Actividad de 11 beta hidroxiesteroide dehidrogenasa tipo 2 en hipertensos chilenos / 11 B-hydroxysteroid dehydrogenase activity in patients with hypertension and low plasma renin activity

Background: Half of hypertensive patients with low plasma renin activity have a primary hyperaldosteronism. Among the remaining half, 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2) deficiency plays an 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 11ßHSD2 deficiency, in low-renin hypertensive patients. Patients and Methods: Twenty eight hypertensive patients with a plasma renin activity of less than 0.5 ng/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 (11.1ñ3.3 and 9.2ñ2.8 µg/dl, respectively; p <0.05). No differences were observed in serum cortisone (3.4ñ1.3 and 3.7ñ1.2 µg/dl, respectively). Four hypertensive subjects had an 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 11ßHSD2 deficiency

Anticuerpos anti-tiroglobulina en el seguimiento de pacientes con cáncer diferenciado de tiroides: ¿marcadores de enfermedad residual o recidivante? / Anti thyroglobulin antibodies in the follow up of patients with differentiated thyroid cancer

Background: Anti thyroglobulin antibodies are present in 25 percent of patients treated for a differentiated thyroid cancer, invalidating thyroglobulin determination. Those patients subjected to total thyroidectomy and free of disease, should reduce the production of these antibodies, due to the lack of antigenic stimulus. Therefore, anti thyroglobulin antibodies could be useful to detect early relapses. Aim: To assess the relationship between anti thyroglobulin antibodies and the evolution of the disease in patients treated for thyroid cancer. Material and methods: Retrospective analysis of 26 patients treated for thyroid cancer with positive anti thyroglobulin antibodies, followed for three years. These were divided in those with or without lymphocytic thyroiditis (19 and 7 respectively). Results: At the first year of follow up, anti thyroglobulin antibody concentration was 401ñ94.9 UI/ml (xñsem) in patients with thyroiditis and 38.9ñ8.9 UI/ml in those without thyroiditis (p < 0.005). During the three years of follow up, no differences in anti thyroglobulin antibodies were observed between patients with or without tumor relapse. Conclusions: Concentration of anti thyroglobulin antibodies was higher in patients with thyroiditis and did not differentiate patients with tumor relapse

Bases clínico moleculares de la hipertensión arterial dependiente de mineralocorticoides / Clinical molecular basis of the mineralocorticoid dependent arterial hypertension

El hiperaldosteronismo primario es una causa potencialmente curable de hipertensión arterial. El uso rutinario de la razón aldosterona/actividad de renina plasmática como test de screenning ha demostrado que existe una alta prevalencia de esta enfermedad, cercana al 10 por ciento de la población de hipertensos. Esta frecuencia es claramente más alta que la clásicamente descrita cuando la hipokalemia es usada como método de screening. Los subtipos más comunes de hiperaldosteronismo primario son el hiperaldosteronismo supresible por glucocorticoides y la hiperplasia adrenal primaria. El diagnóstico de hiperaldosteronismo primario está dirigido en primer lugar a confirmar la autonomía de la secreción de aldosterona del eje renina-angiotensina y posteriormente a diferenciar los tipos subclínicos de la enfermedad. Este artículo es una puesta al día de los nuevos datos acerca de la prevalencia, criterios diagnósticos y describe las características clínicas, bioquímicas y genéticas de los diferentes subtipos de la enfermedad. Además discutimos el diagnóstico diferencial con otros estados de hipermineralocorticoidismo no dependientes de aldosterona como son el déficit de 11ß-hidroxiesteroide deshidrogenasa tipo II, defectos en el canal renal de sodio o las formas hipertensivas de la hiperplasia suprarrenal congénita (11ß-hidroxilasa y 17a-hiroxilasa)

Hiperplasia suprarrenal congénita / Congenital adrenal hyperplasia

La esteroidogénesis suprarrenal es un proceso complejo y secuencial que involucra a una serie de enzimas, las cuales actuando en forma coordinada sobre el colesterol determinan la síntesis de glucocorticoides y mineralocorticoides. El término hiperplasia suprarrenal congénita ha sido tradicionalmente usado para denominar al conjunto de alteraciones en la esteroidogénesis suprarrenal que determinan un decremento en la biosíntesis de cortisol. Este hecho determina una elevación compensatoria de ACTH, la cual, al estimular la síntesis esteroidal, lleva a un aumento de la producción de esteroides localizados antes del bloqueo. El resultado final es una diversidad de cuadros clínicos determinados por el déficit de cortisol y hormonas distales al bloqueo y al exceso de hormonas y metabolitos proximales al bloqueo. Los cuadros más frecuentes de hiperplasia suprarrenal congénita son los déficit de 21 y 11-hidroxilasa, que serán revisados en conjunto con otros déficit enzimáticos de presentación menos frecuente

Alta prevalencia de enfermedad tiroidea subclínica en sujetos que concurren a control de salud / High prevalence of subclinical thyroidal disease among individuals attended in occupational health examinations

