Neonates Born to Mothers with Graves' Disease: 15 Year Experience of a Pediatric Endocrinology Department.

INTRODUCTION: Graves disease is characterized by the existence of autoantibodies directed to the thyrotropin receptor, which can have a stimulatory/inhibitory action, in women with the condition, their fetus or neonate. Our aim was to review the case series of these neonates in order to establish neonatal thyroid function predictors. MATERIAL AND METHODS: Retrospective cohort study of the database of the Department of Pediatric Endocrinology, including patients born to mothers with Graves' disease, between 2002 and 2017. Clinical and biochemical data were collected from mothers and offspring. RESULTS: Fifty newborns, from 46 women with a median of 3.5 years after diagnosis, were included. During all trimesters of pregnancy, more than half of women had positive autoantibodies directed to the thyrotropin receptor. Not every woman had a complete thyroid function evaluation every trimester. In 32 newborns, cord blood screening was done. During the neonatal period, there were three cases of hypothyroidism and two of hyperthyroidism. The mothers of these five newborns had higher levels of free thyroid hormones during the second trimester (p = 0.03). The level of antibodies directed to the thyrotropin receptor was significantly higher in the cord blood (p = 0.03) and in the first neonatal test (p = 0.03) of these dysthyroid newborns. DISCUSSION: Our results reinforce the need for every pregnant woman with Graves' disease to be subject to thyroid function and autoantibodies evaluation during every trimester, as well as the importance of evaluating these antibodies in cord blood. CONCLUSION: High levels of free thyroid hormones during the second trimester of pregnancy and antibodies directed to the thyrotropin receptor value in cord blood are predictors of dysthyroidism in neonates born from women with Grave's disease.

Introdução: A doença de Graves é caraterizada pela existência de autoanticorpos dirigidos ao recetor da tirotrofina, que podem ter uma ação estimuladora/inibitória, ao nível da mulher com a doença, bem como do seu feto ou recém-nascido. Quisemos rever a nossa série de casos de filhos de mães com doença de Graves de forma a estabelecer preditores da função tiroideia neonatal. Material e Métodos: Estudo retrospetivo de uma coorte da base de dados da Unidade de Endocrinologia Pediátrica, composta por filhos de mães com doença de Graves, seguidos entre 2002 e 2017. Foram recolhidos dados clínicos e laboratoriais dos processos clínicos das progenitoras e seus filhos. Resultados: Foram incluídos 50 recém-nascidos, de 46 mulheres com uma mediana de 3,5 anos de diagnóstico. Em todos os trimestres de gravidez, mais de metade das mulheres tinham autoanticorpos dirigidos ao recetor da tirotrofina positivos. Nem todas fizeram uma avaliação trimestral completa da função tiroideia. O rastreio no sangue do cordão foi realizado em trinta e dois recémnascidos. Durante o período neonatal houve três casos de hipotiroidismo e dois de hipertiroidismo. As mães destes recém-nascidos tinham valores mais elevados das frações livres das hormonas tiroideias no segundo trimestre (p = 0,03). O valor dos anticorpos dirigidos ao recetor da tirotrofina no sangue do cordão e na primeira avaliação neonatal foi significativamente mais elevado (p = 0,03 em ambos) nos recém-nascidos distiroideus. Discussão: Os nossos resultados sublinham a importância de todas as mulheres grávidas, com doença de Graves, fazerem a avaliação da função tiroideia e autoanticorpos dirigidos ao recetor da tirotrofina em cada trimestre, bem como da avaliação destes anticorpos no sangue do cordão. Conclusão: Valores elevados das frações livres das hormonas tiroideias no segundo trimestre de gravidez e de anticorpos dirigidos ao recetor da tirotrofina no sangue do cordão são preditores de distiroidismo nos recém-nascidos filhos de mães com doença de Graves.

Cystic nephroma and DICER1 mutations: report of a hitherto unreported mutation / Nefroma quístico e mutações DICER1: relato de uma nova mutação

ABSTRACT Paediatric cystic nephroma is a neoplasm of uncertain pathogenesis characterized by a multilocular architecture that develops in children. Some cases may be sporadic, and others may present a familial association, together with other neoplasms, as part of a DICER1 syndrome. We present a case of a paediatric cystic nephroma with an unreported DICER1 mutation and explore the differential diagnosis mainly with cystic partially differentiated nephroblastoma.

