Effects of ketoconazole on the iodide uptake by FRTL-5 cells.

Ketoconazole is an imidazole derivative used as an antimycotic agent with reported effects on the endocrine system, but very little is known about its possible actions on thyroid function. Our purpose was to study the influence of this substance on the basal and TSH-stimulated iodide uptake in the rat thyroid cell strain FRTL-5. Ketoconazole (1-50 mumol/l) was shown to slightly increase the basal iodide uptake but, at higher concentrations (75-100 mumol/l), it sharply decreased iodide uptake below the basal levels. When the cells were cultured under bTSH stimulation (30 UI/l), the inhibitory effect of ketoconazole was exerted at concentrations as low as 25 mumol/l. This inhibition was observed even if it was added to the culture medium immediately before the Na125I addition. Forskolin, a stimulator of adenylate cyclase activity, was unable to prevent the iodide uptake inhibition. Low doses of ketoconazole increased cAMP concentrations. In the presence of TSH this effect was more evident in an inverse dose-dependent way. Because of its dual action, it can be assumed that ketoconazole could influence the iodide uptake in the FRTL-5 cells through more than one mechanism.

Graves' disease: evolution and prognosis after eight months of treatment with methimazole

We studied 26 patients with Graves' disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1% of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60% and a specificity of 100%. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse

Graves disease: evolution and prognosis after eight months of treatment with methimazole

We studied 26 patients with Graves disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1% of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60% and a specificity of 100%. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse (Au)

Graves' disease: evolution and prognosis after eight months of treatment with methimazole.

We studied 26 patients with Graves' disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1% of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60% and a specificity of 100%. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse.

Graves disease: evolution and prognosis after eight months of treatment with methimazole.

We studied 26 patients with Graves disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1

of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60

and a specificity of 100

. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse.

Graves disease: evolution and prognosis after eight months of treatment with methimazole.

We studied 26 patients with Graves disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1

of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60

and a specificity of 100

. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse.

A correlative study between glucocorticoid receptor levels in human mononuclear leukocytes and biochemical data in Cushing's disease.

UNLABELLED: We determined glucocorticoid receptors in human mononuclear leukocytes in 9 patients with Cushing's disease, in order to correlate them with laboratory data. Receptors were measured by a whole-cell assay method, after incubation with [3H]-dexamethasone in the presence or absence of excess unlabelled hormone. In Cushing's disease, there were 4425 +/- 364 sites/cell (N = 9), similar to in the controls: 4473 +/- 476 (N = 10); average Kd was 2.42 +/- 0.52 nmol/l (N = 3) similar to in the controls: 2.0 +/- 0.20 nmol/l (N = 3). In Cushing's patients we found significant negative correlations between basal glucocorticoid receptors and: 1) morning blood cortisol (r = -0.67, P less than 0.05), and 2) 17-ketogenic steroids after 2 mg of dexamethasone (r = -0.85, P less than 0.01). No correlations were observed with afternoon blood cortisol, free urinary cortisol, basal and post-8-mg dexamethasone 17-ketogenic steroids, TRH-TSH area, urinary calcium, plasma glucose, or systolic blood pressure. CONCLUSIONS: In Cushing's disease, a subtle receptor down-regulation may exist, as suggested by the inverse relationship between glucocorticoid receptors and morning blood cortisol. Secondly, the relationship between basal receptors and 17-ketogenic steroids after 2 mg of dexamethasone suggests that glucocorticoid receptors in human mononuclear leukocytes could reflect the sensitivity of the nervous system-pituitary-adrenal axis to dexamethasone inhibition.

