2%, respectively. Our data confirm that the prevalence of NC21OHD is low among patients with PP. Serum 17-OHP of >200 ng/mL could be helpful to decide, in most cases, which patients should undergo the ACTH test. Bone age advance represented an inadequately specific predictive marker of NC21OHD.
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OBJECTIVES: Lower limb deformities in children need careful orthopedic evaluation to distinguish physiological forms from pathological ones. X-linked hypophosphatemia (XLH) is a rare hereditary condition caused by PHEX gene mutations where tibial varum can be the first sign. CASE PRESENTATION: We report a family presenting with severe tibial varum, harbouring a rare PHEX intron mutation, c.1586+6T>C. This is the first clinical description available in literature for this variant. Despite the previous prediction of a mild phenotype in functional study, our patients showed important bone deformities, rickets and impaired growth since infancy followed by severe bone pain, hearing loss and reduced life quality in adulthood. Burosumab therapy improved biochemical and radiological findings in children and ameliorated quality of life in adults. CONCLUSIONS: This case demonstrated c.1586+6T>C causes a severe XLH phenotype, responsive to Burosumab. Familial genetic screening, enlarged to intronic region analysis, when XLH is suspected, allows precocious diagnosis to start timely the appropriate treatment.
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Raquitismo Hipofosfatémico Familiar , Raquitismo Hipofosfatémico , Humanos , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Raquitismo Hipofosfatémico Familiar/genética , Raquitismo Hipofosfatémico Familiar/diagnóstico , Intrones/genética , Calidad de Vida , Raquitismo Hipofosfatémico/genética , Mutación , Fenotipo , Endopeptidasa Neutra Reguladora de Fosfato PHEX/genéticaRESUMEN
Testicular adrenal rest tumors (TARTs) are a common complication in male patients with congenital adrenal hyperplasia (CAH). The aim of our cross-sectional cohort study is to estimate the frequency of TARTs with the correlation of genotype and disease control on tumor development. Thirty-five male patients, aged 14-26 years, were included in the study, all followed by the same center of pediatric endocrinology in Bologna. We studied genotypes, hormonal profiles at different time intervals and testicular ultrasound. A logistic regression model with multivariant analysis was developed for the statistical analysis. TARTs were detected in 31.4% of the cases, 90.9% of them had a classic form with salt wasting, while 9.1% had a non-classic form. Additionally, a significant correlation between the incidence of TARTs and severity of genotype was detected. Patients with TARTs had markedly worse metabolic control on average (p = 0.027), reflected by high ACTH, 17OH progesterone, and overall delta4-androstenedione. In conclusion, a screening tool is mandatory, especially (but not exclusively) in patients with the most severe forms of CAH and poor endocrine control of the disease.
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BACKGROUND: Few data are available on quarterly 11.25 mg GnRH analog treatment in central precocious puberty (CPP). AIM: To assess the efficacy of triptorelin 11.25 mg in children with CPP. PATIENTS: 17 patients (16 females) with CPP (7.9 ± 0.9 years) were treated with triptorelin 11.25 mg/90 days. METHODS: Gonadotropins, basal-, and GnRH-stimulated peak, gonadal steroids, and pubertal signs were assessed at preinclusion and at inclusion visit, 3 months, 6 months, and 12 months of treatment. Results. At 3, 6, and 12 months, all patients had suppressed LH peak (<3 IU/L after GnRH stimulation), as well as prepubertal oestradiol levels. Mean LH peak values after GnRH test significantly decreased from 25.7 ± 16.5 IU/L at baseline to 0.9 ± 0.5 IU/L at M3 (P < 0.0001); they did not significantly changed at M6 and M12. CONCLUSIONS: Triptorelin 11.25 mg/90 days efficiently suppressed the pituitary-gonadal axis in children with CPP from first administration.
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Pubertad Precoz/tratamiento farmacológico , Pamoato de Triptorelina/uso terapéutico , Niño , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/metabolismo , Hormona Liberadora de Gonadotropina/sangre , Gónadas/metabolismo , Humanos , Hormona Luteinizante/metabolismo , Luteolíticos/sangre , Luteolíticos/uso terapéutico , Masculino , Hipófisis/metabolismo , Factores de Tiempo , Resultado del Tratamiento , Pamoato de Triptorelina/sangreRESUMEN
Narcolepsy type 1 is a central disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy (i.e., sudden loss of muscle tone during wakefulness triggered by emotions), and REM sleep-related manifestations that can present with a peculiar phenotype when arising at a pediatric age. Several features of childhood-onset narcolepsy type 1 are also common in neuropsychiatric conditions; discrete neuropsychiatric comorbidity has also been demonstrated. Here, we report on 3 children with very early narcolepsy type 1. All 3 patients had psychiatric features at the time of symptom onset coupled with peculiar motor disturbances. The course of narcolepsy symptoms also paralleled neuropsychiatric symptoms, suggesting a possible intrinsic link between sleep and psychological features. Multidisciplinary management is mandatory for pediatric narcolepsy type 1 since prompt disease management addressing neuropsychiatric symptoms could lead to better clinical outcomes and quality of life.
Asunto(s)
Cataplejía , Trastornos de Somnolencia Excesiva , Narcolepsia , Neurología , Cataplejía/diagnóstico , Niño , Trastornos de Somnolencia Excesiva/diagnóstico , Humanos , Narcolepsia/diagnóstico , Narcolepsia/terapia , Calidad de VidaRESUMEN
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.