RESUMEN
Pituitary adenomas sometimes show rapid growth and recurrence, and about one third invade the structures surrounding the sella turcica. In an attempt to determine aggressive behavior at an early stage, we used the MIB-1 antibody to identify the Ki-67 antigen. The present study was designed to evaluate pituitary adenomatous tissue in terms of secretion and proliferation and to correlate the Ki-67 index with hormone phenotype and invasive behavior. Material from 159 patients submitted to one or more resections of pituitary adenomas was evaluated. Forty-two non-secretory adenomas and 43 adenomas immunoreactive for growth hormone, 19 for prolactin, 18 for growth hormone and prolactin, 16 for adrenocorticotropic hormone (ACTH), and 21 cases of plurihormonal/gonadotropin adenomas were detected by immunohistochemistry. The MIB-1 antibody was positive in 139 samples and the Ki-67 index ranged from 0.16 to 15.48% (mean = 1.22 +/- 2.09%), with no significant difference between genders, age groups, or secretory and non-secretory status. The Ki-67 index was higher in ACTH-secreting adenomas. Invasive pituitary adenomas had a significantly higher Ki-67 index (2.01 +/- 3.15%) than macroadenomas with or without supra-sellar extension (1.12 +/- 1.87%; P = 0.02). The index was not significantly different in the subgroup of adenomas with invasion of the cavernous sinus compared to groups with other types of invasion. We conclude that tumoral proliferative activity evaluated by the detection of the Ki-67 antigen is significantly higher in invasive than noninvasive adenomas, information which can be useful in therapeutic postoperative management since index cut-off values associated with aggressive behavior can be established.
Asunto(s)
Adenoma/patología , Anticuerpos Antinucleares , Anticuerpos Monoclonales , Antígenos de Neoplasias/análisis , Antígeno Ki-67/análisis , Neoplasias Hipofisarias/patología , Adenoma/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Antinucleares/inmunología , Anticuerpos Monoclonales/inmunología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/inmunología , Invasividad Neoplásica/patología , Fenotipo , Neoplasias Hipofisarias/inmunología , Silla Turca/patologíaRESUMEN
Pituitary adenomas sometimes show rapid growth and recurrence, and about one third invade the structures surrounding the sella turcica. In an attempt to determine aggressive behavior at an early stage, we used the MIB-1 antibody to identify the Ki-67 antigen. The present study was designed to evaluate pituitary adenomatous tissue in terms of secretion and proliferation and to correlate the Ki-67 index with hormone phenotype and invasive behavior. Material from 159 patients submitted to one or more resections of pituitary adenomas was evaluated. Forty-two non-secretory adenomas and 43 adenomas immunoreactive for growth hormone, 19 for prolactin, 18 for growth hormone and prolactin, 16 for adrenocorticotropic hormone (ACTH), and 21 cases of plurihormonal/gonadotropin adenomas were detected by immunohistochemistry. The MIB-1 antibody was positive in 139 samples and the Ki-67 index ranged from 0.16 to 15.48 percent (mean = 1.22 ± 2.09 percent), with no significant difference between genders, age groups, or secretory and non-secretory status. The Ki-67 index was higher in ACTH-secreting adenomas. Invasive pituitary adenomas had a significantly higher Ki-67 index (2.01 ± 3.15 percent) than macroadenomas with or without supra-sellar extension (1.12 ± 1.87 percent; P = 0.02). The index was not significantly different in the subgroup of adenomas with invasion of the cavernous sinus compared to groups with other types of invasion. We conclude that tumoral proliferative activity evaluated by the detection of the Ki-67 antigen is significantly higher in invasive than noninvasive adenomas, information which can be useful in therapeutic postoperative management since index cut-off values associated with aggressive behavior can be established.