RESUMO Nefroma quístico pediátrico é uma neoplasia de patogênese incerta caracterizada por uma arquitetura multilocular, que ocorre maioritariamente em crianças. Alguns casos podem ser esporádicos e outros podem apresentar associação familiar, juntamente com outras neoplasias, constituindo a síndrome DICER1. Apresentamos o caso de um nefroma quístico pediátrico com uma mutação do gene DICER1 não reportada na literatura e exploramos o diagnóstico diferencial, principalmente com o nefroblastoma quístico parcialmente diferenciado.

Autoimmune alternating hyper- and hypo-thyroidism: a rare condition in pediatrics.

UNLABELLED: Alternating between hyper- and hypo-thyroidism may be explained by the simultaneous presence of both types of TSH receptor autoantibodies (TRAbs) - thyroid stimulating autoantibodies (TSAbs) and TSH blocking autoantibodies (TBAbs). It is a very rare condition, particulary in the pediatric age. The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time. Many mechanisms may be involved in fluctuating thyroid function: hormonal supplementation, antithyroid drugs and levels of TSAbs and TBAbs. Frequent dose adjustments are needed in order to achieve euthyroidism. A definitive therapy may be necessary to avoid switches in thyroid function and frequent need of therapeutic changes. We describe an immune-mediated case of oscillating thyroid function in a 13-year-old adolescent. After a short period of levothyroxine treatment, the patient switched to a hyperthyroid state that was only controlled by adding an antithyroid drug. LEARNING POINTS: Autoimmune alternating hypo- and hyper-thyroidism is a highly uncommon condition in the pediatric age.It may be due to the simultaneous presence of both TSAbs and TBAbs, whose activity may be estimated in vitro through bioassays.The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time.The management of this condition is challenging, and three therapeutic options could be considered: I-131 ablation, thyroidectomy or pharmacological treatment (single or double therapy).Therapeutic decisions should be taken according to clinical manifestations and thyroid function tests, independent of the bioassays results.A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment. A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment.

[The Importance of Early Referral in Pediatric Acute Liver Failure]. / A Importância da Referenciação Precoce na Falência Hepática Aguda Pediátrica.

INTRODUCTION: Acute liver failure is a rare disorder associated to high morbidity and mortality despite survival improvement through liver transplantation. The importance of a multidisciplinary approach and early referral to a pediatric liver transplantation center were important conclusions of a national meeting in 2008, from which resulted an actuation consensus. OBJECTIVES: To characterize acute liver failure admissions in a Pediatric Intensive Care Unit of the portuguese pediatric livertransplantation center. To compare results before (A) and after (B) 2008. MATERIAL AND METHODS: Observational, retrospective study during a 20 year period (1994-2014). INCLUSION CRITERIA: age < 18 years old and acute liver failure (INR ≥ 2 without vitamin K response and hepatocellular necrosis). Children with previous liver disease were excluded. RESULTS: Fifty children were included, with median age of 24.5 months. The most common etiology under 2 years old was metabolic (34.6%) and above that age was infectious (29.2%). Forty six percent were submitted to liver transplantation and 78% of them survived. Overall mortality was 34%. Median referral time was 7 days in period A (n = 35) and 2 days in period B (n = 15; p = 0.006). Pediatric risk of mortality's median was 14.7 in period A and 6.5 in B (p = 0.019). Mortality was 37% vs 26% in periods A and B, respectively (p = 0.474). DISCUSSION AND CONCLUSIONS: Overall mortality was similar to the observed in other European centers. Liver transplantation is in fact the most effective therapeutic option. After 2008, there was a reduction in referral time and cases severity on admission; however, mortality has not reduced so far.

