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BACKGROUND: Knowledge regarding the effects and side effects of gender-affirming hormone therapy (GAHT) in adults is rapidly growing, partly through international research networks such as the European Network for the Investigation of Gender Incongruence (ENIGI). However, data on the effects of puberty suppression (PS) and GAHT in transgender and gender diverse (TGD) youth are limited, although these data are of crucial importance, given the controversies surrounding this treatment. AIM: We sought to present a detailed overview of the design of the ENIGI Adolescents study protocol, including the first baseline data. METHODS: The ENIGI Adolescents study is an ongoing multicenter prospective cohort study. This study protocol was developed by 3 European centers that provide endocrine care for TGD adolescents and were already part of the ENIGI collaboration: Amsterdam, Ghent, and Florence. OUTCOMES: Study outcomes include physical effects and side effects, laboratory parameters, bone mineral density, anthropometric characteristics, attitudes toward fertility and fertility preservation, and psychological well-being, which are measured in the study participants during PS and GAHT, up to 3 years after the start of GAHT. RESULTS: Between November 2021 and May 2023, 172 TGD adolescents were included in the ENIGI Adolescents protocol, of whom 51 were assigned male at birth (AMAB) and 121 were assigned female at birth (AFAB); 3 AFAB participants reported a nonbinary gender identification. A total of 76 participants were included at the start of PS, at a median (IQR) age of 13.7 (12.9-16.5) years in AMAB and 13.5 (12.4-16.1) years in AFAB individuals. The remaining 96 participants were included at start of GAHT, at a median (IQR) age of 15.9 (15.1-17.4) years in AFAB and 16.0 (15.1-16.8) years in AMAB individuals. At the time of this report the study was open for inclusion and follow-up measurements were ongoing. CLINICAL IMPLICATIONS: In response to the rising demand for gender-affirming treatment among TGD youth, this ongoing study is fulfilling the need for prospective data on the effects and safety of PS and GAHT, thus providing a foundation for evidence-based healthcare decisions. STRENGTHS AND LIMITATIONS: This study has a strong multicenter, prospective design that allows for systematic data collection. The use of clinical and self-reported data offers a broad range of outcomes to evaluate. Nevertheless, the burden of additional measurements and questionnaires may lead to withdrawal or lower response rates. Few participants with a non-binary gender identity have been included. CONCLUSION: With the ENIGI Adolescents study we aim to create a comprehensive dataset that we can use for a wide range of studies to address current controversies and uncertainties and to improve healthcare for TGD adolescents.
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Disforia de Género , Personas Transgénero , Adulto , Recién Nacido , Humanos , Masculino , Femenino , Adolescente , Identidad de Género , Personas Transgénero/psicología , Estudios Prospectivos , Disforia de Género/tratamiento farmacológico , Disforia de Género/psicología , Proyectos de InvestigaciónRESUMEN
Genetic syndromes often show facial features that provide clues for the diagnosis. However, memorizing these features is a challenging task for clinicians. In the last years, the app Face2Gene proved to be a helpful support for the diagnosis of genetic diseases by analyzing features detected in one or more facial images of affected individuals. Our aim was to evaluate the performance of the app in patients with Silver-Russell syndrome (SRS) and Prader-Willi syndrome (PWS). We enrolled 23 pediatric patients with clinically or genetically diagnosed SRS and 29 pediatric patients with genetically confirmed PWS. One frontal photo of each patient was acquired. Top 1, top 5, and top 10 sensitivities were analyzed. Correlation with the specific genetic diagnosis was investigated. When available, photos of the same patient at different ages were compared. In the SRS group, Face2Gene showed top 1, top 5, and top 10 sensitivities of 39%, 65%, and 91%, respectively. In 41% of patients with genetically confirmed SRS, SRS was the first syndrome suggested, while in clinically diagnosed patients, SRS was suggested as top 1 in 33% of cases (p = 0.74). Face2Gene performed better in younger patients with SRS: in all patients in whom a photo taken at a younger age than the age of enrollment was available, SRS was suggested as top 1, albeit with variable degree of probability. In the PWS group, the top 1, top 5, and top 10 sensitivities were 76%, 97%, and 100%, respectively. PWS was suggested as top 1 in 83% of patients genetically diagnosed with paternal deletion of chromosome 15q11-13 and in 60% of patients presenting with maternal uniparental disomy of chromosome 15 (p = 0.17). The performance was uniform throughout the investigated age range (1-15 years). CONCLUSION: In addition to a thorough medical history and detailed clinical examination, the Face2Gene app can be a useful tool to support clinicians in identifying children with a potential diagnosis of SRS or PWS. WHAT IS KNOWN: ⢠Several genetic syndromes present typical facial features that may provide clues for the diagnosis. ⢠Memorizing all syndromic facial characteristics is a challenging task for clinicians. WHAT IS NEW: ⢠Face2Gene may represent a useful support for pediatricians for the diagnosis of genetic syndromes. ⢠Face2Gene app can be a useful tool to integrate in the diagnostic path of patients with SRS and PWS.