Asunto(s)
Persona de Mediana Edad , Humanos , Masculino , Femenino , Adulto , Adolescente , Adenoma , Antígeno Ki-67 , Neoplasias Hipofisarias , Adenoma , Biomarcadores de Tumor , Inmunohistoquímica , Invasividad Neoplásica , Fenotipo , Neoplasias Hipofisarias , Silla TurcaRESUMEN
Inactivating mutations of TP53, a tumor suppressor gene, are associated with abnormal cell proliferation. Although p53 expression is common in many human malignancies, p53 protein has seldom been evaluated in pituitary tumors. When detected, the percentage of p53-positive cells is low, and, in general, it is exclusive for invasive lesions. The aim of the present study was to use immunohistochemistry to determine the presence of p53 protein in pituitary adenomas from tumor samples of 163 surgeries performed in 148 patients (40% male, 60% female). In 35% of the cases the adenoma was nonfunctional, while in the others it was associated with PRL, GH and/or ACTH endocrine hypersecretion syndrome. Macroadenomas were observed in 83.2% of the cases with available neuroimage evaluation, of which 28% invaded the cavernous, sphenoid and/or ethmoidal sinus, bone, third ventricle or subfrontal lobe. p53 protein was detected in 2/148 patients (1.3%). Immunohistochemistry was positive for PRL and GH in these cases. Due to the high percentage of invasive pituitary adenomas found in our study, the low frequency of p53 detection suggests that it is inadequate as a routine marker for aggressiveness and as a predictive factor of tumor behavior.
Asunto(s)
Adenoma/metabolismo , Neoplasias Hipofisarias/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adenoma/química , Adolescente , Hormona Adrenocorticotrópica/metabolismo , Adulto , Anciano , Biomarcadores de Tumor , Femenino , Hormona del Crecimiento/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Invasividad Neoplásica , Neoplasias Hipofisarias/química , Pronóstico , Prolactina/metabolismo , Proteína p53 Supresora de Tumor/análisis , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Inactivating mutations of TP53, a tumor suppressor gene, are associated with abnormal cell proliferation. Although p53 expression is common in many human malignancies, p53 protein has seldom been evaluated in pituitary tumors. When detected, the percentage of p53-positive cells is low, and, in general, it is exclusive for invasive lesions. The aim of the present study was to use immunohistochemistry to determine the presence of p53 protein in pituitary adenomas from tumor samples of 163 surgeries performed in 148 patients (40 percent male, 60 percent female). In 35 percent of the cases the adenoma was nonfunctional, while in the others it was associated with PRL, GH and/or ACTH endocrine hypersecretion syndrome. Macroadenomas were observed in 83.2 percent of the cases with available neuroimage evaluation, of which 28 percent invaded the cavernous, sphenoid and/or ethmoidal sinus, bone, third ventricle or subfrontal lobe. p53 protein was detected in 2/148 patients (1.3 percent). Immunohistochemistry was positive for PRL and GH in these cases. Due to the high percentage of invasive pituitary adenomas found in our study, the low frequency of p53 detection suggests that it is inadequate as a routine marker for aggressiveness and as a predictive factor of tumor behavior
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adenoma , Neoplasias Hipofisarias , Proteína p53 Supresora de Tumor , Adenoma , Hormona Adrenocorticotrópica , Biomarcadores de Tumor , Hormona del Crecimiento , Mutación , Invasividad Neoplásica , Neoplasias Hipofisarias , Pronóstico , Prolactina , Proteína p53 Supresora de TumorRESUMEN
Psychological symptoms, specially anxiety and depression, have been associated to hyperprolactinemia. To evaluate the presence of these symptoms, 32 patients (5 men and 27 women) with hyperprolactinemia of several etiologies and 15 individuals with normal prolactin levels were submitted to the Composed International Diagnostic Interview, followed by the Hamilton rating scale for depression. The serum prolactin, at the time of evaluation, ranged between 28 and 180 ng/mL. Eleven patients were receiving bromocriptine. The presence of anxiety was detected in 18 patients (56.2%) and 5 controls (32.2%), depression was detected in 10 patients (31.2%) and 2 controls (12.5%), dysthymia in 2 patients and other psychiatric diagnosis in 6 patients (18.7%). The scores of depression ranged between 16 and 31 for the patients, and were 12 and 16 for the controls. The frequency of psychiatric symptoms, as a whole, was significantly higher in the hyperprolactinemic patients (chi-square test), but the difference was not significant in isolated analysis of anxiety and depression. The hyperprolactinemia represents a risk of 3.52 for depression, 3.32 for anxiety and 3.84 for other psychiatric symptoms. There was no significant difference in the frequency of psychiatric symptoms among patients with or without pituitary adenomas nor users or not users of bromocriptine. There was no correlation (r=0,07) between prolactin and the frequency of psychiatric symptoms. These results emphasize the importance of a special attention to the concomitance of hyperprolactinemia and psychiatric disturbance, which will allow a specific therapeutic approach.
