RESUMEN
OBJECTIVE: To evaluate the effects of oral estradiol and transdermal 17ß-estradiol on serum concentrations of IGF1 and its binding proteins in women with hypopituitarism. DESIGN: Prospective, comparative study. METHODS: Eleven patients with hypopituitarism were randomly allocated to receive 2âmg oral estradiol (n=6) or 50âµg/day of transdermal 17ß-estradiol (n=5) for 3 months. RESULTS: The oral estrogen group showed a significant reduction in IGF1 levels (mean: 42.7%±41.4, P=0.046); no difference was observed in the transdermal estrogen group. There was a significant increase in IGFBP1 levels (mean: 170.2%±230.9, P=0.028) in the oral group, but not in the transdermal group. There was no significant difference within either group in terms of median IGFBP3 levels. In relation to lipid profiles, there was a significant increase in mean high-density lipoprotein cholesterol levels in the oral group after 3 months of treatment, (27.8±9.3, P=0.003). We found no differences in the anthropometric measurements, blood pressure, heart rate, glucose, insulin, C-peptide, or the homeostasis model assessment index after treatment. CONCLUSIONS: Our preliminary data indicate that different estrogen administration routes can influence IGF1 and IGFBP1 levels. These findings in patients with hypopituitarism have an impact on their response to treatment with GH, since patients receiving oral estrogen require increased GH dosage. These results suggest that oral estrogens may reduce the beneficial effects of GH replacement on fat and protein metabolism, body composition, and quality of life.
Asunto(s)
Estradiol/administración & dosificación , Hormona de Crecimiento Humana/uso terapéutico , Hipopituitarismo/sangre , Hipopituitarismo/tratamiento farmacológico , Hipopituitarismo/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Administración Cutánea , Administración Oral , Adolescente , Adulto , Glucemia/análisis , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Estradiol/farmacología , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Hipopituitarismo/líquido cefalorraquídeo , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Lípidos/sangre , Persona de Mediana Edad , Calidad de Vida , Resultado del Tratamiento , Adulto JovenAsunto(s)
Quistes del Sistema Nervioso Central/diagnóstico , Hipopituitarismo/diagnóstico , Meningitis/diagnóstico , Quistes del Sistema Nervioso Central/líquido cefalorraquídeo , Quistes del Sistema Nervioso Central/complicaciones , Femenino , Humanos , Hipopituitarismo/líquido cefalorraquídeo , Hipopituitarismo/complicaciones , Meningitis/líquido cefalorraquídeo , Meningitis/complicaciones , Persona de Mediana EdadRESUMEN
A 44-year-old man with a history of Whipple's disease 8 years ago presented with recurrent grand mal seizures and signs of hypopituitarism on physical examination. Magnetic resonance imaging of the brain revealed a hypothalamic lesion of 1 cm diameter in the region of the rostral infundibulum. Hypopituitarism was confirmed by low levels of serum cortisol, free testosterone and free thyroxine without an elevated TSH. Whipple encephalitis with hypothalamic involvement was suggested and verified by positive polymerase chain reaction (PCR) for Tropheryma whippelii in the cerebrospinal fluid. PCR for T. whippelii has become an important diagnostic tool for establishing the diagnosis of Whipple's disease especially in patients with unusual presentations and if the diagnosis cannot be confirmed histologically. Whipple's disease should be included in the differential diagnosis in hypopituitarism caused by infectious disease.
Asunto(s)
Actinobacteria/genética , ADN Bacteriano/líquido cefalorraquídeo , Hipopituitarismo/microbiología , Enfermedad de Whipple/complicaciones , Infecciones por Actinomycetales/líquido cefalorraquídeo , Infecciones por Actinomycetales/microbiología , Adulto , Humanos , Hipopituitarismo/líquido cefalorraquídeo , Hipopituitarismo/diagnóstico , Imagen por Resonancia Magnética , Masculino , Reacción en Cadena de la Polimerasa , Enfermedad de Whipple/líquido cefalorraquídeo , Enfermedad de Whipple/diagnósticoRESUMEN
A Brazilian case of Creutzfeldt-Jakob disease in a hypopituitary patient who had received cadaver-derived human pituitary growth hormone between 1968 and 1977 is reported. The clinical diagnosis was confirmed during his lifetime by the demonstration of two abnormal 30-kDa proteins in the cerebrospinal fluid by two-dimensional gel electrophoresis. These proteins, characteristic of Creutzfeldt-Jakob disease, present isoelectric points of 5.1 and 5.2. Furthermore, both proteins migrate as doublets, each one displaying a molecular weight variant of about 29-kDa. This is one of 16 cases of the disease associated to therapy with cadaver-derived human growth hormone and one of the few examples among such cases of confirmation of the clinical diagnosis by biochemical characterization of abnormal proteins in the cerebrospinal fluid.
