RESUMO
The risk of suffering from gonadal germ cell tumors (GCT) is increased in some patients with different sexual development (DSD), mainly in those with Y chromosome material. This risk, however, varies considerably depending on a multitude of factors that make the decision for prophylactic gonadectomy extremely difficult. In order to make informed recommendations on the convenience of this procedure in cases where there is potential for malignancy, this consensus guide evaluates the latest clinical evidence, which is generally low, and updates the existing knowledge in this field.
Assuntos
Neoplasias Embrionárias de Células Germinativas , Desenvolvimento Sexual , Humanos , Consenso , Neoplasias Embrionárias de Células Germinativas/cirurgia , CastraçãoRESUMO
Some people, including minors, have a gender identity that does not correspond to the sex assigned at birth. They are known as trans* people, which is an umbrella term that encompasses transgender, transsexual, and other identities not conforming to the assigned gender. Healthcare units for trans* minors require multidisciplinary working, undertaken by personnel expert in gender identity, enabling, when requested, interventions for the minor and their social-familial environment, in an individualized and flexible way during the gender affirmation path. This service model also includes hormonal treatments tailored as much as possible to the individual's needs, beyond the dichotomic goals of a traditional binary model. This guide addresses the general aspects of professional care of trans* minors and presents the current evidence-based protocol of hormonal treatments for trans* and non-binary adolescents. In addition, it details key aspects related to expected body changes and their possible side effects, as well as prior counselling about fertility preservation.
Assuntos
Disforia de Gênero , Guias de Prática Clínica como Assunto , Pessoas Transgênero , Transexualidade , Adolescente , Feminino , Disforia de Gênero/tratamento farmacológico , Identidade de Gênero , Humanos , Masculino , Menores de Idade , Transexualidade/terapiaRESUMO
Algunas personas, también las menores de edad, tienen una identidad de género que no se corresponde con el sexo asignado al nacer. Se les conoce como personas trans*, que es el término paraguas que engloba transgénero, transexual y otras identidades no conformes con el género asignado. Las unidades de asistencia sanitaria a menores trans* requieren un trabajo multidisciplinario, realizado por personal experto en identidad de género, que permita, cuando así lo soliciten, intervenciones para el menor y su entorno sociofamiliar, de forma individualizada y flexible durante el camino de afirmación de género. Este modelo de servicio también incluye tratamientos hormonales adaptados en la medida de lo posible a las necesidades del individuo, más allá de los objetivos dicotómicos de un modelo binario tradicional. Esta guía aborda los aspectos generales de la atención profesional de menores trans* y presenta el protocolo actual basado en evidencia de tratamientos hormonales para adolescentes trans* y no binarios. Además, detalla aspectos clave relacionados con los cambios corporales esperados y sus posibles efectos secundarios, así como el asesoramiento previo sobre preservación de la fertilidad. (AU)
Some people, including minors, have a gender identity that does not correspond to the sex assigned at birth. They are known as trans* people, which is an umbrella term that encompasses transgender, transsexual, and other identities not conforming to the assigned gender. Healthcare units for trans* minors require multidisciplinary working, undertaken by personnel expert in gender identity, enabling, when requested, interventions for the minor and their socialfamilial environment, in an individualized and flexible way during the gender affirmation path. This service model also includes hormonal treatments tailored as much as possible to the individual's needs, beyond the dichotomic goals of a traditional binary model. This guide addresses the general aspects of professional care of trans* minors and presents the current evidence-based protocol of hormonal treatments for trans* and non-binary adolescents. In addition, it details key aspects related to expected body changes and their possible side effects, as well as prior counselling about fertility preservation. (AU)
Assuntos
Humanos , Criança , Adolescente , Disforia de Gênero , Pessoas Transgênero , Identidade de Gênero , Serviços de Saúde para Pessoas Transgênero , Fertilidade/efeitos dos fármacosRESUMO
