Excess Mortality Associated With Hypopituitarism in Adults: A Meta-Analysis of Observational Studies

Context: Several previous observational studies showed an association between hypopituitarism and excess mortality. Reports on reduction of standard mortality ratio (SMR) with GH replacement have been published recently. Objective: This meta-analysis assessed studies reporting SMR to clarify mortality risk in hypopituitary adults and also the potential benefit conferred by GH replacement. Data Sources: A literature search was performed in Medline, Embase, and Cochrane library up to March 31, 2014. Eligibility Criteria: Studies with or without GH replacement reporting SMR with 95% confidence intervals (95% CI) were included. Data Extraction and Analysis: Patient characteristics, SMR data, and treatment outcomes were independently assessed by two authors, and with consensus from third author, studies were selected for analysis. Meta-analysis was performed in all studies together, and those without and with GH replacement separately, using the statistical package metafor in R. Results: Six studies reporting a total of 19 153 hypopituiatary adults with a follow-up duration of more than 99 000 person years were analyzed. Hypopituitarism was associated with an overall excess mortality (weighted SMR, 1.99; 95% CI, 1.21-2.76) in adults. Female hypopituitary adults showed higher SMR compared with males (2.53 vs 1.71). Onset of hypopituitarism at a younger age was associated with higher SMR. GH replacement improved the mortality risk in hypopituitary adults that is comparable to the background population (SMR with GH replacement, 1.15; 95% CI, 1.05-1.24 vs SMR without GH, 2.40; 95% CI, 1.46-3.34). GH replacement conferred lower mortality benefit in hypopituitary women compared with men (SMR, 1.57; 95% CI, 1.38-1.77 vs 0.95; 95% CI, 0.85-1.06). Limitations: There was a potential selection bias of benefit of GH replacement from a post-marketing data necessitating further evidence from long-term randomized controlled trials. Conclusions: Hypopituitarism may increase premature mortality in adults. Mortality benefit from GH replacement in hypopituitarism is less pronounced in women than men.