Revisão sistemática da interferência da normalização do fator de crescimento semelhante à insulina tipo 1 (IGF-1) e redução do hormônio de crescimento (GH) randômico na mortalidade dos pacientes com acromegalia
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Data
2017-02-22
Autores
Bolfi, Fernanda [UNESP]
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Universidade Estadual Paulista (Unesp)
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Objetivo: esta revisão sistemática da literatura e metanálise comparou a taxa da mortalidade na acromegalia com a taxa esperada na população geral dos estudos publicados antes de 2009 versus estudos publicados após. Métodos: foram criadas três estratégias de busca gerais e adaptáveis às bases de dados eletrônicas na área da saúde: Embase (1980–2015), Pubmed (1966–2016) e Biblioteca Virtual da Saúde (1982–2016). Foram incluídos estudos observacionais em que a mortalidade na acromegalia foi comparada à da população geral, por meio do número de mortes observadas nessa doença em comparação à taxa de mortalidade esperada para população geral (O/E). A partir do O/E, recalculamos todos os Standardized Mortality Ratio (SMR) e os seus respectivos intervalos de confiança (IC) que foram plotados em uma metanálise. Resultados: foram identificadas 1005 referências, dois revisores independentemente leram os títulos e resumos desses artigos. Dos 27 estudos potencialmente elegíveis, 23 foram incluídos e quatro foram excluídos por não preencherem os critérios de elegibilidade. A mortalidade geral na acromegalia foi significativamente superior a da população geral (SMR: 1,66, IC 1,44 - 1,93, p < 0,00001, I2 84%). Separando os artigos publicados a partir de 2009, a mortalidade na acromegalia não foi significativamente diferente 1,29 (IC 0,95-1,76, p=0,10, I2 86%). Nas análises por subgrupo de acordo com o status da doença, sete estudos consideraram como curados os pacientes que apresentaram a normalização do IGF-1 associado ao GH randômico < 2,5 ng/mL. Nesses indivíduos o SMR da metanálise foi 0,93 (IC 0,74-1,18, p=0,57, I2 33%) e dos que não atingiram esses critérios foi 2,23 (IC 1,53-3,27, p<0,00001, I² 61%). A mortalidade manteve-se significativamente maior nas causas cardiovasculares, respiratórias e cerebrovasculares [SMR: 1,78 (IC 1,52-2,10, p<0,00001, I² 49%), SMR: 2,29 (IC 1,63-3,23, p<0,00001, I² 49%), SMR: 2,62 (1,72-3,98, p<0,00001, I² 83%), respectivamente]. A metanálise dos que realizaram radioterapia evidenciou SMR de 2,15 (1,83-2,53, p<0,00001, I² 0%) e dos que não realizaram de 1,27 (0,95-1,69 p=0,11, I² 65%). Conclusão: apesar da alta inconsistência, não há diferença na mortalidade na acromegalia atualmente em comparação com períodos anteriores (antes e após 2009), e o controle bioquímico da doença com IGF-1 normal e GH randômico < 2,5 ng/mL está relacionado com normalização das taxas de mortalidade.