Las anomalías de la diferenciación sexual (ADS) engloban un amplio espectro de discordancias entre los criterios cromosómico, gonadal y fenotípico (genital) que definen la diferenciación sexual; actualmente, se aboga por la denominación de «desarrollo sexual diferente» (DSD). Su origen es congénito; se clasifican en función de los cromosomas sexuales presentes en el cariotipo; las causas genéticas conocidas son muy diversas y heterogéneas, aunque algunos casos pueden ser secundarios a factores maternos o medioambientales. Su diagnóstico y tratamiento requieren siempre una atención médica y psicosocial multidisciplinar. El diagnóstico etiológico precisa la interacción entre las exploraciones clínicas, bioquímicas (hormonales), genéticas, de imagen y, eventualmente, quirúrgicas. El tratamiento debe abordar la asignación de género, la posible necesidad de tratamiento hormonal substitutivo (suprarrenal si hay insuficiencia suprarrenal y con esteroides sexuales si hay insuficiencia gonadal a partir de la edad puberal), la necesidad de intervenciones quirúrgicas sobre las estructuras genitales (actualmente se tiende a diferirlas) y/o sobre las gónadas (en función de los riesgos de malignización), la necesidad de apoyo psicosocial y, finalmente, una adecuada programación de la transición a la atención médica en las especialidades de adultos. Las asociaciones de personas afectadas tienen un papel fundamental en el apoyo a familias y la interacción con los medios profesionales y sociales. La utilización de Registros y la colaboración entre profesionales en Grupos de Trabajo de sociedades médicas nacionales e internacionales es fundamental para avanzar en mejorar los medios diagnósticos y terapéuticos que precisan los DSD
Disorders of Sex Development (DSD) include a wide range of anomalies among the chromosomal, gonadal, and phenotypic (genital) characteristics that define sexual differentiation. At present, a definition as Different Sexual Development (DSD) is currently preferred. They originate in the pre-natal stage, are classified according to the sex chromosomes present in the karyotype. The known genetic causes are numerous and heterogeneous, although, in some cases, they may be secondary to maternal factors and/or exposure to endocrine-disrupting chemicals (EDCs). The diagnosis and treatment of DSD always requires multidisciplinary medical and psychosocial care. An aetiological diagnosis needs the interaction of clinical, biochemical (hormonal), genetic, imaging and, sometimes, surgical examinations. The treatment should deal with sex assignment, the possible need for hormone replacement therapy (adrenal if adrenal function is impaired, and with sex steroids from pubertal age if gonadal function is impaired), as well as the need for surgery on genital structures (currently deferred when possible) and/or on gonads (depending on the risk of malignancy), the need of psychosocial support and, finally, an adequate organisation of the transition to adult medical specialties. Patient Support Groups have a fundamental role in the support of families, as well as the interaction with professional and social media. The use of Registries and the collaboration between professionals in Working Groups of national and international medical societies are crucial for improving the diagnostic and therapeutic tools required for the care of patients with DSD
Assuntos
Humanos , Masculino , Feminino , Criança , Diferenciação Sexual/genética , Desenvolvimento Sexual , Apoio Social , Aberrações dos Cromossomos Sexuais/classificação , Cariótipo , Diagnóstico DiferencialRESUMO
Disorders of Sex Development (DSD) include a wide range of anomalies among the chromosomal, gonadal, and phenotypic (genital) characteristics that define sexual differentiation. At present, a definition as Different Sexual Development (DSD) is currently preferred. They originate in the pre-natal stage, are classified according to the sex chromosomes present in the karyotype. The known genetic causes are numerous and heterogeneous, although, in some cases, they may be secondary to maternal factors and/or exposure to endocrine-disrupting chemicals (EDCs). The diagnosis and treatment of DSD always requires multidisciplinary medical and psychosocial care. An aetiological diagnosis needs the interaction of clinical, biochemical (hormonal), genetic, imaging and, sometimes, surgical examinations. The treatment should deal with sex assignment, the possible need for hormone replacement therapy (adrenal if adrenal function is impaired, and with sex steroids from pubertal age if gonadal function is impaired), as well as the need for surgery on genital structures (currently deferred when possible) and/or on gonads (depending on the risk of malignancy), the need of psychosocial support and, finally, an adequate organisation of the transition to adult medical specialties. Patient Support Groups have a fundamental role in the support of families, as well as the interaction with professional and social media. The use of Registries and the collaboration between professionals in Working Groups of national and international medical societies are crucial for improving the diagnostic and therapeutic tools required for the care of patients with DSD.
