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Pruebas de Función de la Tiroides , Glándula Tiroides , Humanos , Estado de Salud , TirotropinaRESUMEN
INTRODUCTION: Gender dysphoria (GD) in childhood and adolescence is characterized by an incongruence between sex at birth and gender identity, which usually increases during puberty. Gender dysphoric children and adolescents often suffer from psychological comorbidities such as depression. The purpose of our study is to give an overview of the patients treated in our clinic. METHODS: We analyzed data of 66 patients who presented with GD at our outpatient clinic between 2005 and 2018. RESULTS: We noted a rise of presentations with one or no patient with GD per year between 2005 and 2008 up to 18 patients in 2018, although the percentage of all 14.339 endocrinological outpatients (2005-2018) is low. 54 patients were assigned as female and 12 as male at birth resulting in a ratio of 4.5:1. The mean age at their first appointment was 13.6 years. 49 patients (74%) had reached tanner stadium P3/B3 or P3/G3. 30 (45%) showed symptoms of a comorbidity related to GD. 48 (73%) showed symptoms of GD before puberty. 15 patients (23%) experienced a negative response regarding their outing and 17 (26%) were victims of mobbing in school. CONCLUSION: The number of patients increased in the last years. About half of the patients suffered from a psychological comorbidity. They often experienced negative response regarding their GD in the family. The variability of appearance and the comorbidities pose the challenge in the treatment of gender dysphoric children and adolescents.
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Disforia de Género/psicología , Disforia de Género/cirugía , Cirugía de Reasignación de Sexo , Personas Transgénero/psicología , Adolescente , Niño , Comorbilidad , Femenino , Disforia de Género/diagnóstico , Identidad de Género , Humanos , Masculino , Maduración SexualRESUMEN
Amiodarone-induced hyperthyroidism is a known side effect of amiodarone treatment. In the pediatric population, long-term amiodarone treatment is rarely indicated because of its severe side effects including thyroid function impairment. Treatment is therefore restricted to therapy-resistant arrhythmias. In the literature, scarce data are available on the management and therapy of amiodarone-induced thyroid dysfunction at a young age. We present three adolescent patients developing amiodarone-induced thyrotoxicosis in the months after amiodarone therapy. A latency period for thyroid dysfunction has been described in adulthood but was not previously reported in pediatric patients. The gap between amiodarone treatment and the development of symptoms and the diagnosis of hyperthyroidism was between 3 and 10 months. In two patients, hyperthyroidism was transient and resolved without treatment. These two patients, one boy and on girl, were almost asymptomatic. In contrast, in one male patient overt and severe hyperthyroidism developed. We began treatment with thiamazole without benefit. Control of hyperthyroidism was achieved under prednisone treatment, which was continued for 9 months. Clinical evaluation proved an amiodarone-induced destructive thyroiditis in this patient. Amiodarone-induced thyroid dysfunction is frequent also in pediatric patients with long-term amiodarone treatment. Patients and clinicians should be aware of the impact of amiodarone on thyroid function during and also in the months and maybe years after treatment. Careful follow-up is needed, as symptoms might be associated with the underlying cardiac disease in these patients. Amiodarone-induced thyrotoxicosis often resolves without treatment but can be challenging in some cases.
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Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Hipertiroidismo/inducido químicamente , Adolescente , Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Antitiroideos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Hipertiroidismo/tratamiento farmacológico , Masculino , Metimazol/uso terapéutico , Prednisolona/uso terapéutico , Pruebas de Función de la Tiroides/métodos , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patologíaRESUMEN
Androgens are responsible for the development and maintenance of male sex characteristics. Dysfunctions in androgen action due to mutations in the androgen receptor gene (AR) can lead to androgen insensitivity syndrome (AIS) that can be classified as mild (MAIS), partial (PAIS), or complete (CAIS). We have analyzed functional effects of p.Ser760Thr, p.Leu831Phe, p.Ile899Phe, p.Leu769Val, and p.Pro905Arg mutations and the combination p.Gln799Glu + p.Cys807Phe that were identified in patients with PAIS or CAIS. The p.Leu769Val and p.Pro905Arg mutations showed complete disruption of AR action under physiological hormone concentrations; however, they differed in high DHT concentrations especially in the N/C terminal interaction assay. Mutations p.Ser760Thr, p.Leu831Phe, p.Ile899Phe presented transactivation activities higher than 20% of the wild type in physiological hormone concentrations and increased with higher DHT concentrations. However, each one showed a different profile in the N/C interaction assay. When p.Gln799Glu and p.Cys807Phe were analyzed in combination, transactivation activities <10% in physiologic hormone conditions indicated an association with a CAIS phenotype. We conclude that the functional analysis elucidated the role of mutant ARs, giving clues for the molecular mechanisms associated with different clinical AIS manifestations. Differences in hormone-dependent profiles may provide a basis for the response to treatment in each particular case.
