Síndrome de interrupción del tallo pituitario: Relaciones clínicas, bioquímicas y neurorradiológicas / Pituitary stalk interruption syndrome: Clinical, biochemical and neuroradiological relationships

El síndrome de interrupción del tallo pituitario (PSIS) se caracteriza por la demostración neurorradiológica de un tallo pituitario ausente, interrumpido o hipoplásico, adenohipófisis aplásica/hipoplásica o neurohipófisis ectópica. Este síndrome se ha relacionado con formas severas de hipopituitarismo congénito (HPC), asociado a múltiples deficiencias de hormonas pituitarias (MPHD). Evaluamos a pacientes con HPC y PSIS, analizando los signos y los síntomas neonatales al diagnóstico, relacionándolos con las deficiencias hormonales pituitarias y signos neurorradiológicos presentes. Estudiamos retrospectivamente a 80 pacientes asistidos en el Hospital de Niños de Córdoba, con diagnóstico de HPC, de los cuales 42 (52%) presentaron PSIS; 22 mujeres y 20 varones, EC: 5 días-9,5 años. El 62% presentó MPHD y el 38% insuficiencia somatotrófica aislada (IGHD). El análisis de las variables perinatales demostró antecedentes de parto natural en el 52% (11/21) de las MPHD vs. 13% (2/15) de las IGHD. Cuatro pacientes, 2 con MPHD y 2 con IGHD presentaban antecedentes obstétricos consistentes en presentación podálica y transversa respectivamente, todos ellos resueltos mediante operación cesárea. Los signos y los síntomas perinatales fueron hipo- glucemia: 61% en MPHD vs. 19% en IGHD, p: 0,0105; ictericia: 38% en MPHD vs. 25% en IGHD; micropene: 77% en MPHD y colestasis: 19% en MPHD. Convulsiones neonatales se presentaron en el 75% de los niños con MPHD e hipoglucemia. EC media de consulta: 2,1 años en MPHD (30% en el período neonatal, 70% antes de 2 años) y 3,6 años en IGHD (44% en menores de 2 años). Los pacientes con MPHD presentaban: tallo no visible 81% (n: 21/26) vs. tallo hipoplásico: 19% (n: 5/26), p: 0,0001; en IGHD 56% (n: 9/16) vs. 44% (n: 7/16), p: 0,5067, respectivamente. El 100% de los neonatos con HPC tenían tallo pituitario ausente. Concluimos que la demostración de PSIS en niños con HPC proporciona información valiosa como predictor de la severidad fenotípica, la presencia de MPHD y de la respuesta al tratamiento. La baja frecuencia de antecedentes obstétricos posicionales potencialmente distócicos, como parte de los mecanismos fisiopatogénicos responsables de PSIS, indicaría la necesidad de analizar la importancia de posibles factores genéticos y epigenéticos involucrados. El diagnóstico precoz de HPC debe sospecharse en presencia de signos y síntomas clínicos, tales como hipoglucemia, colestasis, micropene y defectos asociados en la línea media facial. La resonancia magnética cerebral debe formar parte de los estudios complementarios en pacientes con esta presunción diagnóstica, especialmente a edades tempranas. El reconocimiento tardío de esta entidad puede aumentar la morbilidad y la mortalidad con efectos potenciales deletéreos y permanentes.

