RESUMO
The relationship between the presence of estrogen receptors in pituitary adenomas and the post surgical evolution of the patients in order to find another prognostic parameter for these tumors have been studied to improve the treatment selection. Estrogen receptors were studied by immunocytochemistry in histological sections of paraffin embedded 42 pituitary adenomas. Only 19% of these tumors were positive for estrogen receptors. As expected, the higher concentration (60%) was found in prolactin secreting adenomas, although we found estrogen receptors in one somatotroph and in one nonsecreting. The most aggressive tumors were those negative for estrogen receptors within the prolactinomas and the positive somatotrophinoma. The results of this work suggest that the determination of estrogen receptors in pituitary tumors might help as a prognostic factor in these adenomas.
Assuntos
Adenoma/metabolismo , Neoplasias Hipofisárias/metabolismo , Receptores de Estrogênio/metabolismo , Adenoma Hipofisário Secretor de ACT/metabolismo , Adulto , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Prolactinoma/metabolismoRESUMO
BACKGROUND: The diagnosis of thyroid follicular carcinoma by fine needle aspiration biopsy is a well known problem in thyroid pathology. METHODS: We evaluated telomerase activity (TA) in 85 fine needle aspiration biopsy (FNAB) samples from patients with thyroid nodules. Surgery samples from patients with tumor or follicular adenomas were also analyzed. RESULTS: Twenty of the FNAB samples corresponded to carcinomas and were positive to telomerase assay (TA >10 Units). Among them, 4 follicular carcinomas and 1 papillary carcinoma were labeled as indeterminate by FNAB cytological examination. Four percent false positive cases and no false negative cases for TA in FNABs were reported. FNAB samples from follicular adenomas were diagnosed as indeterminate by cytological examination, but they showed no detectable TA. Tumor tissues from patients with follicular or papillary thyroid carcinomas presented TA >10 Units, whereas follicular adenoma tissues (benign nodules) showed no TA. CONCLUSION: Our results showed a good correlation between TA in FNAB samples and tumor/nodule thyroid tissue. This suggested that use of TA as a biological marker of malignancy might be a useful tool in the diagnosis of follicular thyroid carcinomas or follicular thyroid adenomas using FNAB samples.
Assuntos
Biópsia por Agulha Fina/métodos , Telomerase/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/enzimologia , Biomarcadores Tumorais , Humanos , Proteína Supressora de Tumor p53/metabolismoRESUMO
Prolactinomas are one of the most frequent tumors of the human anterior pituitary. Dopamine agonists are the choice in the medical treatment of this disease. Bromocriptine (BC) is a well known anti-neoplasic agent in human PRL secreting adenomas although its effect on PRL cells is far from clear. We decided to investigate its influence on cell proliferation parameters: (3H)thymidine incorporation, expression of c-myc and c-fos, and number of estrogen receptors present in the samples. A total of 28 patients were included in this protocol. They were treated with BC (5-7.5mg day(-1) patient(-1)) or with vehicle orally 15 days before surgery. We found that in BC treated patients (3H)thymidine incorporation was lower than in vehicle treated patients. The oncogenes expression were diminished in BC comparing with vehicle-treated patients. No difference in the number of estrogen receptors was observed in the samples from BC or vehicle-treated patients. These results clearly demonstrate that one mechanism to reduce the size of human PRL secreting adenomas by BC is the inhibition of DNA duplication.
Assuntos
Antineoplásicos/uso terapêutico , Bromocriptina/uso terapêutico , Replicação do DNA/efeitos dos fármacos , Agonistas de Dopamina/uso terapêutico , Prolactinoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , DNA/biossíntese , Replicação do DNA/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Prolactina/sangue , Prolactina/metabolismo , Prolactinoma/sangue , Prolactinoma/fisiopatologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Timidina , Resultado do Tratamento , TrítioRESUMO
An antioxidant mixture (LAROTABE) was evaluated in the treatment of Graves disease. Fifty-six hyperthyroid patients were treated with methimazol (MMI) (A), LAROTABE (B), or MMI plus LAROTABE (C). According to a clinical score, improvement was obtained at 8 weeks in A and 4 weeks in B and C. Group A diminished their thyroid hormone concentration to normal levels, while patients with LAROTABE did not reduce T3 and T4 unless MMI was introduced. Hyperthyroid patients had increased malondialdehyde (MDA) content and SOD activity and decreased catalase activity compared to controls. Within group A, MDA decreased to control values while SOD was reduced 38.3% and catalase increased 21.6%. Similar results were obtained for MDA and for both enzymes after treatment with LAROTABE. Signs and symptoms of Graves disease might be related to an increase in free radicals; antioxidants could be a new therapeutic tool to improve the clinical manifestation of this illness.
