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Browsing by Author "Mosso, L."

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Actividad de 11 beta hidroxiesteroide dehidrogenasa tipo 2 en hipertensos chilenos
(2002) Mosso, L.; Carvajal, C.; Campino, C.; Rojas, A.; Gonzalez, A.; Barraza, A.; Montero, J.; Fardella, C.
Background: Half of hypertensive patients with, low plasma renin activity have a primary hyperaldosteronism. Among the remaining half 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) deficiency plays all important role. This enzyme catalyzes the conversion of cortisol to cortisone, avoiding the interaction of cortisol with, the mineralocorticoid receptor. If the enzyme fails, cortisol will stimulate sodium and water reabsorption and increase blood pressure. Aim: To determine biochemical alterations, suggestive of 11betaSHSD2 deficiency, in low-renin hypertensive patients. Patients and Methods: Twenty eight hypertensive patients with a plasma renin activity of less than 0.5 ug/ml/h and with a plasma aldosterone of less than 5 ng/dl were studied. Twenty eight normotensive patients were studied as controls. Serum. cortisol (RIA), cortisone (ELISA) and the serum cortisol/cortisone ratio were determined in all of them, between, 9 and 10 AM. Measurements were confirmed by high pressure liquid chromatography. The serum cortisol/cortisone ratio was considered abnormal when its Ln (cortisol/cortisone) value was over 2 standard deviations of the mean. Results: Serum cortisol was higher in hypertensive subjects than in controls (11.1 +/- 3.3 and 9.2 +/- 2.8 mug/dl, respectively; p <0.05). No differences were observed in serum cortisone (3.4 +/- 1.3 and 3.7 +/- 1.2 μg/dl, respectively). Four hypertensive subjects bad all abnormally high Ln (cortisol/cortisone) value (1.86; 1.73; 2.07 and 2.01, considering a normal value of less than 1.61). Conclusions: Four of 28 hypertensive subjects with, low plasma renin activity and aldosterone had biochemical alterations suggestive of 11.1βHSD2 deficiency.
A−6G variant of angiotensinogen gene and aldosterone levels in hypertensives
(1999) Fardella, C.; Zamorano, P.; Mosso, L.; Gomez, L.; Pinto, M.; Soto, J.; Oestreicher, E.; Cortes, P.; Claverie, X.; Montero, J.
Recently, a novel mutation in the promoter region of the angiotensinogen gene that involves the presence of an adenine instead of a guanine 6 bp upstream from the transcription initiation site (A(-6)G) has been shown to induce an increase in gene transcription. The aim of this study was to determine the prevalence of the A(-6)G mutation in essential hypertensive patients and to correlate it with aldosterone and renin activity levels. We studied 191 hypertensives. We measured levels of aldosterone (plasma and urinary) and plasma renin activity. We determined the variants A and G using a mutagenically separated polymerase chain reaction technique. In 191 hypertensives, the A variant was detected in 266 of 382 (69.6%) and the G variant in 116 of 382 alleles (30.4%). Plasma aldosterone was significantly higher in patients homozygous for AA than in those homozygous for GG (369+/-208 versus 246+/-142 pmol/L). Urinary aldosterone was significantly higher in homozygous AA than in AG or GG patients (62.4+/-39.4 versus 50.8+/-25.2 and 37.4+/-22.3 nmol/d, respectively). When the patients were grouped according to the presence or absence of the A allele, the aldosterone levels and the plasma aldosterone/plasma renin activity ratio were significantly higher in patients with the A allele, The presence of the A variant was associated with higher levels of aldosterone. These results suggest that the presence of the A variant could determine the appearance of arterial hypertension through higher transcription activity of the angiotensinogen gene and concomitant aldosterone production.
Bone turnover in lactating teenagers: Assessment at the end of pregnancy, during and after the breast feeding period
(2000) Cattani, A.; Zubarew, T.; Maddaleno, M.; Mosso, L.; Lopez, J.M.