Pituitary stalk interruption syndrome (PSIS) is characterised by the combination of an interrupted or thin pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia. It is manifested as isolated (IGHD) or combined pituitary hormone deficiencies (CPHD) of variable degrees and timing of onset, with a wide spectrum of clinical phenotypes. PSIS may be an isolated morphological abnormality or be part of a syndrome. A retrospective evaluation is presented of clinical signs and symptoms present at early life stages, as well as an analysis of their relationship with hormone laboratory tests and diagnostic imaging in children with congenital hypopituitarism (CHP), and PSIS. This study was performed in a single centre on a sample of 42 children out of a total of 80 CHP patients, with a chronological age range between 5 days and 9.5 years from a database analysed over a period of 26 years. The study included 26/42 (62%) with CPHD and 16/42 (38%) with IGHD. The analysis of perinatal variables showed a natural delivery in 52% (11/21) of CPHD vs 13% (2/15) of IGHD. Four patients, two with CPHD and two IGHD had breech and transverse presentation respectively. All of them were resolved by caesarean section. The perinatal histories showed hypoglycaemia (61% CPHD vs 19% IGHD, P=.0105), jaundice (38% CPHDvs25% IGHD), micropenis (75%CPHD), hypoglycaemic seizures (75% CPHD), and cholestasis (19% CPHD). The mean CA of consulting for CPHD patients was 2.1 years, 30% in neonatal period and 70% before 2 years. The mean chronical age (CA) was 3.6 years in IGHD patients, with 44% of them less than 2 years. MRI showed that 81% of CPHD patients had absence of pituitary stalk vs 19% with thin pituitary stalk (P=.0001); Patients with IGHD presented 56% absence of pituitary stalk vs 44% with thin pituitary stalk (P=.5067). All (100%) of the patients diagnosed in the neonatal stage had absent pituitary stalk. The characterisation of GH deficient patients by presence and type of hypothalamic-pituitary imaging abnormality provides valuable information as a predictor of phenotypic severity, treatment response, and the potential to develop additional hormonal deficiencies. We conclude that demonstrating PSIS in children with HPC provides valuable information as a predictor of phenotypic severity, presence of MPHD, and response to treatment. The low frequency of potentially dysfunctional positional obstetric history, as part of the pathophysiological mechanisms responsible for PSIS, would indicate the need to analyse the importance of possible genetic and epigenetic factors involved. Early diagnosis of HPC should be suspected in the presence of clinical signs and symptoms, such as hypoglycaemia, cholestasis, micropenis, and associated facial midline defects. MRI should be part of complementary studies in patients with this diagnostic suspicion, especially at an early age. Late recognition of this entity may increase morbidity and mortality with potential permanent deleterious effects.

Hipoglicemia transitória em recém-nascidos a termo em aleitamento materno exclusivo: estudo de caso controle / Transient hypoglycemia in full term infant newborn on exclusive breastfeeding: a case-control study

Introdução: a hipoglicemia transitória é uma ocorrência comum que afeta 3% a 29% dos recém-nascidos que, se não tratada prontamente, leva a sequelas neurológicas e morte. A incidência de hipoglicemia transitória em neonatos a termo, filho de gestantes não diabéticas, em regime de aleitamento materno exclusivo, em instituições certificadas como Hospital Amigo da Criança tem sido pouco investigada. Objetivos: determinar a incidência acumulada de hipoglicemia transitória neonatal associados à hipoglicemia em neonatos a termo, internados na unidade de alojamento conjunto de uma instituição hospitalar certificada como Hospital Amigo da Criança. Método: Estudo de caso-controle pareado, cujos dados foram obtidos de um banco de dados de um estudo retrospectivo que caracterizou o perfil dos neonatos internados em alojamento conjunto, submetidos ao controle de glicemia capilar nas primeiras 24 horas de vida por suspeita ou por se enquadrarem no grupo de risco de desenvolver hipoglicemia transitória neonatal. Os dados foram coletados de registro de prontuário maternos e de seus neonatos internados na unidade de alojamento conjunto do Hospital Universitário da Universidade de São Paulo (HU/USP), que permaneceram internados no período de junho de 2007 a junho de 2008. A instituição recebeu certificação como Hospital Amigo da Criança em 01 de junho de 2007 pelo Ministério da Saúde, portanto os recém-nascidos recebem o aleitamento materno exclusivo, evitando-se oferecer outro tipo de alimento. Foram compostos dois grupos amostrais, o primeiro denominado caso, com os neonatos que apresentaram todos os resultados de glicemia capilar coletados nas primeiras 24 horas de vida maior que 40mg/dL. A relação de casos para controle foi de 1:2. No período estudado foram internados na unidade 3113 neonatos, dos quais 719 elegíveis para o estudo e incluídos 699 para compor a base populacional. Foram analisadas as variáveis anteparto, intraparto, pós-natal maternas e variáveis neonatais e a associação entre a variável dependente (desfecho) e as variáveis explanatórias (exposição) foi realizada pelo teste qui quadrado. Subsequentemente, o modelo de análise de regressão múltipla foi realizado com todas as variáveis que resultaram em valor p < 0,25. o passo seguinte foi selecionar no modelo de regressão múltipla, as variáveis com valor p < 0,05, mantidas no modelo final. A medida de estimativa de risco utilizada foi a odds ratio (OR), apresentado como OR bruta (análise univariada) e OR ajustado, com o intervalo de confiança de 95% (IC) (análise multivariada). O projeto de pesquisa recebeu aprovação do Comitê de Ética em Pesquisa da instituição, campo do estudo. Resultados: a incidência cumulativa de hipoglicemia na amostra analisada transitória foram recém-nasicdo adequado para a idade gestacional, OR 3,859, IC 95% [1.071-13,905] e a presença de sinais clínicos de hipoglicemia, OR 5,552, IC 95% [1,325-23,270]. Conclusão: os fatores de risco para hipoglicemia transitória adotados na prática clínica aos recém-nascidos a termo, em aleitamento materno exclusivo, devem ser revistos e os sinais de hipoglicemia são preditivos de hipoglicemia transitória.