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Síndrome de Resistencia Androgénica/genética , Receptores Androgénicos/genética , Adolescente , Adulto , Preescolar , Femenino , Humanos , Masculino , Mutación/genética , Receptores Androgénicos/metabolismo , Técnicas del Sistema de Dos Híbridos , Adulto JovenRESUMEN
Nicotinamide phosphoribosyl transferase (NAMPT) is an inflammatory adipocytokine shown to interact in immune modulation in chronic inflammatory diseases, acute respiratory distress syndrome, sepsis, cancer and obesity in adulthood. It is, however, not clear whether this association reflects a chronic elevation or acute inflammatory response. We analyzed NAMPT concentrations in distinct states of inflammation in 102 children and found consistently significantly increased NAMPT levels in subjects with acute infections. NAMPT concentrations in children with stable chronic inflammatory diseases were not significantly different, whereas in patients with acute relapse of chronic disease NAMPT was significantly higher than in children in remission or healthy controls. In states of low-grade inflammation (children with atopic disease or obesity) we did not detect alterations in NAMPT serum levels. NAMPT correlated positively with inflammatory markers such as CRP. The most predictive factor for NAMPT serum concentrations was leucocyte count and therein the neutrophil count. Furthermore, systemic circulating NAMPT levels were closely associated with NAMPT release from corresponding cultured PBMCs. In conclusion, NAMPT is selectively increased in states of acute but not chronic inflammation in children. The close relationship between systemic circulating NAMPT with leucocyte counts and release indicate that leucocytes most probably are the source of inflammation related NAMPT levels.
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Enfermedades Transmisibles/enzimología , Citocinas/sangre , Inflamación/enzimología , Nicotinamida Fosforribosiltransferasa/sangre , Adolescente , Niño , Enfermedad Crónica , Estudios de Cohortes , Enfermedades Transmisibles/sangre , Femenino , Humanos , Inflamación/sangre , Masculino , RecurrenciaRESUMEN
Acrodysostosis is a very rare congenital multisystem condition characterized by skeletal dysplasia with severe brachydactyly, midfacial hypoplasia, and short stature, varying degrees of intellectual disability, and possible resistance to multiple G protein-coupled receptor signalling hormones. Two distinct subtypes are differentiated: acrodysostosis type 1 resulting from defects in protein kinase type 1-α regulatory subunit and acrodysostosis type 2 caused by mutations in phosphodiesterase 4D (PDE4D). Most cases are sporadic. We report on a rare multigenerational familial case of acrodysostosis type 2 due to a novel autosomal dominantly inherited PDE4D mutation. A 3.5-year-old boy presented with short stature, midfacial hypoplasia, severe brachydactyly, developmental delay, and behavioural problems. Laboratory investigations revealed mild thyrotropin resistance. His mother shared some characteristic features, such as midfacial hypoplasia and severe brachydactyly, but did not show short stature, intellectual disability or hormonal resistance. Genetic analysis identified the identical, novel heterozygous missense mutation of the PDE4D gene c.569C>T (p.Ser190Phe) in both patients. This case illustrates the significant phenotypic variability of acrodysostosis even within one family with identical mutations. Hence, a specific clinical diagnosis of acrodysostosis remains challenging because of great interindividual variability and a substantial overlap of the two subtypes as well as with other related Gsα-cAMP-signalling-linked disorders.
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Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/genética , Disostosis/genética , Discapacidad Intelectual/genética , Mutación Missense , Osteocondrodisplasias/genética , Adulto , Sustitución de Aminoácidos , Preescolar , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Femenino , Humanos , Masculino , Madres , Núcleo Familiar , Fenotipo , Fosforilación , Serina/genéticaAsunto(s)
Medicina de Precisión , Pubertad Tardía/terapia , Pubertad Precoz/terapia , Adolescente , Animales , Niño , Enfermedad Crónica , Progresión de la Enfermedad , Disruptores Endocrinos/toxicidad , Contaminantes Ambientales/toxicidad , Salud de la Familia , Femenino , Variación Genética , Humanos , Masculino , Pubertad Tardía/inducido químicamente , Pubertad Tardía/etiología , Pubertad Tardía/genética , Pubertad Precoz/inducido químicamente , Pubertad Precoz/etiología , Pubertad Precoz/genéticaRESUMEN
Recent studies suggested the persistence of brown adipocytes in adult humans, as opposed to being exclusively present in infancy. In this study, we investigated the presence of brown-like adipocytes in adipose tissue (AT) samples of children and adolescents aged 0 to 18 years and evaluated the association with age, location, and obesity. For this, we analysed AT samples from 131 children and 23 adults by histological, immunohistochemical and expression analyses. We detected brown-like and UCP1 positive adipocytes in 10.3% of 87 lean children (aged 0.3 to 10.7 years) and in one overweight infant, whereas we did not find brown adipocytes in obese children or adults. In our samples, the brown-like adipocytes were interspersed within white AT of perirenal, visceral and also subcutaneous depots. Samples with brown-like adipocytes showed an increased expression of UCP1 (>200fold), PRDM16 (2.8fold), PGC1α and CIDEA while other brown/beige selective markers, such as PAT2, P2RX5, ZIC1, LHX8, TMEM26, HOXC9 and TBX1 were not significantly different between UCP1 positive and negative samples. We identified a positive correlation between UCP1 and PRDM16 within UCP1 positive samples, but not with any other brown/beige marker. In addition, we observed significantly increased PRDM16 and PAT2 expression in subcutaneous and visceral AT samples with high UCP1 expression in adults. Our data indicate that brown-like adipocytes are present well beyond infancy in subcutaneous depots of non-obese children. The presence was not restricted to typical perirenal locations, but they were also interspersed within WAT of visceral and subcutaneous depots.
