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

Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Aarhus, Denmark.
European Journal of Internal Medicine (Impact Factor: 2.89). 04/2012; 23(3):278-82. DOI: 10.1016/j.ejim.2011.10.013
Source: PubMed


Data on mortality associated with Cushing's disease (CD) and Cushing's syndrome (CS) are scarce.
To perform a systematic review and meta-analysis of mortality studies in patients with CD and CS secondary to a benign adrenal adenoma.
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.
Studies were appraised by two authors and were synthesized using a weighted estimate based on the standard error of the SMR.
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.
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.

Download full-text


Available from: Claus Højbjerg Gravholt
  • Source
    • "The effects of Cushing’s disease include metabolic and cardiovascular complications, osteoporosis and other bone alterations, kidney stones, autoimmune diseases, and susceptibility to opportunistic infections [4–15]. Mortality in patients with active Cushing’s disease is 4-times higher than in age- and sex-matched controls [3, 16]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To recommend an approach to monitoring and treating hyperglycemia in pasireotide-treated patients with Cushing's disease, a severe clinical condition caused by a pituitary adenoma hypersecreting adrenocorticotropic hormone. Advisory Board meeting of ten European experts in pituitary disease and diabetes mellitus in Munich, Germany, on February 23, 2012, to obtain expert recommendations. Cushing's disease presents a number of management challenges. Pasireotide, a novel agent for the treatment of Cushing's disease with proven biochemical and clinical efficacy, improves outcomes and expands treatment options. Clinical trials have shown that the pasireotide adverse event profile is similar to that of other somatostatin analogs, except for a higher frequency of hyperglycemia. Mechanistic studies in healthy volunteers suggest that pasireotide-associated hyperglycemia is due to reduced secretion of glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide, and insulin; however, it is associated with intact postprandial glucagon secretion. Individual patients' results demonstrate effective hyperglycemia management by following standard guidelines for the treatment of diabetes mellitus with individual adaptation to the specific underlying pathophysiology, i.e., preferential use of GLP-1 based-medications. Patients on pasireotide treatment should be monitored for changes in glucose metabolism and hyperglycemia. Diabetes mellitus should be managed by initiation of medical therapy with metformin and staged treatment intensification with a dipeptidyl peptidase-4 inhibitor, with a switch to a GLP-1 receptor agonist and initiation of insulin, as required, to achieve and maintain glycemic control. Further research into hyperglycemia following pasireotide treatment will help refine the optimal strategy in Cushing's disease.
    Full-text · Article · Apr 2013 · Pituitary
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cushing's disease (CD) is a rare endocrine disorder characterized by excess secretion of ACTH due to a pituitary adenoma. Current treatment options are limited and may pose additional risks. A literature review was conducted to assess the holistic burden of CD. Studies published in English were evaluated to address questions regarding the epidemiology of CD, time to diagnosis, health-related quality of life (HRQoL), treatment outcomes, mortality, prevalence of comorbidities at diagnosis, and reversibility of comorbidities following the treatment. a two-stage literature search was performed in Medline, EMBASE, and Science Citation Index, using keywords related to the epidemiology, treatment, and outcomes of CD: i) articles published from 2000 to 2012 were identified and ii) an additional hand search (all years) was conducted on the basis of bibliography of identified articles. At the time of diagnosis, 58-85% of patients have hypertension, 32-41% are obese, 20-47% have diabetes mellitus, 50-81% have major depression, 31-50% have osteoporosis, and 38-71% have dyslipidemia. Remission rates following transsphenoidal surgery (TSS) are high when performed by expert pituitary surgeons (rates of 65-90%), but the potential for relapse remains (rates of 5-36%). Although some complications can be partially reversed, time to reversal can take years. The HRQoL of patients with CD also remains severely compromised after remission. These findings highlight the significant burden associated with CD. As current treatment options may not fully reverse the burden of chronic hypercortisolism, there is a need for both improved diagnostic tools to reduce the time to diagnosis and effective therapy, particularly a targeted medical therapy.
    No preview · Article · Jun 2012 · European Journal of Endocrinology
  • [Show abstract] [Hide abstract]
    ABSTRACT: CONTEXT: Prevalence of Cushing's syndrome (CS) in patients presenting with hirsutism is not well-known. OBJECTIVE: Screening of CS in patients with hirsutism. SETTING: Referral hospital PATIENTS AND OTHER PARTICIPANTS: This study was carried out on 105 patients who admitted to Endocrinology Department with the complaint of hirsutism. INTERVENTION: All the patients were evaluated with low dose dexamethasone suppression test (LDDST) for CS. MAIN OUTCOME MEASURE: Response to LDDST in patients presenting with hirsutism RESULTS: All the patients had suppressed cortisol levels following low dose dexamethasone administration excluding CS. The etiology of hirsutism were polycystic ovary syndrome in 79%, idiopathic hirsutism in 13%, idiopathic hyperandrogenemia in 6% and non-classical congenital hyperplasia in 2% of the patients. CONCLUSION: Routine screening for CS in patients with a referral diagnosis of hirsutism is not required. For the time being, diagnostic tests for CS in hirsute patients should be limited to patients who have accompanying clinical stigmata of hypercortisolism.
    No preview · Article · Dec 2012 · European Journal of Endocrinology
Show more