Objective: This systematic literature review and meta-analysis compared the mortality rate in acromegaly with the expected rate in the general population of studies published before 2009 versus studies published after. Methods: three general and adaptive search strategies were created from the electronic databases in the health area: Embase (1980-2015), Pubmed (1966-2016) and Virtual Health Library. Observational studies were included in which the mortality in acromegaly was compared to the general population, the number of deaths observed compared to the expected mortality rate in the general population (O/E). From O/E, we recalculated all the Standardized Mortality Ratio (SMR) and their respective confidence intervals (CI) that were plotted in a meta-analysis. Results: 1005 references were identified and two reviewers independently read the titles and abstracts of these articles. Of the 27 potentially eligible studies, 23 were included and four were excluded because they did not meet the eligibility criteria. Overall mortality in acromegaly was significantly higher than the general population (SMR: 1.66, CI 1.44 - 1.93, p <0.00001, I² 84%). Analyzing articles published as of 2009, the mortality in acromegaly was not significantly different, SMR 1.29 (CI 0.95-1.76, p = 0.10, I² 86%). In subgroup analyzes according to disease status, seven studies considered patients with IGF-1 normalization associated with random GH <2.5 ng / mL as cured. In these individuals, the SMR was 0.93 (CI 0.74-1.18, p = 0.57, I² 33%) and in those who did not meet these criteria were 2.23 (CI 1.53-3.27, p<0.00001, I² 61%). Mortality was significantly higher in cardiovascular, respiratory and cerebrovascular causes [SMR: 1.78 (CI 1.52-2.10, p <0.00001, I² 49%), SMR: 2.29 (CI 1.63-3.23, p <0.00001, I² 49%), SMR: 2.62 (1.72-3.98, p <0.00001, I² 83%), respectively]. The meta-analysis of those who underwent radiotherapy showed SMR 2.15 (1.83-2.53, p <0.00001, I² 0%) and those who did not performed, 1.27 (0.95-1.69 p = 0.11, I² 65%). Conclusion: Although there is a lot of inconsistency, there is no difference in acromegaly mortality compared to previous periods (before and after 2009), and the biochemical control of the disease with normal IGF-1 and random GH <2.5 ng / ml is related to normalization in mortality rates.
Objective: This systematic literature review and meta-analysis compared the mortality rate in acromegaly with the expected rate in the general population of studies published before 2009 versus studies published after. Methods: three general and adaptive search strategies were created from the electronic databases in the health area: Embase (1980-2015), Pubmed (1966-2016) and Virtual Health Library. Observational studies were included in which the mortality in acromegaly was compared to the general population, the number of deaths observed compared to the expected mortality rate in the general population (O/E). From O/E, we recalculated all the Standardized Mortality Ratio (SMR) and their respective confidence intervals (CI) that were plotted in a meta-analysis. Results: 1005 references were identified and two reviewers independently read the titles and abstracts of these articles. Of the 27 potentially eligible studies, 23 were included and four were excluded because they did not meet the eligibility criteria. Overall mortality in acromegaly was significantly higher than the general population (SMR: 1.66, CI 1.44 - 1.93, p <0.00001, I² 84%). Analyzing articles published as of 2009, the mortality in acromegaly was not significantly different, SMR 1.29 (CI 0.95-1.76, p = 0.10, I² 86%). In subgroup analyzes according to disease status, seven studies considered patients with IGF-1 normalization associated with random GH <2.5 ng / mL as cured. In these individuals, the SMR was 0.93 (CI 0.74-1.18, p = 0.57, I² 33%) and in those who did not meet these criteria were 2.23 (CI 1.53-3.27, p<0.00001, I² 61%). Mortality was significantly higher in cardiovascular, respiratory and cerebrovascular causes [SMR: 1.78 (CI 1.52-2.10, p <0.00001, I² 49%), SMR: 2.29 (CI 1.63-3.23, p <0.00001, I² 49%), SMR: 2.62 (1.72-3.98, p <0.00001, I² 83%), respectively]. The meta-analysis of those who underwent radiotherapy showed SMR 2.15 (1.83-2.53, p <0.00001, I² 0%) and those who did not performed, 1.27 (0.95-1.69 p = 0.11, I² 65%). Conclusion: Although there is a lot of inconsistency, there is no difference in acromegaly mortality compared to previous periods (before and after 2009), and the biochemical control of the disease with normal IGF-1 and random GH <2.5 ng / ml is related to normalization in mortality rates.
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Palavras-chave
Acromegalia, Mortalidade, Coeficiente de mortalidade padronizada, Revisão sistemática, Metanálise, Acromegaly, Mortality, Standardized mortality ratio, Systematic review, Meta-analysis