Título:	Efeito da cabergolina no adenoma hipofisário clinicamente não funcionante e correlação dos polimorfismos do gene do receptor do glicocorticoide e da proteína AIP nos corticotropinomas
Autor(es):	Garcia, Érica Correia
Orientador(es):	Azevedo, Monalisa Ferreira
Coorientador(es):	Neves, Francisco de Assis Rocha
Assunto:	Síndrome de Cushing Cortisol Mutação genética Polimorfismo (Genética)
Data de publicação:	24-Out-2017
Data de defesa:	6-Jul-2017
Referência:	GARCIA, Érica Correia. Efeito da cabergolina no adenoma hipofisário clinicamente não funcionante e correlação dos polimorfismos do gene do receptor do glicocorticoide e da proteína AIP nos corticotropinomas. 2017. 160 f., il. Tese (Doutorado em Ciências da Saúde)—Universidade de Brasília, Brasília, 2017.
Abstract:	The approach of hypothalamic-pituitary diseases represents a challenge in endocrinology. In general, pathologies involving the pituitary have high morbidity, mortality rates above what is observed in the general population, and complex diagnostic and therapeutic. A better understanding of the mechanisms involved in the pathogenesis of these conditions is certainly a pathway for the development of therapeutic alternatives in this context. In the present study, we investigated the efficacy of a drug treatment modality for nonfunctioning pituitary adenoma (NFPA), and analyzed genetic aspects in correlation with tumorigenesis and phenotype in patients with corticotropinomas - Cushing's disease (CD). In the investigation of the NFPA, we evaluated the efficacy of cabergoline (2mg / week) in the treatment of these tumors in a short-term follow-up (6 months). Nineteen patients (10 men and 9 women) underwent treatment at the Hospital Universitário de Brasília (HUB). Eleven of these had undergone transsphenoidal surgery (TSS) previously and 8 of them had undergone no procedure. 57.89% of the patients had tumor progression in the last year before the onset of cabergoline. After the use of this medication for 6 months, only 21% presented increased tumor volume. There was a reduction of the initial tumor volume in 78.5% of patients (significant reduction, above 25%, in 31.5% and reduction of at least 10% in 47% of patients). The Cushing's disease study included 53 patients matched in HUB and 2 genes were investigated (the glucocorticoid receptor gene - GR and the aryl hydrocarbon receptor binding protein gene - AIP). There is evidence that polymorphisms in the GR gene lead to vulnerability to psychiatric disorders in the general population. As Cushing's disease is extensively associated with various psychiatric disorders, and its signs and symptoms are a consequence of the chronic hypersecretion of glucocorticoids, a better understanding of the genetic mechanisms involved in the phenotypic expression of this disease may contribute, in the future, to a better conduction of these patients. The polymorphisms rs6190 (R23K) and rs41423247 (BclI) were investigated. The R23K polymorphism of the GR gene was not found among the 53 patients, however the BclI polymorphism was found at high frequency in this sample. The group with psychiatric disorder presented BclI in homozygosis significantly higher than the control group (45% and 8%, respectively). Mutations in the AIP gene have been shown to cause familial isolated pituitary adenoma (FIPA), and have been described in patients with sporadic pituitary tumors, especially in growth hormone or prolactin secreting tumors. In Cushing's disease, the prevalence of mutations in this gene is low. We evaluated the AIP genotype in patients with corticotropinomas. In agreement with the literature data, no mutation was found in our sample. However, what aroused interest was the high prevalence of the polymorphism located in exon 1 of this gene (rs139459091, variant protein R9Q) and the presence of the variant K201 *. Future investigations including a larger number of patients, as well as conducting functional studies, are necessary to understand the real importance of these findings. The investigation of cabergoline use in ACNF was encouraging (tumor reduction with this medication), as well as the study of genetic aspects in the phenotypic expression of pituitary adenomas (BclI homozygous polymorphism of the GR gene was statistically more significant in DC). Regarding the research on tumorigenesis in DC, more studies are needed to establish its relationship with the AIP protein gene.
Unidade Acadêmica:	Faculdade de Ciências da Saúde (FS)
Informações adicionais:	Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2017. Texto parcialmente liberado pelo autor. Conteúdo restrito: Capítulos 3. Tumor Hipofisário Secretor de ACTH e 4. Conclusão.
Programa de pós-graduação:	Programa de Pós-Graduação em Ciências da Saúde
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