Mortality in Cushing's syndrome: A systematic review and meta-analysis

Published:November 16, 2011DOI:https://doi.org/10.1016/j.ejim.2011.10.013

      Abstract

      Context

      Data on mortality associated with Cushing's disease (CD) and Cushing's syndrome (CS) are scarce.

      Objective

      To perform a systematic review and meta-analysis of mortality studies in patients with CD and CS secondary to a benign adrenal adenoma.

      Data sources

      A search was performed in seven electronic databases. Sixty-six articles were retrieved for analysis and 7 included in the final study. The main outcome measure was standardized mortality ratio (SMR).

      Study eligibility criteria, participants, and interventions

      Studies reporting SMR for patients diagnosed with CD and/or CS. Outcomes were stratified by subtype of Cushing's syndrome.

      Study appraisal and synthesis methods

      Studies were appraised by two authors and were synthesized using a weighted estimate based on the standard error of the SMR.

      Results

      The weighted mean of SMR for patients with CD was 1.84 (95% confidence interval (CI): 1.28–2.65). CD patients with persistent disease after initial surgery had a SMR of 3.73 (95% CI: 2.31–6.01), whereas mortality of CD patients with initial remission did not differ significantly from the general population (SMR: 1.23 (95% CI: 0.51–2.97)). SMR for patients with a benign adrenal adenoma was 1.90 (95% CI: 0.93–3.91). Age, sex and observation time did not significantly impact mortality.

      Conclusions

      CD as opposed to CS due to a benign adrenal adenoma is associated with an excess mortality, which is attributed to patients in whom initial surgical cure is not obtained. This underlines the importance of a rigorous and early follow-up of newly operated patients with CD.

      Keywords

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      References

        • Mancini T.
        • Kola B.
        • Mantero F.
        • Boscaro M.
        • Arnaldi G.
        High cardiovascular risk in patients with Cushing's syndrome according to 1999 WHO/ISH guidelines.
        Clin Endocrinol. 2004; 61: 768-777
        • Newell-Price J.
        • Bertagna X.
        • Grossman A.B.
        • Nieman L.K.
        Cushing's syndrome.
        Lancet. 2006; 367: 1605-1617
        • Colao A.
        • Pivonello R.
        • Spiezia S.
        • et al.
        Persistence of increased cardiovascular risk in patients with Cushing's disease after five years of successful cure.
        J Clin Endocrinol Metab. 1999; 84: 2664-2672
        • Faggiano A.
        • Pivonello R.
        • Spiezia S.
        • et al.
        Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing's disease during active disease and 1 year after disease remission.
        J Clin Endocrinol Metab. 2003; 88: 2527-2533
        • Bourdeau I.
        • Bard C.
        • Forget H.
        • Boulanger Y.
        • Cohen H.
        • Lacroix A.
        Cognitive function and cerebral assessment in patients who have Cushing's syndrome.
        Endocrinol Metab Clin North Am. 2005; 34: 357-369
        • Pivonello R.
        • De Martino M.C.
        • De Leo M.
        • Tauchmanova L.
        • Faggiano A.
        • Lombardi G.
        Cushing's syndrome: aftermath of the cure.
        Arq Bras Endocrinol Metabol. 2007; 51: 1381-1391
        • Steffensen C.
        • Bak A.M.
        • Rubeck K.Z.
        • Jorgensen J.O.L.
        Epidemiology of Cushing's syndrome.
        Neuroendocrinology. 2010; 92: 1-5
        • Iacobone M.
        • Mantero F.
        • Basso S.M.
        • Lumachi F.
        • Favia G.
        Results and long-term follow-up after unilateral adrenalectomy for ACTH-independent hypercortisolism in a series of fifty patients.
        J Endocrinol Invest. 2005; 28: 327-332
        • Lindholm J.
        • Juul S.
        • Jorgensen J.O.L.
        • et al.
        Incidence and late prognosis of Cushing's syndrome: a population-based study.
        J Clin Endocrinol Metab. 2001; 86: 117-123
        • Etxabe J.
        • Vazquez J.A.
        Morbidity and mortality in cushings-disease—an epidemiologic approach.
        Clin Endocrinol. 1994; 40: 479-484
        • Swearingen B.
        • Biller B.M.K.
        • Barker F.G.
        • Katznelson L.
        • Grinspoon S.
        • Klibanski A.
        • Zervas N.T.
        Long-term mortality after transsphenoidal surgery for Cushing disease.
        Ann Intern Med. 1999; 130: 821-824
      1. Prisma [internet] [cited 2010 Jan 15] Available from: www.prisma-statement.org.

      2. Danish Agency for Libraries and Media [internet] [cited 2010 Aug 8]. Available from: www.bibliotek.dk.

      3. Karolinska Institutet [internet] [cited 2010 Aug 8] Available from: http://micr.kib.ki.se.

      4. Ottawa Hospital Research Instituet [internet] [cited 2010 Jan 15] Available from: www.ohri.ca.

        • Dekkers O.M.
        • Biermasz N.R.
        • Pereira A.M.
        • Roelfsema F.
        • van Aken M.O.
        • Voormolen J.H.
        • Romijn J.A.
        Mortality in patients treated for Cushing's disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma.
        J Clin Endocrinol Metab. 2007; 92: 976-981
        • Pikkarainen L.
        • Sane T.
        • Reunanen A.
        The survival and well-being of patients treated for Cushing's syndrome.
        J Intern Med. 1999; 245: 463-468
        • Hammer G.D.
        • Tyrrell J.B.
        • Lamborn K.R.
        • et al.
        Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results.
        J Clin Endocrinol Metab. 2004; 89: 6348-6357
        • Böhning D.
        Monographs on statistics and applied probability.
        in: Computer-assisted analysis of mixtures and applications: meta-analysis, disease mapping and others. Chapman&Hall/CRC, 2000: 1-19
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560