Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8+) cytotoxic T lymphocytes (CD8+-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8+-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8+-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8+ T cell recognition may provide insights for future pre-clinical studies.
RESUMOObjetivos: Avaliar o programa de rastreamento neonatal da Secretaria de Estado da Saúde de Santa Catarina, em relação ao hipotireoidismo congênito (HC), e estimar sua prevalência nas crianças rastreadas. Método: Foram rastreadas 390.759 crianças no período de 01/94 a 12/98, sendo avaliada: a cobertura do programa, as idades na coleta da 1ª amostra de sangue para dosagem de TSH, os tempos para envio da amostra ao laboratório central (LACEN), resultado da dosagem do TSH e localização das crianças com exames alterados e as idades na 1 a consulta e no início do tratamento e a dose de L-T4 prescrita. Resultados: A cobertura do programa foi de 81%, tendo sido detectadas 123 crianças com HC, com prevalência de 1:3.177. A idade média das crianças na coleta da 1 a amostra foi de 17,6 dias. As médias de tempo foram: 7,4 dias para a chegada da amostra ao LACEN, 2,4 dias para o resultado da dosagem do TSH e 7,6 dias para a localização da criança e a 1 a consulta. Todas as crianças detectadas foram atendidas no Hospital Infantil Joana de Gusmão e tinham, em média, idade de 40,2 dias na 1 a consulta e no início do tratamento. A dose média de L-T4 prescrita foi 12,5µg/kg/dia. Conclusão: O tempo para a dosagem do TSH e a dose de L-T4 prescrita são adequados. As demais variáveis estão fora do tempo preconizado, acarretando atraso no início do tratamento. A prevalência de HC é de 1 caso para cada 3.177 crianças rastreadas. Methods: 390,759 newborns were screened for CH between 01/94 and 12/98 to evaluate: the program coverage, children's age at the time of the 1 st blood sample for TSH measurement, time to transport blood samples to the core laboratory (LACEN), time to obtain TSH results, time to locate children with abnormal exams, maternal age at the time of the 1 st clinical appointment and beginning of treatment, and dose of L-T4 prescribed. Results: Program coverage was 81% and 123 children were diagnosed with CH and the estimated prevalence was 1:3,177. The mean age at the time of the 1 st blood sample was 17.6 days. The mean intervals between blood sampling and the various outcomes were: 7.4 days to transport samples to LACEN, 2.4 days to obtain laboratory results, 7.6 days to locate positive-screened children and bring them to their 1 st clinical appointment. All positive-screened children were evaluated at Joana de Gusmão Sick Children Hospital. The mean age at the time of the 1 st clinical appointment and beginning of treatment was 40.2 days. The mean dose of L-T4 prescribed was 12.5µg/kg/day. Conclusion: Time between TSH dosage and prescription of L-T4 is appropriate. All other variables are outside the recommended time frame, resulting in delays artigo original
Congenital hypothyroidism (CH) is the most common congenital endocrine disorder, with an incidence of 1:2,000 to 1:4,000 live births and it is a leading preventable mental retardation. Neonatal Screening Programs allow early identification of the disease and the adequate treatment of affected children can avoid the complications related to deprivation of the hormone. Most cases of primary congenital hypothyroidism (85%) are due to thyroid dysgenesis (ectopia, hypoplasia or agenesis) while the remaining result from defects in hormone synthesis. Affected children (> 95%) usually have no symptoms suggesting the disease at birth. The most frequent symptoms and signs are prolonged neonatal jaundice, hoarse cry, lethargy, slow movements, constipation, macroglossia, umbilical hernia, large fontanelle, hypotonia and dry skin. Around the world, various strategies are used for the screening of the CH. In Brazil, screening for CH is mandatory by law and usually done by serum TSH in dried blood collected from the heel. The recommended age for performing this test is after 48 hours of life until the 4 th day. Diagnostic confirmation is required dosing TSH and free T 4 or total T 4 in serum. Arq Bras Endocrinol Metab. 2013;57(3):184-92Keywords Congenital hypothyroidism; neonatal screening RESUMO O hipotireoidismo congênito (HC) é o distúrbio endócrino congênito mais frequente, com incidência variando de 1:2.000 a 1:4.000 crianças nascidas vivas e uma das principais causas de retardo mental que pode ser prevenida. Os Programas de Triagem Neonatal para a doença permitem a identificação precoce dos afetados e seu tratamento de modo a evitar as complicações da falta do hormônio. A maioria dos casos de hipotireoidismo congênito é decorrente de disgenesias tireoidianas (85%), entre elas a ectopia, hipoplasia ou agenesia tireoidianas, e os demais resultam de defeitos de síntese hormonal. As crianças afetadas (> 95%) geralmente não apresentam sintomas sugestivos da doença ao nascimento. Os sintomas e sinais mais comuns são: icterícia neonatal prolongada, choro rouco, letargia, movimentos lentos, constipação, macroglossia, hérnia umbilical, fontanelas amplas, hipotonia e pele seca. Várias estratégias são utilizadas para a triagem do HC. No Brasil, esta é obrigatória por lei e geralmente é feita com a dosagem de TSH em sangue seco coletado do calcanhar. A idade recomendada para sua realização é após as 48 horas de vida até o quarto dia. A confirmação diagnóstica é obrigatória com as dosagens de TSH e T 4 livre ou T 4 total. Arq Bras Endocrinol Metab. 2013;57(3):184-92 Descritores Hipotireoidismo congênito; triagem neonatal