Variaciones de la función tiroidea expresadas por el cálculo del área bajo la curva de TRn-TSH / Variations of thyroid function expressed by the calculation of the area under the TRH-TSH curve

En este trabajo, tomando un método descripto por Ridgway y col. se analizaron pruebas de TRH-TSH con el objeto de: a) expresar este examen funcional mediante un valor numérico; b) establecer sus valores en sujetos normales; c) comparar la capacidad discriminativa de esta prueba en relación con otros parámetros de función y diagnóstico clínico, y d) estudiar la validez de una prueba corta estableciendo los tiempos más adecuados para la misma. El área bajo la curva de TRS-TSH discriminó perfectamente al grupo testigo (877 ñ 57 micronUI/ml1/min) de los tirotóxicos (145 ñ 25) y de los hipotiroideos (8846 ñ 1092). El análisis de las tiroideopatías eutiroideas mostró la presencia de dos grupos que se ubicaron funcionalmente uno entre los tirotóxicos y los testigos (266 ñ 17 micronUI/ml1/min) y otro entre los hipotiroideos y los testigos (2610 ñ 195). Estos eran dos grupos estadísticamente diferentes a los clásicamente conocidos, que no se podían diferenciar por los niveles séricos de T3 y T4, ya que estaban dentro de parámetros normales y a los que definimos como hipertiroideos subclínicos e hipotiroideos subclínicos, respectivamente. El análisis global de todas las curvas estudiadas mostró que de los cuatro parámetros de función analizados, T4, T3, TSH basal y área de TRH-TSH, el que mostró mayor poder discriminativo fue el último, pudiéndose establecer nueve estadios funcionales diferentes que abarcan toda una gama que va desde la tirotoxicosis franca hasta el hipotiroidismo manifiesto. Se buscó la correlación entre el área total y una área corta de 20 y 30min, siendo la misma altamente significaticva (r + 0,975; p <0,000001). El delta de TSH se produjo en el 77% de los casos entre los 20 y 30min en el 12,8% a los 40min. Se puede concluir que el cálculo del área bajo la curva de TRH-TSH es el método más válido para valorar función tiroidea

Variaciones de la función tiroidea expresadas por el cálculo del área bajo la curva de TRn-TSH / Variations of thyroid function expressed by the calculation of the area under the TRH-TSH curve

En este trabajo, tomando un método descripto por Ridgway y col. se analizaron pruebas de TRH-TSH con el objeto de: a) expresar este examen funcional mediante un valor numérico; b) establecer sus valores en sujetos normales; c) comparar la capacidad discriminativa de esta prueba en relación con otros parámetros de función y diagnóstico clínico, y d) estudiar la validez de una prueba corta estableciendo los tiempos más adecuados para la misma. El área bajo la curva de TRS-TSH discriminó perfectamente al grupo testigo (877 ñ 57 micronUI/ml1/min) de los tirotóxicos (145 ñ 25) y de los hipotiroideos (8846 ñ 1092). El análisis de las tiroideopatías eutiroideas mostró la presencia de dos grupos que se ubicaron funcionalmente uno entre los tirotóxicos y los testigos (266 ñ 17 micronUI/ml1/min) y otro entre los hipotiroideos y los testigos (2610 ñ 195). Estos eran dos grupos estadísticamente diferentes a los clásicamente conocidos, que no se podían diferenciar por los niveles séricos de T3 y T4, ya que estaban dentro de parámetros normales y a los que definimos como hipertiroideos subclínicos e hipotiroideos subclínicos, respectivamente. El análisis global de todas las curvas estudiadas mostró que de los cuatro parámetros de función analizados, T4, T3, TSH basal y área de TRH-TSH, el que mostró mayor poder discriminativo fue el último, pudiéndose establecer nueve estadios funcionales diferentes que abarcan toda una gama que va desde la tirotoxicosis franca hasta el hipotiroidismo manifiesto. Se buscó la correlación entre el área total y una área corta de 20 y 30min, siendo la misma altamente significaticva (r + 0,975; p <0,000001). El delta de TSH se produjo en el 77% de los casos entre los 20 y 30min en el 12,8% a los 40min. Se puede concluir que el cálculo del área bajo la curva de TRH-TSH es el método más válido para valorar función tiroidea (AU)