Recommendations of the neuroendocrinology department of the Brazilian society of endocrinology and metabolism for the diagnosis of Cushing’s disease in Brazil

Although it is a rare condition, the accurate diagnosis and treatment of Cushing’s disease is important due to its higher morbidity and mortality compared to the general population, which is attributed to cardiovascular diseases, diabetes mellitus and infections. Screening for hypercortisolism is recommended for patients who present multiple and progressive clinical signs and symptoms, especially those who are considered to be more specific to Cushing’s syndrome, abnormal findings relative to age (e.g., spinal osteoporosis and high blood pressure in young patients), weight gain associated with reduced growth rate in the pediatric population and for those with adrenal incidentalomas. Routine screening is not recommended for other groups of patients, such as those with obesity or diabetes mellitus. Magnetic resonance imaging (MRI) of the pituitary, the corticotropin-releasing hormone (CRH) test and the high-dose dexamethasone suppression test are the main tests for the differential diagnosis of ACTH-dependent Cushing’s syndrome. Bilateral and simultaneous petrosal sinus sampling is the gold standard method and is performed when the triad of initial tests is inconclusive, doubtful or conflicting. The aim of this article is to provide information on the early detection and establishment of a proper diagnosis of Cushing’s disease, recommending follow-up of these patients at experienced referral centers

A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

The treatment objectives for a patient with Cushing’s disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails.There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition

Birth weight prediction by fetal limbs volume measurement with use of three-dimensional ultrasonography

Objectives: to determine a formula for birth weight prediction with use of the fetal upper-arm and thigh volumetry obtained by three-dimensional ultrasonography (3DUS); to compare this formula with the Hadlock’s and Shepard’s; to assess the reliability of the method. Patients and methods: a cross seccional study was carried out involving 81 singleton pregnant women without fetal structural anomaly or aneuploidy, within 48 hours before delivery. After measured the BPD, HC, AC and F, the upper-arm (ArmVol) and thigh volume (ThVol) were assessed by 3DUS, slice by slice at 5 mm intervals. From linear and polinomial regression, we generate the best formula for predicting birth weight on the basis of ArmVol and ThVol. The errors of these formulas were compared with the Shepard’s and Hadlock’s formulas erros, with one-way ANOVA. To assess the reliability of ArmVol and ThVol, the intraclass correlation coefficients had been calculated. Level of significance of 5% was adopted. Results: The ArmVol formula is linear (Birthweight = 803,91 + 39,89 ArmVol) and the ThVol, polynomial of second degree (Birthweight = 32,37 ThVol - 0,06 ThVol²). Another formula was determined using the two parameters (Birthweight = 792,87 + 22,81 ArmVol + 7,54 ThVol). The error, absolute error, percentile error and absolute percentile error of the ArmVol formula was 0 g, 0.5%, 163,4 g and 5.4%; the ThVol, -0,99 g, 0.3%, 155,5 g and 5.2%; and the ArmVol and ThVol, 0 g, -0.4%, 138.4 g and 4.6%. When compared with the Hadlock’s and Shepard’s formulas, the ArmVol and ThVol showed lower errors, but only the absolute error and percentile absolute erros were significant lower than Shepard’s. The formula with the two parameters also showed lower errors, but only the error, percentile error and absolute percentile error had been significant, also in relation to the Shepard’s formula. The measure of the ArmVol and the ThVol are reliables with intraclass correlation coefficients of intraobserver 0,98 and 0,99; interobserver e 0.96 and 0.97, respectively. Conclusions: it was generated three formulas for predicting birth weight by ArmVol and ThVol; these formulas showed lower errors than Shepard’s and Hadlock’s formulas, despite only in relation to the first one, some types of errors had been significants; the measure of the ArmVol and the ThVol was well reproductible.Objetivos: determinar uma fórmula para predição de peso fetal ao nascimento por meio da ultrassonografia tridimensional (US3D), com base no volume do braço e da coxa; comparar estas fórmulas com as fórmulas de Hadlock e Shepard; testar a reprodutibilidade do método. Pacientes e método: foi realizado um estudo tipo transversal envolvendo de 81 gestações únicas de fetos vivos, sem sinais de aneuploidia ou malformações estruturais, dentro de 48 horas antes do nascimento. Depois de medidos o DBP, CC, CA e F, o volume do braço (VolBra) e da coxa (VolCox) eram aferidos por meio da US3D, utilizando o modo multiplanar a intervalos de 5 mm. Estes dados foram submetidos à análise de regressão linear e polinomial para determinação da melhor fórmula para predizer o peso fetal com base no VolBra e VolCox. Os erros obtidos com essas fórmulas foram comparados com os obtidos com as fórmulas de Shepard e Hadlock por meio de ANOVA. Para testar a reprodutibilidade do método foram calculados os coeficientes de correlação intraclasse. Foi adotado nível de significância de 5 %. Resultados: A fórmula que utiliza o VolBra é linear simples (Peso = 803,91+39,89 VolBra) e o VolCox, polinomial de segundo grau (Peso=32,37VolCox–0,06 VolCox²). Foi determinada uma terceira fórmula utilizando os dois parâmetros (Peso=792,87+22,81VolBra+7,54VolCox). O erro, erro absoluto, erro percentual e erro percentual absoluto da fórmula que utiliza o VolBra foram 0 g, 0,5%, 163,4 g e 5,4%; o VolCox, -0,99 g, 0,3%, 155,5 g, e 5,2%; e o VolBra e VolCox, 0 g, - 0,4%, 138,4 e 4,6%. Quando comparados com as fórmulas de Hadlock e Shepard, a fórmula que utiliza o VolBra e a que utiliza o VolCox obtiveram erros menores, embora somente o erro absoluto e percentual absoluto foram estatisticamente significativos relação à de Shepard. A fórmula com os 02 parâmetros também obteve menores erros, mas somente o erro, erro percentual e percentual absoluto foram estatisticamente significativos, também em relação à de Shepard. As medidas do VolBra e do VolCox mostraram-se altamente reprodutíveis, com coeficientes de correlação intraobservador 0,98 e 0,99; e interobservador 0,96 e 0,97, respectivamente. Conclusões: foram determinadas três fórmulas para predição de peso com base no VolBra e VolCox; estas obtiveram erros menores que as fórmulas de Shepard e Hadlock, embora somente em relação à primeira, alguns tipos de erros foram significativos; as medidas do VolBra e do VolCox foram altamente reprodutíveis.TED

