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J Clin Endocrinol Metab. 2011 Mar;96(3):632-42. doi: 10.1210/jc.2010-1942. Epub 2010 Dec 30.

Mortality and morbidity in Cushing's disease over 50 years in Stoke-on-Trent, UK: audit and meta-analysis of literature.

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1
Department of Endocrinology, University Hospital of North Staffordshire, Stoke-on-Trent ST4 7PX, Staffordshire, United Kingdom. mea23@keele.ac.uk

Abstract

CONTEXT:

Pituitary ACTH-dependent Cushing's disease (CD) is uncommon, and there are very limited data on long-term mortality.

OBJECTIVE:

The aim was to summarize what is known about mortality in ACTH-dependent CD, to report on our own data, and to provide a meta-analysis of six other reports that addressed mortality of CD.

DESIGN AND METHODS:

Vital status of 60 CD patients was recorded as of December 31, 2009, and the standardized mortality ratio (SMR) was calculated and compared with the general population of England and Wales, United Kingdom. A meta-analysis of SMRs from seven studies (including ours) was performed for overall mortality in CD. Where reported (four studies), a similar meta-analysis was performed for those patients whose hypercortisolism was in remission after treatment compared to those patients from the same center with persistent disease.

RESULTS:

1. From Stoke-on-Trent, 51 of 60 patients were female, median age at diagnosis was in the range of 36-46 yr, and median follow-up was 15 yr. There were 13 deaths, nine due to cardiovascular disease. Overall SMR for the whole cohort was 4.8 (95% confidence interval, 2.8-8.3) (P < 0001). SMR for vascular disease was 13.8 (7.2-36.5) (P < 0001). For persistent disease (n = 6), SMR was 16 (6.7-38.4) vs. remission (n = 54) SMR of 3.3 (1.7-6.7); after adjustment for age and sex, relative risk of death for persistent disease was 10.7 (2.3-48.6) (P = 0.002). Hypertension and diabetes mellitus were associated with significantly worse survival. 2. Using a random effects model meta-analysis revealed an overall (remission plus persistent disease) SMR of 2.2 (1.45-3.41) (P < 0.001). Pooled SMR was 1.2 (0.45-3.2) (P = not significant) for patients in remission and 5.5 (2.7-11.3) (P = 0.001) for patients with persistent disease. Persistence of disease, older age at diagnosis, and presence of hypertension and diabetes are the main determinants of mortality.

CONCLUSIONS:

Overall mortality in CD is double that of the general population. However, patients with CD in remission fare much better than those with persistence of hypercortisolism, and they appear not to have an increased mortality rate. Hypertension and diabetes mellitus are risk factors for worse outcome. Because diagnosis and treatment of patients are at a young age, much longer follow-up of patients in remission is required before one can be confident that their mortality outcome is no different from that of the general population, especially because cardiovascular risk factors may persist after successful biochemical control of the disease.

PMID:
21193542
DOI:
10.1210/jc.2010-1942
[Indexed for MEDLINE]
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