Background: There is paucity of information about bone metabolism during pregnancy or breast feeding in teenagers. Aim: To study bone turnover at the end of pregnancy and during breast feeding in teenagers and correlate it with environmental, hormonal or nutritional variables. Subjects and methods: Thirty teenagers during their breast feeding period after a first pregnancy and 30 nulliparous girls matched for age, age of menarche and body mass index were assessed three weeks after delivery (period 1), at six months of breast feeding (period 2) and one year after the lactating period (period 3). Calcium intake and plasma calcium, phosphorus, alkaline phosphatases, parathormone, estradiol and prolactin were measured. Calcium, creatinine and hydroxypyroline were also measured in a morning urine samples. Results: Lactating and control girls were aged 16.3+/-0.8 and 16.1+/-0.7 years old respectively. Calcium intake in lactating and control girls was 798+/-421 and 640+/-346 g/day respectively in period 1, 612+/-352 and 592+/-309 mg/day in period 2 and 495+/-180 and 456+/-157 g/day in period 3. During periods 1 and 2, lactating girls had higher alkaline phosphatases (161+/-37 compared to 119+/-28 U/l and 149+/-37 compared to 106+/-23 U/l), parathormone (4.3+/-2.6 compared to 2/8+/-0.8 ng/dl and 3.6+/-1.6 compared to 3.0+/-0.9 ng/dl) and urinary hydroxyproline (95+/-16 compared to 63+/-15 mg/g creatinine and 84+/-19 compared to 59+/-15 mg/g creatinine). No differences were observed in period 3. No correlation between bone turnover variables, body mass index or hormonal parameters, was observed. Conclusions: In teenagers, there is an increase in bone turnover at the end of pregnancy, that persists during the lactating period. These changes are not relaxed to nutritional or hormonal variables.
Diseño de una escala ecográfica predictora de malignidad en nódulos tiroideos: Comunicación preliminar
(2009) Domínguez, J.M.; Baudrand, R.; Arteaga, E.; Campusano, C.; González, G.; Mosso, L.; Fardella, C.; Arias, T.; Pizarro, A.; Gómez, M.; Cruz, F.; Torres, J.; Solar, A.; Cavada, G.; NCD Risk Factor Collaboration (NCD-RisC)
Background: Thyroid nodules are common and associated to a low risk of malignancy. Their clinical assessment usually includes a fine neddle aspiration biopsy (FNAB). Aim: To identify ultrasonographic characteristics associated to papillary thyroid carcinoma (PTC) and generate a score that predicts the risk of PTC. Material and methods: Retrospective review of all fine needle aspiration biopsies of the thyroid performed in a lapse of two years. Biopsies that were conclusive for PTC were selected and compared with an equal amount of randomly selected biopsies that disclosed a benign diagnosis. Results: One hundred twenty two biopsies of a total of 1,498 were conclusive for PTC. Univariate analysis showed associations with PTC for the presence of micro-calcifications (Odds ratio (OR) 49.2: 95% confidence intervals (CI) 18.7-140.9), solid predominance (OR 25.1; 95% CI 6-220), hypoechogenicity (OR 23.5, 95% CI 6.5-122.6), irregular borders (OR 17, 95% CI 7.2-42.9), lymph node involvement (OR 12.3, 95% CI 2.7-112), central vascularization (OR 12.2, 95% CI 4.8-33.3), local invasion and hyperechogenicity (OR 0.2; CI 95% CI 0.03-0.6). Multivariate analysis disclosed microcalcifications (OR 28.1; CI 95% 8.9-89), hypoechogenicity (OR 9.4; 95% CI 1.5-59.5) and irregular borders (OR 4.7; CI 95% 1.5-15) as the variables independently associated with the presence of PTC. The prevalence of PTC in the presence of the three variables was 97.6% (Likelihood ratio (LR) 45) and 5.4% in their absence (LR 0.06). Conclusions: This scale predicts the presence or absence of PTC using simple ultrasound characteristics.
High prevalence of undiagnosed primary hyperaldosteronism among patients with essential hypertension
(1999) Mosso, L.; Fardella, C.; Montero, J.; Rojas, P.; Sanchez, O.; Rojas, V.; Rojas, A.; Huete, A.; Soto, J.; Foradori, A.; NCD Risk Factor Collaboration (NCD-RisC)
Background: Classically, primary hyperaldosteronism was diagnosed in no more than 1% of patients with hypertension, when hypokalemia was used as the screening test. However, numerous patients with primary hyperaldosteronism do not have hypokalemia nod the disease remains undiagnosed. Aim: To assess the prevalence of normokalemic primary hyperaldosteronism among patients classified as having essential hypertension. Patients and methods: One hundred hypertensive patients with a blood pressure over 145/95 were studied. Plasma aldosterone and plasma renin activity were measured in all. A primary hyperaldosteronism was diagnosed when high aldosterone levels (over 16 ng/dl) and low plasma renin activity (below 0.5 ng/ml/h) coexisted in two blood tests of the aldosterone/plasma renin activity ratio was over 50. A probable primary hyperaldosteronism was diagnosed whet? the ratio was between 25 and 50 and these patients were subjected to a Fludrocortisone test to confirm the diagnosis. A dexametasone suppression test was done to discard glucocorticoid remediable aldosteronism. An adrenal TAC scan was done to all patients with primary hyperaldosteronism. Results: A diagnosis of primary hyperaldosteronism was reached in ten patients. Seven had elevated aldosterone and low plasma renin activity. In three the diagnosis was confirmed with the fludrocortisone test. All ten patients had normal serum potassium levels. Dexametasone suppression test was positive in three patients that normalized their blood pressure levels. Adrenal TAC scans showed an adenoma in one patient and hyperplasia in another. Conclusions: Primary hyperaldosteronism is more frequent than previously thought, it is overlooked when hypokalemia is used as the screening test and it can only be diagnosed measuring plasma aldosterone and renin activity.
