Browsing by Author "Fardella, C"

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    Evidences for mineralocorticoid excess in essential hypertension
    (2000) Cortes, P; Fardella, C; Oestreicher, E; Gac, H; Mosso, L; Soto, J; Foradori, A; Claverie, X; Ahuad, J; Montero, J
    Background: Primary hyperaldosteronism is more frequent among subjects with essential hypertension than previously thought. The prevalence, according to local and international evidence could fluctuate between 9 and 10%. Aim: To investigate if subjects with essential hypertension have different aldosterone and renin plasma levels than normotensive subjects. Patients and methods: One hundred twenty five subjects with essential hypertension, not receiving medications for a least two weeks prior to the study and 168 age and sex matched normotensive controls were studied. Blood was drawn between 9 and 10 AM during a sodium free diet to determine plasma aldosterone, plasma renin activity and potassium. Results: Plasma aldosterone was higher in hypertensive subjects than controls (11.6 +/- 7.6 and 9.9 +/- 5.1 ng/dl respectively; p = 0.04). Plasma renin activity was lower in hypertensives than controls (1.42 +/- 1.28 and 1.88 +/- 1.39 ng/ml/h respectively; p < 0.001). Thus, plasma aldosterone/plasma renin activity ratio was higher in hypertensives (13.8 +/- 13.5 and 8.3 +/- 7.8; p < 0.001), A pathological ratio was defined as over 25, corresponding to the mean plus two standard deviations of the control group. Primary hyperaldosteronism was found in 5/125 hypertensives (4%) and 1/168 normotensive subject (0.6%). None had hypokalemia. Conclusions: Subjects with essential hypertension have higher plasma aldosterone and lower plasma renin activity than normal controls. A plasma aldosterone/plasma renin activity over 25 was defined as abnormal.
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    Free urinary cortisol is elevated in patients with low-renin essential hypertension
    (2004) Krall, P; Mosso, L; Carvajal, C; Rojas, A; Fardella, C
    Background: Glucocorticoids play a key role in blood pressure (BP) control and are associated with hypertension in patients with Cushing's syndrome. A number of reports indicate that cortisol (F) may be involved in etiology of essential hypertension (EH). F can bind to the mineralocorticoid receptor, triggering both sodium and water reabsorption in kidney, increase BP and cause renin suppression. Aim: To evaluate urinary free cortisol (UFF) excretion as a potential intermediate phenotype of essential hypertension and correlate F level with plasma renin activity (PRA) and serum aldosterone (SA). Patients and Methods: We recruited 132 EH patients and 16 normotensive healthy controls. Blood samples and 24 hours urine were collected for PRA, SA and UFF analysis. Differences in UFF excretion between sexes were normalized by urinary creatinine (Creat) excretion. The upper limit of UFF/Creat was determined in normotensives considering the mean value plus 2 standard deviations. According to this value, subjects were classified as having high or normal UFF. Results: In EH patients and in normotensives, the UFF/Creat was 36.9 +/- 17.0 mug/gr and 30.9 +/- 8.8 mug/gr, respectively. The upper limit was set at 48.5 mug/gr. A high UFF/Creat was found in 20/132 EH (15%) patients and 0/16 normotensive subjects. EH patients with high UFF showed lower PRA levels than patients with normal cortisol levels (0.78 +/- 0.47 vs 1.13 +/- 0.66 ng/ml*h, respectively, p = 0.027) and lower SA values (4.52 +/- 1.65 vs 6.34 +/- 3.37 ng/dl, respectively, p = 0.018). There was a negative correlation between UFF and PRA (r = -0.176, p = 0.044) and between UFF and SA (r = -0.183, p = 0.036). Conclusions: We have identified a subgroup of EH patients with increased UFF excretion. Patients with the highest UFF showed lower renin and aldosterone levels. These data suggest a potential influence of cortisol in the genesis of hypertension.
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    Genetic studies in dexamethasone supressible aldosteronism.