Asunto(s)
Hiperprolactinemia/complicaciones , Trastornos Mentales/etiología , Adolescente , Adulto , Anciano , Trastornos de Ansiedad/etiología , Bromocriptina/uso terapéutico , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Trastorno Depresivo/etiología , Agonistas de Dopamina/uso terapéutico , Femenino , Humanos , Hiperprolactinemia/tratamiento farmacológico , Entrevista Psicológica , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Factores de RiesgoRESUMEN
We report a boy with possible Proteus syndrome and precocious puberty. This appears to be the first report of this association.
Asunto(s)
Síndrome de Proteo/complicaciones , Pubertad Precoz/complicaciones , Niño , Humanos , Masculino , Síndrome de Proteo/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Secretion of the alpha-subunit of pituitary glycoprotein hormones usually follows the secretion of intact gonadotropins and is increased in gonadal failure and decreased in isolated gonadotropin deficiency. The aim of the present study was to determine the levels of the alpha-subunit in the serum of patients with cirrhosis of the liver and to compare the results obtained for eugonadal cirrhotic patients with those obtained for cirrhotic patients with hypogonadotropic hypogonadism. Forty-seven of 63 patients with cirrhosis (74.6%) presented hypogonadism (which was central in 45 cases and primary in 2), 7 were eugonadal, and 9 women were in normal menopause. The serum alpha-subunit was measured by the fluorimetric method using monoclonal antibodies. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1%, respectively, with an intra-assay coefficient of variation (CV) of less than 5% and an interassay CV of 5%, and sensitivity limit of 4 ng/l. The serum alpha-subunit concentration ranged from 36 to 6253 ng/l, with a median of 273 ng/l. The median was 251 ng/l for patients with central hypogonadism and 198 ng/l for eugonadal patients. The correlation between the alpha-subunit and basal LH levels was significant both in the total sample (r = 0.48, P < 0.01) and in the cirrhotic patients with central hypogonadism (r = 0.33, P = 0.02). Among men with central hypogonadism there was a negative correlation between alpha-subunit levels and total testosterone levels (r = -0.54, P < 0.01) as well as free testosterone levels (r = -0.53, P < 0.01). In conclusion, although the alpha-subunit levels are correlated with LH levels, at present they cannot be used as markers for hypogonadism in patients with cirrhosis of the liver.
Asunto(s)
Hormonas Glicoproteicas de Subunidad alfa/sangre , Hipogonadismo/sangre , Cirrosis Hepática/sangre , Adulto , Anciano , Femenino , Humanos , Hipogonadismo/diagnóstico , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Testosterona/sangreRESUMEN
Secretion of the alpha-subunit of pituitary glycoprotein hormones usually follows the secretion of intact gonadotropins and is increased in gonadal failure and decreased in isolated gonadotropin deficiency. The aim of the present study was to determine the levels of the alpha-subunit in the serum of patients with cirrhosis of the liver and to compare the results obtained for eugonadal cirrhotic patients with those obtained for cirrhotic patients with hypogonadotropic hypogonadism. Forty-seven of 63 patients with cirrhosis (74.6 percent) presented hypogonadism (which was central in 45 cases and primary in 2), 7 were eugonadal, and 9 women were in normal menopause. The serum alpha-subunit was measured by the fluorimetric method using monoclonal antibodies. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1 percent, respectively, with an intra-assay coefficient of variation (CV) of less than 5 percent and an interassay CV of 5 percent, and sensitivity limit of 4 ng/l. The serum alpha-subunit concentration ranged from 36 to 6253 ng/l, with a median of 273 ng/l. The median was 251 ng/l for patients with central hypogonadism and 198 ng/l for eugonadal patients. The correlation between the alpha-subunit and basal LH levels was significant both in the total sample (r = 0.48, P<0.01) and in the cirrhotic patients with central hypogonadism (r = 0.33, P = 0.02). Among men with central hypogonadism there was a negative correlation between alpha-subunit levels and total testosterone levels (r = 0.54, P<0.01) as well as free testosterone levels (r = -0.53, P<0.01). In conclusion, although the alpha-subunit levels are correlated with LH levels, at present they cannot be used as markers for hypogonadism in patients with cirrhosis of the liver