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Síndrome de Prader-Willi , Síndrome de Silver-Russell , Humanos , Niño , Lactante , Preescolar , Adolescente , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/genética , Familia , Computadores , Cromosomas Humanos Par 15/genéticaRESUMEN
Osteoporosis is a condition of increased bone fragility associated with fractures. Apart from primary genetic osteoporotic conditions, secondary osteoporosis in children is being increasingly recognized. As a result, there is growing interest in its prevention and treatment. Important goals of care are to prevent fractures, increase bone mass and trabecular and cortical thickness, reshape vertebral fractures, prevent (or correct) skeletal deformities, and improve mobility, independence, and quality of life. Secondary pediatric osteoporosis is often of multifactorial origin since affected children frequently have more than one acquired factor that is detrimental to bone health. Typical conditions causing osteoporosis are leukemias, progressive muscle or neurological disorders, as well as chronic inflammatory conditions and their treatment. Management of children with osteoporosis involves a multidisciplinary team involving pediatric experts from different subspecialties. With regard to prevention and early intervention, it is important to provide optimal management of any underlying systemic conditions including avoidance, or dose-reduction, of osteotoxic medications. Basic supporting life-style measures, such as appropriate nutrition, including adequate calcium intake and vitamin D, and physical activity are recommended, where possible. When pediatric treatment criteria for osteoporosis are met, antiresorptive drugs constitute the first pharmacological line treatment. CONCLUSION: This clinical review focuses on the prevention, treatment, and follow-up of children with, or at risk of developing, osteoporosis and the transition from pediatric to adult care. WHAT IS KNOWN: ⢠Osteoporosis and associated fractures can cause significant morbidity and reduce the quality of life. ⢠The developing skeleton has huge potential for recovery and reshaping, thus early detection of fractures, assessment of recovery potential, and treatment of children with osteoporosis can prevent future fractures, deformities, and scoliosis, improve function and mobility, and reduce pain. WHAT IS NEW: ⢠Osteoporosis in children and adolescents requires a multidisciplinary approach with a thorough assessment of recovery potential, and indication for therapy should be personalized. ⢠Although bisphosphonates still represent the drug most commonly used to increase bone mass, improve mobility, and reduce pain and recurrence of fractures, new agents are being developed and could be beneficial in children with specific conditions.
