Síndrome de Cushing na gravidez: uma visão geral

Cushing's syndrome (CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature. Adrenal adenomas were found to be the commonest cause, followed by Cushing's disease. The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, resulting in increased hepatic production of corticosteroid-binding globulin (CBG), increased levels of serum, salivary and urinary free cortisol, lack of suppression of cortisol levels after dexamethasone administration and placental production of CRH and ACTH. Moreover, a blunted response of ACTH and cortisol to exogenous CRH may also occur. Therefore, the diagnosis of CS during pregnancy is much more difficult. Misdiagnosis of CS is also common, as the syndrome may be easily confused with preeclampsia or gestational diabetes. Because CS during pregnancy is usually associated with severe maternal and fetal complications, its early diagnosis and treatment are critical. Surgery is the treatment of choice for CS in pregnancy, except perhaps in the late third trimester, with medical therapy being a second choice. There does not seem to be a rationale for supportive treatment alone.A ocorrência de síndrome de Cushing (SC) durante a gravidez é rara, com menos de 150 casos reportados na literatura. Os adenomas adrenais parecem ser a causa mais comum seguidos da doença de Cushing. A gestação afeta de maneira dramática o eixo hipotálamo-hipófise-adrenal materno resultando em aumento da produção hepática da globulina ligadora de corticosteróides (CBG), aumento dos níveis séricos, salivares e livres urinários de cortisol, falta de supressão do cortisol após administração de dexametasona e produção placentária de CRH e ACTH. Além disso, pode também ocorrer bloqueio da resposta do ACTH e do cortisol ao CRH exógeno. Assim, o diagnóstico de SC durante a gravidez torna-se muito mais difícil. A falha em diagnosticar SC é também comum, já que a síndrome pode ser facilmente confundida com pré-eclampsia ou diabetes gestacional. Uma vez que a SC de ocorrência na gravidez é usualmente associada com graves complicações materno-fetais, seu diagnóstico e tratamento precoces tornam-se críticos. A cirurgia é o tratamento de escolha para a SC na gravidez, exceto, talvez, no final do 3º trimestre, sendo o tratamento medicamentoso a segunda escolha. Não parece haver nenhum arrazoado para o tratamento de suporte isoladamente.Federal University of Pernambuco Hospital das Clínicas Division of Endocrinology and MetabolismHospital Getúlio Vargas Pernambuco University Medical School Division of Endocrinology and MetabolismFederal University of São Paulo Department of Medicine Division of Endocrinology and MetabolismUNIFESP, Department of Medicine Division of Endocrinology and MetabolismSciEL

Brazilian Diabetes Society consensus statement: intensive insulin therapy and insulin pump therapy

This article reports the Brazilian Diabetes Society consensus statement on intensive insulin therapy and insulin pump therapy, arrived at during an update symposium held in 2003 for this specific purpose. The concepts underlying these modalities of diabetes treatment are outlined, their fundaments are given, and practical issues about their indications, feasibility, limits, techniques and cost-benefit relationships are analyzed. The techniques comprise the suggested self-monitoring schedules and the insulin doses, types, forms of administration and correction factors used in each modality of intensive treatment, for both type 1 and 2 diabetes. The roles of SBD in the implementation of these treatments and of the different professionals involved are discussed and commented. The conclusions are based on consensual answers to some orienting questions formulated during the symposium's presentation.Este artigo relata a posição de consenso da Sociedade Brasileira de Diabetes sobre a insulinoterapia intensiva e a terapêutica com bombas de infusão de insulina, obtida durante simpósio de atualização realizado especificamente para esta finalidade, em 2003. Estas modalidades de tratamento do diabetes são aqui conceituadas, seus fundamentos são colocados, e os aspectos práticos de indicações, exeqüibilidade, limites, técnicas e relação custo-benefício são analisados. As técnicas envolvem os esquemas de auto-monitorização glicêmica sugeridos e as doses, tipos, formas de administração da insulina e fatores de cálculo utilizados em cada modalidade de tratamento intensivo, tanto no DM1 quanto no DM2. O papel da SBD na implementação dos tratamentos intensivos do diabetes e a atuação dos vários profissionais envolvidos são discutidos e comentados. Conclui-se com as respostas de consenso a questões orientadoras do tema, formuladas na apresentação do simpósio.Sociedade Brasileira de DiabetesUniversidade de São PauloHospital Geral de GoiâniaUniversidade Federal de São Paulo (UNIFESP)Universidade Federal do ParanáUniversidade Federal de PernambucoUNIFESPSciEL

SGLT1 activity in lung alveolar cells of diabetic rats modulates airway surface liquid glucose concentration and bacterial proliferation