Introduction: transient hypoglycaemia is a common occurrence that affects 3% to 29% of newborns and if not treated promptly, leads to neurological sequelae and death. The incidence of transient hypoglycaemia in full term newborns of nondiabetic pregnant women on exclusive breastfeeding admitted at institutions certified as a Baby Friendly Hospital has been little investigated. Objectives: to determine the cumulative incidence of transient neonatal hypoglycemia and the antepartum, intrapartum, pospartum and neonatal hypoglycemia risk factors in full-term infants hospitalized in rooming unit at a hospital certified as a Baby-Friendly Hospital. Method: Analysis of matched case-control and data were obtained from the charts of mother and their babies. A retrospective study that characterized the profile of newborns hospitalized in rooming underwent control of glycemia in the first 24 hours of life for suspecting of hypoglycemia or due attend criteria or risk group develop neonatal hypoglycaemia. Data were collected from the charts of mothers and their children admitted from 2007, July to 2008 June at the secondary level School Hospital of University of São Paulo, São Paulo, Brazil. The institution received accreditation as a Baby Friendly Hospital on 2007, June 1, by the Brazilian Health Ministry, so newborns received exclusive breastfeeding, avoiding offer another type of food as formula fed. Two sample groups were composed the infants who showed at least one result of capillary blood glucose obtained by heel lancing, equal or less 40mg / dL. The control-group consisted of neonates who had all blood glucose results collected in the first 24 hours of life higher than 40 mg / dL. The ratio of cases to control was one per two. In the period were admitted at the rooming-in ward 3113 neonates, of which 719 eligible for the study and 699 were include to compose the population. The antepartum, intrapartum, maternal postnatal and neonatal variables and the association between the dependent variable (outcome) and the explanatory variables (exposure) were analyzed by Chi-square test. Subsequently, the model of multiple regression analysis was performed with all variables that resulted in p value < 0.25. The next step was to select the multiple regression model, variables with p < 0.05, retained in the final model. The measure of risk assessment used was the odds ratio (OR), presented as crude OR (univariate) and adjusted OR, with a confidence interval of 95% (CI) (multivariate analysis). The research project was approved by the Committee of Ethics in Research of the Hospital where the study was carried out. Results: the cumulative incidence in the sample was 3.14%. In the final multiple regression model, the variables that remained associated with the occurrence of transient hypoglycaemia were appropriate for gestational age (AGA) newborn, OR=3,859, 95% CI [1,071-13,905] and the presence of clinical signs of hypoglycemia, OR 5,552 95% CI [1,325- 23,270]. Conclusion: the risk factors for transient hypoglycemia adopted in clinical practice to assessment full term newborns, in inclusive breastfed should be reviewed and signs of hypoglycaemia are predictive of transient hypoglycaemia.

Glycated haemoglobin is a good predictor of neonatal hypoglycaemia in pregnancies complicated by diabetes

We investigated the usefulness of a single value of maternal HbA1c in late pregnancy as a predictor for neonatal hypoglycaemia and secondly, to fi nd the appropriate threshold value. A prospective analysis of the HbA1c concentration between 36 to 38 weeks of gestation in 150 pregnant mothers with either pre-existing or gestational diabetes was performed. At delivery, glucose levels in the cord blood were analysed. Neonatal hypoglycaemia was defi ned as a blood sugar level of < 2.6 mmol/l. Receiver operator characteristic curve was constructed to evaluate the value of HbA1c concentration in predicting hypoglycaemia. There were 16 foetuses who were hypoglycaemic at delivery. The area under the ROC curve for predicting neonatal hypoglycaemia was 0.997 with a 95% confi dence interval of 0.992 to 1, a very good prediction rate. The optimal threshold value for HbA1c in predicting hypoglycaemia in the foetus was 6.8% (51 mmol/mol). HbA1c level in late pregnancy is a good predictor for hypoglycaemia in the newborn.