Assuntos
Antioxidantes/uso terapêutico , Doença de Graves/tratamento farmacológico , Adulto , Idoso , Antioxidantes/administração & dosagem , Antitireóideos/administração & dosagem , Antitireóideos/uso terapêutico , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Within a population of 16 pituitary adenomas we found high levels of glycoprotein alpha subunits in the sera of patients with somatotrophic tumors. This finding was correlated with the presence of mRNA alpha subunit in these tumors indicating the adenomas themselves as the origin of the circulating alpha-subunit. Synthesis of these two hormones, which are chemically very different, by the same tumor cells indicates a high degree of differentiation of these cells. We are unable at this time to conclusively correlate differentiation of these tumors aggressively.
Assuntos
Acromegalia/sangue , Adenoma/sangue , Subunidade alfa de Hormônios Glicoproteicos/sangue , Subunidade alfa de Hormônios Glicoproteicos/genética , Neoplasias Hipofisárias/sangue , Acromegalia/etiologia , Adenoma/complicações , Adenoma/metabolismo , Northern Blotting , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/genética , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/genética , Humanos , Hormônio Luteinizante/sangue , Hormônio Luteinizante/genética , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/metabolismo , Prolactina/sangue , Prolactina/metabolismo , RNA Mensageiro/análise , Tireotropina/sangue , Tireotropina/genéticaRESUMO
Presentamos una serie de 48 pacientes (de 14 a 20 años) con adenoma hipofisario. De éstos, 46 (96 por ciento) presentaban tumores secretantes, 3 enfermedad de Cushing, 9 somatotrofinomas y 34 (29 mujeres y 5 hombres) prolactinomas. Treinta casos fueron diagnosticados como adenomas intraselares (62 por ciento) mientras los restantes 18 (38 por ciento) presentaron expansión extraselar. De los 9 pacientes acromegálicos, 7 desarrollaron bioquímica y clínica típica de la enfermedad mientras 2 fueron exclusivamente diagnosticadas con niveles de GH basales normales, pero pruebas dinámicas anormales. Los prolactinomas fueron no invasivos en mujeres y de crecimiento rápido y de mayor tamaño en hombres. Cuarenta y siete pacientes fueron sometidos a cirugía. Cinco de ellos requirieron craneotomía y el resto fueron abordados por víatranseptoesfenoidal (TSE). Se consiguió remisión de la enfermedad de Cushing, acromegalia y prolactinoma intraselar femeninos. Los resultados en tumores mayores tales como los adenomas no secretantes y prolactinomas masculinos fueron malos luego de haber sido tratados mediante una resección subtotal y los disturbios endocrinológicos persistieron. Nuestros hallazgos demuestran que estos tumores son más agresivos en los jóvenes que en los adultos. Como hubo una estrecha relación entre el tamaño del tumor, su invasividad y el resultado final del paciente, concluímos que el diagnóstico temprano y el tratamiento son esenciales. Las frecuentes consultas de adolescentes tales como menstruaciones irregulares, retraso puberal y alteraciones de crecimiento deberían ser investigadas cuidadosamente y no simplemente consideradas como hechos transitorios o funcionales (AU)
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Neoplasias Hipofisárias/diagnóstico , Adenoma/complicações , Neoplasias Hipofisárias/classificação , Acromegalia/diagnóstico , Acromegalia/etiologia , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Prolactina/antagonistas & inibidores , Prolactina/sangue , Octreotida/uso terapêutico , Amenorreia/etiologia , Oligomenorreia/etiologia , Ergolinas/uso terapêutico , Prolactinoma/diagnóstico , Prolactinoma/tratamento farmacológicoRESUMO
Presentamos una serie de 48 pacientes (de 14 a 20 años) con adenoma hipofisario. De éstos, 46 (96 por ciento) presentaban tumores secretantes, 3 enfermedad de Cushing, 9 somatotrofinomas y 34 (29 mujeres y 5 hombres) prolactinomas. Treinta casos fueron diagnosticados como adenomas intraselares (62 por ciento) mientras los restantes 18 (38 por ciento) presentaron expansión extraselar. De los 9 pacientes acromegálicos, 7 desarrollaron bioquímica y clínica típica de la enfermedad mientras 2 fueron exclusivamente diagnosticadas con niveles de GH basales normales, pero pruebas dinámicas anormales. Los prolactinomas fueron no invasivos en mujeres y de crecimiento rápido y de mayor tamaño en hombres. Cuarenta y siete pacientes fueron sometidos a cirugía. Cinco de ellos requirieron craneotomía y el resto fueron abordados por víatranseptoesfenoidal (TSE). Se consiguió remisión de la enfermedad de Cushing, acromegalia y prolactinoma intraselar femeninos. Los resultados en tumores mayores tales como los adenomas no secretantes y prolactinomas masculinos fueron malos luego de haber sido tratados mediante una resección subtotal y los disturbios endocrinológicos persistieron. Nuestros hallazgos demuestran que estos tumores son más agresivos en los jóvenes que en los adultos. Como hubo una estrecha relación entre el tamaño del tumor, su invasividad y el resultado final del paciente, concluímos que el diagnóstico temprano y el tratamiento son esenciales. Las frecuentes consultas de adolescentes tales como menstruaciones irregulares, retraso puberal y alteraciones de crecimiento deberían ser investigadas cuidadosamente y no simplemente consideradas como hechos transitorios o funcionales