Assuntos
Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/terapia , Algoritmos , Criança , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Genetic activation of the insulin signal-transducing kinase AKT2 causes syndromic hypoketotic hypoglycaemia without elevated insulin. Mosaic activating mutations in class 1A phospatidylinositol-3-kinase (PI3K), upstream from AKT2 in insulin signalling, are known to cause segmental overgrowth, but the metabolic consequences have not been systematically reported. We assess the metabolic phenotype of 22 patients with mosaic activating mutations affecting PI3K, thereby providing new insight into the metabolic function of this complex node in insulin signal transduction. METHODS: Three patients with megalencephaly, diffuse asymmetric overgrowth, hypoketotic, hypoinsulinaemic hypoglycaemia and no AKT2 mutation underwent further genetic, clinical and metabolic investigation. Signalling in dermal fibroblasts from one patient and efficacy of the mTOR inhibitor Sirolimus on pathway activation were examined. Finally, the metabolic profile of a cohort of 19 further patients with mosaic activating mutations in PI3K was assessed. RESULTS: In the first three patients, mosaic mutations in PIK3CA (p.Gly118Asp or p.Glu726Lys) or PIK3R2 (p.Gly373Arg) were found. In different tissue samples available from one patient, the PIK3CA p.Glu726Lys mutation was present at burdens from 24% to 42%, with the highest level in the liver. Dermal fibroblasts showed increased basal AKT phosphorylation which was potently suppressed by Sirolimus. Nineteen further patients with mosaic mutations in PIK3CA had neither clinical nor biochemical evidence of hypoglycaemia. CONCLUSIONS: Mosaic mutations activating class 1A PI3K cause severe non-ketotic hypoglycaemia in a subset of patients, with the metabolic phenotype presumably related to the extent of mosaicism within the liver. mTOR or PI3K inhibitors offer the prospect for future therapy.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Hipoglicemia/genética , Insulina/genética , Megalencefalia/genética , Mosaicismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Pré-Escolar , Feminino , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/metabolismo , Insulina/metabolismo , Masculino , Megalencefalia/diagnóstico , Megalencefalia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
Pyogenic granuloma, also named lobular capillary hemangioma, is a common proliferative vascular lesion known as a benign condition despite its rapid growth. It may appear in any cutaneous or mucosal surface but is usually restricted to the oral cavity. It is characterized by a friable mulberry-like lesion that can be sessile or pedunculated. Bleeding is usually its first clinical manifestation. Locations on respiratory, digestive and genital tracts are uncommon and sporadic. We describe the occurrence of an intravaginal pyogenic granuloma in a peripubertal girl with recurrent vaginal bleeding. This is the first reported case of a genital tract lobular capillary hemangioma in pediatric age to our knowledge. Therefore, we suggest this entity in the differential diagnosis of an unclear peripubertal vaginal bleeding.
Assuntos
Granuloma Piogênico/patologia , Hemorragia Uterina/patologia , Doenças Vaginais/patologia , Criança , Diagnóstico Diferencial , Feminino , Granuloma Piogênico/complicações , Humanos , Puberdade , Hemorragia Uterina/etiologia , Doenças Vaginais/complicaçõesRESUMO
Type 1 diabetes mellitus is one of the most common chronic disorders of childhood. The metabolic control is lost due to the lack of insulin, which is the main treatment for the disease. Nevertheless, long-term complications appear even under good glycemic control. Metabolomics, an emerging strategy, can help in diagnosis, prognosis, and monitoring of metabolic disorders. The objective of the present study was to investigate the alterations in plasma (by LC-MS) and urine (CE-MS) of type 1 diabetic children that were under insulin treatment and good glycemic control. Even without remarkable biochemical differences between the two groups (diabetic and control) except for glucose level and glycosilated hemoglobin, metabolomic tools were able to capture subtle metabolic differences. The main changes in plasma were associated to lipidic metabolism (nonesterified fatty acids, lysophospholipids, and other derivatives of fatty acids), and some markers of the differential activity of the gut microflora were also found (bile acids, p-cresol sulfate). In urine, changes associated to protein and amino acid metabolism were found (amino acids, their metabolites and derivatives), and among them one advanced glycation end product (carboxyethylarginine) and one early glycation end product (fructosamine) were excreted in higher proportion in the diabetic group.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/urina , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Eletroforese Capilar/métodos , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Plasma/efeitos dos fármacos , Plasma/metabolismoRESUMO
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency. Mutations in the ACTH receptor (melanocortin 2 receptor, MC2R) or the MC2R accessory protein (MRAP) cause FGD types 1 and 2, respectively. A 2-year-old adopted Chinese girl presented with hypertonic seizures associated with hypoglycemia, skin hyperpigmentation, muscle weakness and mild jaundice. Hormonal analyses revealed high ACTH, low serum cortisol along with normal blood electrolytes. On hydrocortisone supplementation, the disease symptoms disappeared and the child recovered, although further episodes occurred with infection. To date, her physical and neurocognitive development progress is normal. A clinical diagnosis of FGD was given. We undertook MC2R and MRAP mutation screening. Two novel MC2R mutations were identified: p.D107G localized in the transmembrane region, predicted to be trafficking-competent but is unable to bind to ACTH, and p.R145C, situated in the second intracellular loop, predicted to be trafficking-defective.
