title: Management of endocrine disease: Mortality remains increased in Cushing's disease despite biochemical remission: a systematic review and meta-analysis.
abstract: The aim of this systematic review and meta-analysis was to investigate whether mortality is increased in patients biochemically cured after initial treatment for Cushing's disease. This is a systematic review and meta-analysis of follow-up studies in patients cured from Cushing's disease after initial treatment was performed. Eight electronic databases were searched from 1975 to March 2014 to identify potentially relevant articles. Original articles reporting the standardized mortality ratio (SMR) for patients cured of Cushing's disease were eligible for inclusion. SMRs were pooled in a random effects model. I(2) statistics was used for quantification of heterogeneity. Eight cohort studies with a total of 766 patients were included. Out of eight studies, seven showed an SMR above 1.0 for cured patients. The pooled SMR was 2.5 (95% CI 1.4-4.2). The I(2) statistics showed evidence for statistical heterogeneity (78%, Q-statistics P<0.001), which was largely explained by two outliers. This meta-analysis reveals that mortality remains increased in patients with Cushing's disease even after initial biochemical cure remission, suggesting that cure does not directly reverse the metabolic consequences of long-term overexposure to cortisol. Other conditions such as hypopituitarism, including persistent adrenocortical insufficiency after surgery, may also contribute to the increased mortality risk.
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Centre, Leiden 2300RC, The NetherlandsDepartment of EndocrinologyAarhus University, 8000 Aarhus C, DenmarkDepartment of Clinical EpidemiologyAarhus University, Aarhus, Denmark.
authors.forename: Femke M
authors.initials: FM
authors.lastname: van Haalen
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Centre, Leiden 2300RC, The NetherlandsDepartment of EndocrinologyAarhus University, 8000 Aarhus C, DenmarkDepartment of Clinical EpidemiologyAarhus University, Aarhus, Denmark.
authors.forename: Leonie H A
authors.initials: LH
authors.lastname: Broersen
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Centre, Leiden 2300RC, The NetherlandsDepartment of EndocrinologyAarhus University, 8000 Aarhus C, DenmarkDepartment of Clinical EpidemiologyAarhus University, Aarhus, Denmark.
authors.forename: Jens O
authors.initials: JO
authors.lastname: Jorgensen
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Centre, Leiden 2300RC, The NetherlandsDepartment of EndocrinologyAarhus University, 8000 Aarhus C, DenmarkDepartment of Clinical EpidemiologyAarhus University, Aarhus, Denmark.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
authors.affiliation: Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Centre, Leiden 2300RC, The NetherlandsDepartment of EndocrinologyAarhus University, 8000 Aarhus C, DenmarkDepartment of Clinical EpidemiologyAarhus University, Aarhus, Denmark Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Centre, Leiden 2300RC, The NetherlandsDepartment of EndocrinologyAarhus University, 8000 Aarhus C, DenmarkDepartment of Clinical EpidemiologyAarhus University, Aarhus, Denmark Departments of EndocrinologyClinical EpidemiologyLeiden University Medical Centre, Leiden 2300RC, The NetherlandsDepartment of EndocrinologyAarhus University, 8000 Aarhus C, DenmarkDepartment of Clinical EpidemiologyAarhus University, Aarhus, Denmark o.m.dekkers@lumc.nl.
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
mesh_terms: D015982:Bias; D015415:Biomarkers / Q000097:blood; D006801:Humans; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers