Objetivos: Comparar el efecto de dos esquemas de terapia hormonal (TH) combinada cíclica, sobre la presión arterial (PA), índices de resistencia a la insulina y cociente Tg/C-HDL en mujeres postmenopáusicas hipertensas. Métodos: Estudio clínico realizado en 19 posmenopáusicas hipertensas. Todas iniciaron la TH con estrógenos equinos conjugados (Premarin®: 0,625mg) durante 8 semanas (TH-O). Después de un periodo de 4 semanas sin tratamiento se inició TH transdérmica (TH-TD) con 17βestradiol (Estraderm®, 50mg,) durante el mismo período de tiempo. Acetato de medroxiprogesterona (5mg, Provera®) fue administrado durante las semanas 3a-4a y 7a-8a de cada esquema de tratamiento. Se registró la PA y se tomaron muestras de sangre en condición basal y después de cada período de tratamiento para determinación de lípidos, glucemia, insulina, FSH, estradiol, androstenediona y DHEAS. Resultados: La TH disminuyó la PA significativamente (p<0,05), la TH-TD tuvo un efecto más favorable. La TH-O disminuyó significativamente el Ct, C-LDL, apoB, índices Tg/C-HDL, Ct/C-HDL y aumentó significativamente el C-HDL. El C/C-LDL no fue modificado por la TH. La concentración de Tg disminuyó significativamente durante ambos esquemas de tratamiento, con un efecto mayor durante la TH-TD. La glucosa e insulina en ayunas y en respuesta a la carga de glucosa oral fueron similares en ambos grupos; la TH-TD aumentó significativamente los índices de sensibilidad (ISI y QUICKI) y disminuyó el índice HOMAIR. La androstenediona disminuyó (p<0,05) con ambos esquemas. Conclusiones: La TH combinada, cíclica tiene efectos favorables sobre la PA, dislipidemia, índice Tg/C-HDL e índices de acción insulínica, lo cual podría disminuir el riesgo de ECV en la mujer posmenopáusica hipertensa. Se sugiere que en pacientes postmenopáusicas con hipertrigliceridemia e hipertensión arterial la TH-TD debería ser considerada como primera opción terapéutica.

Abstract Objectives: To compare the effect of two routes of hormonal therapy (HT) on blood pressure, insulin resistance indexes, Tg/ HDL-C ratio in postmenopausal hypertensive women. Méthods: A clinical study was performed in 19 postmenopausal women. All women were treated with equine conjugated estrogens (Premarin®: 0,625mg) for 8 weeks (O-HT). After 4 weeks period without treatment, patients were switched to transdermal estrogen therapy (TD-HT) using 17βestradiol (Estraderm®, 50mg). Medroxyprogesterone (5mg, Provera®) acetate was administered during 3rd-4th week and seventh-eighth week in each treatment cycle. Blood pressure and blood samples were taken at baseline and after each period o treatment. Laboratory protocol included determinations of FSH, estradiol, androstendione, DHEAS and glucose and insulin during a standard oral glucose test. Results: HT caused a significant decrease in BP but TD-HT was more efficient (p<0,05). Oral treatment was associated with a significant decrease in Tg/C-HDL, Ct/C-HDL indexes and a significant increase in HDL-C. Plasma Tg decreased significantly after both routes of treatment with more pronounced effect during TD-HT. No significant differences between groups were observed in plasma glucose and insulin during fasting and post oral glucose load. TD-HT showed a significant decrease in HOMA-IR and a significant increase in sensitivity indexes QUICKI and ISI. Serum androstenedione levels were decreased after both routes of treatment (p<0,05). Conclusions: Combined cyclical HT has beneficial effects on blood pressure, lipoproteins, Tg/C-HDL ratio and insulin action indexes leading to a lower risk of cardiovascular disease in postmenopausal hypertensive women. We suggest that in this population, transdermal HT should be considered as a first therapeutic option.

Objetivos: Evaluar el efecto del tratamiento con Levotiroxina sobre el metabolismo de los lípidos en niños con hipotiroidismo subclínico (HS). Métodos: Se hizo seguimiento durante 20 meses a 11 niños, cinco varones y seis hembras, entre 4 y 11 años, con HS permanente (T4L normal y TSH elevada en dos determinaciones realizadas con 4 meses de diferencia). Se les indicó tratamiento con Levotiroxina (2 ug/kg/día) y se les realizaron pruebas de función tiroidea y lipidograma a los 4 meses y al año. Para afianzar la relación entre el perfil lipídico y el tratamiento con Levotiroxina, se suspendió el tratamiento a nueve niños durante cuatro meses y se reinició por cuatro meses mas, realizando los mismos análisis, sin tratamiento y con tratamiento nuevamente. Resultados: El perfil lipídico mejoró al lograr el eutiroidismo; disminuyó la concentración de colesterol total (Ct), de colesterol de la lipoproteína de baja densidad (C-LDL), de triglicéridos (Tg), y aumentó el colesterol de la lipoproteína de alta densidad (CHDL). Los cambios en el C-HDL, el C-LDL y el índice C-LDL/C-HDL fueron significativos al año de tratamiento (p=0,03; 0,02 y 0,02 respectivamente). Al suspender la Levotiroxina se produjo una elevación significativa en la concentración promedio de TSH (6,7 uU/mL), y su normalización al reiniciar la terapia (2 uU/mL), con niveles de T4L dentro del rango normal. Se observó elevación de Ct, Tg y C-LDL y disminución del C-HDL al suspender el tratamiento y mejoría al reiniciarlo, siendo significativos los cambios en los Tg (p=0,004) y en el C-HDL (p=0,02). Un comportamiento similar presentaron los índices aterogénicos (p=0,04 para el Ct/C-HDL y p=0,003 para el C-LDL/C-HDL). La dosis promedio de levotiroxina para lograr el eutiroidismo fue de 0.043mg/día (2,1 ug/kg/día). Conclusiones: El perfil lipídico de niños con HS mejora significativamente con el tratamiento de Levotiroxina.

Objectives: to assess the effect of Levothyroxine treatment on lipid metabolism in children with subclinical hypothyroidism (SH). Methods: Eleven children, 5 boys and 6 girls, aged from 4 to 11, all of them with permanent SH (normal FT4 and high TSH in two determinations made at an interval of four months of difference) were follow up during 20 months. Treatment with Levothyroxine (2 ug/kg/day) was given, and thyroid function tests and lipid profile were analyzed after four and twelve months. To assure the relationship between the lipid profile and the Levothyroxine treatment, this therapy was discontinued to nine patients during four months, and then it was continued for four months more. The same tests were analyzed, with and without treatment. Results: Lipid profile improved when euthyroidism was obtained; total cholesterol (Tc) levels, low-density lipoprotein cholesterol (LDL-C) levels, and triglyceride (Tg) levels decreased and high-density lipoprotein cholesterol (HDL-C) levels increased. Changes in HDL-C, LDL-C, and the HDL-C/LDL-C index were significant after a year of treatment (p=0,03; 0,02, and 0,02 respectively). When Levothyroxine was discontinued, elevated levels in the mean concentration of TSH (6,7 uU/ml) were observed, and when the treatment continued, the levels normalized (2 uU/ml). The FT4 levels were in normal rates. Elevated levels of Tc, Tg, and LDL-C and low levels of HDL-C were observed when the treatment was discontinued, and a significant recuperation was observed at restarting the treatment with significant changes in Tg (p=0,004) and HDL-C (p=0,02). The atherogenic indexes showed a similar behavior (p=0,04 for Tc/HDL-C and p=0,003 for LDL-C/HDL-C). Mean dose of Levothyroxine to reach euthyroidsm was 0.043 mg/day (2,1 ug/kg/day). Conclusions: Lipid profile of children with SH improves considerably following the treatment with Levothyroxine.

