ABSTRACT
OBJECTIVES: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease. METHODS: Sixty-four patients presenting with Cushing's disease were diagnosed based on adrenocorticotrophic hormone levels, high-dose dexamethasone suppression tests and/or inferior petrosal sinus sampling and magnetic resonance imaging. The A3669G, ER22/23EK, N363S BclI-NR3C1 and HSD11B1-rs12086634 variants were screened. RESULTS: The BclI, HSD11B1-rs12086634 and A3669G variants were found in 36%, 19.5% and 14% of alleles, respectively. The N363S and ER22/23EK polymorphisms were identified in heterozygosis once in only two patients (1.5% of alleles). There were no differences in the weight gain or prevalence of diabetes and hypertension in the patients carrying the abovementioned alleles compared to the wild-type carriers. Interestingly, the mean body mass index (BMI) of the BclI carriers was significantly higher than the non-carriers (34.4±7 kg/m2 vs. 29.6±4.7 kg/m2, respectively). None of the polymorphisms were associated with the basal adrenocorticotrophic hormone, FU levels or F level after dexamethasone suppression testing. CONCLUSION: Although Cushing's disease results from increased glucocorticoid secretion, we observed that interindividual variability in the peripheral glucocorticoid sensitivity, mediated by the glucocorticoid receptor, could modulate the obesity phenotype. .
Subject(s)
Female , Humans , Male , Middle Aged , Alleles , /genetics , Genetic Predisposition to Disease , Pituitary ACTH Hypersecretion/genetics , Polymorphism, Genetic/genetics , Receptors, Glucocorticoid/genetics , Body Mass Index , Genotype , Phenotype , Pituitary ACTH Hypersecretion/bloodABSTRACT
OBJETIVO: O cateterismo dos seios petrosos inferiores (SPI) ajuda a diferenciar as formas hipofisária e ectópica na síndrome de Cushing (SC). O objetivo desse trabalho é descrever a técnica empregada em nosso serviço, discutir a solução de dificuldades e verificar o índice de sucesso atingido. CASUÍSTICA E MÉTODO: Foram submetidos a cateterismo bilateral dos SPI 42 pacientes com SC, entre setembro de 2000 e setembro de 2005. As dificuldades para o posicionamento do cateter foram correlacionadas com as soluções empregadas. RESULTADOS: As variações anatômicas, a semelhança entre o SPI e a veia emissária do plexo basilar e a dificuldade de contrastar as estruturas a contrafluxo para localizá-las foram os principais problemas. Foram utilizados cateter pré-moldado, fio-guia semicurvo e dirigível, road-maping e venografia por injeção contralateral, além de critérios para diferenciar o SPI da veia emissária. Dos 84 SPI abordados, um apresentava trombose, e dos 83 possíveis, 80 (96,4 por cento) foram cateterizados. Não se observaram complicações. CONCLUSÃO: A cateterização dos SPI pode ser feita na maioria dos pacientes. A identificação da veia emissária do plexo basilar e o uso de flebografia por injeção contralateral melhoraram o desempenho do método.
PURPOSE: Inferior petrosal sinus catheterization and sampling for corticotropin dosage helps to differentiate hypophisary and ectopic forms of Cushing syndrome. The aim of this paper is to describe the technique used in inferior petrosal sinus catheterization in our service, emphasizing the solution found for frequent difficulties, and verify the success rate achieved. PATIENTS AND METHODS: Between September/2000 and September/2005, forty-two (eighty-four sinuses) patients were submitted to inferior petrosal sinus sampling. The difficulties for correct catheter positioning were identified and correlated with their solutions. RESULTS: Anatomical variations, similarity between IPS and emissary vein of the basilar plexus and unfavorable flow to the contrastation of the structures (retrograde catheterization) were the main problems. Using pre-shaped catheters, curved, steerable guide-wires, road-maping and venography by contalateral injection, besides criteria to differentiate IPS from the emissary vein. Of the 84 sinuses approached, one was thrombosed, and 80 (96.4 percent) of 83 possible were selectively catheterized. No clinical complication occurred. CONCLUSION: IPSC can be safe and successfully performed in most cases. The identification of the emissary vein of the basilar plexus and use of venography by contralateral injection, improved the method performance.