Browsing by Author "Owen, G."

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    Central Obesity and the Metabolic Syndrome Are Associated with Portal and Not Systemic Hypercortisolism Supported by the Raise of Urinary Corticosteroid Metabolites
    (2010) Baudrand, R.; Campino, C.; Carvajal, C. A.; Olivieri, O.; Guidi, G.; Faccini, G.; Pasini, F.; Sateler, J.; Cornejo, J.; San Martin, B.; Dominguez, J. M.; Mosso, L. M.; Owen, G.; Kalergis, A. M.; Fardella, C.
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    Regiones polimórficas del gen 11β-hidroxiesteroide deshidrogenasa tipo 1 (11βHSD1) en hipertensión arterial esencial: Posible rol etiopatogénico
    (2008) Morales, M.; Carvajal, C.; Ortiz, E.; Mosso, L.; Artigas, R.; Fardella, C.; Owen, G.; Morales, M.; Fardella, C.
    Background: Cortisol has been implicated in hypertension and lately reported to be regulated at the pre-receptor level by the 11βHSD1 enzyme, which converts cortisone (E) to cortisol (F). Over expression of this enzyme in adipose tissue could determine an increase in available cortisol that interacts with the mineralocorticoid receptor (MR) in renal, brain and heart tissue, leading to similar hypertensive effects as in 11βHSD2 impaired patients. Several polymorphisms have been reported in HSD11B1 gene (CA15, CA19 and InsA83557), which could modify HSD11B1 gene expression or activity. Aim: To determine the distribution and prevalence of CA15, CA19 and InsA83557 in the HSD11B1 gene, and to correlate these results with biochemical parameters in cortisol/ACTH (HPA) and renin-angiotensin-aldosterone (RAA) axis in patients with essential hypertension (EH). Patients and Methods: We studied 113 EH patients (76 non-obese and 37 obese, with a body mass index >30 kg/m 2) and 30 normotensive adults (NT). In each patient, we measured serum levels of F, E, serum aldosterone (SA), plasma renin activity (PRA), adrenocorticotrophic hormone (ACTH), the urinary free cortisol/creatinine (UFF/Cr), F/ACTH and SA/PRA ratios. Each polymorphism was studied by PCR and 8% polyacrylamide gel electrophoresis. Statistical associations were evaluated by Pearson correlations and the genetic equilibrium by the Hardy-Weinberg (H-W) equation. Results: We found all three polymorphisms in the EH and the NT group, both in genetic equilibrium. In obese essential hypertensives, the CA15 polymorphism showed association with SA/PRA ratio (r =0.189, p =0.012) and F/ACTH (r =0.301, p 0.048); CA19 also showed correlation with F/ACTH in obese EH (r =-0.220, p 0.009). The InsA83557 polymorphism correlated with UFF/Cr in both EH (r =0.206; p =0.03), and in obese EH (r =0.354; p =0.05). Conclusions: The CA15 and CA19 polymorphism correlated with changes in biochemical parameters in HPA and RAA axis of obese essential hypertensives. These changes may result of modifications in the expression of 11βHSD1, leading to increased cortisol and aldosterone levels independent of ACTH and renin control, respectively.
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    Visceral Hypercortisolism Observed in Central Obesity and Metabolic Syndrome Is Associated with Insulin Resistance and Beta Cell Dysfunction.
    (2010) Baudrand, R.; Campino, C.; Carvajal, C. A.; Olivieri, O.; Guidi, G.; Faccini, G.; Pasini, F.; Sateler, J.; Cornejo, J.; San Martin, B.; Dominguez, J. M.; Tabilo, C.; Mosso, L. M.; Owen, G.; Kalergis, A. M.; Fardella, C.
    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.