    (2001) Fardella, C; Pinto, M; Mosso, L; Oestreicher, E; Montero, J
    We report two women presenting with parathyroid cysts. A 20 years old woman presented with goiter and a cystic lesion in the left thyroid lobe was identified on ultrasound examination and CAT scan. The patient had hypercalcemia and elevated PTH levels. The content of the cyst, obtained by needle aspiration, had an extremely high PTH concentration. The patient was operated, removing the cyst and a remaining thymus. Pathological study confirmed the diagnosis of a parathyroid cyst. An 11 years old girl presented with a mass in the left thyroid lobe. An ultrasound examination disclosed the presence of a cystic nodule. The patient was otherwise asymptomatic and laboratory work up was normal. The patient was operated and pathological examination of the surgical piece revealed a parathyroid cyst.
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    Glucocorticoid treatable hypertension. Report of one case
    (1997) Montero, J; Fardella, C; Mosso, L
    Lately, a series of hypertensive syndromes of unknown etiology that respond to new forms of therapy, have been described One of these is glucocorticoid remediable hypertension, that evolves with suppressed plasma renin activity and normal or high serum aldosterone levels, that lead to an aldosterone/plasma renin activity ratio over 30. We report a 45 years old woman with a severe hypertension despite the use of antihypertensive medications. She had a plasma renin activity of less than 0.3 ng/ml/h, normal serum aldosterone levels (10 ng/ml) and thus a high aldosterone/plasma renin activity ratio. She had normal serum potassium and sodium levels. Due to the bad results of conventional antihypertensive medications, a treatment with dexamethasone was started that normalized blood pressure and allowed to discontinue other antihypertensive medications. This type of hypertensive must besought since non conventional treatments could be used for refractory hypertensive syndromes.
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    High prevalence of thyroid abnormalities in a Chilean psychiatric outpatient population
    (2000) Fardella, C; Gloger, S; Figueroa, R; Santis, R; Gajardo, C; Salgado, C; Barroilhet, S; Foradori, A
    The aim of the present study was to establish the prevalence of thyroid disturbances in patients consulting for panic and mood disorders. These data may be relevant because thyroid functional alterations affect the success of treatment in these pathologies. We studied prospectively 268 psychiatric outpatients (204 females and 64 males) diagnosed by DSM-IV criteria. We excluded patients with addictive disorders and major medical disease. We measured TSH, Free T4 (FT4) and antimicrosomal antibodies (AMA). We diagnosed classical hypothyroidism when the TSH value was >10 mu UI/ml (NV=0.25-4.3) and subclinical hypothyroidism when the TSH value was between 5-10 mu UI/ml. Hyperthyroidism was diagnosed when FT4 >1.4 (NV=0.81.4), the TSH suppressed and the radioiodine uptake >20% (NV=5-15). Positive antimicrosomal antibodies (AMA) titres were >1:100 dilution. Hypothyroidism was diagnosed in 26/268 patients (9.7%); 10 cases corresponded to the classical form (38.5%) and 16 cases to the subclinical form (61.5%). Hyperthyroidism was found in 6/268 patients (2.2%). Normal thyroid function with positive AMA was found in 28/268 patients (10.4%). Hypothyroidism was more common in patients with mood disorders, and hyperthyroidism in patients with panic disorders. Patients with panic disorder had significant higher levels of FT4. The prevalence of positive AMA, hypothyroidism and hyperthyroidism was higher in women than men. We found a high frequency of thyroid abnormalities in a psychiatric outpatient population. These data suggests that routine evaluation of thyroid function should be considered in patients consulting for mood and panic disorders. (J. Endocrinol. Invest. 23: 102-106, 2000) (C)2000, Editrice Kurtis.