Introdução: A falência hepática aguda é uma doença rara associada a elevada morbilidade e mortalidade apesar do aumento da sobrevida devido ao transplante hepático. Em 2008, decorreu em Portugal uma reunião sobre esta patologia em pediatria, resultando num consenso de atuação que salientou a importância da abordagem multidisciplinar e referenciação precoce para um centro de transplantação hepática. Objetivos: Caracterizar as admissões por falência hepática aguda no Serviço de Cuidados Intensivos Pediátricos do centro português com transplante hepático pediátrico. Comparar resultados antes (A) e depois de 2008 (B). Material e Métodos: Estudo observacional retrospetivo de 20 anos (1994-2014). Critérios de inclusão: idade < 18 anos e falência hepática aguda (INR ≥ 2 sem resposta à vitamina K e necrose hepatocelular). Excluíram-se as crianças com doença hepática crónica. Resultados: Incluíram-se 50 crianças com idade mediana de 24,5 meses. A causa mais comum de falência hepática aguda abaixo dos 2 anos foi metabólica (34,6%) e acima infeciosa (29,2%). Foram submetidos a transplante hepático 46%, tendo sobrevivido 78%. A mortalidade global foi 34%. A mediana do tempo de referenciação foi 7 dias no período A (n = 35) e 2 no B (n = 15; p = 0,006). A mediana do risco de mortalidade prevista pelo PRISM foi 14,7% no período A e 6,5% no B (p = 0,019). A mortalidade foi 37% vs 26% no período A e B respetivamente (p = 0,474).Discussão e Conclusões: A mortalidade global foi sobreponível à de outros centros europeus, sendo o transplante hepático a opção terapêutica mais eficaz. Após 2008 o tempo de referenciação e a gravidade dos casos na admissão reduziram, ainda sem tradução significativa na mortalidade.

Renovascular hypertension: a case with atypical neurological signs.

Secondary hypertension is the most frequent form of hypertension in children. Renovascular disease accounts for 5-10% of all childhood hypertension and should be suspected in the presence of severe hypertension found difficult to manage with medical therapy. Uncontrolled hypertension can lead to severe target organ damage. We describe the case of a 13-month-old baby boy with failure to thrive, recent muscular weakness of the lower extremities and irritability. Hypertension was detected and he was admitted to the paediatric intensive care unit with a refractory hypertensive emergency, despite multiple antihypertensive therapies. Bilateral renal artery stenosis was diagnosed through renal angiography and balloon dilation was performed, leading to lower blood pressure. He is currently withdrawing from antihypertensive medication, and slowly gaining weight and recovering from target organ damage. However, weakness of the lower extremities persists and he has been diagnosed with a neurogenic bladder.

[Hodgkin's Lymphoma and Autoimmunity: Is There a Relationship?]. / Linfoma de Hodgkin e Autoimunidade: Existirá uma Relação?

INTRODUCTION: The relationship between lymphomas and autoimmune diseases has been reported as bi-directional, however there is a few data in pediatric population. The aim of this work is to evaluate the prevalence of autoimmune diseases in children and adolescents with Hodgkin's lymphoma followed in a Pediatric Oncology Unit. MATERIAL AND METHODS: By reviewing Hodgkin's lymphomas data from the past 16 years (collected prospectively), an apparently large incidence of autoimmune diseases, mostly in female patients, was noted. We decided to do this retrospective study with an update on follow-up. Data analyzed: age, gender, autoimmune disease, temporal relation with lymphoma, lymphoma's stage, histologic subtype and treatment. RESULTS: Fifty-two cases were included, 7 (13.5%) of which, all female, had an autoimmune disease diagnosed previously, simultaneously or after lymphoma. Autoimmune diseases were: juvenile idiopathic arthritis, inflammatory bowel disease, Behçet's disease, autoimmune hepatitis, systemic erythematosus lupus, Hashimoto's thyroiditis and idiopathic thrombocytopenic purpura. The diagnosis was made after lymphoma in 4 patients, before in 2 and simultaneously in 1 patient. All cases, except the one with simultaneous diagnosis, are out of treatment and without oncologic disease relapse. No deaths were registered. DISCUSSION: There was an important prevalence of autoimmune diseases in girls with Hodgkin's lymphoma. We present data and discuss the possible causes based on a literature review. CONCLUSIONS: This relationship should be invoked, requiring more studies, especially in pediatric age.