Predição de peso ao nascimento pela ultra-sonografia tridimensional usando o volume do braço fetal: resultados preliminares Prediction of birth weight by three-dimensional ultrasonography using fetal upper arm volume: preliminary results

OBJETIVO: determinar a acurácia do volume do braço fetal aferido pela ultra-sonografia tridimensional (USG3D) na predição de peso ao nascimento. MÉTODOS: realizou-se um estudo prospectivo, do tipo corte transversal, com 25 gestantes sem anormalidades estruturais ou cromossomopatias. Os parâmetros bidimensionais (diâmetro biparietal, circunferência abdominal e comprimento do fêmur) e o volume do braço fetal pela USG3D foram avaliados em até 48 horas antes do parto. Para o cálculo do volume do braço fetal, utilizou-se o método multiplanar, por meio de múltiplos planos seqüenciais com intervalos de 5,0 mm. Realizaram-se regressões polinomiais para se determinar a melhor equação de predição de peso fetal. A acurácia desta nova fórmula foi comparada com as fórmulas bidimensionais de Shepard e Hadlock. RESULTADOS: o volume do braço fetal foi altamente correlacionado com o peso ao nascimento (r=0,83; p<0,005). Por regressão linear, obteve-se a melhor equação [peso ao nascimento=681,59 + 43,23 x volume do braço fetal]. O erro médio (0 g), o erro médio absoluto (196,6 g) e o erro percentual médio absoluto (6,5%) do volume do braço fetal foram menores que a fórmula de Shepard, mas não mostraram diferença estatisticamente significativa (p>0,05). Em relação à fórmula de Hadlock, apenas o erro médio foi menor, mas não estatisticamente significante (p>0,05). CONCLUSÕES: o volume do braço fetal aferido pela USG3D mostrou acurácia similar às fórmulas bidimensionais na predição do peso ao nascimento. Há necessidade de estudos com maiores casuísticas para se comprovar esses achados.<br>PURPOSE: to evaluate the accuracy of fetal upper arm volume, using three-dimensional ultrasound (3DUS), in the prediction of birth weight. METHODS: this prospective cross-sectional study involved 25 pregnancies without structural or chromosomal anomalies. Bidimensional parameters (biparietal diameter, abdominal circumference and femur length) and the 3DUS fetal upper arm volume were obtained in the last 48 hours before delivery. The multiplanar method, using multiple sequential planes with 5.0-mm intervals, was used to calculate fetal upper arm volume. Polynomial regressions were used to determine the best equation in the prediction of fetal weight. The accuracy of this new formula was compared with Shepard's and Hadlock's formulas. RESULTS: fetal upper arm volume was strongly correlated to birth weight (r=0.83; p<0.005). Linear regression was the best equation [birth weight=681.59 + 43.23 x fetal upper arm volume]. The fetal upper arm volume mean error (0 g), mean absolute error (196.6 g) and mean percent absolute error (6.5%) were lower than using Shepard's formula; however, the difference did not reach significance (p>0.05). Birth weight predicted by fetal upper arm volume had a mean error lower than Hadlock's formula, but this difference was not statistically significant (p>0.05). CONCLUSIONS: the accuracy of fetal upper arm volume obtained through 3DUS is similar to the accuracy of bidimensional ultrasound in the prediction of birth weight. These findings need to be confirmed by larger studies