Hipertiroxinemia con eutiroidismo clínico: análisis a propósito de un caso
(1999) Lopez, J.M.; Mosso, L.; Campino, C.
The association of hyperthyroxinemia and euthyroidism is frequent and characterized by high plasma thyroxin concentrations, normal TSH values and absence of clinical signs of hyperthyroidism. We report an asymptomatic 28 years old male presenting with a serum total plasma thyroxin of 18.5 mu g.gl (N 6.1-12.5), a free thyroxin of 2.9 ng/dl (N 0.8-1.4) a TSH of 3.4 mu IU/ml (N 0.5-5), and a triiodothyronine of 128 ng/dl (N 80-180). Laboratory assessment did not find high thyroxin binding globulin, albumin or prealbumin concentrations or antithyroxin antibodies. The thyroxin binding capacity of albumin was elevated to 58.2 mu g/dl (N 11.5-34.1). TSH responded normally to TRH stimulus and was suppressed with exogenous triiodothyronine, which caused an hyperthyroid syndrome. We concluded that this patient had a familial dysalbuminemia.
Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents
(2004) Mulatero, P.; Stowasser, M.; Loh, K.C.; Fardella, C.E.; Gordon, R.D.; Mosso, L.; Gomez Sanchez, C.E.; Veglio, F.; Young, W.F.
Recently, some genetic forms of hypertension have been well characterized. These forms can be globally called mineralocorticoid hypertension and are due to different alterations of the renin-angiotensin-aldosterone system (SRAA). Among these, classic primary hyperaldosteronism and its glucocorticoid remediable variety, in which hypertension is secondary to aldosterone production, must be considered. There are also conditions in which mineralocorticoid activity does not depend on aldosterone production. These conditions generate a hyporeninemic hyperaldosteronism, observed in Liddle syndrome, apparent mineralocorticoid hypertension, 11- and 17-hydroxilase deficiency, among others. The detection of these forms of hypertension is only feasible if the renin-angiotensin-aldosterone system is assessed, measuring renin and aldosterone levels. This article reviews these forms of hypertension, their clinical workup and their relevance in the usual hypertensive patients.
Isquemia miocárdica reversible en el hipotiroidismo: comunicación de un caso
(2001) Quevedo, I.; Mosso, L.; Dominguez, J.M.; Fajuri, A.; Quintana, J.C.; NCD Risk Factor Collaboration (NCD-RisC)
A silent, reversible myocardial ischemia with normal coronary angiography and reversible with thyroid hormone substitution, has been recently described in hypothyroid patients. We report a 49 years old male with an abnormal exercise electrocardiogram detected in a preventive medical examination. He had laboratory evidence of hypothyroidism and a history of two years of asthenia and progressive coarsening of the voice. The Thallium myocardial perfusion study, showed an alteration of coronary flow during exercise in the septum and lower wall of the left ventricle. Thyroid hormone substitution was started and three months later, a coronary angiography was normal. After six months a repeated Thallium perfusion study and exercise electrocardiogram were informed as normal (Rev Med Chile 2001; 129: 1320-4).
Microcarcinoma tiroideo de evolución agresiva
(2005) Mosso, L.; Jimenez, M.; Gonzalez, H.; Solar, A.; Torres, J.; Fardella, C.; NCD Risk Factor Collaboration (NCD-RisC)
The treatment of papillary thyroid carcinoma of less than 10 mm diameter is a matter of controversy. The incidental finding of papillary microcarcinomas in autopsies is frequent and some authors postulate that these tumors are biologically inactive and should only be observed. We report a 21 years old woman with a papillary thyroid cancer of 6x5x5 mm and bilateral paratracheal metastases, that leas subjected to a total thyroidectomy. She received 200 mCi of radioiodine. Two years after surgery, a new nodule of 9.6 Mm diameter was detected by ultrasound, that was treated with a new dose of 200 1,170 of radioiodine. One year later a suprasternal mass of 2 cm diameter and 3 enlarged lymph nodes were detected. She was subjected to a surgical lymph node dissection of the neck and the biopsy confirmed the presence of cancer. She received a new dose of 300 mCi of radioiodine. The mother of the patient had a 7 mm thyroid nodule that was also a papillary carcinoma.
