Browsing by Author "Mosso, L"
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- ItemExtensive personal experience - Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents(ENDOCRINE SOC, 2004) Mulatero, P; Stowasser, M; Loh, KC; Fardella, CE; Gordon, RD; Mosso, L; Gomez Sanchez, CE; Veglio, F; Young, WFPrimary aldosteronism (PA) is a common form of endocrine hypertension previously believed to account for less than 1% of hypertensive patients. Hypokalemia was considered a prerequisite for pursuing diagnostic tests for PA. Recent studies applying the plasma aldosterone/plasma renin activity ratio (ARR) as a screening test have reported a higher prevalence. This study is a retrospective evaluation of the diagnosis of PA from clinical centers in five continents before and after the widespread use of the ARR as a screening test. The application of this strategy to a greater number of hypertensives led to a 5- to 15-fold increase in the identification of patients affected by PA. Only a small proportion of patients ( between 9 and 37%) were hypokalemic. The annual detection rate of aldosterone-producing adenoma (APA) increased in all centers ( by 1.3-6.3 times) after the wide application of ARR. Aldosterone-producing adenomas constituted a much higher proportion of patients with PA in the four centers that employed adrenal venous sampling ( 28 - 50%) than in the center that did not (9%). In conclusion, the wide use of the ARR as a screening test in hypertensive patients led to a marked increase in the detection rate of PA.
- ItemGenetic 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, JGlucocorticoid-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.
- Itemgps Mutations in Chilean patients harboring growth hormone-secreting pituitary tumors(WALTER DE GRUYTER GMBH, 1999) Johnson, MC; Codner, E; Eggers, M; Mosso, L; Rodriguez, JA; Cassorla, FHypersecretion of GH is usually caused by a pituitary adenoma and about 40% of these tumors exhibit missense gsp mutations in Arg(201) or Gln(227) of the Gs(alpha) gene. We studied 20 pituitary tumors obtained from patients with GH hypersecretion, One tumor was resected from an 11 year-old boy with a 3 year history of accelerated growth, associated with increased concentrations of serum GH and IGF-I, which were not suppressed by glucose administration, The remaining 19 tumors were obtained from adult acromegalic patients, who had elevated baseline serum GH levels that did not show evidence of suppression after administration of glucose, The gsp mutations were studied by enzymatic digestion of the amplified PCR fragment of exon 8 (Arg(201)) and exon 9 (Gln(227)) with the enzymes NlaIII and NgoAIV, respectively. The tumors obtained from the boy and from nine of the 19 patients with acromegaly exhibited the gsp mutation R201H. None of the tumors had the Gln(227) mutation. The gsp positive patients tended to be older, had smaller tumors, and had preoperative basal serum GH levels which were significantly lower (21 +/- 6 vs 56 +/- 16 mu g/l, p < 0.05) than the gsp negative patients, In this study, we documented the presence of a gsp mutation in Arg(201) in a boy with gigantism and in approximately half of 19 Chilean adult patients with acromegaly, similar to other populations.
- ItemSerum 18-hydroxycortisol in primary aldosteronism, hypertension, and normotensives(LIPPINCOTT WILLIAMS & WILKINS, 2001) Mosso, L; Gomez Sanchez, CE; Foecking, MF; Fardella, CThis study reports the determination of plasma 18-hydroxycortisol (18-OHF) using a new and easy enzyme-linked immunosorbent assay (ELISA) method in primary aldosteronism and compares the values found in essential hypertensives and normotensive controls. In primary aldosteronism, we evaluated usefulness of plasma 18-OHF determination and the dexamethasone suppression test in the diagnosis of glucocorticoid-remediable aldosteronism using the genetic test as the gold standard. We studied 31 primary aldosteronism patients, 101 essential hypertensives, and 102 healthy normotensive controls. The plasma 18-OHF was measured using a biotin-avidin enzyme-linked assay by a new and purified polyclonal antibody. The 18-OHF value in primary aldosteronism was 6.3 +/- 8.05 nmol/L; this value is significantly higher than the value found in essential hypertensives and normotensive controls (2.81 +/- 1.42 and 2.70 +/- 1.41 nmol/L, respectively; P <0.0005). In primary aldosteronism, 4 of 31 patients had 18-OHF levels that were 10 times higher than the normal upper limit (2.983 nmol/L). The dexamethasone suppression test in primary aldosteronism patients was positive (serum aldosterone <4 ng/dL) in 13 of 31 cases. A chimeric CYP11B1/CYP11B2 gene was demonstrated in 4 primary aldosteronism patients, corresponding to the same cases that had higher level of 18-OHF. In conclusion, plasma 18-OHF determination by this ELISA method is reliable for detecting glucocorticoid-remediable aldosteronism, and it does so better than the dexamethasone suppression test.