Background: There is no information about the prevalence of thyroidal diseases in the general Chilean population. Aim: To assess the prevalence of thyroidal diseases in individuals attended in occupational health examinations. Subjects and methods : Four hundred seventy two individuals were examined between 1998 and 1999. In all, serum levels of thyroid hormones, TSH and anti thyroidal antibodies (anti microsomal, anti thyroid peroxidase and anti thyroglobulin) were measured. Results: Forty four subjects were excluded from the study due to an incomplete medical record and 18 due to a personal history of thyroidal disease. Abnormal serum levels of thyroid hormones or TSH were detected in 28 subjects (6.8 percent). Four (1 percent) had hypothyroidism, 23 a subclinical hypothyroidism (5.6 percent) and one (0.2 percent) had hyperthyroidism. In 87 subjects (21.2 percent) at least one of the antibodies was positive. Positive anti thyroid antibodies were found in 14 of 28 subjects (50 percent) with abnormal thyroid hormone levels, compared with 73 of 382 subjects (19.1 percent) with normal thyroid hormone levels. Thyroid dysfunction was twice as frequent in women than in men. Conclusions: In this sample, a 6.8 percent prevalence of abnormal thyroid function tests was detected

Trastorno de pánico e hipertiroidismo: curso clínico en dos pacientes / Panic disorder and hyperthyroidism: report of 2 cases

In two females aged 27 and 32 years old, an aggravation of their panic disorder coincided with the appearance of clinical signs of hyperthyroidism. The clinical diagnosis was confirmed with the finding of raised thyroid hormone levels and undetectable TSH levels. These two cases highlight the importance of routine thyroid function assessment in patients with panic disorder, mainly in those with partial response to medications or when symptoms aggravate, despite an adequate treatment

Exceso de mineralocorticoides en hipertensos esenciales: enfoque clínico diagnóstico / Evidences for mineralocorticoid excess in essential hypertension: clinic and diagnosis viewpoint

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 percent. 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 at 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 ñ 7.6 and 9.9 ñ 5.1 ng/dl respectively; p=0.04). Plasma renin activity was lower in hypertensives than controls (1.42 ñ 1.28 and 1.88 ñ 1.39 ng/ml/h respectively; p<0.001). Thus, plasma aldosterone/plasma renin activity ratio was higher in hypertensives (13.8 ñ 13.5 and 8.3 ñ 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 percent) and 1/168 normotensive subject (0.6 percent). 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

Alta prevalencia de hiperaldosteronismo primario no diagnosticado en hipertensos catalogados como esenciales / High prevalence of undiagnosed primary hyperaldosteronism among patients with essential hypertension

Background: Classically, primary hyperaldosteronism was diagnosed in no more than 1 percent of patients with hypertension, when hypokalemia was used as the screening test. However, numerous patients with primary hyperaldosteronism do not have hypokalemia and 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 or the aldosterone/plasma renin activity ratio was over 50. A probable primary hyperaldosteronism was diagnosed when 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

Hipertensión arterial y mineralocorticoides: utilidad de las mediciones de renina y aldosterona / Hypertension and mineralcorticoids: usefulness of renin and aldosterone measurements

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

Síndrome de Cushing por secreción ectópica de ACTH: análisis del mecanismo fisiopatológico de la hipokalemia: comunicación de dos casos / Cushing syndrome with severe hipokalemia caused by ectopic ACTH secretion: report of two cases

We report a 42 years old male and a 66 years old female with a Cushing syndrome caused by ectopic ACTH secretion secondary to a carcinoid tumor. These patients had both severe hypokalemia, resistant to medical treatment and that subsided with bilateral adrenalectomy and supplementation with dexametasone. Cushing syndrome caused by ectopic ACTH secretion is characterized by a severe and rapidly evolving hypercortisolism. Hypokalemia is present in 90 percent of cases and is probably caused by a defect in 11 ß hydroxysteroid dehydrogenase, that limits the binding of cortisol to aldosterone receptor, metabolizing it to cortisone. Therefore, this alteration will increase the mineralocorticoid action of cortisol

Prevalencia de la deleción 185AG del gen BRCA1 en mujeres chilenas con cáncer de mama / Prevalence of BRCA1 gene 185AG deletion in Chilean women with breast cancer

Background: The most important identified pathogenic factor for breast cancer is the presence of mutations in BRCA1 gene. These are associated with familial breast cancer in up to 80 percent of cases. The most frequent mutation of BRCA1 gene in Caucasian populations is the exon 2 185AG deletion. Aim: To study the presence of 185AG deletion in Chilean women with sporadic or familial breast cancer. Patients and methods: We studied 15 women with familial breast cancer, in whom at least one close relative was affected, and 40 women with sporadic breast cancer. In genomic DNA obtained from a blood sample, an allele specific polymerase chain reaction was done. This reaction allows the identification of 185AG deletion and uses two pairs of primers. One for the native form that renders a 118 base pairs product and one for the deletion that renders a 170 base pairs product, both with a respective 280 base pairs internal control. Results: The diagnosis of breast cancer was done at 40ñ5 and 65ñ10 years old in women with familial and sporadic breast cancer, respectively. In none of the samples, the amplification of the 170 base pairs band that corresponds to 185AG deletion, was obtained. In both groups, the product of the amplification was the 118 base pairs band, that corresponds to the native form of BRCA1 gene. The polymerase chain reaction was optimized for a duration of 90 minutes. Conclusions: 185AG deletion of BRCA1 gene was not detected in this group of Chilean women with sporadic or familial breast cancer