Asunto(s)
Proteínas del Líquido Cefalorraquídeo/efectos de los fármacos , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquídeo , Síndrome de Creutzfeldt-Jakob/tratamiento farmacológico , Hormona del Crecimiento/uso terapéutico , Adulto , Brasil , Proteínas del Líquido Cefalorraquídeo/líquido cefalorraquídeo , Enfermedad Crónica , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/etiología , Electroforesis en Gel Bidimensional , Hormona del Crecimiento/efectos adversos , Humanos , Hipopituitarismo/líquido cefalorraquídeo , Hipopituitarismo/complicaciones , Hipopituitarismo/tratamiento farmacológico , Masculino , Peso MolecularRESUMEN
A Brazilian case of Creutzfeldt-Jakob disease in a hypopituitary patient who had received cadaver-derived human pituitary growth hormone between 1968 and 1977 is reported. The clinical diagnosis was confirmed during his lifetime by the demonstration of two abnormal 30-kDa proteins in the cerebrospinal fluid by two-dimensional gel electrophoresis. These proteins, characteristic of Creutzfeldt-Jakob disease, present isoelectric points of 5.1 and 5.2. Furthermore, both proteins migrate as doublets, each one displaying a molecular weight variant of about 29-kDa. This is one of 16 cases of the disease associated to therapy with cadaver-derived human growth hormone and one of the few examples among such cases of confirmation of the clinical diagnosis by biochemical characterization of abnormal proteins in the cerebrospinal fluid
Asunto(s)
Humanos , Masculino , Proteínas del Líquido Cefalorraquídeo/efectos de los fármacos , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquídeo , Síndrome de Creutzfeldt-Jakob/tratamiento farmacológico , Hormona del Crecimiento/uso terapéutico , Adulto , Brasil , Enfermedad Crónica , Proteínas del Líquido Cefalorraquídeo/líquido cefalorraquídeo , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/etiología , Electroforesis en Gel Bidimensional , Hipopituitarismo/complicaciones , Hipopituitarismo/líquido cefalorraquídeo , Hipopituitarismo/tratamiento farmacológico , Peso MolecularRESUMEN
Corticotropin-releasing hormone (CRH) levels in the human plasma and cerebrospinal fluid (CSF), and those in the rat hypothalamus, peripheral and hypophyseal portal plasma were studied by a specific h/r CRH RIA and an immunoaffinity procedure. CRH levels in the plasma and CSF were low in patients with hypercortisolemia and those with hypothalamic hypopituitarism, but high in patients with hypocortisolemia except for patients with hypothalamic hypopituitarism. Plasma CRH responded to insulin-induced hypoglycemia (ITT) those with Addison's disease and those with primary hypopituitarism, but not in patients with Cushing's syndrome or in patients with hypothalamic hypopituitarism. The results suggest that the major component of plasma CRH may be of hypothalamic origin, but other extrahypothalamic tissues cannot be ruled out as minor sources of plasma CRH. In addition, the measurement of CRH levels in the plasma and CSF seems to be of value in evaluating the hypothalamic function. The short negative feedback mechanism regulating CRH release was demonstrated in humans and rats. In the absence of the long negative feedback control of ACTH secretion by glucocorticoids, ACTH originating from the pituitary may regulate ACTH secretion form the pituitary through inhibition of CRH release.
Asunto(s)
Hormona Liberadora de Corticotropina/análisis , Enfermedad de Addison/sangre , Enfermedad de Addison/líquido cefalorraquídeo , Enfermedad de Addison/metabolismo , Animales , Hormona Liberadora de Corticotropina/sangre , Hormona Liberadora de Corticotropina/líquido cefalorraquídeo , Síndrome de Cushing/sangre , Síndrome de Cushing/líquido cefalorraquídeo , Síndrome de Cushing/metabolismo , Humanos , Hipopituitarismo/sangre , Hipopituitarismo/líquido cefalorraquídeo , Hipopituitarismo/metabolismo , Hipotálamo/análisis , Hipotálamo/metabolismo , Inmunoensayo , Síndrome de Nelson/sangre , Síndrome de Nelson/líquido cefalorraquídeo , Síndrome de Nelson/metabolismo , Hipófisis/análisis , Hipófisis/metabolismo , Radioinmunoensayo , Ratas , Valores de Referencia , Distribución TisularRESUMEN
Somatomedin levels in cerebrospinal fluid (CSF) were determined in patients with acromegaly, pituitary deficiency, prolactinoma, and Cushing's disease by radioimmunoassay (RIA) for insulin-like growth factor 1 (IGF-1) and for IGF-2 as well as a radioreceptor assay (RRA) with adult human brain plasma membranes and IGF-2 as ligand. The mean value of RIA-IGF-2 (31 +/- 1.6 ng/ml) predominated over that of RIA-IGF-1 (5.8 +/- 0.3 ng/ml), but 10 times higher levels were found by RRA-IGF-2. Patients with acromegaly were not found to have higher values than those with GH deficiency even after corrections were made for possible leakage across the blood-CSF barrier. No correlations were found between CSF somatomedin levels determined by different techniques and immunoreactive IGF-1 or GH in the peripheral circulation except for a positive correlation between CSF RIA-IGF-2 and serum IGF-1 in patients with acromegaly. These findings suggest that somatomedins in CSF consist primarily of IGF-2-like peptides which are derived from production within the central nervous system or pituitary gland rather than from transport across the blood-CSF barrier.
Asunto(s)
Enfermedades de la Hipófisis/líquido cefalorraquídeo , Somatomedinas/líquido cefalorraquídeo , Acromegalia/líquido cefalorraquídeo , Adolescente , Adulto , Factores de Edad , Barrera Hematoencefálica , Síndrome de Cushing/líquido cefalorraquídeo , Femenino , Hormona del Crecimiento/deficiencia , Humanos , Hipopituitarismo/líquido cefalorraquídeo , Insulina/sangre , Masculino , Persona de Mediana Edad , Péptidos/sangre , Neoplasias Hipofisarias/líquido cefalorraquídeo , Prolactina/metabolismo , Radioinmunoensayo , Ensayo de Unión Radioligante , Somatomedinas/sangreRESUMEN
The concentrations of immunoreactive corticotropin-releasing factor (I-CRF) in human cerebrospinal fluid (CSF) were measured utilizing immunoaffinity chromatography and RIA in patients with no endocrine disease, patients with Cushing's disease, Nelson's syndrome, Sheehan's syndrome, Addison's disease and steroid treated patients. On high performance liquid chromatography, the elution profile and retention time of I-CRF in CSF were not identical with ovine CRF. I-CRF concentrations in CSF from patients with Cushing's disease and Sheehan's syndrome were lower than those from normal subjects, however those from patients with Nelson's syndrome and Addison's disease were within the normal range. I-CRF concentrations in CSF from patients with Cushing's disease returned to normal levels 2-9 months after pituitary adenomectomy. These results suggest that CSF I-CRF concentrations are reduced by increased plasma corticosteroid levels.
Asunto(s)
Enfermedades de las Glándulas Suprarrenales/líquido cefalorraquídeo , Hormona Liberadora de Corticotropina/líquido cefalorraquídeo , Enfermedades de la Hipófisis/líquido cefalorraquídeo , Enfermedad de Addison/líquido cefalorraquídeo , Corticoesteroides/uso terapéutico , Síndrome de Cushing/líquido cefalorraquídeo , Síndrome de Cushing/cirugía , Enfermedades del Sistema Endocrino/tratamiento farmacológico , Femenino , Humanos , Hipopituitarismo/líquido cefalorraquídeo , Cinética , Masculino , Síndrome de Nelson/líquido cefalorraquídeoRESUMEN
beta-endorphin is a brain peptide with potent morphine-like activity structurally related to the anterior pituitary hormone beta-lipotrophin (beta-L.P.H.). We have developed a radioimmunoassay for human beta-endorphin in plasma and cerebrospinal fluid (C.S.F.). Since the antiserum also reacts with beta-L.P.H., beta-endorphin was distinguished by using a second antiserum which measures beta-L.P.H. alone. With these two immunoassay systems and gel chromatography, we found beta-endorphin in all 20 C.S.F. samples tested at a concentration always higher than, but with no other relationship to, that in plasma. beta-endorphin was found in C.S.F. of patients who had hypopituitarism and undetectable plasma-beta-endorphin, suggesting that it is synthesized in the brain rather in the pituitary.