Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies

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.

This meta-analysis assessed studies reporting SMR to clarify mortality risk in hypopituitary adults and also the potential benefit conferred by GH replacement.

A literature search was performed in Medline, Embase, and Cochrane library up to March 31, 2014.

Studies with or without GH replacement reporting SMR with 95% confidence intervals (95% CI) were included.

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.

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).

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.

Hypopituitarism may increase premature mortality in adults. Mortality benefit from GH replacement in hypopituitarism is less pronounced in women than men.