Medición de la actividad de renina plasmática a niveles bajos: optimización del método / Measurement of low levels of plasma renin activity: a methodological improvement

Background: The present method to measure plasma renin activity is cumbersome and imprecise, factors that limit its clinical application. Aim: To assess the importance of blood sampling conditions and the usefulness of increasing incubation time to measure plasma renin activity at low levels. Patients and methods: Twenty hypertensive patients, 14 female, aged 14 to 76 years old, were studied. Two blood samples were obtained after a 10 min rest in the sitting position and after a 30 min rest in supine position. One blood sample, of each condition was sent lo the laboratory at room temperature and the other sample was sent refrigerated. Angiotensin I concentration was determined after 3 h of enzymatic incubation at 37°C and, in subjects with an activity of less than 1 ng/ml/h, after 18 h of incubation. Results: No significant differences in plasma renin activity were observed between the samples obtained with different rest times or different transportation methods. In people with low plasma renin activity, the 18 h enzymatic incubation reduced the lower detection from 0.3 to 0.014 ng/ml/h and the coefficient of variation from 14.4 to 3.2 percent. Conclusions: A simplified blood sampling method does not change plasma renin activity values, and tbe longer enzymatic incubation in people with low plasma renin activity improves both the sensitivitv and accuracy of the determination

Relevancia del estudio tiroideo en pacientes con trastornos psiquiátricos / Thyroid function assessment in psychiatric patients

Background: Thyroid dysfunction is frequent in psychiatric outpatients and the correction of their endocrine abnormalities seems to improve the response to psychopharmacologic treatment. Aim: To retrospectively explore the frequency of thyroid abnormalities in psychiatric autpatients. Material and methods: Clinical charts and thyroid assesment of 102 psychiatric patients aged 40.8ñ15 years old (28 male) seen between April 1995 and 1996 were reviewed. Endocrine diagnosis was made according to international criteria and psychiatric diagnosis was made by a single psychiatryist following DSM IV criteria. Results: Forty patients (39.2 percent) had thyroid abnormalities. Thirteen (12.7 percent) had a diagnosis of thyroid problems and were in treatment before they came to the psychiatric clinic. Sixteen patients had hypothyroidism (40 percent), seven had subclinical hypothyroidism (17.5 percent), 12 were euthyroid but had goiter or positive thyroid antibodies (30 percent) and 5 individuals had hyperthyroidism (12.5 percent). The most frequent thyroid abnormality was the presence of positive thyroid antibodies in 16 cases (15.7 percent). No specific associaton was found between psychiatric and endocrine diagnoses. Conclusions: The desing of this study prevents to draw conclusions about prevalence of thyroid alterations in psychiatric patients. Nevertheless results support the need for routine thyroid assessment in this specific population

Hipertensión arterial tratable con glucocorticoides: comunicación de un caso / Glucocorticoid treatable hypertension: report of one case

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, despide 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 normalized blood pressure and allowed to discontinue other antihypertensive medications. This type of hypertension must be sought since non conventional treatments could be used for refractory hypertensive syndromes

Diagnóstico molecular de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa, variedad perdedora de sal, en población chilena / Molecular diagnosis of salt wasting congenital adrenal hyperplasia, caused by deficit of 21-hydroxylase, in the Chilean population

Twenty five patients with salt wasting congenital adrenal hyperplasia, that had 17-hydroxyprogesterone levels above 30 ng/ml, were studied. In all patients, a polymerase chain reaction (PCR) with selective primers was done with extracted genomic DNA, to amplify the active gene and specific primers for normal or mutated alleles of 50 chromosomes of the 25 patients. The higher frequency affected the ASIn2 in 26 percent of cases, followed by mutations Arg357Trp in 22 percent of cases and Gln319Stop in 12 percent and deletion in 12 percent. The frequent genotypes were homozygosity for ASIn2 (16 percent), homozygosity for Arg357Trp (12 percent) and the homozygote deletion of the gene in 12 percent. The most frequent mechanisms of genetic deficiency of 21-hydroxylase were the mutations ASIn2 Arg357Trp. This type of studies allows prenatal diagnosis and genetics counseling

Macrotumor suprarrenal diagnosticado por tomografía axial computarizada: experiencia clínica en 33 casos / Adrenal macrotumor diagnosed by computarized tomography: clinical experience in 33 cases

Thirty three patients aged 9 to 86 years old, 15 female, with an adrenal macrotumor diagnosed by CAT scan, were analized. Thirty percent of tumors were functioning (70 percent secreted cathecolamines and 30 percent cortisol). Eighty two percent had an adrenal localization and 18 percent were para-adrenal. Thirty four percent were malignant. These tumors were mostly non functioning, 70 percent occured in men and 67 percent were metastatic. Most adrenal macrotumors in this series were non functioning and 36 percent were malignant