Comprimento cervical como preditor do período de latência e de infecção na rotura prematura pré-termo de membranas Cervical length as a predictor of the latent period and infection in preterm premature membranes rupture

OBJETIVO: Avaliar o comprimento cervical, por ultrassonografia transvaginal, em pacientes entre 28 e 34 semanas de idade gestacional, correlacionando com o período de latência e o risco de infecção materna e neonatal. MÉTODOS: Foram avaliadas 39 pacientes divididas em relação ao comprimento cervical nos pontos de corte de 15, 20 e 25 mm. Em relação ao período de latência, foram avaliados os parâmetros de 72 horas. Foram incluídas gestantes com feto vivo e idade gestacional entre 28 e 34 semanas, com diagnóstico confirmado na admissão de rotura prematura de membranas. Pacientes com corioamnionite, gestação múltipla, malformações fetais, malformações uterinas (útero bicorno, septado e didelfo), antecedentes de cirurgia prévia no colo uterino (conização e cerclagem) e dilatação do colo maior de 2 cm nas nulíparas e 3 cm nas multíparas foram excluídas no estudo. RESULTADOS: O comprimento do colo PURPOSE: To verify cervical length using transvaginal ultrasonography in pregnant women between 28 and 34 weeks of gestation, correlating it with the latent period and the risk of maternal and neonatal infections. METHODS: 39 pregnant women were evaluated and divided into groups based on their cervical length, using 15, 20 and 25 mm as cut-off points. The latency periods evaluated were three and seven days. Included were pregnant women with live fetuses and gestational age between 28 and 34 weeks, with a confirmed diagnosis on admission of premature rupture of membranes. Patients with chorioamnionitis, multiple gestation, fetal abnormalities, uterine malformations (bicornus septate and didelphic uterus), history of previous surgery on the cervix (conization and cerclage) and cervical dilation greater than 2 cm in nulliparous women and 3 cm in multiparae were excluded from the study. RESULTS: A <15 mm cervical length was found to be highly related to a latency period of up to 72 hours (p=0.008). A <20 mm cervical length was also associated with a less than 72 hour latency period (p=0.04). A <25 mm cervical length was not found to be statistically associated with a 72 hour latency period (p=0,12). There was also no significant correlation between cervical length and latency period and maternal and neonatal infection. CONCLUSION: The presence of a short cervix (<15 mm) was found to be related to a latency period of less than 72 hours, but not to maternal or neonatal infections

Perfil epidemiológico e nível de conhecimento de pacientes diabéticos sobre diabetes e retinopatia diabética

OBJETIVO: Conhecer o perfil epidemiológico e nível de conhecimento de pacientes diabéticos sobre diabetes e retinopatia diabética (RD). MÉTODOS: Estudo transversal com pacientes atendidos no Ambulatório de Retina e Vítreo do Hospital do Servidor Público Estadual de São Paulo, os quais foram divididos em dois grupos: pacientes diabéticos encaminhados para primeira avaliação oftalmológica (G1) e pacientes já acompanhados no Ambulatório (G2). Os pacientes responderam questionário e submeteram-se a exame oftalmológico. Foram utilizados os testes x², exato de Fisher e não paramétricos de Mann-Whitney, presumindo nível de significância de 5%. RESULTADOS: A amostra total foi composta por 357 pacientes (109 no G1 e 248 no G2). A maioria dos pacientes era do sexo feminino, casada, com ensino fundamental incompleto, com média de idade de 63,3 anos e afirmou saber o que é diabetes. Entretanto, 53,2% não sabiam qual o seu tipo de diabetes. As complicações visuais do diabetes são as mais conhecidas. Menos de um terço dos pacientes já tinha ouvido falar em RD e 77,3% não sabiam se eram acometidos. A maioria dos pacientes nunca havia recebido alguma explicação ou algum tipo de material escrito sobre diabetes ou RD. Somente 3,6% dos pacientes participavam de algum programa de educação sobre diabetes. A AV média na amostra, em logMAR, foi de 0,57 no OD e 0,51 no OE. Metade dos pacientes não tinha RD. CONCLUSÃO: A maioria dos pacientes, apesar de receber acompanhamento multidisciplinar, apresentou pouco conhecimento sobre o diabetes e suas complicações

A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

The treatment objectives for a patient with Cushing’s disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails.There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition