RESUMEN
Cushing's disease (CD) is rare in paediatric practice but requires prompt investigation, diagnosis and therapy to prevent long-term complications. Key presenting features are a change in facial appearance, weight gain, growth failure, virilization, disturbed puberty and psychological disturbance. Close consultation with an adult endocrinology department is recommended regarding diagnosis and therapy. The incidence of CD, a form of ACTH-dependent Cushing's syndrome (CS), is equal to approximately 5% of that seen in adults. The majority of ACTH-secreting adenomas are monoclonal and sporadic, although recent studies of pituitary tumours have shown links to several deubiquitination gene defects. Diagnosis requires confirmation of hypercortisolism followed by demonstration of ACTH-dependence. Identification of the corticotroph adenoma by pituitary MRI and/or bilateral inferior petrosal sampling for ACTH may contribute to localisation before pituitary surgery. Transsphenoidal surgery (TSS) with selective microadenomectomy is first-line therapy, followed by external pituitary irradiation if surgery is not curative. Medical therapy to suppress adrenal steroid synthesis is effective in the short-term and bilateral adrenalectomy should be considered in cases unfit for TSS or radiotherapy or when urgent remission is needed after unsuccessful surgery. TSS induces remission of hypercortisolism and improvement of symptoms in 70-100% of cases, particularly when performed by a surgeon with experience in children. Post-TSS complications include pituitary hormone deficiencies, sub-optimal catch-up growth, and persisting excess of BMI. Recurrence of hypercortisolism following remission is recognised but infrequent, being less common than in adult CD patients. With experienced specialist medical and surgical care, the overall prognosis is good. Early referral to an experienced endocrine centre is advised.
Asunto(s)
Síndrome de Cushing , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Neoplasias Hipofisarias , Adulto , Niño , Síndrome de Cushing/etiología , Humanos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/epidemiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/etiología , Hipófisis/cirugía , Neoplasias Hipofisarias/cirugía , Resultado del TratamientoRESUMEN
CONTEXT: Analysis of a 2-screen program for congenital hypothyroidism (CH) was performed using differential dried-blood spot thyrotropin (bTSH) cutoffs of 10 mU/L at first screening (all infants) and 5 mU/L at second screening (selected infants). OBJECTIVES: This work aimed to characterize CH infants identified by the second screening and compare infants with bTSH of 5.0 to 9.9 and 10 mU/L or greater on second screening. DESIGN AND PATIENTS: Maternal and neonatal clinical features were retrospectively analyzed for 119 CH babies detected on the second screen in the Lombardy region of Italy, 2007 to 2014. RESULTS: Fifty-two (43.7%) of the 119 CH neonates showed bTSH values ranging from 5.0 to 9.9 mU/L at the second screening (low bTSH group) and 67 (56.3%) bTSH of 10.0 mU/L or greater (high bTSH group). The frequency of thyroid dysgenesis and eutopic gland was similar in both groups, as was the frequency of permanent and transient CH. Moreover, a high frequency of extrathyroidal malformations was found in both groups. The percentage of preterm infants (57.7% vs 23.9%, Pâ <â .001) and infants admitted to the neonatal intensive care unit (50.0% vs 17.9%, Pâ <â .001) was significantly higher in the low vs the high bTSH group. In addition, maternal treatment with glucocorticoids in pregnancy was significantly more frequent in the low bTSH group than in the high bTSH group (11.5% vs 1.5%, Pâ =â .042), as well as maternal hypothyroidism and/or goiter (26.9% vs 10.4%, Pâ =â .036). CONCLUSIONS: This study has demonstrated that a lower TSH cutoff at the second screening can detect additional cases of CH and that a second bTSH cutoff of 5.0 mU/L is appropriate for identifying preterm newborns and babies with associated risk factors.
