Study of major genetic factors involved in pituitary tumorigenesis and their impact on clinical and biological characteristics of sporadic somatotropinomas and non-functioning pituitary adenomas

Genetic and functional aberrations of guanine nucleotide-binding protein, alpha stimulating (GNAS), aryl hydrocarbon receptor interacting protein (AIP), and pituitary tumor transforming gene (PTTG) are among the most prominent events in pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas (n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary-referral center were evaluated for GNAS and AIP mutations and gene expression of AIP and PTTG. Results were compared to the clinical and biological (Ki67 and p53 expression) characteristics of tumors and their response to therapy, if applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of NFPA harbored GNAS mutations (P=0.05). However, no differences were observed in clinical characteristics, tumor extension, response to somatostatin analog therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression between mutated and non-mutated somatotropinomas patients. PTTG overexpression (RQ mean=10.6, min=4.39, max=11.9) and AIP underexpression (RQ mean=0.56, min=0.46-max=0.92) were found in virtually all cases without a statistically significant relationship with clinical and biological tumor features. No patients exhibited somatic or germline pathogenic AIP mutations. In conclusion, mutations in GNAS and abnormal PTTG and AIP expression had no impact on tumor features and treatment outcomes in this cohort. Our data support some previous studies and point to the need for further investigations, probably involving epigenetic and transcriptome analysis, to improve our understanding of pituitary tumor behavior.

Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas

The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-α catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number ≥4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland.

Exercício físico e obesidade / Exercise and obesity

A obesidade é o principal distúrbio nutricional nas sociedades desenvolvidas. Ela é responsável por aumento da mobidade e mortalidade cardiovascular, diretamente ou pela associaçäo com fatores de risco como hipertensäo arterial, diabe melito e dislipemias. Sendo condiçäo crônica, seu tratamento é frequentemente desapontador, principalmente a longo prazo. Dessa forma, devemos associar a seu principal recurso terapêutico, a dieta hipocalórica outras modalidades, entre asquais destacam-se os exercíciofísico. Além do efeito benéfico na reduçäo da massa adiposa, pelo aumento da lipólise e provavelmente pela reduçäo da lipogênese, os exercícios atuam favoravelmente em outros fatores de risco cardiovascular, auxiliando na reduçäo da pressäo arterial, no controle do diabete melito, no aumento do HDl-colesterol e na reduçäo dos triglicérides e do LDL-colesterol. Além disso, os exercícios atuam positivamente na esfera psicológica, reduzindo a tensäo, fator adicional de hiperfagia. No entanto para serem eftvos, os exercícios deves ser realizados com duraçäo e frequência adequadas. As atividades aeróbias säo os mais indicadas, ams é importante que os exercícios sejam prazeirosos, condiçäo fundamental para sua manutençäo a longo prazo. Devem-se também incentivar atividades cotidianas, como andar a pé para o trabalho e utilizar escada ao invés de elevador.

Hiperprolactinemia: consideracoes diagnosticas e terapeuticas. / Hyperprolactinemia: diagnostic and therapeutic considerations

O autor apresenta revisao sobre aspectos fisiopatologicos, diagnosticos e terapeuticos dos estudos hiperprolacnemicos.Ressalta o grande avanco alcancado neste campo da Endocrinologia na ultima decada e expoe o seu ponto de vista sobre que dados deste avanco auxiliam no diagnostico diferencial e nas opcoes terapeuticas da hiperprolactinemia

Poliadenomatose endocrina tipo 1 associada a hiperprolactinemia: apresentacao de um caso com insulinoma e provaveis adenomas de paratiroides e prolactinoma. / Endocrine polyadenomatosis type I associated with hyperprolactinemia:presentation of a case with insulinoma and probable parathyroid adenomas and prolactinoma

Os autores apresentam um caso de poliadenomatose endocrina tipo 1, associada a hiperprolactinemia. O quadro clinico caracteriza-se por hipersonia e galactorreia-amenorreia.Constatou-se hipoglicemia, induzida por insulinoma. A sela turca mostrou-se radiologicamente normal. Hiperparatiroidismo, sem manisfestacoes clinicas ou alteracoes osseas radiologicas, foi detectado laboratorialmente e por arteriografia cervical. Os autores discutem as possiveis associacoes entre hipoglicemia e hiperprolactinemia e citam os raros casos descritos na literatura, nos quais hipersecrecao de prolactina e demonstrada em pacientes portadores de poliadenomatose endocrina. Finalmente, discutem as opcoes terapeuticas para os setores comprometidos

Hiperlipoproteinemia tipo IIa, tendinite e xantomas. / Hyperlipoproteinemia type II, tendinitis and xanthomas

Muitos poucos sao os trabalhos sobre patologia osteoarticular relacionadas aos varios tipos de lipidemias, bem como nao ha relato na literatura nacional. A hipercolesterolemia essencial familial e a mais estudada. Os autores estudaram dois casos desta molestia, com comprovacao clinica, radiologica, bioquimica, bem como anatomopatologica. Discutem os possiveis mecanismos etiopatogenicos, bem como a orientacao terapeutica