SUMÁRIOO hipotireoidismo congênito (HC) é uma das causas mais frequentes de deficiência mental passível de prevenção. Esforços devem ser utilizados na sua detecção e no tratamento precoces. O atraso no diagnóstico e no tratamento resultará em sequela neurocognitiva. A triagem neonatal mudou a evolução natural dessa enfermidade. O nível de corte do TSH utilizado é 10 mUI/l. No Brasil, a triagem neonatal é realizada há três décadas. Atualmente todos os estados brasileiros e o Distrito Federal a realizam. Analisando os últimos dados do Programa Nacional de Triagem Neonatal (PNTN), observamos que existe uma diferença enorme entre os Serviços de Referência nos vários estados. A cobertura do PNTN é de 81,61% dos recém-nascidos. Apenas 56,94% colheram a amostra até sete dias de vida. Os tempos médios da coleta até a chegada da amostra ao laboratório, da realização da dosagem do TSH, da liberação do resultado e reconvocação das crianças suspeitas estão fora do preconizado, culminando numa idade média de início de tratamento muito acima da ideal. Isso resulta na impossibilidade de cumprimento do principal objetivo da triagem, que é o início precoce do tratamento para a prevenção de sequelas. Estudos recentes têm sugerido mudança do nível de corte do TSH para 6 mUI/l para reduzir os falso-negativos. Medidas devem ser adotadas para que os índices ideais do PNTN sejam atingidos. Arq Bras Endocrinol Metab. 2011;55(8):528-33 Descritores Triagem neonatal; hipotireoidismo congênito SUMMARY Congenital hypothyroidism (CH) is one of the most common treatable causes of mental retardation. Efforts should be done in its early detection and treatment. Delays in diagnosis and treatment will result in impaired neurocognitive outcomes. Neonatal screening changed the natural history of this disease. The cutoff value for TSH is 10 mUI/L. In Brazil, neonatal screening has been done for three decades. Currently, it is performed in all Brazilian States and the Brazilian Federal District. Looking at recent data on the National Program for Neonatal Screening (NPNS) we can see a huge difference in the results among Brazilian States. NPNS involved 81.61% of the newborns. Only in 56.94% of the cases, samples were collected from newborns up to 7 days of life. Mean time of collection to arrival of the specimen in the lab, TSH determination, release of results and summoning the patient are far longer than the ideal times, causing a delay in early treatment to prevent neurological sequelae. Recent studies have suggested that changing TSH cutoff values to 6 mUI/L may reduce false negative results. Strategies should be adopted to achieve the goals established by the NPNS. Arq Bras Endocrinol Metab. 2011;55(8):528-33
Objective: Evaluate the Neonatal Screening Program (NSP) for congenital adrenal hyperplasia (CAH) of the Department of Health of the State of Santa Catarina (Secretaria de Estado da Saúde de Santa Catarina, SES/SC), and provide information to improve the program. Subjects and methods: Descriptive, retrospective study of 748,395 children screened between January 2001 and December 2010. We analyzed the coverage of the NSP-SES/SC prevalence of CAH, child's age when the first sample for 17-hydroxyprogesterone (17OHP) measurement was collected, levels of 17OHP, mean age at treatment onset and main clinical manifestations. Results: The NSP-SES/ SC covered 89% of the live newborns in the State. It diagnosed 50 cases of CAH, yielding an incidence of 1:14,967. Mean age at collection of the first sample was 7.3 days and mean level of 17OHP was 152.9 ng/mL. The most frequent manifestations were virilized genitalia with nonpalpable gonads, clitoromegaly and genital hyperpigmentation. In three girls, the genre established at birth was incorrect. The salt-wasting form was present in 74% of the cases. There was no occurrence of shock or death. Mean age at treatment onset in the salt-wasting form was 17.4 days compared with 54.9 days in those without the salt-wasting form of the disease. All children were treated with hydrocortisone, and those with salt-wasting CAH were also treated with fludrocortisone. Conclusions: The incidence of CAH was 1 case to 14,967 live newborns. Collection of the first sample occurred outside the recommended time, resulting in delays in treatment onset. Arq Bras Endocrinol Metab. 2014;58(7):765-71