Asunto(s)
Hipotiroidismo Congénito/diagnóstico , Tamizaje Neonatal , Pruebas de Función de la Tiroides/normas , Tirotropina/sangre , Hipotiroidismo Congénito/sangre , Hipotiroidismo Congénito/epidemiología , Hipotiroidismo Congénito/genética , Pruebas con Sangre Seca/normas , Femenino , Pruebas Genéticas/métodos , Pruebas Genéticas/estadística & datos numéricos , Humanos , Incidencia , Recién Nacido , Italia/epidemiología , Masculino , Tamizaje Neonatal/métodos , Tamizaje Neonatal/organización & administración , Tamizaje Neonatal/normas , Evaluación de Programas y Proyectos de Salud , Estándares de Referencia , Estudios Retrospectivos , Pruebas de Función de la Tiroides/métodosRESUMEN
OBJECTIVE: Hyperinsulinaemic hypoglycaemia (HH) is one of the commonest causes of hypoglycaemia in children. The molecular basis includes defects in pathways that regulate insulin release. Syndromic conditions like Beckwith-Wiedemann (BWS), Kabuki (KS) and Turner (TS) are known to be associated with a higher risk for HH. This systematic review of children with HH referred to a tertiary centre aims at estimating the frequency of a syndromic/multisystem condition to help address stratification of genetic analysis in infants with HH. METHODS: We performed a retrospective study of 69 patients with syndromic features and hypoglycaemia in a specialist centre from 2004 to 2018. RESULTS: Biochemical investigations confirmed HH in all the cases and several genetic diagnoses were established. Responsiveness to medications and the final outcome following medical treatment or surgery were studied. CONCLUSIONS: This study highlights the association of HH with a wide spectrum of syndromic diagnoses and that children with features suggestive of HH-associated syndromes should be monitored for hypoglycaemia. If hypoglycaemia is documented, they should also be screened for possible HH. Our data indicate that most syndromic forms of HH are diazoxide-responsive and that HH resolves over time; however, a significant percentage continues to require medications years after the onset of the disease. Early diagnosis of hyperinsulinism and initiation of treatment is important for preventing hypoglycaemic brain injury and intellectual disability.
Asunto(s)
Hiperinsulinismo Congénito , Niño , Hiperinsulinismo Congénito/tratamiento farmacológico , Hiperinsulinismo Congénito/genética , Diazóxido/uso terapéutico , Estudios de Seguimiento , Humanos , Lactante , Estudios Retrospectivos , SíndromeRESUMEN
Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.
Asunto(s)
Enfermedades de las Glándulas Suprarrenales/complicaciones , Enfermedades de las Glándulas Suprarrenales/terapia , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/terapia , Enfermedades de las Glándulas Suprarrenales/epidemiología , Edad de Inicio , Estatura/fisiología , Niño , Desarrollo Infantil/fisiología , Endocrinología/normas , Endocrinología/tendencias , Humanos , Pediatría/normas , Pediatría/tendencias , Guías de Práctica Clínica como Asunto , PrevalenciaRESUMEN
CONTEXT: Newborn screening program for congenital hypothyroidism (CH) adopting rescreening in at-risk neonates. OBJECTIVES: To estimate the concordance rate for CH in twin pairs discordant at the first screening; to verify whether long-term follow-up of healthy cotwins belonging to CH discordant pairs may be useful to diagnose thyroid hypofunction during development; to evaluate the importance of genetic and environmental influences on liability to permanent and transient CH. DESIGN AND PATIENTS: Forty-seven screening discordant twin pairs were investigated. Proband was defined as the twin in the pair with a positive test at the first screening and a confirmed diagnosis of CH. RESULTS: Seven screening discordant twin pairs became concordant for CH within the first month of life (pairwise concordance of 14.9%) because seven screening negative cotwins showed high TSH values when retested. During long-term follow-up (range, 3 to 21 years), hypothyroidism was diagnosed in two monozygotic screening negative cotwins at the age of 9 months and 12 years, respectively. Furthermore, the twin analysis showed that 95% of liability to transient CH was explained by genetic factors and 5% by environmental (unshared) factors, whereas 64% of phenotypic variance of permanent CH was explained by common environmental factors (shared during the fetal life) and 36% by unshared environmental factors. CONCLUSIONS: This study showed that the introduction of rescreening permits the diagnosis of CH in a greater number of twins. It also showed the importance of long-term follow-up in both twins in the pair, and the role of nongenetic factors in the etiology of permanent CH.