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    Intracellular calcium and blood pressure: Comparison between primary hyperparathyroidism and essential hypertension
    (1995) Fardella, C; RodriguezPortales, JA
    Intracellular calcium has been reported to be increased in essential hypertension, and thought to play a role in its genesis through facilitation of vascular smooth muscle contraction, Since hypertension is more prevalent in primary hyperparathyroidism, intracellular calcium may also be increased in this condition, To investigate whether the hyperparathyroid condition, i.e., hypercalcemia and increased PTH per se, could be associated with high intracellular calcium, we measured intracellular calcium in platelets with the Quin-2 AM fluorometric method in 11 normotensive patients with primary hyperparathyroidism, 15 patients with essential hypertension, and 18 normal controls, all matched for age and sex. We repeated the measurements in 9 of the hyperparathyroid patients after successful surgery, We found that intracellular calcium was higher in normotensive patients with primary hyperparathyroidism than in normal controls (198 +/- 24 vs 113 +/- 11 nM, p < 0.05), but lower than in patients with essential hypertension (198 +/- 24 vs 286 +/- 38 nM, p < 0.05). Successful removal of a parathyroid adenoma decreased intracellular calcium from 215 +/- 22 to 116 +/- 19 nM, (p < 0.01), In the patients with primary. hyperparathyroidism, intracellular calcium was strongly correlated with the levels of PTH (r = 0.87, p < 0.01), but not with the total serum calcium levels (r = 0.04, NS). The decrease in intracellular calcium after parathyroidectomy was also strongly correlated with the decrease in PTH (r = 0.84, p < 0.01), but not with the decrease in total serum calcium (r = 0.16, NS). In the patients with essential hypertension, intracellular calcium correlated well with systolic (r = 0.69, p < 0.01), diastolic (r = 0.76, p < 0.01) and especially mean arterial pressure (r = 0.86, p < 0.01), There was no correlation between blood pressure and intracellular calcium in the patients with primary hyperparathyroidism. We conclude that normotensive patients with primary hyperparathyroidism, as well as patients with essential hypertension, can have increased concentrations of intracellular calcium in platelets. The correction of the hyperparathyroid condition normalizes intracellular calcium concentration. The dose correlation between PTH and intracellular calcium suggests that PTH may act as a ionophore for calcium entry into cells, Whether the increased levels of intracellular calcium may reflect a pre-hypertensive condition in normotensive patients with primary hyperparathyroidism remains to be determined.
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    Pathological characteristics of thyroid microcarcinoma. A review of 402 biopsies
    (2005) Fardella, C; Jimenez, M; Gonzalez, H; Leon, A; Goni, I; Cruz, F; Solar, A; Torres, J; Mosso, L; Gonzalez, G; Rodriguez, JA; Campusano, C; Lopez, JM; Arteaga, E
    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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    Persistent hypokalemia after successful adrenalectomy in a patient with Cushing's syndrome due to ectopic ACTH secretion
    (1999) Arteaga, E; Fardella, C; Campusano, C; Cárdenas, I; Martinez, P
    Ectopic ACTH secretion is characterized by a high incidence of hypokalemia. The pathophysiology of hypokalemia has not been totally clarified, although it has been postulated that excessive amounts of adrenal steroids may play a role, as well as a possible role of the inhibition of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). This enzyme normally converts cortisol to cortisone avoiding the mineralocorticoid action of cortisol. We present a patient with ectopic ACTH secretion due to a metastatic carcinoid tumor. The clinical picture was characterized by maintained hypokalemia (1.4 mmol/l) resistant to potassium, spironolactone and ketoconazole administration. A bilateral adrenalectomy was performed but the hypokalemia persisted while he was receiving a physiological dose of cortisol. Eight days after adrenalectomy cortisol was replaced by an equivalent dose of dexamethasone. This change was followed by a rapid and persistent normalization of hypokalemia suggesting a mineralocorticoid effect of cortisol. In conclusion, the origin of hypokalemia in our patient with ectopic ACTH secretion was secondary to cortisol. We postulate that this peculiar effect of cortisol could have happened if an inhibition of 11 beta-OHSD occurred. (J. Endocrinol. Invest. 22: 857-859, 1999) (C) 1999, Editrice Kurtis.
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    Serum 18-hydroxycortisol in primary aldosteronism, hypertension, and normotensives
    (LIPPINCOTT WILLIAMS & WILKINS, 2001) Mosso, L; Gomez Sanchez, CE; Foecking, MF; Fardella, C
    This 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.
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    The A-6G mutation in the angiotensinogen gene is associated to high levels of aldosterone in essential hypertensives
    (1999) Fardella, C; Zamorano, P; Gomez, L; Oestreicher, E; Pinto, M; Rojas, A; Montero, J; Soto, J; Mosso, L; Foradori, A
    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 was 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 mCi 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.