Objetivo: Evaluar la efectividad de los métodos de cálculo de la dosis de radioyodo, así como las dosis utilizadas en el tratamiento del hipertiroidismo. Métodos: Se revisaron 46 historias de pacientes con hipertiroidismo, 29 con bocio difuso tóxico (BDT) y 17 con bocio nodular tóxico (BN), tratados con radioyodo en la Unidad de Medicina Nuclear desde Enero de 1984 hasta Enero de 2004. Se planteó el hipotiroidismo a los 3 meses post-terapia como criterio de cura y efectividad. Resultados: De los pacientes con BDT, el 26,9% presentó hipotiroidismo a los 3 meses y el 44% a los 12 meses. La mayoría de los pacientes que recibieron dosis calculadas según el método Quimby Marinelli lograron hipotiroidismo a los 3 meses (p<0,01) y se asociaron con dosis altas de radioyodo (p<0,01), en comparación con los otros métodos (Marinelli 404 y Marinelli 680). La mayoría de los pacientes que permanecieron hipertiroideos fueron tratados con dosis bajas de radioyodo (<10 mCi). El análisis de regresión lineal demostró que la dosis administrada de radioyodo tuvo mayor relación con la efectividad del tratamiento que el método de cálculo de la misma (p<0,005). En los pacientes con BN no se encontró diferencia entre los métodos de cálculo y la dosis administrada en relación a la efectividad del tratamiento. Conclusiones: Los resultados demostraron que el método de Quimby Marinelli y sobre todo, las dosis altas de radioyodo tuvieron la mayor efectividad en el tratamiento del BDT.

Objective: To evaluate the effectiveness of the different methods to calculate the 131I doses and the final doses used on the treatment of the hyperthyroidism. Methods: Forty six clinical records from patients with hyperthyroidism who received 131I therapy in the Nuclear Medicine Unit, were reviewed; 29 had toxic diffuse goiter (TDG) and 17 had toxic nodular goiter (TNG). The information about the follow up at 3, 6 and 12 months after therapy was obtained. Getting hypothyroidism in 3 months after therapy was taken as cure criterion and effectiveness of the treatment. Results: Among the patients with TDG, the 27% showed hypothyroidism in 3 months and the 45% in 12 months. A high percentage of patients treated with the Quimby-Marinelli method to calculate the 131I, showed hypothyroidism in 3 months (p<0,01); this method was associated with high doses of 131I (p<0,01). The patients who remained with hyperthyroidism received low doses. The lineal regression analysis showed that the doses administered, instead of the method of calculation, had the major relation with the effectiveness of the treatment (p<0,005). There were not differences between the different methods of calculation and doses of 131I in the patients with TNG. Conclusions: These results showed that the Quimby-Marinelli method and the high doses of 131I had the best effectiveness in the hyperthyroidism treatment.

RESUMEN Objetivo: Investigar en mujeres posmenopáusicas la influencia de la terapia hormonal de reemplazo en la concentración plasmática de leptina y la distribución de la grasa corporal. Método: Estudio transversal de 95 mujeres posmenopáusicas: 45 con terapia hormonal de reemplazo combinada durante un período mayor o igual a 3 meses y 50 mujeres sin ella. Ambiente: Servicio de Ginecología del Instituto Autónomo Hospital Universitario de Los Andes y Laboratorio de Neuroendocrinología y Reproducción, Facultad de Medicina, Universidad de Los Andes. Resultados: Las mujeres obesas con terapia hormonal de reemplazo mostraron un índice cintura:cadera y una concentración plasmática de leptina significativamente menor (P< 0,05) que las obesas sin terapia. En las no obesas la concentración de leptina y el índice cintura:cadera no fue diferente entre la mujeres con y sin terapia. La concentración de leptina se correlacionó en forma lineal con el índice de masa corporal y con índice cintura:cadera. Conclusión: Los resultados sugieren que la terapia hormonal de reemplazo en la mujer posmenopáusica obesa favorece una mejor distribución de la grasa corporal acompañado de una menor concentración plasmática de leptina.