Asunto(s)
Hipotiroidismo Congénito/diagnóstico , Enfermedades en Gemelos/diagnóstico , Tamizaje Neonatal/métodos , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genética , Hipotiroidismo Congénito/genética , Enfermedades en Gemelos/genética , Femenino , Humanos , Recién Nacido , MasculinoAsunto(s)
Trastorno Autístico , Deleción Cromosómica , Trastornos de los Cromosomas , Hiperinsulinismo Congénito , Discapacidad Intelectual , Cromosomas Humanos Par 16 , Hiperinsulinismo Congénito/tratamiento farmacológico , Hiperinsulinismo Congénito/genética , Hiperinsulinismo Congénito/fisiopatología , Diazóxido/farmacología , Humanos , Lactante , Recién Nacido , Masculino , Fenotipo , Vasodilatadores/farmacologíaRESUMEN
AIMS: To evaluate physicians' adjustments of insulin pump settings based on continuous glucose monitoring (CGM) for patients with type 1 diabetes and to compare these to automated insulin dose adjustments. METHODS: A total of 26 physicians from 16 centres in Europe, Israel and South America participated in the study. All were asked to adjust insulin dosing based on insulin pump, CGM and glucometer downloads of 15 patients (mean age 16.2 ± 4.3 years, six female, mean glycated haemoglobin 8.3 ± 0.9% [66.8 ± 7.3 mmol/mol]) gathered over a 3-week period. Recommendations were compared for the relative changes in the basal, carbohydrate to insulin ratio (CR) and correction factor (CF) plans among physicians and among centres and also between the physicians and an automated algorithm, the Advisor Pro (DreaMed Diabetes Ltd, Petah Tikva, Israel). Study endpoints were the percentage of comparison points for which there was full agreement on the trend of insulin dose adjustments (same trend), partial agreement (increase/decrease vs no change) and full disagreement (opposite trend). RESULTS: The percentages for full agreement between physicians on the trend of insulin adjustments of the basal, CR and CF plans were 41 ± 9%, 45 ± 11% and 45.5 ± 13%, and for complete disagreement they were 12 ± 7%, 9.5 ± 7% and 10 ± 8%, respectively. Significantly similar results were found between the physicians and the automated algorithm. The algorithm magnitude of insulin dose change was at least equal to or less than that proposed by the physicians. CONCLUSIONS: Physicians provide different insulin dose recommendations based on the same datasets. The automated advice of the Advisor Pro did not differ significantly from the advice given by the physicians in the direction or magnitude of the insulin dosing.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adolescente , Adulto , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea/métodos , Automonitorización de la Glucosa Sanguínea/normas , Calibración , Niño , Diabetes Mellitus Tipo 1/epidemiología , Relación Dosis-Respuesta a Droga , Europa (Continente)/epidemiología , Femenino , Geografía , Humanos , Sistemas de Infusión de Insulina/normas , Israel/epidemiología , Estudios Longitudinales , Masculino , América del Sur/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: Mutations in TSH receptor (TSHR) are associated with TSH resistance, a genetic defect characterized by a heterogeneous phenotype ranging from severe hypothyroidism to subclinical hypothyroidism (SCH). We assessed the clinical and hormonal pattern of TSHR variants in a series of pediatric patients, and the long-term outcome of growth, biochemical measurements of metabolism, and neuropsychological functions in TSHR mutations carriers. DESIGN: Observational, retrospective study. PATIENTS: Thirty four children (age 7 days to 11 years) and 18 adult carriers of TSHR variants. MEASUREMENTS: The TSHR gene was sequenced by PCR-amplified direct sequencing in 111 pediatric patients with slight to moderate elevation of TSH and normal FT4 levels. The study focused on the: auxological and biochemical parameters, thyroid ultrasound, bone age, bone mineral density (BMD), and intellectual outcome (IQ) were collected during the long follow-up (1-15 years). RESULTS: Seventeen different TSHR variants (eight novel) were identified in 34 of the 111 pediatric patients, with a high prevalence of familial cases (27/34). Neonatal screening for congenital hypothyroidism was positive in half of the TSHR carriers. Growth, IQ, BMD, and biochemical parameters were normal in all subjects. Twenty patients received L-T4 replacement therapy, in all cases before genetic analysis. After re-evaluation, six patients resumed L-T4 therapy: they were compound heterozygous, or single heterozygous and with associated conditions at risk of thyroid impairment (SGA). No adults presented clinical features consistent with impaired thyroid function. CONCLUSIONS: Children carriers of TSHR variants, regardless of L-T4 treatment, show regular growth and neuropsychological development, with no evident biochemical and US alterations.