Normokalemic primary hyperaldosteronism - A common cause of secondary hypertension
(1999) Mosso, L.; Fardella, C.; Montero, J.; Rojas, P.; Sanchez, O.; Rojas, A.; Soto, J.; Foradori, A.; Huete, A.; NCD Risk Factor Collaboration (NCD-RisC)
Recently, some genetic forms of hypertension have been well characterized. These forms can be globally called mineralocorticoid hypertension and are due to different alterations of the renin-angiotensin-aldosterone system (SRAA). Among these, classic primary hyperaldosteronism and its glucocorticoid remediable variety, in which hypertension is secondary to aldosterone production, must be considered. There are also conditions in which mineralocorticoid activity does not depend on aldosterone production. These conditions generate a hyporeninemic hyperaldosteronism, observed in Liddle syndrome, apparent mineralocorticoid hypertension, 11- and 17-hydroxilase deficiency, among others. The detection of these forms of hypertension is only feasible if the renin-angiotensin-aldosterone system is assessed, measuring renin and aldosterone levels. This article reviews these forms of hypertension, their clinical workup and their relevance in the usual hypertensive patients.
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.
Primary aldosteronism and hypertensive disease
(2003) Mosso, L.; Carvajal, C.; Gonzalez, A.; Barraza, A.; Avila, F.; Montero, J.; Huete, A.; Gederlini, A.; Fardella, C.E.
Recent studies in hypertensive populations that have used the serum aldosterone (SA) to plasma renin activity (PRA) ratio as a screening test have demonstrated a high prevalence of primary aldosteronism (PA). This frequency is higher than that previously described when hypokalemia was used as a screening tool. However, other factors, such as the characteristics of hypertensive disease, could also influence the prevalence of PA. We studied 609 essential hypertensive patients, classified according to the Joint National Committee VI (JNC VI), in 3 different stages depending on the severity of their hypertensive disease. We measured SA and PRA and calculated the SA-PRA ratio for all patients. An SA-PRA ratio 25 was detected in 63 of 609 patients, and the fludrocortisone test confirmed the PA diagnoses in 37 of 609 (6.1%) cases. PA prevalence according to hypertension stage was as follows: stage 1, 6 of 301 cases (1.99%); stage 2, 15 of 187 cases (8.02%); and stage 3, 16 of 121 cases (13.2%). PA patients were slightly younger than the other hypertensive patients (48.410.5 vs 53.610.2 years; P0.05). Serum potassium levels were normal in 36 of 37 PA patients; only 1 patient had minor hypokalemia. Computed tomography scans showed bilateral adrenal enlargement in 7 and an adrenal nodule in 2 cases. In summary, we found a high frequency of PA in essential hypertensives classified in stages 2 and 3 according to the JNC VI. The low frequency of computed tomography scan abnormalities and hypokalemia suggests that the diagnosis for most PA patients corresponds to attenuated forms of the disease.
Primary hyperaldosteronism in essential hypertensives: Prevalence, biochemical profile, and molecular biology
(2000) Fardella, C.E.; 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.
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.
Utilidad de la PTH intraoperatoria como predictor de curación quirúrgica en hiperparatiroidismo primario
(2009) Domínguez, J.M.; Velasco, S.; Arteaga, E.; Campusano, C.; Fardella, C.; López, J.M.; Mosso, L.; Rodríguez, J.A.; González, G.; Goñi, I.; León, A.; González, H.; Claure, R.
The aim of the surgical treatment of primary hyperparathyroidism (PHPT) is to achieve its complete cure, evidenced by a normal serum calcium in the postoperative period. Measurement of intraoperative serum parathormone (PTH) can be useful to predict complete cure of the disease. Aim: To assess the usefulness of intraoperative PTH measurement to predict complete cure of PHPT. Material and methods: Serum PTH was measured to all patients operated for PHPT between 2003 and 2008, before and five and ten minutes after the excision of the parathyroid gland causing the disease. The criteria for complete cure were a normal serum calcium at 24 hours and 6 months after surgery and the pathological confirmation of parathyroid gland excision. Results: Eighty eight operated patients, aged 58±15 years (72 females) were studied. Sixty four percent were asymptomatic and their preoperative serum calcium was 11.6±1.2 mg/dl. A normal serum calcium was achieved in 86 patients (98%) at 24 hours and 50 of 52 patients followed for six months (96%). The pathological study disclosed an adenoma in 69 (78%), and multiglandular disease in 16 (18%), a parathyroid cancer in one and a normal gland in one patient. Intraoperative PTH predicted early and definitive cure in 97% and 100% of patients with a single adenoma, respectively. Among patients with multiglandular disease, the predictive figures were 94% and 100%, respectively. Conclusions: Intraoperative PTH measurement efficiently predicts early and definitive surgical cure of PHPT.

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