ABSTRACT
La oftalmopatía de Graves (OG) es un desorden autoinmune que representa la manifestación extratiroidea más frecuente de la Enfermedad de Graves. Se describen múltiples factores que pueden influir en el desarrollo/progresión de la enfermedad, entre ellos el tratamiento con I131. El objetivo de esta monografía es analizar la bibliografía existente sobre la relación entre OG y tratamiento con I131, teniendo en cuenta su fisiopatología así como los factores de riesgo asociados y su profilaxis.
Graves´ ophthalmopathy (GO) is an autoimmune disorder representing the most common extrathyroidal manifestation of Graves' disease. Multiple factors can influence the development / progression of the disease, including treatment with 131I. The aim of this paper is to analyze the existing literature on the relationship between OG and treatment with I131, considering the pathophysiology and associated risk factors and prophylaxis.
ABSTRACT
Glucocorticoid receptors (GcR) were determined by a whole cell assay in human mononulear leukocytes (hMNL) from control subjects, patients receiving glucocorticoid therapy for systemic diseases and Cushing's disease patients with or without ketoconazole therapy. Prolonged corticosteroid treatment resulted in down-regulation of GcR, while the mean level of GcR in Cushing's disease was normal. In this group, however, receptor levels and morning plasma cortisol values showed a negative correlation, indicating a subtle down-regulatory effect. Furthermore, GcR were unaltered after these patients received ketoconazole, in spite of a marked reduction in morning plasma cortisol and urinary free cortisol. We also observed that ketoconazole was a weak competitor of GcR in intact cells, although it significantly inhibited [3H] dexamethasone binding in cytosolic preparations from rat tissues. The results suggested that GcR in hMNL are down-regulated by synthetic steroids given in vivo, but they showed very mild down-regulation in hypercortisolemic patients suffering from Cushing's disease. Finally, we did not observed either up-regulation or antagonism of GcR by ketoconazole treatment, at the time that cortisol levels of patients with Cushing's disease were reduced. This indicates that the beneficial effects of ketoconazole in Cushing's disease are due to adrenal cortisol suppression and not to interaction with GcR of target cells, and that the process of GcR regulation in hMNL is a complex phenomenon awaiting further elucidation.
Subject(s)
Cushing Syndrome/metabolism , Glucocorticoids/pharmacology , Ketoconazole/pharmacology , Leukocytes, Mononuclear/metabolism , Receptors, Glucocorticoid/metabolism , Adolescent , Adult , Female , Humans , Hydrocortisone/blood , Hydrocortisone/urine , Leukocytes, Mononuclear/drug effects , Male , Middle Aged , Receptors, Glucocorticoid/drug effectsABSTRACT
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.
Subject(s)
Cushing Syndrome/metabolism , Leukocytes, Mononuclear/metabolism , Receptors, Glucocorticoid/metabolism , 17-Ketosteroids/urine , Adolescent , Adult , Calcium/urine , Dexamethasone/administration & dosage , Female , Humans , Hydrocortisone/metabolism , Male , Middle Aged , Thyrotropin/bloodABSTRACT
Se estudia una paciente de 37 anos con las caracteristicas de un sindrome de Werner: cataratas, canicie precoz, esclerosis, hiperqueratosis y pigmentacion cutanea. Cambios de voz, osteoporosis, calcificaciones tendinosas, hipogenitalismo, alteracion del test de tolerancia a la glucosa, dislipoidosis, hiperreflexia profunda generalizada, baja estatura, facies y proporciones corporales propias del mismo. Se efectua una revision de hallazgos experimentales y posible explicacion patogenica del sindrome y otros caracterizados por senilidad precoz, cuyos diagnosticos diferenciales son resumidos
Subject(s)
Adult , Humans , Female , Werner SyndromeABSTRACT
Se estudia una paciente de 37 anos con las caracteristicas de un sindrome de Werner: cataratas, canicie precoz, esclerosis, hiperqueratosis y pigmentacion cutanea. Cambios de voz, osteoporosis, calcificaciones tendinosas, hipogenitalismo, alteracion del test de tolerancia a la glucosa, dislipoidosis, hiperreflexia profunda generalizada, baja estatura, facies y proporciones corporales propias del mismo. Se efectua una revision de hallazgos experimentales y posible explicacion patogenica del sindrome y otros caracterizados por senilidad precoz, cuyos diagnosticos diferenciales son resumidos
Subject(s)
Adult , Humans , Female , Werner SyndromeABSTRACT
A case of diabetes insipidus is presented which appeared in a 13 year old girl associated with hormone-resistant amenorrhea; she went through two normal pregnancies and partutition at 22 and 25, indicating a fertile amenorrhea. During a total of 17 years of observation the amenorrhea persisted, with the exception of a few normal menstruation periods at the beginning of the disease. She remained permanently under treatment with pitressin tannate. Repeated administrations of estrogens, gestagens and chorionic gonadotrophin, had no effect. An endometrial biopsy revealed a presecretory phase. Acidophilic index in vaginal smears as well as serial determinations of urinary pregnanodiol indicated cyclic changes. Daily determinations of urinary pregnanodiol indicated cyclic changes. Daily determinations of plasma gonadotrophins during 28 days revealed normal levels, with normal FSH pulse and ovulatory type peak of LH. An LH-RH test gave marked and characteristic increase of both hormones. The data indicate the integrity of the hypothalamo-hypophyso-ovaric system, with cyclic changes and formation of corpus luteum, vaginal trophism and endometrial changes, concordant with the two normal pregnancies. In this case, the amenorrhea can only be explained by alteration of the usual endometrial vascular changes. The coexistence of diabetes insipidus and fertile amenorrhea is discused in relation with the possible participation of vasopressin in the mechanism of menstruation.