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Conservadores de la Densidad Ósea , Osteoporosis , Transición a la Atención de Adultos , Adulto , Niño , Adolescente , Humanos , Calidad de Vida , Osteoporosis/diagnóstico , Osteoporosis/etiología , Osteoporosis/terapia , Conservadores de la Densidad Ósea/uso terapéutico , Vitamina D/uso terapéutico , Densidad Ósea , Difosfonatos/uso terapéuticoRESUMEN
Early recognition of osteoporosis in children and adolescents is important in order to establish an appropriate diagnosis of the underlying condition and to initiate treatment if necessary. In this review, we present the diagnostic work-up, and its pitfalls, of pediatric patients suspected of osteoporosis including a careful collection of the medical and personal history, a complete physical examination, biochemical data, molecular genetics, and imaging techniques. The most recent and relevant literature has been reviewed to offer a broad overview on the topic. Genetic and acquired pediatric bone disorders are relatively common and cause substantial morbidity. In recent years, there has been significant progress in the understanding of the genetic and molecular mechanistic basis of bone fragility and in the identification of acquired causes of osteoporosis in children. Specifically, drugs that can negatively impact bone health (e.g. steroids) and immobilization related to acute and chronic diseases (e.g. Duchenne muscular dystrophy) represent major risk factors for the development of secondary osteoporosis and therefore an indication to screen for bone mineral density and vertebral fractures. Long-term studies in children chronically treated with steroids have resulted in the development of systematic approaches to diagnose and manage pediatric osteoporosis. CONCLUSIONS: Osteoporosis in children requires consultation with and/or referral to a pediatric bone specialist. This is particularly relevant since children possess the unique ability for spontaneous and medication-assisted recovery, including reshaping of vertebral fractures. As such, pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children. WHAT IS KNOWN: ⢠Both genetic and acquired pediatric disorders can compromise bone health and predispose to fractures early in life. ⢠The identification of children at risk of osteoporosis is essential to make a timely diagnosis and start the treatment, if necessary. WHAT IS NEW: ⢠Pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children and children at risk of osteoporosis. ⢠We offer an extensive but concise overview about the risk factors for osteoporosis and the diagnostic work-up (and its pitfalls) of pediatric patients suspected of osteoporosis.
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Conservadores de la Densidad Ósea , Osteoporosis , Fracturas de la Columna Vertebral , Adolescente , Densidad Ósea , Conservadores de la Densidad Ósea/uso terapéutico , Niño , Humanos , Osteoporosis/diagnóstico , Osteoporosis/etiología , Factores de Riesgo , Fracturas de la Columna Vertebral/etiologíaRESUMEN
BACKGROUND: Neurological complications due to reactivation of varicella-zoster virus (VZV) are very uncommon in immunocompetent patients. Generally a vesicular rash is present on one or more dermatomes, preceding or following the main manifestation. Few cases are reported in the international literature, but they concern mainly adult or elderly patients. CASE PRESENTATION: A 12-year-old girl was referred to our hospital for persisting headache, cough and rhinitis for six days. After first examination, diagnosis of anterior sinusitis was made by nasal endoscopy. The day after, the girl developed psychotic symptoms and altered mental status. Computed tomography (CT) scan was immediately performed but was unremarkable; lumbar puncture revealed leukocytosis with lymphocytic predominance and cerebrospinal fluid polymerase chain reaction (PCR) detected varicella-zoster virus DNA. The diagnosis of acute VZV encephalitis was made. The patient was promptly treated with acyclovir infused intravenously and her clinical conditions rapidly improved. Tests made did not show any condition of immunosuppression. CONCLUSIONS: Although if rare, reactivation of VZV can occur in immunocompetent children and its complications can involve central nervous system. Among these complications, meningitis is more common, but cerebral parenchyma can also be involved leading to a severe medical condition that is defined meningoencephalitis. In rare cases vesicular rash may be absent; therefore high level of suspicion is required even in those patients in which suggestive clinical features are not present to guide the diagnosis. Intravenous acyclovir represents the treatment of choice to obtain a fast clinical response and to prevent the onset of late-term complications.
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Exantema , Herpes Zóster , Meningoencefalitis , Aciclovir/uso terapéutico , Adulto , Anciano , Niño , Femenino , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3 , HumanosRESUMEN
Type 1 diabetes (T1D) is the most common chronic metabolic disease in children and adolescents. The etiology of T1D is not fully understood but it seems multifactorial. The genetic background determines the predisposition to develop T1D, while the autoimmune process against ß-cells seems to be also determined by environmental triggers, such as endocrine disrupting chemicals (EDCs). Environmental EDCs may act throughout different temporal windows as single chemical agent or as chemical mixtures. They could affect the development and the function of the immune system or of the ß-cells function, promoting autoimmunity and increasing the susceptibility to autoimmune attack. Human studies evaluating the potential role of exposure to EDCs on the pathogenesis of T1D are few and demonstrated contradictory results. The aim of this narrative review is to summarize experimental and epidemiological studies on the potential role of exposure to EDCs in the development of T1D. We highlight what we know by animals about EDCs' effects on mechanisms leading to T1D development and progression. Studies evaluating the EDC levels in patients with T1D were also reported. Moreover, we discussed why further studies are needed and how they should be designed to better understand the causal mechanisms and the next prevention interventions.