IntroduçãoO hipotireoidismo congênito (HC) consiste num distúr-bio metabólico sistêmico, caracterizado por uma secreção inadequada de hormônios tireoidianos, provocada por alterações funcionais e/ou anatômicas, e, mais raramente, por uma resistência periférica 1 . É uma causa de retardo mental grave e facilmente evitável, desde que seja diagnosticada e tratada precocemente [2][3][4][5][6] .A primeira descrição de uma criança com este distúrbio foi feita por Thomas Curling na Grã-Bretanha em 1850 7 .As dificuldades para o diagnóstico clínico precoce do HC se devem a ausência ou mesmo inespecificidade dos sinais e sintomas no período neonatal. O diagnóstico clíni-co precoce do HC é incomum. Os sinais e sintomas encontrados são: fontanela posterior aberta, icterícia prolongada, ResumoObjetivo: Os autores têm por objetivo relatar os primeiros resultados do programa de detecção precoce de hipotireoidismo congênito (HC), realizado no período de julho de 1993 a dezembro de 1994 no estado de Santa Catarina.Métodos: Foram estudados todos os lactentes triados para HC pelo Laboratório Central de Saúde do Estado de Santa Catarina (LACEN), no período de julho de 1993 a dezembro de 1994. Foi coletada uma amostra de sangue em papel filtro para dosagem de TSH por imunofluorometria, em triplicata. Na persistência de valores de TSH acima dos de corte, após a reconvocação, os pacientes foram encaminhados para avaliação especializada.Resultados: Dos 135.865 nascimentos ocorridos neste período, foram triadas 82.709 crianças com idade de 0 a 60 dias (61%). Das 82.709 amostras, 304 tiveram resultados anormais (TSH em sangue do cordão > 30µU/ml; de 2 a 7 dias > 20µU/ml; acima de 7 dias > 10µU/ml) e destes, 34 tiveram diagnóstico de HC. A média de idade na primeira consulta foi de 45 dias.Conclusões: A prevalência observada (1:2500) foi maior que a mundial, provavelmente devido a alguns casos de hipotireoidismo congênito transitório. Contudo, a distribuição por sexos (2:1) foi semelhante à descrita na literatura. As manifestações clínicas eram inespecíficas, o que reforça a necessidade do programa. Esforços estão sendo feitos para aperfeiçoar a estrutura do programa no intuito de iniciar a terapêutica o mais precocemente possível.J. pediatr. (Rio J.). 1997; 73(3):176-179: hipotireoidismo congênito, triagem neonatal, nível de corte. AbstractObjective: The authors report early results of a screening program for Congenital Hypothyroidism in Santa Catarina, Brazil.Methods: All the assays (82.709) analysed by Laboratório Central (LACEN) between July 1993 and December 1994 were studied. A blood sample was collected on filter paper for serum Thyroid Stimulating Hormone (TSH) measurement by fluoroimmunoassay, in triplicate. All children who had persistent abnormal TSH values (cord blood: TSH > 30 µU/ml; from 2 to 7 days: >20 µU/ml; older than 7 days: > 10 µU/ml) were recalled for clinical evaluation.Results: Out of 82.709 infants aged from 0 to 60 days (40% of the deliveries in this period), 304 presented abnormal results of TSH and 34 were co...
For the etiological diagnosis, history, physical examination, and additional tests (TSH, free thyroxine, thyroglobulin, bone age assessment, thyroid ultrasound) were carried out in the first visit. Results: The etiology was established in the first visit in 53.3% of cases. Thyroid dysgenesis represented 51.11% of the cases, from which 20% showed hypoplastic thyroid, 13.3% showed athyreosis, and 17.7% showed ectopic glands; 2.2% were diagnosed with dyshormonogenesis. Umbilical hernia was the most prevalent sign (48.89%) and 20% had no clinical manifestations. Patients with dysgenesis showed significant differences (p < 0.05) in terms of cesarean section delivery, delayed bone age, and very high serum TSH. Conclusions: The diagnostic approach used at first visit for PCH patients may determine the etiology in 53.3% of cases. Half of patients had thyroid dysgenesis. Arq Bras Endocrinol Metab. 2012;56(9):627-32
Background/Aims: Premature pubarche is associated with conditions such as virilizing congenital adrenal hyperplasia, androgen-secreting tumors, and exogenous exposure to androgen products. We describe the clinical and hormonal features of a series of children who were referred to endocrine evaluation due to premature pubarche. Methods: This is a retrospective case series study of 14 children with premature pubarche and/or virilization. Five were unintentionally exposed to testosterone gel (parental use). Nine patients were intensely exposed to diaper rash prevention creams. Clinical and laboratory data were revised. Results: Moderate to severe virilization was detected in the 5 patients (2 boys and 3 girls) who were exposed to testosterone gel. These patients had pubic hair development associated with clitoromegaly (3/3), penile enlargement (2/2), and accelerated growth (5/5). Testosterone levels were elevated in 4/5 patients associated with normal prepubertal gonadotropin levels and adrenal androgen precursors. The 9 children who were intensely exposed to diaper rash prevention creams had mild pubarche (intermediate hair) without any other clinical manifestation of pubertal development. Three of them exhibited pubic hair thinning after cream withdrawal. Conclusion: Unintentional topical androgen exposure or the intense use of diaper rash prevention cream should be ruled out in children with precocious pubarche and/or virilization signs to avoid misdiagnosis and expendable investigation.
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