Assuntos
Bromocriptina/efeitos adversos , Cefaleia/induzido quimicamente , Antagonistas de Hormônios/efeitos adversos , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Adulto , Feminino , Cefaleia/etiologia , Humanos , Neoplasias Hipofisárias/complicações , Prolactinoma/complicaçõesRESUMO
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to tumors of the parathyroid, endocrine pancreas, anterior pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has been assigned, by linkage analysis and loss of heterozygosity, to chromosome 11q13 and recently has been identified by positional cloning. In this study, a total of 84 families and/or isolated patients with either MEN1 or MEN1-related inherited endocrine tumors were screened for MEN1 germ-line mutations, by heteroduplex and sequence analysis of the MEN1 gene-coding region and untranslated exon 1. Germ-line MEN1 alterations were identified in 47/54 (87%) MEN1 families, in 9/11 (82%) isolated MEN1 patients, and in only 6/19 (31.5%) atypical MEN1-related inherited cases. We characterized 52 distinct mutations in a total of 62 MEN1 germ-line alterations. Thirty-five of the 52 mutations were frameshifts and nonsense mutations predicted to encode for a truncated MEN1 protein. We identified eight missense mutations and five in-frame deletions over the entire coding sequence. Six mutations were observed more than once in familial MEN1. Haplotype analysis in families with identical mutations indicate that these occurrences reflected mainly independent mutational events. No MEN1 germ-line mutations were found in 7/54 (13%) MEN1 families, in 2/11 (18%) isolated MEN1 cases, in 13/19 (68. 5%) MEN1-related cases, and in a kindred with familial isolated hyperparathyroidism. Two hundred twenty gene carriers (167 affected and 53 unaffected) were identified. No evidence of genotype-phenotype correlation was found. Age-related penetrance was estimated to be >95% at age >30 years. Our results add to the diversity of MEN1 germ-line mutations and provide new tools in genetic screening of MEN1 and clinically related cases.
Assuntos
Mutação em Linhagem Germinativa , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla/genética , Mutação , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas , Substituição de Aminoácidos , Éxons , Feminino , Triagem de Portadores Genéticos , Humanos , Íntrons , Masculino , Neoplasia Endócrina Múltipla/classificação , Neoplasia Endócrina Múltipla Tipo 1/classificação , Mutação de Sentido Incorreto , Linhagem , Mutação Puntual , Deleção de SequênciaRESUMO
Polycystic ovary syndrome (PCOS) is an association of oligomenorrhoea, anovulation, hyperandrogenism, obesity and enlarged polycystic ovaries. It provides a model of loss of cyclic ovarian function. It is classical to distinguish between type I and type II PCOS. In type I, the primary mechanism seems to be hypothalamic dysfunction, which causes an increase in the frequency and amplitude of LH pulses, with diminished FSH release. LH hypersecretion stimulates ovarian stroma hyperplasia while FSH insufficiency results in the failure of folliculare maturation and hence anovulation. Aromatization of androgens to oestrogens is responsible for permanent oestrogen overproduction, which favours LH hypersecretion. Type II PCOS is more frequent and may have multiple causes (local, endocrine, systemic, iatrogenic) that interfere with the gonadotropic axis and alter the FSH/LH ratio. The most efficient treatment of hirsutism is cyproterone acetate which alone has both antiandrogenic and antigonadotropic properties. Clomifene citrate remains the "first choice" treatment of infertility associated with anovulation.