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Diabetes Mellitus Tipo 1/etiología , Diabetes Mellitus Tipo 1/metabolismo , Susceptibilidad a Enfermedades , Disruptores Endocrinos/efectos adversos , Animales , Estudios Clínicos como Asunto , Modelos Animales de Enfermedad , Disruptores Endocrinos/clasificación , Exposición a Riesgos Ambientales/efectos adversos , HumanosRESUMEN
BACKGROUND: X-linked Adrenal Hypoplasia Congenita (AHC) is a rare cause of primary adrenal insufficiency due to mutations in the NR0B1 gene, causing a loss of function of the nuclear receptor protein DAX-1. Adrenal insufficiency usually appears in the first 2 months of life, but can sometimes emerge during childhood. Hypogonadotropic Hypogonadism is often associated later in life and patients may develop azoospermia. We describe an unusual onset of AHC started with isolated hypoaldosteronism as first and only sign of the disease. CASE PRESENTATION: A 18-days-old newborn presented with failure to thrive and feeding difficulties. Blood tests showed severe hyponatremia, hyperkalemia and hypochloremia. Renin was found over the measurable range and aldosterone was low whereas cortisol level was normal with a slightly increased ACTH. In the suspicion of Primary Hypoaldosteronism, correction of plasmatic electrolytes and replacement therapy with Fludrocortisone were promptly started. The subsequent evidence of low plasmatic and urinary cortisol and increased ACTH required the start of Hydrocortisone replacement therapy and it defined a clinical picture of adrenal insufficiency. Genetic analysis demonstrated a novel mutation in the DAX-1 gene leading to the diagnosis of AHC. CONCLUSIONS: AHC onset may involve the aldosterone production itself, miming an isolated defect of aldosterone synthesis. NR0B1/DAX-1 mutations should be considered in male infants presenting with isolated hypoaldosteronism as first sign of adrenal insufficiency.
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Receptor Nuclear Huérfano DAX-1/genética , Insuficiencia Corticosuprarrenal Familiar/genética , Hipoaldosteronismo/genética , Mutación , Insuficiencia Suprarrenal/etiología , Insuficiencia Suprarrenal/genética , Insuficiencia de Crecimiento/etiología , Insuficiencia de Crecimiento/genética , Humanos , Insuficiencia Corticosuprarrenal Familiar/complicaciones , Hipoaldosteronismo/etiología , Recién Nacido , MasculinoRESUMEN
The advancement of genetic knowledge and the discovery of an increasing number of genetic disorders has made the role of the geneticist progressively more complex and fundamental. However, most genetic disorders present during childhood; thus, their early recognition is a challenge for the pediatrician, who will be also involved in the follow-up of these children, often establishing a close relationship with them and their families and becoming a referral figure. In this review, we aim to provide the pediatrician with a general knowledge of the approach to treating a child with a genetic syndrome associated with dysmorphic features. We will discuss the red flags, the most common manifestations, the analytic collection of the family and personal medical history, and the signs that should alert the pediatrician during the physical examination. We will offer an overview of the physical malformations most commonly associated with genetic defects and the way to describe dysmorphic facial features. We will provide hints about some tools that can support the pediatrician in clinical practice and that also represent a useful educational resource, either online or through apps downloaded on a smartphone. Eventually, we will offer an overview of genetic testing, the ethical considerations, the consequences of incidental findings, and the main indications and limitations of the principal technologies.
