There are very limited data on long-term mortality in pituitary ACTH dependent Cushings disease (CD).
We report on our data from Stoke-on-Trent, UK, spanning 50 years and provide a meta-analysis of six other reports which addressed mortality of CD. Case records of 60 CD patients from 1958-31 Dec 2009 from Stoke-on-Trent were reviewed. The standardised mortality ratio (SMR) overall and separately for patients in remission and having persistent disease was calculated. Remission was defined as resolution of clinical features and normalisation of biochemical hypercortisolism according to the methods extant at the time within 3 years of diagnosis. Overall SMR for the whole cohort was 4.8 (2.88.3 95% confidence intervals) P=<0.001. SMR for vascular disease=13.8 (7.236.5) P=<0.001. For persistent disease (n=6 pts) SMR=16 (6.738-4) vs remission (n=54) SMR=3.3 (1.76.7); after adjustment for age and sex relative risk of death for persistent disease was 10.7 (2.348.6) P=0.002. Hypertension and diabetes mellitus were associated with significantly worse survival. Using a random effects model meta-analysis of seven studies (including our own) revealed an overall SMR of 2.2 (1.453.41) P=<0.001 indicating decreased survival. Pooled SMR for patients in remission (4 studies which compared the remission versus persistent disease) was 1.2 (0.453.2) P=NS and 5.5 (2.711.3) P=0.001 for patients with persistent disease. Persistence of disease, older age at diagnosis, and presence of hypertension and diabetes appear as the main determinants of mortality.
Conclusions: Overall mortality in CD is double that of the general population. Patients in remission fare much better than those with persistence of hypercortisolism. SMR of 1.2 for patients in remission may not be statistically significant but could become so with larger numbers followed for a much longer time (3040 years).