Assuntos
Glucocorticoides/deficiência , Mutação de Sentido Incorreto , Receptor Tipo 2 de Melanocortina/genética , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos , Povo Asiático/genética , Sequência de Bases , Pré-Escolar , DNA/genética , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Hidrocortisona/uso terapêutico , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
Type 1 diabetes mellitus is a major endocrine disorder, affecting approximately 5% of the world's population. It not only leads to hyperglycaemia but also causes many complications, and numerous studies have demonstrated that oxidative stress contributes to these complications. As a new strategy to improve the oxidative damage in diabetes, interest has grown in the usage of natural antioxidants, even more in the long term. Among them, Rosmarinus officinalis (rosemary) has been widely accepted as one of the species with the highest antioxidant activity. In addition, omega-3 polyunsaturated fatty acids were efficient in delaying and decreasing cardiovascular risk factors associated with diabetes. Type 1 diabetic children and the corresponding controls were enrolled in the assay. The aim was evaluating the effect of a special additive containing rosemary extract, vitamin E and PUFAs added to their standard diet through the meat. In the analytical point of view, a metabolomic approach with CE-UV was used to detect possible differences in urine of diabetic children as compared to controls. After the application of the appropriate multivariate statistical tools, clear differences could be observed between treated and non-treated diabetic children and some of the metabolites associated could be identified. This was specially challenging as most of the clinical biochemical parameters measured by target analysis showed no differences between the groups.
Assuntos
Diabetes Mellitus Tipo 1/dietoterapia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Metabolômica/métodos , Extratos Vegetais/uso terapêutico , Rosmarinus , Criança , Diabetes Mellitus Tipo 1/metabolismo , Suplementos Nutricionais/análise , Método Duplo-Cego , Eletroforese Capilar/métodos , Ácidos Graxos Ômega-3/análise , Feminino , Humanos , Masculino , Extratos Vegetais/análise , Vitamina E/uso terapêuticoRESUMO
Los síndromes de osteólisis hereditaria se caracterizan por destrucción esquelética debida a una incontrolada resorción ósea. Constituyen un grupo heterogéneo de entidades infrecuentes de clasificación aún discutida, en la que se incluyen formas multicéntricas carpotarsales: síndromes de Winchester, de nodulosis-artropatía-osteólisis (NAO) y de Torg, de herencia autosómica recesiva. Se presenta el caso de un niño de13 años y origen marroquí, con incapacidad para la bipedestación y la manipulación por deformidad progresiva de las manos y los pies, así como fracturas patológicas ante mínimos traumatismos. Radiológicamente faltan carpo y tarso, y hay fracturas en las extremidades y osteoporosis intensa, sin alteraciones en el metabolismo fosfocálcico. Presenta alteraciones corneales y agudeza visual muy disminuida. Su único hermano tiene los mismos síntomas; sus padres son primos y están sanos. Ante tales hallazgos, se establece el síndrome de Winchester como diagnóstico más probable (AU)
Hereditary osteolysis syndromes are characterized by the destruction of skeletal groups produced by uncontrolled bone resorption. These syndromes constitute aheterogeneous group of infrequent entities. The classification of these entities is still controversial and includes the following multicentric carpal-tarsal forms: Winchester, NAO (nodulosis-arthropathyosteolysis) and Torg syndromes, all of which show autosomal recessive inheritance. We present a 13-year-old boy of Moroccan origin with impaired walking and hand function due to progressive deformity of the hands and feet, as well aspathological fractures after minimal trauma. Radiographic examination revealed dissolution of carpal and tarsal bones, fractures in the extremities and intense osteoporosis, without alterations inphosphocalcic metabolism. The patient had corneous alterations and highly diminished visual keenness. The boys only brother showed the same symptoms but his parents and cousins were healthy. Based on the findings in our patient, Winchester syndrome was established as the most probable diagnosis (AU)