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BACKGROUND: Gender incongruence (GI) is a term used to describe a marked and persistent incompatibility between the sex assigned at birth (SAAB) and the experienced gender. Some persons presenting with GI experience a severe psychological distress defined as gender dysphoria (GD).. Although the prevalence of GI is probably underestimated, recently a great increase in numbers of transgender and gender diverse (TGD) youths presenting at the gender clinics has been registered. After a careful multidisciplinary evaluation and upon acquisition of informed consent from the youth and the legal guardian(s), puberty suppression can be started in TGD youths, followed by the addition of gender affirming hormones (GAH) by the age of 16 years. Although Italian specific guidelines are available, their application is often complex because of (among other reasons) lack of specialized centers and healthcare professional with experience in the field and the regional differences within the Italian healthcare system. MAIN BODY: To investigate the care offered to TGD youths across Italy, we proposed a survey of 20 questions to the directors of the 32 Italian Centers of pediatric endocrinology participating to the Study Group on Growth and Puberty of the Italian Society of Pediatric Endocrinology (ISPED). Eighteen pediatric endocrinologists representative of 16 different centers belonging to 11 different regions responded to the survey. In the large majority of centers TGD youths are taken in charge between the age of 12 and 18 years and at least three healthcare professional are involved. Most of Italian pediatric endocrinologists follow only a very limited number of TGD youths and reference centers for TGD youths are lacking. CONCLUSION: There is an urgent need for gender clinics (homogeneously distributed on the national territory) where TGD youths can access high standard care.
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Endocrinología , Disforia de Género , Recién Nacido , Niño , Adolescente , Humanos , Disforia de Género/diagnóstico , Disforia de Género/terapia , Endocrinólogos , Pediatras , ItaliaRESUMEN
BACKGROUND: Early puberty suppression (ePS; Tanner stages 2 and 3) through gonadotropin-releasing hormone agonists (GnRHas) and gender-affirming hormones (GAHs) interferes with growth and may impact final height (FH). AIM: To investigate the impact of ePS and GAH on FH in trans boys and trans girls. METHODS: Retrospective study, including 10 trans boys and 22 trans girls at FH. Bone age (BA) was determined at the start of ePS and at the start of GAH according to Greulich and Pyle; predicted adult height (PAH) was calculated according to Bayley and Pinneau's tables; target height (TH) was calculated as adjusted mean of maternal and paternal height. Target height, PAH, and BA were determined according to sex registered at birth (SRAB) and experienced gender (EG). RESULTS: The age at the start of PS was 12.37 ± 0.74 years in trans boys and 13.10 ± 1.12 years in trans girls. Total height gain since the start of ePS in trans boys was 14.62 ± 4.08â cm, with 70% achieved before the start of GAH. In trans girls, it was 20.68 ± 7.66â cm, with 61% achieved before GAH. Target height for SRAB was the most accurate predictor for FH in both trans boys and girls: the difference with FH was 1.57â cm ± 3.1 (P = .168) and -0.98â cm ± 4.17 (P = .319), respectively. Also the difference between FH and PAH at the start of PS for SRAB was nonsignificant in both trans boys and girls (2.62â cm ± 3.79, P = .056 and -2.35â cm ± 5.2, P = .051, respectively). CONCLUSION: Early puberty suppression and GAH do not impact FH, supporting the safety of the treatment; however, trans adolescents achieve a FH in line with SRAB, rather than EG.
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Pubertad Precoz , Personas Transgénero , Adulto , Recién Nacido , Masculino , Femenino , Adolescente , Humanos , Estudios Retrospectivos , Familia , PubertadRESUMEN
The ACTH (adrenocorticotropic hormone) stimulation test is the gold standard for the diagnosis of adrenal insufficiency (AI), performed with ACTH high dose (HDT) or low dose (LDT). As salivary cortisol has been proposed as an alternative to serum cortisol, our aim was to evaluate the reliability of salivary cortisol compared to serum cortisol for diagnosing AI in children. Data were collected retrospectively. Salivary and serum cortisol values derived by 80 ACTH stimulation tests were obtained (39 F, 36 M; median age 11.5 years, IQR 6.9). Sampling was performed at baseline and after 30 and 60 min from ACTH administration during the HDT, and at baseline and 10, 20, 30, 40 and 60 min after the stimulation for the LDT. A serum cortisol level > 420 nmol/L ruled out AI. The correlation coefficients between serum and salivary cortisol for the HDT (n = 24) were 0.80 at t0, 0.48 at t30 and 0.75 at t60. All patients were adrenal sufficient. In 41% of the LDT, peak serum cortisol indicated insufficient adrenal function. The correlation coefficients between serum and salivary cortisol were 0.59 at t0 and 0.33 at the peak. For a cut-off of salivary cortisol < 15 nmol/L, sensitivity was 73.9% and specificity 69.6%. Our data do not support salivary cortisol as a valid alternative to serum cortisol during LDT. Regarding the HDT, results are more encouraging, however, further studies are needed.