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Acromegalia/diagnóstico , Acromegalia/etiologia , Adenoma/complicações , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/diagnóstico , Amenorreia/etiologia , Ergolinas/uso terapêutico , Octreotida/uso terapêutico , Oligomenorreia/etiologia , Prolactinoma/diagnóstico , Prolactinoma/tratamento farmacológico , Prolactina/antagonistas & inibidores , Prolactina/sangue , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologiaRESUMO
We studied the concentration of mRNA from the oncogenes c-myc and c-fos in human pituitary adenomas by Northern blot hybridization (35 somatotrophinomas, 9 prolactinomas, 21 nonsecreting and 3 adrenocorticotrophinomas). The concentration of estrogens and progesterone receptors was also investigated. The levels of c-myc and c-fos mRNA was higher in nonsecreting tumors which were generally the largest and had a higher percentage of recurrence after surgery than the other groups. High concentration of estrogen receptors was observed in tumors derived from cells which are normally the target of this hormone, mainly prolactinomas. They were also present in somatotrophic and nonsecreting adenomas, related to the presence of prolactin or gonadotrophin cells in these tumors. The presence of estrogen receptors indicates that the tumor cells maintain their differentiation and a good prognosis as is the case for prolactinomas. We did not find any relationship between estrogen receptors and the concentration of c-myc and c-fos oncogenes. Larger adenomas (mainly nonsecreting) had higher levels of c-myc and c-fos mRNA than the other tumors and they had an important percentage of recurrence after surgery. It is clear that tumor size is related to the outcome after surgery and that nonsecreting adenomas are usually large because of the late diagnosis. However two large somatotrophinomas with extrasellar expansion also had overexpression of both oncogenes and both relapsed after surgery.
Assuntos
Adenoma/metabolismo , Estradiol/metabolismo , Neoplasias Hipofisárias/metabolismo , Progesterona/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adenoma/química , Adenoma/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hipofisárias/química , Neoplasias Hipofisárias/genética , Prognóstico , Prolactinoma/genética , Prolactinoma/metabolismo , Ligação Proteica/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
We report on a series of 48 patients, ages 14 to 20 year, with hypophyseal adenomas. Of these, 46 (96%) had secreting tumors, 3 had Cushing's disease, 9 had somatotrophinomas, and 34 (29 females and 5 males) had prolactinomas. Thirty cases were diagnosed as intrasellar adenomas (62%) while the remaining eighteen (38%) presented extrasellar expansion. Of 9 acromegalic patients, 7 had typical clinical and biochemical features 2 were exclusively prognatic with normal basal GH levels, but abnormal dynamic tests. Prolactinomas were noninvasive in women and faster growing and more extensive in men. Forty seven patients underwent surgery. Five of these required craniotomy and the rest approached through the sphenoidal bone (TSE). Remission was achieved in Cushing's disease, acromegaly, and female intrasellar prolactinomas. Larger tumors such as nonsecreting adenomas and male prolactinomas showed poor results after undergoing subtotal resections, with persistence of endocrinological disturbances. From our findings it appears that these tumors are aggressive in youth than in adults. Because there was a close relationship between tumor size, invasiveness, and the patients' final outcome, we conclude that early diagnosis and treatment is essential. Frequent complaints in adolescents such as irregular menses, retarded puberty, and growth disorders should be thoroughly investigated and not merely considered as transient or 'functional'.
Assuntos
Adenoma/cirurgia , Neoplasias Hipofisárias/cirurgia , Acromegalia/cirurgia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adolescente , Adulto , Síndrome de Cushing/cirurgia , Feminino , Humanos , Incidência , Masculino , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Prolactinoma/diagnóstico , Prolactinoma/epidemiologia , Prolactinoma/cirurgia , Caracteres SexuaisRESUMO
Indomethacin decreases the level of prolactin (50%) and growth hormone (70%) mRNA in the anterior pituitary gland of the rat. Actin mRNA increases (59%). Ultrastructurally there is a decrease in the number of secretory granules. Indomethacin also prevents the increase in prolactin secretory granules produced by the administration of estradiol. The results indicate that indomethacin inhibits hormonal synthesis in the APG at a transcriptional level. This effect appears selective because mRNA level for actin synthesis in the pituitary gland was higher than in nontreated rats.