Asunto(s)
Hipotiroidismo/genética , Mutación , Receptores de Tirotropina/genética , Adulto , Niño , Preescolar , Terapia de Reemplazo de Hormonas/métodos , Humanos , Hipotiroidismo/tratamiento farmacológico , Lactante , Recién Nacido , Estudios Longitudinales , Receptores de Hormona Tiroidea/sangre , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the evolution of congenital hypothyroidism in preterms and the clinical features of permanent forms. STUDY DESIGN: We retrospectively evaluated 24 preterm children detected by newborn screening for congenital hypothyroidism: first screening with blood-thyroid stimulating hormone cutoff ≥10 mU/L and second screening with blood-thyroid stimulating hormone cutoff ≥5 mU/L. After the age of 2 years, patients with eutopic thyroid had diagnostic reevaluations, including thyroid function testing and thyroid ultrasonography after L-thyroxine therapy withdrawal. RESULTS: The first screening identified 21.7% of patients with thyroid stimulating hormone elevation, and the second screening identified 73.9% of patients. One patient (4.4%) was identified with a third screening test; 21 patients had an eutopic thyroid and 3 patients a thyroid dysgenesis. At reevaluation, 5 patients (23.8%) showed permanent hypothyroidism (serum-thyroid stimulating hormone [s-TSH] >10 mU/L) resulting in the need to reintroduce therapy, 5 patients (23.8%) showed persistent hyperthyrotropinemia (s-TSH 5-10 mU/L), and 11 infants (52.4%) transient hypothyroidism (s-TSH <5 mU/L). The main clinical features of patients affected by permanent hypothyroidism were 1 case of assisted reproduction, 2 twins, 2 small for gestational age, 1 maternal thyroiditis, and 2 patients with malformations/syndromes. CONCLUSIONS: Premature birth is a significant risk for congenital hypothyroidism with eutopic thyroid. In preterm infants, the evolution of congenital hypothyroidism remains difficult to predict. Our data emphasizes the high incidence of transient hypothyroidism in preterm infants, and the importance of diagnostic reevaluation to determine the definitive diagnosis.
Asunto(s)
Hipotiroidismo Congénito/diagnóstico , Recien Nacido Prematuro , Tamizaje Neonatal/métodos , Tirotropina/sangre , Estudios de Cohortes , Hipotiroidismo Congénito/tratamiento farmacológico , Hipotiroidismo Congénito/epidemiología , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Incidencia , Recién Nacido , Masculino , Estudios Retrospectivos , Medición de Riesgo , Pruebas de Función de la Tiroides , Tiroxina/uso terapéutico , Resultado del TratamientoAsunto(s)
Pulmón/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Femenino , Humanos , Masculino , UltrasonografíaRESUMEN
The most frequent clinical presentation of intestinal polyps is painless rectal bleeding. Although colonoscopy is the modality of choice for the diagnosis of intestinal polyps, sonography may be the first diagnostic tool in the evaluation of children with bloody stools. Ultrasonography has the advantage of being safe and noninvasive.
Asunto(s)
Hemorragia Gastrointestinal/diagnóstico , Pólipos Intestinales/diagnóstico , Preescolar , Colonoscopía , Femenino , Hemorragia Gastrointestinal/etiología , HumanosRESUMEN
Acquired autoimmune hypothyroidism is common in late childhood and adolescence but is very rare in the first 3 years of life. We report on three cases of autoimmune thyroiditis (AT) in young children who presented with constipation, decreased appetite, and increased hours of sleep. Our cases highlight that AT may remain undiagnosed for a long time in young children owing to the rarity of the disease.
Asunto(s)
Enfermedad de Hashimoto/diagnóstico , Glándula Tiroides/fisiopatología , Apetito/efectos de los fármacos , Preescolar , Estreñimiento/etiología , Estreñimiento/prevención & control , Diagnóstico Tardío , Monitoreo de Drogas , Fatiga/etiología , Fatiga/prevención & control , Femenino , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/prevención & control , Enfermedad de Hashimoto/tratamiento farmacológico , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/fisiopatología , Terapia de Reemplazo de Hormonas , Humanos , Lactante , Masculino , Trastornos del Sueño-Vigilia/etiología , Trastornos del Sueño-Vigilia/prevención & control , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/inmunología , Tiroiditis Autoinmune , Tiroxina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: The diagnosis of community-acquired pneumonia (CAP) is based mainly on the patient's medical history and physical examination. However, in severe cases a further evaluation including chest X-ray (CXR) may be necessary. At present, lung ultrasound (LUS) is not included in the diagnostic work-up of pneumonia. AIM: To describe the ultrasonographic appearance of CAP at presentation and during the follow-up. METHODS: A total of 102 patients with clinical signs and symptoms suggesting pneumonia, who underwent a clinically driven CXR, were evaluated by LUS on the same day. LUS signs of pneumonia included subpleural lung consolidation, B-lines, pleural line abnormalities, and pleural effusion. The diagnostic gold standard was the ex-post diagnosis of pneumonia made by two independent experienced pediatricians on the basis of clinical presentation, CXR and clinical course following British Thoracic Guidelines recommendations. RESULTS: A final diagnosis of pneumonia was confirmed in 89/102 patients. LUS was positive for the diagnosis of pneumonia in 88/89 patients, whereas CXR was positive in 81/89. Only one patient with normal LUS examination had an abnormal CXR, whereas 8 patients with normal CXR had an abnormal LUS. LUS was able to detect pleural effusion resulting from complicated pneumonia in 16 cases, whereas CXR detected pleural effusion in 3 cases. CONCLUSIONS: LUS is a simple and reliable imaging tool, not inferior to CXR in identifying pleuro-pulmonary alterations in children with suspected pneumonia. During the course of the disease, LUS allows a radiation-free follow-up of these abnormalities.