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Transgender youth increasingly present at pediatric gender services. Some of them receive long-term puberty suppression with gonadotropin-releasing hormone analogues (GnRHa) before starting gender-affirming hormones (GAH). The impact of GnRHa use started in early puberty on bone composition and bone mass accrual is unexplored. It is furthermore unclear whether subsequent GAH fully restore GnRHa effects and whether the timing of GAH introduction matters. To answer these questions, we developed a mouse model mimicking the clinical strategy applied in trans boys. Prepubertal 4-week-old female mice were treated with GnRHa alone or with GnRHa supplemented with testosterone (T) from 6 weeks (early puberty) or 8 weeks (late puberty) onward. Outcomes were analyzed at 16 weeks and compared with untreated mice of both sexes. GnRHa markedly increased total body fat mass, decreased lean body mass, and had a modest negative impact on grip strength. Both early and late T administration shaped body composition to adult male levels, whereas grip strength was restored to female values. GnRHa-treated animals showed lower trabecular bone volume and reduced cortical bone mass and strength. These changes were reversed by T to female levels (cortical bone mass and strength) irrespective of the time of administration or even fully up to adult male control values (trabecular parameters) in case of earlier T start. The lower bone mass in GnRHa-treated mice was associated with increased bone marrow adiposity, also reversed by T. In conclusion, prolonged GnRHa use started in prepubertal female mice modifies body composition toward more fat and less lean mass and impairs bone mass acquisition and strength. Subsequent T administration counteracts GnRHa impact on these parameters, shaping body composition and trabecular parameters to male values while restoring cortical bone architecture and strength up to female but not male control levels. These findings could help guide clinical strategies in transgender care. © 2023 American Society for Bone and Mineral Research (ASBMR).
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Both in the United States and Europe, the number of minors who present at transgender healthcare services before the onset of puberty is rapidly expanding. Many of those who will have persistent gender dysphoria at the onset of puberty will pursue long-term puberty suppression before reaching the appropriate age to start using gender-affirming hormones. Exposure to pubertal sex steroids is thus significantly deferred in these individuals. Puberty is a critical period for bone development: increasing concentrations of estrogens and androgens (directly or after aromatization to estrogens) promote progressive bone growth and mineralization and induce sexually dimorphic skeletal changes. As a consequence, safety concerns regarding bone development and increased future fracture risk in transgender youth have been raised. We here review published data on bone development in transgender adolescents, focusing in particular on differences in age and pubertal stage at the start of puberty suppression, chosen strategy to block puberty progression, duration of puberty suppression, and the timing of re-evaluation after estradiol or testosterone administration. Results consistently indicate a negative impact of long-term puberty suppression on bone mineral density, especially at the lumbar spine, which is only partially restored after sex steroid administration. Trans girls are more vulnerable than trans boys for compromised bone health. Behavioral health measures that can promote bone mineralization, such as weight-bearing exercise and calcium and vitamin D supplementation, are strongly recommended in transgender youth, during the phase of puberty suppression and thereafter.
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In case of primary hypothyroidism, reactive pituitary hyperplasia can manifest as pituitary (pseudo) macroadenoma. We report the case of a 12-year-old boy who was evaluated for impaired growth velocity and increased body weight. Because of low insulin-like growth factor 1 levels and poor response to the growth hormone stimulation test, brain magnetic resonance imaging was performed and a pituitary macroadenoma was found. Treatment with levothyroxine was started, and thyroid function was evaluated approximately every 40 days to titrate the dosage. After few months of therapy, the size of the macroadenoma decreased and growth hormone secretion normalized. The pituitary returned to normal size in approximately 5 years. The boy went through puberty spontaneously and reached a normal adult height. In a patient affected by primary hypothyroidism, reactive pituitary hyperplasia can cause growth hormone deficiency; however, growth hormone secretion usually normalizes after starting levothyroxine treatment. Pituitary macroadenoma can be difficult to distinguish from severe pituitary hyperplasia; however, pituitary macroadenomas are rare in childhood, and our clinical case underlines how the hormonal evaluation is essential to achieve a correct diagnosis and prevent unnecessary surgery in a context of pituitary mass.