Introdução: A relação entre linfomas e doenças autoimunes é descrita na literatura como bidirecional, existindo poucos dados em idade pediátrica. Este trabalho tem como objetivo avaliar a prevalência de doenças autoimunes em crianças e adolescentes com linfoma de Hodgkin seguidos num Serviço de Oncologia Pediátrica. Material e Métodos: Ao rever a casuística do Serviço de linfomas de Hodgkin nos últimos 16 anos (dados colhidos prospetivamente), constatou-se uma incidência aparentemente elevada de doenças autoimunes nas raparigas pelo que se realizou um estudo retrospetivo, com atualização do seguimento fora de tratamento, relativamente à existência de doenças autoimunes. Avaliaram-se: idade, sexo, tipo de doença autoimune, relação temporal com o linfoma, estádio e grupo histológico do linfoma e terapêutica efetuada. Resultados: Incluíram-se 52 casos de linfoma de Hodgkin, dos quais sete (13,5%), todos do sexo feminino, tiveram uma doença autoimune diagnosticada previamente, em simult'neo ou posteriormente ao linfoma. As doenças autoimunes encontradas foram: artrite idiopática juvenil, doença inflamatória intestinal, doença de Behçet, hepatite autoimune, lúpus eritematoso sistémico, tiroidite de Hashimoto e púrpura trombocitopénica idiopática. Em quatro doentes o diagnóstico foi posterior ao linfoma, em dois, prévio, e num simult'neo. Todos os casos, exceto o diagnóstico simult'neo, estão fora de tratamento e sem recidiva da doença oncológica. Não se verificaram óbitos. Discussão: Verificou-se uma importante prevalência de doenças autoimunes nas raparigas com linfoma de Hodgkin. Apresentamos os dados e discutimos possíveis causas desta relação com base numa revisão bibliográfica. Conclusões: Esta associação deve ser evocada, sendo necessário mais estudos, sobretudo em idade pediátrica.

A rare manifestation of neonatal alloimmune thrombocytopaenia.

Neonatal alloimmune thrombocytopaenia (NAIT) results from a fetomaternal incompatibility with maternal sensitisation against a fetal human platelet antigen (HPA) and antibodies transfer to the fetal circulation, leading to platelet destruction. The clinical presentation is variable and isolated intraocular haemorrhage is rare. We present the case of a male newborn, with intrauterine growth restriction, born at 29 weeks due to pre-eclampsia. He presented proptosis of the left eye, hyphaema and elevated intraocular pressure, with no other signs of haemorrhage. Severe thrombocytopaenia was found (27×10(9)/L). Perinatal infection and maternal thrombocytopaenia were excluded. Positive anti-HPA-1a and antihuman leucocyte antigen class I alloantibodies were found in the mother. Platelet crossmatch between the father's platelets and mother's plasma was positive. Platelet transfusions and intravenous immunoglobulin were given with favourable response. This case highlights an unusual presentation of NAIT, which should be suspected in the presence of severe thrombocytopaenia in the first 24-72 h of life.

Twin pregnancy complicated by vasa previa.

Perinatal morbidity and mortality rates for vasa previa are high when it is not diagnosed antenatally. In this report, a case of vasa previa in a twin pregnancy was diagnosed postnatally, which leads to complications with the first twin. Serial ultrasound during pregnancy did not diagnose a bilobed placenta, a velamentous insertion of the umbilical cord or vasa previa. At 37 weeks, vaginal bleeding was detected in the expulsive stage and vaginal-assisted delivery of both fetuses was undertaken. The first fetus was born pale and anaemic, and required a blood transfusion and therapeutic hypothermia. A high risk of vasa previa is associated with placentas with low-lying insertion, bilobed placentas, velamentous insertions of the umbilical cord, multiple pregnancy and pregnancies conceived after the use of assisted reproductive technologies. Transvaginal ultrasound screening with colour flow Doppler can allow antenatal diagnoses of vasa previa and an improved outcome.