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Hypopituitarism is a rare disorder with significant morbidity. To study the evidence on the association of premature mortality and hypopituitarism. A comprehensive search of multiple databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August, 2015. Eligible studies that evaluated patients with hypopituitarism and reported mortality estimates were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. We included 12 studies (published 1996–2015) that reported on 23,515 patients. Compared to the general population, hypopituitarism was associated with an overall excess mortality (weighted SMR of 1.55; 95 % CI 1.14−2.11), I 2 = 97.8 %, P = 0.000. Risk factors for increased mortality included younger age at diagnosis, female gender, diagnosis of craniopharyngioma, radiation therapy, transcranial surgery, diabetes insipidus and hypogonadism. Hypopituitarism may be associated with premature mortality in adults. Risk is particularly higher in women and those diagnosed at a younger age.

Growth hormone replacement therapy has benefits for patients with hypopituitarism. The safety profile in regard to tumor recurrence or progression, development of secondary malignancies, or cerebrovascular stroke is still an area of debate. A comprehensive search of multiple databases—MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August 2015. Eligible studies that evaluated long-term adverse events in adult patients with hypopituitarism treated with growth hormone replacement therapy and reported development of pituitary tumor recurrence or progression, secondary malignancies, or cerebrovascular stroke were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. Random-effects meta-analysis was used to pool relative risks and 95 % confidence intervals. We included 15 studies (published 1995–2015) that reported on 46,148 patients. Compared to non-replacement, growth hormone replacement therapy in adults with hypopituitarism was not associated with statistically significant change in pituitary tumor progression or recurrence (relative risk, 0.77; 95 % confidence interval, 0.53–1.13) or development of secondary malignancy (relative risk, 0.99; 95 % confidence interval, 0.70–1.39). In two retrospective studies, there was higher risk of stroke in patients who did not receive replacement (relative risk, 2.07; 95 % confidence interval, 1.51–2.83). The quality of evidence is low due to study limitations and imprecision. This systematic review and meta-analysis supports the overall safety of growth hormone therapeutic use in adults with hypopituitarism with no clear evidence of increased risk of pituitary tumor recurrence, malignancy, or stroke.