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Adipocitos Marrones/citología , Adipocitos/citología , Tejido Adiposo Pardo/citología , Tejido Adiposo Blanco/citología , Adipocitos/metabolismo , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Adolescente , Adulto , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Índice de Masa Corporal , Niño , Preescolar , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Femenino , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Grasa Intraabdominal/citología , Grasa Intraabdominal/metabolismo , Canales Iónicos/genética , Canales Iónicos/metabolismo , Masculino , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Obesidad , Sobrepeso , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Grasa Subcutánea/citología , Grasa Subcutánea/metabolismo , Simportadores/genética , Simportadores/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteína Desacopladora 1RESUMEN
RATIONALE: The newly discovered myokine irisin has been proposed to affect obesity and metabolism by promoting browning of white adipose tissue. However, clinical and functional studies on the association of irisin with obesity, muscle mass, and metabolic status remain controversial. Here we assessed the effect of 4 distinct exercise regimens on serum irisin levels in children and young adults and systematically evaluated the influence of diurnal rhythm, anthropometric and metabolic parameters, and exercise on irisin. RESULTS: Serum irisin levels did not show diurnal variations, nor were they affected by meal intake or defined glucose load during oral glucose tolerance testing. Irisin levels decreased with age. In adults, irisin levels were higher in men than in women, and obese subjects had significantly higher levels than lean control subjects. Irisin levels were closely correlated with muscle-associated bioimpedance parameters such as fat-free mass and body cell mass. Of the 4 exercise regimens that differed in duration and intensity, we identified a clear and immediate increase in serum irisin levels after acute strenuous exercise (cycling ergometry) and a 30-minute bout of intensive exercise in children and young adults, whereas longer (6 weeks) or chronic (1 year) increases in physical activity did not affect irisin levels. SUMMARY: We show that irisin levels are affected by age, sex, obesity, and particularly muscle mass, whereas diurnal rhythm and meals do not contribute to the variation in irisin levels. Short bouts of intensive exercise but not long-term elevations in physical activity, acutely and transiently increase serum irisin levels in children and adults.
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Ejercicio Físico/fisiología , Fibronectinas/sangre , Obesidad Infantil/sangre , Adolescente , Adulto , Factores de Edad , Niño , Ritmo Circadiano , Femenino , Glucosa/farmacología , Humanos , Hidrocortisona/sangre , Masculino , Comidas , Metaboloma/efectos de los fármacos , Obesidad Infantil/terapia , Esfuerzo Físico/fisiología , Factores Sexuales , Adulto JovenRESUMEN
Infants born small for gestational age (SGA) are at risk to develop metabolic complications. Insulin-like growth factor 1 (IGF-1) resistance due to IGF-1 receptor (IGF1R) mutations is a rare genetic condition that causes proportionate growth retardation. The contribution of an impaired IGF1R function to the development of comorbidities such as disturbed glucose homeostasis is not well understood. Genetic analysis and detailed auxological, endocrine and psychological investigations in two male SGA siblings were performed. The two patients and their father bear a novel heterozygous mutation (p.Cys1248Tyr) in the IGF1R gene. Both brothers displayed very similar growth pattern before and during recombinant human growth hormone treatment, whereas oral glucose tolerance tests showed variable manifestations of progressive impaired glucose tolerance. The father had already developed type 2 diabetes mellitus. Growth retardation in our patients is likely caused by the IGF1R mutation that might predispose to disturbances of carbohydrate homeostasis. Therefore, a close metabolic monitoring of affected patients is indicated, particularly if growth hormone therapy is commenced.