Asunto(s)
Pulmón/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Adolescente , Niño , Preescolar , Infecciones Comunitarias Adquiridas/complicaciones , Infecciones Comunitarias Adquiridas/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Lactante , Masculino , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/etiología , Neumonía/complicaciones , Radiografía , Método Simple Ciego , UltrasonografíaRESUMEN
BACKGROUND: There is a high incidence of congenital anomalies of the kidneys and urinary tract (CAKUT). Early diagnosis of these defects may allow the best medical and/or surgical treatment to be implemented as rapidly as possible, preventing or at least slowing down an evolution toward chronic kidney disease. METHODS: Ultrasound mass screening for kidney and urinary tract abnormalities in infants at 2 months of age was carried out in Salento, Italy. The centers involved in the study examined a total of 17,783 infants between January 1992 and December 2010. RESULTS: A total of 171 CAKUT were identified in the course of the mass screening. The frequency of CAKUT was 0.96%. Vesicoureteral reflux (n = 39) was the most frequent renal abnormality found, followed by ureteropelvic junction obstruction (n = 33), ectopic kidney (n = 26), and renal dysplasia (n = 19). In addition, nephrogenic rests (n = 2), as well as several extra-renal pathologies, including abdominal neuroblastoma (n = 3), were diagnosed incidentally. CONCLUSION: Ultrasound has been effective for early detection of renal and urinary tract anomalies. In addition, this screening has proved to be very useful for the early identification and management of both renal and extra-renal precancerous as well as cancerous lesions. However, most patients requiring surgery in this study (0.24%) would probably have been symptomatic and come to medical attention without routine screening. On the basis of our results screening is not justified.
Asunto(s)
Riñón/anomalías , Riñón/diagnóstico por imagen , Tamizaje Masivo/métodos , Sistema Urinario/anomalías , Sistema Urinario/diagnóstico por imagen , Anomalías Urogenitales/diagnóstico por imagen , Diagnóstico Precoz , Humanos , Hallazgos Incidentales , Lactante , Italia , Riñón/cirugía , Neoplasias Renales/diagnóstico por imagen , Lesiones Precancerosas/diagnóstico por imagen , Valor Predictivo de las Pruebas , Evaluación de Programas y Proyectos de Salud , Ultrasonografía , Obstrucción Ureteral/diagnóstico por imagen , Sistema Urinario/cirugía , Anomalías Urogenitales/cirugía , Reflujo Vesicoureteral/diagnóstico por imagenRESUMEN
The diagnosis of bronchiolitis is based mainly on the patient's medical history and physical examination. However, in severe cases, a further evaluation including chest X-ray (CXR) may be necessary. At present, lung ultrasound (LUS) is not included in the diagnostic work-up of bronchiolitis. This study aimed to compare the diagnostic accuracy of LUS and CXR in children with bronchiolitis, and to evaluate the correlation between clinical and ultrasound findings. Only patients with a diagnosis of bronchiolitis, who had undergone a CXR, were enrolled in the study. Fifty-two infants underwent LUS and CXR. LUS was also performed in 52 infants without clinical signs of bronchiolitis. LUS was positive for the diagnosis of bronchiolitis in 47/52 patients, whereas CXR was positive in 38/52. All patients with normal LUS examination had a normal CXR, whereas nine patients with normal CXR had abnormal LUS. In these patients, the clinical course was consistent with bronchiolitis. We found that LUS is a simple and reliable tool for the diagnosis and follow-up of bronchiolitis. It is more reliable than CXR, can be easily repeated at the patient's bedside, and carries no risk of irradiation. In some patients with bronchiolitis, LUS is able to identify lung abnormalities not revealed by CXR. Furthermore, there is a good correlation between clinical and ultrasound findings. Given the short time needed to get a US report, this technique could become the routine imaging modality for patients with bronchiolitis.