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The spectrum of thyroid disorders presenting to paediatricians is different to that seen by adult physicians. Referrals reflect cases detected by the neonatal screening programme for congenital hypothyroidism and many of the inherited defects of thyroid hormone generation or action will be manifest in early life. Autoimmune thyroid disease can be particularly challenging to manage in the young and the potential impact of thyroid status on neurodevelopment and schooling are key considerations throughout childhood and adolescence.
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Enfermedades de la Tiroides , Humanos , Enfermedades de la Tiroides/diagnóstico , Niño , Hipotiroidismo Congénito/diagnóstico , Adolescente , Recién Nacido , Tamizaje Neonatal , PreescolarRESUMEN
INTRODUCTION/AIMS: Recent clinical guidelines recommend that adolescents with Duchenne muscular dystrophy (DMD) who are on daily glucocorticoid treatment should be offered pubertal induction in order to ensure adult levels of sex hormones as they reach adulthood. However, it remains unclear how gonadal status, including androgen concentrations, impacts physical function and future fertility. The aim of this study was to give a voice to adults with DMD, exploring their perspectives around sexual health, hormone treatment, and fertility. METHODS: Qualitative data was collected from six adults with DMD through two online focus groups. Participants were recruited through Pathfinders Neuromuscular Alliance and Duchenne UK and invited to take part if they had DMD and were 18 years of age or older. Conversations were transcribed verbatim and an interpretivist paradigm was used with thematic analysis. RESULTS: The main themes identified were (1) the need for communication and information about sexual health, (2) dealing with the potential fear of rejection, (3) physical barriers to relationships including sex, (4) testosterone supplementation in DMD, and (5) parenthood and fertility. DISCUSSION: We recommend that clinicians work with young people with DMD individually, to explore the benefits of testosterone treatment for them and their personal sexual health needs. If they are offered treatment, this should always be accompanied by the opportunity for psychological support. This work highlights the need for further research to establish the role of testosterone supplementation in adults with DMD and its effects on fertility and the value of specific emotional and practical support for sexual health.
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Fertilidad , Distrofia Muscular de Duchenne , Salud Sexual , Humanos , Distrofia Muscular de Duchenne/psicología , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/fisiopatología , Masculino , Adulto , Fertilidad/fisiología , Femenino , Adulto Joven , Testosterona/uso terapéutico , Testosterona/sangre , Adolescente , Investigación Cualitativa , Grupos FocalesRESUMEN
"What's in a name? That which we call a rose/By any other name would smell as sweet." (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and pediatric endocrine societies now proposes changing the name of "diabetes insipidus" to "Arginine Vasopressin Deficiency (AVP-D)" for central etiologies, and "Arginine Vasopressin Resistance (AVP-R)" for nephrogenic etiologies. This editorial provides both the historical context and the rational for this proposed name change.
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Arginina Vasopresina , Diabetes Insípida , Humanos , Arginina Vasopresina/deficiencia , Diabetes Insípida/clasificación , Diabetes Mellitus , Sociedades MédicasRESUMEN
Many paediatricians will be faced with a sick infant who on investigation is found to have hyponatraemia and hyperkalaemia at some time in their career. The focus of initial management includes the treatment of potentially life-threatening hyperkalaemia with concurrent investigation aiming to elucidate whether the underlying cause reflects a primarily renal or endocrine pathology. We describe the presentation of two infants who each presented with one of the more common underlying diagnoses that led to this biochemical disturbance and discuss the approach to immediate treatment, diagnostic work-up and longer term management.
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Hiperpotasemia , Hiponatremia , Humanos , Hiperpotasemia/diagnóstico , Hiperpotasemia/terapia , Hiponatremia/diagnóstico , Hiponatremia/etiología , Hiponatremia/terapia , Lactante , Potasio , Solución de Problemas , SodioRESUMEN
Glucocorticoids (GC) are used in paediatric practice for a broad range of conditions and all paediatricians will prescribe GC, in some form, during their career. A wide variety of GC formulations, doses and administration routes are used for periods of time ranging from days to years. Exposure to exogenous GC can result in hypothalamic-pituitary-adrenal axis suppression-otherwise known as adrenal suppression (AS). Patients with AS may be well most of the time but if GC therapy is reduced or stopped or if additional endogenous GC cannot be generated during illness, then an absolute or relative lack of GC can result in severe illness or death. Here, we highlight the relevance of AS to all paediatricians by providing an overview of the background and discussing the presentation and approaches to the management of this clinical entity.
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Glucocorticoides/uso terapéutico , Insuficiencia Suprarrenal/inducido químicamente , Insuficiencia Suprarrenal/diagnóstico , Niño , Humanos , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Derivación y ConsultaRESUMEN
Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutation's age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same ~123 kb haplotype whose population frequency is ≤10%. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction.