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BACKGROUND/AIMS: Obesity is a multifactorial disease caused by the interaction of genetic, environmental, and behavioral factors. Currently, only a small number of obese children undergo genetic analysis, usually when obesity is associated with dysmorphic features. The aim of this study was to identify genomic rearrangement causing obesity. METHODS: We analyzed the DNA of children and adolescents by single-nucleotide polymorphism-array (platform CytoScan HD, Affymetrix). Patients included in this study were obese with dysmorphic features and/or intellectual disabilities and/or neuropsychomotor signs. RESULTS: Ninety-four children and adolescents with obesity (9.25 ± 4.04 years old, 60 males) were enrolled in the study. Dysmorphic features were found in 64 out of 94 subjects (68.1%), intellectual disability was found in 23 subjects (24.5%), and other neuropsychomotor signs in 31 (32.9%). Copy number variations (CNVs) were identified in 43 out of 94 patients (45.7%): among these 14 subjects showed at least 1 deletion, 22 duplication, whereas 7 patients showed both deletion and duplication. In 20 subjects (13 males), CNVs were linked or possibly related with obesity; in 23 subjects, this correlation cannot be inferred. CONCLUSION: A genetic origin of obesity was detected in about half of our obese children and adolescents with associated dysmorphic features and/or intellectual disability and/or neuropsychomotor signs. In these children, array-CGH analysis can be useful to identify causative genetic mutations, with consequent advantage in therapeutic management and follow-up of these patients.
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Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN/genética , Pruebas Genéticas , Mutación , Obesidad Infantil/genética , Adolescente , Niño , Femenino , Humanos , Discapacidad Intelectual/genéticaRESUMEN
Cartilage hair hypoplasia syndrome (OMIM # 250250) is a rare autosomal recessive metaphyseal dysplasia, characterized by disproportionate short stature, hair hypoplasia and variable extra-skeletal manifestations, including immunodeficiency, anemia, intestinal diseases and predisposition to cancers. Cartilage hair hypoplasia syndrome has a broad phenotype and it is caused by homozygous or compound heterozygous mutation in the mitochondrial RNA-processing endoribonuclease on chromosome 9p13. Although it is well known as a primordial dwarfism, descriptions of the prenatal growth are missing. To add further details to the knowledge of the phenotypic spectrum of the disease, we report on two siblings with cartilage hair hypoplasia syndrome, presenting n.64C > T homozygous mutation in the mitochondrial RNA-processing endoribonuclease gene. We describe the prenatal and postnatal growth pattern of the two affected patients, showing severe pre- and post-natal growth deficiency.
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Cabello/anomalías , Enfermedad de Hirschsprung/genética , Osteocondrodisplasias/congénito , Enfermedades de Inmunodeficiencia Primaria/genética , ARN Largo no Codificante/genética , Femenino , Cabello/patología , Enfermedad de Hirschsprung/patología , Homocigoto , Humanos , Lactante , Masculino , Osteocondrodisplasias/genética , Osteocondrodisplasias/patología , Fenotipo , Mutación Puntual , Enfermedades de Inmunodeficiencia Primaria/patología , HermanosRESUMEN
BACKGROUND: The involvement of myocardium and pericardium at the same time is very uncommon as first manifestation of juvenile idiopathic arthritis with systemic onset (soJIA). CASE: A fourteen years-old boy, referred with symptoms of acute gastroenteritis, developed a perimyocarditis as first manifestation of Still's Disease, after only one day from the admission. The rheumatologic disease was not responding to glucocorticoid treatment. The use of anakinra was the key point of the therapy and after its administration the patient started to recover fastly. CONCLUSIONS: This case report describes cardiac involvement as first sign of soJIA and the successful use of anakinra inducing remission of soJIA not-responding to steroid therapy.