Assuntos
Hormônio do Crescimento/genética , Indometacina/farmacologia , Adeno-Hipófise/fisiologia , Prolactina/genética , Actinas/genética , Animais , DNA Complementar , Estradiol/farmacologia , Expressão Gênica/efeitos dos fármacos , Masculino , Microscopia Eletrônica , Adeno-Hipófise/citologia , Adeno-Hipófise/ultraestrutura , RNA Mensageiro/análise , Ratos , Ratos WistarRESUMO
Decreased dopaminergic and increased oestrogenic effects induce prolactin release and DNA synthesis in prolactin secreting cells of the adult male rats. Oestrogen treatment for 7 days significantly increased the levels of prolactin, c-myc and c-fos mRNAs. The effect of oestrogens was reversed by the administration of the dopaminergic agonist bromocriptine. There was an early gradual increase of c-myc mRNA levels beginning 30 min after the injection of the steroid. c-fos mRNA levels increased sharply 15 min after oestrogen administration and decreased to basal values 15 min later to remain at this level over the period of time evaluated. Administration of the dopaminergic antagonist haloperidol did not change the levels of protooncogenes mRNA. However, in rats previously treated with oestrogens for 7 days c-myc mRNA levels increased 90 min after the injection of haloperidol and decreased to basal values after 2.5 h. c-fos mRNA levels increased sharply 30 min after haloperidol administration and also decreased to basal values 1 h later. We propose that changes in protooncogenes expression may be involved in the stimulation of cell proliferation induced by prolactin secretion.
Assuntos
Antagonistas de Dopamina , Estradiol/análogos & derivados , Regulação da Expressão Gênica/efeitos dos fármacos , Genes fos/efeitos dos fármacos , Genes myc/efeitos dos fármacos , Haloperidol/farmacologia , Adeno-Hipófise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/biossíntese , Proteínas Proto-Oncogênicas c-myc/biossíntese , Animais , Bromocriptina/farmacologia , Divisão Celular/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Estradiol/administração & dosagem , Estradiol/farmacologia , Injeções Subcutâneas , Masculino , Adeno-Hipófise/metabolismo , Prolactina/biossíntese , Prolactina/genética , Prolactina/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-myc/genética , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Receptores Dopaminérgicos/fisiologiaRESUMO
Searching for differences in gene expression between different types of human pituitary adenomas, we evaluated the concentration of mRNA from hormonal genes (prolactin and growth hormone) and oncogenes (c-myc and c-fos) in 12 growth hormone-secreting 7 prolactin-secreting and 11 nonsecreting adenomas. We found a positive correlation between clinical diagnoses and hormonal gene expression in all the cases. Our reports indicate the presence of c-myc and c-fos mRNA in all the adenomas evaluated. The concentration of c-myc mRNA was higher in somatotrophic adenomas than in prolactinomas and nonsecreting adenomas whereas c-fos mRNA concentration was similar in the different types of tumours analysed. Oncogenes products, in turn, might stimulate DNA synthesis and cell proliferation and eventually lead to the formation of pituitary adenomas. This is a working hypothesis.
Assuntos
Adenoma/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Hormônio do Crescimento/metabolismo , Neoplasias Hipofisárias/genética , Prolactina/metabolismo , Adenoma/metabolismo , Adulto , Feminino , Hormônio do Crescimento/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/metabolismo , Prolactina/genética , RNA Mensageiro/análiseRESUMO
We investigated the relationship between the level of c-myc mRNA and histologic aggressiveness in thyroid tumors obtained at surgery. In thyroid carcinomas, there was a positive correlation between these two parameters, while in benign tumors there was no correlation between cellularity and the expression of the proto-oncogene c-myc. These results might be useful in the prognosis of thyroid tumors and consequently helpful in the management of the patient.
Assuntos
Genes myc , RNA Mensageiro/metabolismo , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Carcinoma Papilar, Variante Folicular/genética , Carcinoma Papilar, Variante Folicular/patologia , Humanos , Invasividade Neoplásica , Hibridização de Ácido Nucleico , Prognóstico , Proto-Oncogene Mas , Neoplasias da Glândula Tireoide/genéticaRESUMO
Two inhibitors of prostaglandin synthesis, indomethacin and aspirin, blocked the increase of oestrogen-binding sites in the nuclear subcellular fraction, an increase which occurs after the administration of oestradiol. Consequently the biological effects of oestrogens in the anterior pituitary gland of the rat (prolactin synthesis, concentration of progesterone-binding sites and cell proliferation) are diminished. The anterior pituitary gland synthesized prostaglandin F2 alpha (PGF2 alpha), PGE2 and PGD2 from arachidonic acid. This synthesis was blocked when indomethacin was added to the culture media. Oestrogen increased the concentration of PGE2: an increase that was partially prevented by indomethacin. Prostaglandins may have an important role on the effects of oestrogen in the anterior pituitary gland of the rat.