Browsing by Author "Gomez Sanchez, C"

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    Genetic study of patients with dexamethasone-suppressible aldosteronism without the chimeric CYP11B1/CYP11B2 gene
    (ENDOCRINE SOC, 2001) Fardella, CE; Pinto, M; Mosso, L; Gomez Sanchez, C; Jalil, J; Montero, J
    Glucocorticoid-remediable aldosteronism is an inherited disorder caused by a chimeric gene duplication between the CYP11B1 (11 beta -hydroxylase) and CYP11B2 (aldosterone synthase) genes. The disorder is characterized by hyperaldosteronism and high levels of 18-hydroxycortisol and 18-oxocortisol, which are under ACTH control. The diagnosis of glucocorticoid-remediable aldosteronism had been traditionally made using the dexamethasone suppression test; however, recent studies have shown that several patients with primary aldosteronism and a positive dexamethasone suppression test do not have the chimeric CYP11B1/CYP11B2 gene. The aim of this work was to evaluate whether other genetic alterations exist in CYP11B genes (gene conversion in the coding region of CYP11B1 or in the promoter of CYP11B2) that could explain a positive dexamethasone suppression test and to determine another genetic cause of glucocorticoid-remediable aldosteronism. We also evaluated the role of 18-hydroxycortisol. as a specific biochemical marker of glucocorticoid-remediable aldosteronism. We studied eight patients with idiopathic hyperaldosteronism, a positive dexamethasone suppression test, and a negative genetic test for the chimeric gene. In all patients we amplified the CYP11B1 gene by PCR and sequenced exons 3-9 of CYP11B1 and a specific region (-138 to -284) of CYP11B2 promoter. We also measured the levels of 18-hydroxycortisol, and we compared the results with those found in four subjects with the chimeric gene. None of eight cases showed abnormalities in exons 3-9 of CYP11B1, disproving a gene conversion phenomenon. In all patients a fragment of 393 bp corresponding to a specific region of the promoter of CYP11B2 gene was amplified. The sequence of the fragment did not differ from that of the wild-type promoter of the CYP11B2 gene. The 18-hydroxycortisol levels in the eight idiopathic hyperaldosteronism patients and four controls with chimeric gene were 3.9 +/- 2.3 and 21.9 +/- 3.5 nmol/liter, respectively (P < 0.01). In summary, we did not find other genetic alterations or high levels of 18-hydroxycortisol that could explain a positive dexamethasone suppression test in idiopathic hyperaldosteronism. We suggest that the dexamethasone suppression test could lead to an incorrect diagnosis of glucocorticoid-remediable aldosteronism.
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    Plasma 18-hydroxycortisol as screening test in aldosteronism
    (2001) Mosso, L; Gomez Sanchez, C; Foecking, M; Fardella, C
    Background: Thyroid microcarcinoma is a tumor of 10 mm or less. that should have a low risk of mortality. However a subgroup of these carcinomas is as aggressive as bigger tumors. Aim To describe the pathological presentation of these tumors.. and compare them with larger tumors. Material and methods. All Pathological samples of thyroid carcinoma that were obtained between 1992 and 2003, were studied. In all biopsies, the pathological type, tumor size. the focal or multifocal character the presence of lymph node involvement and the presence of lymphocytic thyroiditis or thyroid hyperplasia, were recorded. Results: One hundred eighteen microcarcinomas and 284 larger tumors were studied. The mean age of patients with microcarcinoma and larger tumors was 42.7 +/- 14 and 49.3 +/- 16 years respectively (p < 0,00.1) and 83% were female. without gender differences between tumor types. klean size of microcarcinomas was 8.6 mm and 116 (98%) were papillary carcinomas. Of these. 109 (94% were well differentiated and seven (6%) were moderatly differentiated. Thirty six(31%) were multifocal and in 10 (8,6%), there was lymph node involvement. The mean size of larger tumors was 23.8 mm and 241 (85%) were papillary carcinomas. Of these, 200 (83%) were well differentiated, and 41 (17%) were moderately differentiated.Eighty five (35%) were multifocal and in 44 (18%) there was lymph node involvement. The prevalence of thyroiditis and hyperplasia was significantly higher among microcardinomas than in larger tumors (15 and 2.5%, respectively, p < 0.001, for the former; 32.4 and 1.7%, respectively, p < 0.001, for the latter. Conclusions. In this series. one third of microcarcinomas were multifocal and 10% had lymph node involvement. Therefore, aggresiveness of these tumors is higher than what is reported in the literature and they should be treated with total thyroidectomy.
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    Primary hyperaldosteronism in essential hypertensives: Prevalence, biochemical profile, and molecular biology
    (2000) Fardella, CE; Mosso, L; Gomez Sanchez, C; Cortes, P; Soto, J; Gomez, L; Pinto, M; Huete, A; Oestreicher, E; Foradori, A; Montero, J
    There is evidence that primary aldosteronism (PA) may be common in patients with essential hypertension (EH) when determinations of serum aldosterone (SA), plasma renin activity(PRA), and the SA/PRA ratio are used as screening. An inherited form of primary hyperaldosteronism is the glucocorticoid-remediable aldosteronism (GRA) caused by an unequal crossing over between the CYP11B1 and CYP11B2 genes that results in a chimeric gene, which has aldosterone synthase activity regulated by ACTH. The aim of this study was to evaluate the prevalence of PA and the GRA in 305 EH patients and 205 normotensive controls. We measured SA (1-16 ng/dL) and PRA (1-2.5 ng/mL . h) and calculated the SA/PRA ratio in all patients. A SA/PRA ratio level greater than 25 was defined as being elevated. PA was diagnosed in the presence of high SA levels (>16 ng/dL), low PRA levels (<0.5 ng/mL . h), and very high SA/PRA ratio (>50). Probable PA was diagnosed when the SA/PRA ratio was more than 25 but the other criteria were not present. A Fludrocortisone test was done to confirm the diagnosis. GRA was differentiated from other forms of PA by: the aldosterone suppression test with dexamethasone, the high levels of 18-hydroxycortisol, and the genetic detection of the chimeric gene. In EH patients, 29 of 305 (9.5%) had PA, 13 of 29 met all the criteria for PA, and 16 of 29 were initially diagnosed as having a probable PA and confirmed by the fludrocortisone test. Plasma potassium was normal in all patients. The dexamethasone suppression test was positive for GRA in 10 of 29 and 18-hydroxycortisol levels were high in 2 of 29 patients who had also a chimeric gene. In normotensive subjects, 3 of 205 (1.46%) had PA, and 1 of 205 had a GRA. In summary, we found a high frequency of normokalemic PA in EH patients. A high proportion of PA suppressed SA with dexamethasone, but only a few had a chimeric gene or high levels of 18-hydroxycortisol. These results emphasize the need to further investigate EH patients.