SUMMARY Objective: The present transversal study was designed to investigate the effect of hormone replacement therapy on body fat distribution and plasma leptin levels in postmenopausal women. Method: Ninety five postmenopausal women were studied: forty five on sequential oral estrogen and progesterone therapy and fifty without therapy. Setting: Gynecology Unit, Hospital Universitario de Los Andes, and Neuroendocrinology and Reproduction Laboratory, Faculty of Medicine, Universidad de Los Andes, Merida-Venezuela. Results: Obese women on therapy showed significant lower waist-to-hip-ratio and plasma leptin concentration than obese women without therapy. In non-obese women no significant differences in leptin concentrations and waist-to-hip-ratio were observed. Leptin concentration was significantly correlated with body mass index and waist-to-hip-ratio. Conclusion: The results suggest that hormone replacement therapy in postmenopausal women has a beneficial effect on body fat distribution and leptin levels.

Administramos arecoline a ratos com miocadite chagásica induzida experimentalmente, a fim de pesquisar a sensibilidade do nodo sinusal frente a um agonista muscarínico. Ratos de 16 meses de idade foram inoculados com 200.000 parasitas de T. cruzi (variedade Y). Entre os dias 18 e 21 (estádio agudo), 8 ratos infestados e 8 ratos controle receberam arecoline por via intravenosa nas doses seguintes: 5.0, 10.0, 20.0, 40.0 e 80.0 mig/kg. A frequência cardíaca foi registrada durante e após cada dose de arecoline. Os 8 ratos infestados restantes e mais outros 8 controles, foram submetidos a uma pesquisa similar, embora em um período de estádio subagudo da doença nos dias 60 e 70 pós inoculação. A frequência cardíaca de base dos animais estudados durante o estádio agudo (349 ± 68 bpm. Média ± SD), foi maior que a frequência dos ratos controles (250 ± 50 bpm, p<0,005). As alterações na frequência cardíaca foram expressadas como alterações de percentagem sobre o valor basal. Foi feita curva da dose-resposta para cada grupo de animais. Foram usadas escalas logarítmicas para simular sistematicamente as duplas doses de arecoline e as alterações de frequência induzidos. A inclinição da linha de regressão para os animais agudamente infestados (r = - 0.99, b = 1.78) não foi diferente daquela dos animais de controles (r = - 0.97, b = 1.61). Os animais infestados estudados no estádio subagudo (r = - 0.99, b = 1.81) também não apresentaram diferenças dos respectivos animais do grupo controle (r = - 0.99, b = 1.26 NS). Em consequência, os nossos resultados não mostraram evidências farmacológicas de hipersensibilidade do tecido post nodo sinusal ao agonista muscarínico arecoline. Porém, o resultado indiretamente é sugestivo de que a inervação parassimpática postgangliônica do nodo sinusal dos ratos com autópsia, com comprovada miocardite chagásica, não é irreversivelmente afetada pelo Trypanosoma cruzi.

We administered arecoline to rats, with experimentally induced chagasic myocarditis, in order to study the sinus node sensitivity to a muscarinic agonist. Sixteen month old rats were inoculated with 200,000 T. cruzi parasites ("Y" strain). Between days 18 and 21 (acute stage), 8 infected rats and 8 age-matched controls received intravenous arecoline as a bolus injection at the following doses: 5.0, 10.0, 20.0, 40.0, and 80.0 mug/kg. Heart rate was recorded before, during and after each dose of arecoline. The remaining 8 infected animals and 8 controls were subjected to the same experimental procedure during the subacute stage, i.e., days 60 to 70 after inoculation. The baseline heart rate, of the animals studied during the acute stage (349 ± 68 bpm, mean ± SD), was higher than that of the controls (250 ± 50 bpm, p < 0.005). The heart rate changes were expressed as percentage changes over baseline values. A dose-response curve was constructed for each group of animals. Log scales were used to plot the systematically doubled doses of arecoline and the induced-heart rate changes. The slope of the regression line for the acutely infected animals (r = - 0.99, b =1.78) was not different from that for the control animals (r = - 0.97, b = 1.61). The infected animals studied during the subacute stage (r = - 0.99, b = 1.81) were also not different from the age-matched controls (r = - 0.99, b = 1.26, NS). Consequently, our results show no pharmacological evidence of postjunctional hypersensitivity to the muscarinic agonist arecoline. Therefore, these results indirectly suggest that the postganglionic parasympathetic innervation, of the sinus node of rats with autopsy proved chagasic myocarditis, is not irreversibly damaged by Trypanosoma cruzi.