High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-resistant Sthaphylococcus aureus, MRSA and Pseudomonas aeruginosa, P. aeruginosa) were analyzed in bronchoalveolar lavage (BAL); and alveolar SGLT1 was analyzed by immunohistochemistry. BAL glucose concentration and bacterial proliferation increased in diabetic animals: isoproterenol stimulated SGLT1 migration to luminal membrane, and reduced (50%) the BAL glucose concentration; whereas phlorizin increased the BAL glucose concentration (100%). These regulations were accompanied by parallel changes of in vitro MRSA and P. aeruginosa proliferation in BAL (r = 0.9651 and r = 0.9613, respectively, Pearson correlation). The same regulations were observed in in vivo P. aeruginosa proliferation. In summary, the results indicate a relationship among SGLT1 activity, ASL glucose concentration and pulmonary bacterial proliferation. Besides, the study highlights that, in situations of pulmonary infection risk, such as in diabetic subjects, increased SGLT1 activity may prevent bacterial proliferation whereas decreased SGLT1 activity can exacerbate it.CAPESFederal University of UberlandiaFAPEMIGFAPEALFAPESPFAPEAL fellowshipUniv Fed Alagoas, Inst Biol Sci & Hlth, Alagoas, BrazilUniv Fed Sao Paulo, Dept Physiol, Sao Paulo, BrazilUniv Fed Uberlandia, Natl Reference Ctr Leprosy & Sanit Dermatol, Uberlandia, MG, BrazilUniv Sao Paulo, Inst Biomed Sci, Dept Physiol, Sao Paulo, BrazilUniv Fed Uberlandia, Inst Genet & Biochem, Uberlandia, MG, BrazilUniv Calif Davis, Dept Med Microbiol & Immunol, Davis, CA USAUniv Fed Uberlandia, Inst Biomed Sci, Dept Physiol, Uberlandia, MG, BrazilUniv Fed Sao Paulo, Dept Physiol, Sao Paulo, BrazilFAPESP: 201/04831-1Web of Scienc

The importance of routine screening for macroprolactin in symptomatic patients with idiopathic hyperprolactinemia

Objective: To evaluate the importance of screening for macroprolactin in symptomatic patients with apparent idiopathic hyperprolactinemia. Methods: During 20 months, the prevalence of macroprolactinemia was evaluated among consecutive symptomatic female patients with apparent idiopathic hyperprolactinemia routinely followed in two neuroendocrinology reference centers from Recife. This prevalence has never been systematically evaluated. Results: A total of 82 patients (mean age, 36.1±7.3 yrs; age range, from 25 to 50) were included; 69 of them (84.1%) had been treated with cabergoline. The screening for macroprolactin was positive in 22 patients (26.8%), 15 of whom (68.2%) misleadingly received longterm treatment with cabergoline. The clinical and demographic features, as well as baseline prolactin levels, were comparable in patients with true idiopathic hyperprolactinemia and in those with macroprolactinemia. Conclusion: Macroprolactinemia was found in about one quarter of the patients with apparent idiopathic hyperprolactinemia. Our findings highlight the importance of routine screening for macroprolactin in all patients with idiopathic hyperprolactinemia, regardless their clinical features, in order to avoid misdiagnosis and unnecessary treatment with dopamine agonists.

The Role of Isotretinoin Therapy for Cushing’s Disease: Results of a Prospective Study

Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing’s disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6–12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6–12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism

Epidemiologia e genética molecular do diabetes mellitus tipo 2 no município de Triunfo, Pernambuco

O Diabetes Mellitus é um importante e crescente problema de saúde no mundo, sua prevalência vem aumentando nas últimas décadas, adquirindo características de epidemia. O número de pessoas com esse tipo da doença deverá duplicar nos próximos 10 a 25 anos. Juntamente a essa doença, cresce também o número de portadores de obesidade, hipertensão arterial e síndrome metabólica. O gene fator de transcrição 2 semelhante ao 7 (TCF7L2) está localizado no cromossomo 10 e está envolvido na via de sinalização Wnt, que faz parte de uma classe de ligantes de profunda importância no processo de desenvolvimento dos organismos multicelulares. Este gene tem sido fortemente associado com aumento de risco para diabetes mellitus tipo 2. Até o momento não existem estudos a respeito dessa associação na população nordestina. Numa amostra de 112 diabéticos e 228 não diabéticos residentes em Triunfo, foram analisados quatro SNPs (polimorfismos de nucleotídeo simples) do gene TCF7L2: rs7903146; rs7901695; rs12255372 e rs11196205, as freqüências genotípicas para cada SNP e as freqüências dos respectivos alelos de risco. Verificou-se que esta associação existe também no Sertão Nordestino. A análise genética mostrou associação significante com diabetes mellitus tipo 2 para os SNPs rs7903146 e rs12255372 (p = 0,03 e p = 0,01, respectivamente) bem como para os haplótipos em duplas, triplas e quádruplas. Foi ainda realizado no Distrito de Canaã, Município de Triunfo PE, um levantamento dos dados das famílias locais a fim de estabelecer a prevalência de hipertensão arterial, síndrome metabólica e diabetes mellitus 2 naquela população. As prevalências de hipertensão arterial, síndrome metabólica e diabetes mellitus 2 foram submetidas à análise estatística e genético-populacional, tendo como background o sexo, idade, renda mensal, grau de escolaridade, atividade física, tabagismo, índice de massa corpórea. Numa amostragem, de 198 indivíduos a prevalência de hipertensão arterial foi 64,0%, de síndrome metabólica 48,5% e de DM2 13,6%. A prevalência de DM2 supera a encontrada no último estudo multicêntrico nacional (7,6.%) o que é um fato a ser anotado para as condições de vida do Sertão Nordestin