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Cited by 208Pituitary Gland Disorders and TreatmentsAdrenal and Paraganglionic TumorsNeuroendocrine Tumor Research Advances

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.

Mortality in patients with Cushing’s disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study

Open access
Clayton, Richard N, Jones, Peter W, Reulen, Raoul C, Stewart, Paul M, Hassan-Smith, Zaki K, Ntali, Georgia, Karavitaki, Niki, Dekkers, Olaf M, Pereira, Alberto M, Bolland, Mark, Holdaway, Ian, Lindholm, Jorgen·2016·The Lancet Diabetes & Endocrinology
DOI 10.1016/s2213-8587(16)30005-5
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Abstract

Background No agreement has been reached on the long-term survival prospects for patients with Cushing's disease. We studied life expectancy in patients who had received curative treatment and whose hypercortisolism remained in remission for more than 10 years, and identified factors determining their survival.Methods We did a multicentre, multinational, retrospective cohort study using individual case records from specialist referral centres in the UK, Denmark, the Netherlands, and New Zealand. Inclusion criteria for participants, who had all been in studies reported previously in peer-reviewed publications, were diagnosis and treatment of Cushing's disease, being cured of hypercortisolism for a minimum of 10 years at study entry, and continuing to be cured with no relapses until the database was frozen or death. We identified the number and type of treatments used to achieve cure, and used mortality as our primary endpoint. We compared mortality rates between patients with Cushing's disease and the general population, and expressed them as standardised mortality ratios (SMRs). We analysed survival data with multivariate analysis (Cox regression) with no corrections for multiple testing.Findings The census dates on which the data were frozen ranged from Dec 31, 2009, to Dec 1, 2014. We obtained data for 320 patients with 3790 person-years of follow-up from 10 years after cure (female:male ratio of 3:1). The median patient follow-up was 11·8 years (IQR 17-26) from study entry and did not differ between countries. There were no significant differences in demographic characteristics, duration of follow-up, comorbidities, treatment number, or type of treatment between women and men, so we pooled data from both sexes for survival analysis. 51 (16%) of the cohort died during follow-up from study entry (10 years after cure). Median survival from study entry was similar for women (31 years; IQR 19-38) and men (28 years; 24-42), and about 40 years (IQR 30-48) from remission. The overall SMR for all-cause mortality was 1·61 (95% CI 1·23-2·12; p=0·0001). The SMR for circulatory disease was increased at 2·72 (1·88-3·95; p<0·0001), but deaths from cancer were not higher than expected (0·79, 0·41-1·51). Presence of diabetes, but not hypertension, was an independent risk factor for mortality (hazard ratio 2·82, 95% CI 1·29-6·17; p=0·0095). We noted a step-wise reduction in survival with increasing number of treatments. Patients cured by pituitary surgery alone had long-term survival similar to that of the general population (SMR 0·95, 95% CI 0·58-1·55) compared with those who were not (2·53, 1·82-3·53; p<0·0001).Interpretation Patients with Cushing's disease who have been in remission for more than 10 years are at increased risk of overall mortality compared with the general population, particularly from circulatory disease. However, median survival from cure is excellent at about 40 years of remission. Treatment complexity and an increased number of treatments, reflecting disease that is more difficult to control, appears to negatively affect survival. Pituitary surgery alone is the preferred treatment to secure an optimum outcome, and should be done in a centre of surgical excellence.Funding None.

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Authors
Clayton, R. N., Jones, P. W., Reulen, R. C., Stewart, P. M., Hassan-Smith, Z. K., Ntali, G., Karavitaki, N., Dekkers, O. M., Pereira, A. M., Bolland, M., Holdaway, I., & Lindholm, J.
Affiliations
  • Keele University (GB)
  • University of Birmingham (GB)
  • University of Leeds (GB)
  • University of Oxford (GB)
  • Leiden University Medical Center (NL)
  • University of Auckland (NZ)
Corresponding author
Clayton, Richard N
ORCID
Venue
The Lancet Diabetes & Endocrinology
Publisher
Elsevier BV
Published
2016-07
Volume
4
Issue
7
Pages
569-576
ISSN
2213-8587 (ISSN-L)
DOI
10.1016/s2213-8587(16)30005-5
OpenAlex
W2409671948
Cited by
208
References
28
Citations by year
2026: 13 · 2025: 20 · 2024: 21 · 2023: 18 · 2022: 29 · 2021: 31 · 2020: 22 · 2019: 21 · 2018: 20 · 2017: 10 · 2016: 3
FWCI
18.12
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Diabetes & Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (acceptedVersion, cc-by-nc-nd)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
  • VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
Funders
  • National Institute for Health and Care Research (NF-SI-0514-10090, NF-SI-0508-10356)
  • Medical Research Council (MC_G0802521, MR/K015176/1, MR/K015176/2, MR/K015184/1, MC_PC_15055, MC_PC_15046, MR/K00414X/1, MC_PC_13066, MC_G0802531, MC_PC_14109)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
Keywords
Cushing's disease, mortality, long-term survival, remission, hypercortisolism, standardized mortality ratio, circulatory diseases, diabetes mellitus, pituitary surgery, transsphenoidal surgery, adrenalectomy, adrenocortical carcinoma, remission duration, sex differences, comorbidities, mortality risk factors, quality of life
MeSH terms
Adult, Cushing Syndrome, Europe, Female, Humans, Male, Middle Aged, New Zealand, Remission Induction, Retrospective Studies

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