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Efecto Fundador , Mutación Missense , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/genética , Reproducción , Evolución Molecular , Femenino , Hormona Liberadora de Gonadotropina/deficiencia , Haplotipos , Humanos , Masculino , Linaje , Polimorfismo de Nucleótido Simple , Grupos Raciales/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/metabolismoRESUMEN
BACKGROUND: Preterm infants represent up to 10% of births worldwide and have an increased risk of adverse metabolic outcomes in later life. Early life exposures are key factors in determining later health but current lifestyle factors such as diet and physical activity are also extremely important and provide an opportunity for targeted intervention. METHODS/DESIGN: This current study, GROWMORE, is the fourth phase of the Newcastle Preterm Birth Growth Study (PTBGS), which was formed from two randomised controlled trials of nutrition in early life in preterm (24-34 weeks gestation) and low birthweight infants. 247 infants were recruited prior to hospital discharge. Infant follow-up included detailed measures of growth, nutritional intake, morbidities and body composition (Dual X Ray Absorptiometry, DXA) along with demographic data until 2 years corrected age. Developmental assessment was performed at 18 months corrected age, and cognitive assessment at 9-10 years of age. Growth, body composition (DXA), blood pressure and metabolic function (insulin resistance and lipid profile) were assessed at 9-13 years of age, and samples obtained for epigenetic analysis. In GROWMORE, we will follow up a representative cohort using established techniques and novel metabolic biomarkers and correlate these with current lifestyle factors including physical activity and dietary intake. We will assess auxology, body composition (BODPOD), insulin resistance, daily activity levels using Actigraph software and use 31P and 1H magnetic resonance spectroscopy to assess mitochondrial function and intra-hepatic lipid content. DISCUSSION: The Newcastle PTBGS is a unique cohort of children born preterm in the late 1990's. The major strengths are the high level of detail of early nutritional and growth exposures, and the comprehensive assessment over time. This study aims to examine the associations between early life exposures in preterm infants and metabolic outcomes in adolescence, which represents an area of major translational importance.
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Protocolos Clínicos , Recien Nacido Prematuro/crecimiento & desarrollo , Recien Nacido Prematuro/metabolismo , Absorciometría de Fotón , Antropometría , Composición Corporal , Niño , Desarrollo Infantil , Cognición , Estudios de Cohortes , Inglaterra , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Resistencia a la Insulina , Lípidos/análisis , Hígado/química , Espectroscopía de Resonancia Magnética , Masculino , Modelos Biológicos , Actividad Motora , Estado Nutricional , Fosforilación Oxidativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The specific mechanisms driving autoimmunity in Graves' disease (GD) remain largely unknown. Kappa-deleting recombination excision circles (KRECs) are circular DNA molecules generated during B cell maturation in the bone marrow which provide a measure of B cell production and proliferation. We aimed to investigate the association between KRECs and B cell subpopulations, with thyroid status and clinical outcome in GD patients. METHODS: Kappa-deleting recombination excision circles were measured by quantitative real-time PCR using a triple-insert plasmid control in 132 GD patients and 140 healthy controls. In addition, KRECs in GD patients on withdrawal of antithyroid drug (ATD) and 6-10 weeks later were analysed according to a clinical outcome at 1 year. Flow cytometry was performed on isolated CD19+ B cells to quantitate 7 B lymphocyte subpopulations in 65 GD patients. RESULTS: Circulating KRECs were higher in GD vs. controls (P = 1.5 × 10-9) and demonstrated a positive correlation to thyroid hormones and autoantibodies (free thyroxine: P = 2.14 × 10-5, rho = .30; free triiodothyronine: P = 1.99 × 10-7, rho = .37; thyroid stimulating hormone receptor autoantibodies: P = 1.36 × 10-5, rho = .23). Higher KRECs in GD patients 6-10 weeks after ATD withdrawal were associated with relapse of hyperthyroidism at 1 year (P = .04). The KRECs were positively correlated to the total CD19+ B cell count (P = 3.2 × 10-7). CONCLUSIONS: This study reports a robust association between KRECs and GD, highlighting the importance of B cells in the pathogenesis of GD and the influence of thyroid status on B cell activity. The findings indicate a potential role for KRECs as a marker of disease activity and outcome in GD.
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Enfermedad de Graves , Hipertiroidismo , Humanos , Células Precursoras de Linfocitos B/patología , Antitiroideos/uso terapéutico , Triyodotironina , Hormonas TiroideasRESUMEN
Glucocorticoids (GC) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown. OBJECTIVE: To assess hypothalamic-pituitary-gonadal axis, muscle volume and function 5 years after pubertal induction. METHODS: A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2y) then evaluated at +2.5y and +5y (final follow-up~ 3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function and limb muscle MRI. RESULTS: Participants were 18.7 years (SD 1.6) at final follow-up and had been on GC for 11.2 years (SD 2.2). Testosterone levels were similar at +2.5y (8.6nmol/l (SD 3.4) and 5y (11.0 nmol/l (SD 6.1). TV increased from 2.8 mls (SD 0.9) at +2y to 7.1 mls (SD 1.8) then 10.6 mls (SD 3.5) at +2.5y and +5.0y(p<0.001). Inhibin B levels increased from 55.6 pg/ml (SD 47.0) at baseline to 158.2 pg/ml (SD 87.6), p=0.004 at 5y but remained lower than reference values (mean 305 pg/ml). Muscle contractile bulk decreased. INTERPRETATION: Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in Inhibin B, TV and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle and wellbeing, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important.
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CONTEXT: Quality of life (QoL) has been inconsistently reported in children and young people (CYP) with congenital adrenal hyperplasia (CAH). OBJECTIVE: Assess QoL in CYP with CAH in the UK alongside biometric and androgen profiles. DESIGN: To define the evidence base for health care delivery, we conducted a cross-sectional study in CYP with CAH in the UK. Questionnaire results were compared with normative data and between groups, and modelled for association with sex, height, weight, body mass index, or steroid biomarkers of CAH control. SETTING: Tertiary care in 14 UK centers. PATIENTS: Results from 104 patients, 55% female, mean age 12.7 years (SD 3.0), paired responses from parents. INTERVENTIONS: Strengths and Difficulties questionnaire (SDQ) and pediatric QoL questionnaire. MAIN OUTCOME MEASURE: Total QoL scores as assessed by SDQ and a pediatric QoL questionnaire in comparison to normative data. RESULTS: Total scores were worse in parents than normative data, but similar in patients. Patient QoL was rated better in social functioning but worse in emotional, school, and peer domains by patients, and worse in total scores and domains of peer problems, and psychosocial, emotional, and school functioning by parents. Parents consistently scored QoL of their children lower than their child. Larger height-SD score and lower weight-SD score were associated with better QoL. Girls with lower steroid biomarkers had worse SDQ scores. CONCLUSIONS: In CYP with CAH, reduced height, increased weight, and hormonal biomarkers consistent with overtreatment were associated with worse QoL; addressing these problems should be prioritized in clinical management.Clinical Trials Registration Number: SCH/15/088.
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Hiperplasia Suprarrenal Congénita , Niño , Humanos , Femenino , Adolescente , Masculino , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Calidad de Vida/psicología , Estudios Transversales , Biomarcadores , Esteroides , Reino Unido/epidemiologíaRESUMEN
Objective: Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design: A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy. Methods: Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results: There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations. Conclusions: DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy.
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Hyperthyroidism caused by Graves' disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults - antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.
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'What's in a name? That which we call a rose/By any other name would smell as sweet.' (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rationale for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology, nephrology and pediatric societies now proposes changing the name of 'diabetes insipidus' to 'arginine vasopressin deficiency (AVP-D)' for central etiologies and 'arginine vasopressin resistance (AVP-R)' for nephrogenic etiologies. This editorial provides both the historical context and the rationale for this proposed name change.
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Diabetes Insípida , Diabetes Mellitus , Arginina , Arginina Vasopresina , Niño , Diabetes Insípida/terapia , HumanosRESUMEN
Recent data show that patients with a diagnosis of diabetes insipidus (DI) are coming to harm. Here we give the rationale for a name change to arginine vasopressin deficiency and resistance for central and nephrogenic DI, respectively.
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Diabetes Insípida Nefrogénica , Diabetes Insípida Neurogénica , Diabetes Insípida , Diabetes Mellitus , Humanos , Diabetes Insípida/diagnóstico , Diabetes Insípida/terapia , Diabetes Insípida Nefrogénica/diagnóstico , Diabetes Insípida Neurogénica/diagnóstico , Diabetes Insípida Neurogénica/terapiaRESUMEN
'What's in a name? That which we call a rose/By any other name would smell as sweet' (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word, and it therefore represents a convention with no intrinsic meaning. While this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rationale for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology, and pediatric endocrine societies now proposes changing the name of 'diabetes insipidus' to 'arginine vasopressin deficiency (AVP-D)' for central etiologies, and 'arginine vasopressin resistance (AVP-R)' for nephrogenic etiologies. This article provides both the historical context and the rationale for this proposed name change.
RESUMEN
"What's in a name? That which we call a rose / By any other name would smell as sweet" (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and endocrine pediatric societies now proposes changing the name of "diabetes insipidus" to "Arginine Vasopressin Deficiency (AVP-D)" for central etiologies, and "Arginine Vasopressin Resistance (AVP-R)" for nephrogenic etiologies This editorial provides both the historical context and the rational for this proposed name change.