Incidence and late prognosis of Cushing’s syndrome: a population-based study. J Clin Endocrinol Metab

Department of Epidemiology and Social Medicine, Aarhus University, Aarhus, Central Jutland, Denmark
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 02/2001; 86(1):117-23. DOI: 10.1210/jcem.86.1.7093
Source: PubMed


The main purpose was to assess the incidence and late outcome of Cushing's syndrome, particularly in Cushing's disease. Information for all patients diagnosed with Cushing's syndrome during an 11-yr period in Denmark was retrieved. The incidence was 1.2-1.7/million.yr (Cushing's disease), 0.6/million.yr (adrenal adenoma) and 0.2/million.yr (adrenal carcinoma). Other types of Cushing's syndrome were rare. In 139 patients with nonmalignant disease, 11.1% had died during follow-up (median, 8.1 yr; range, 3.1-14.0), yielding a standard mortality ratio (SMR) of 3.68 [95% confidence interval (CI), 2.34-5.33]. The SMR was partly attributable to an increased mortality within the first year after diagnosis. Eight patients died before treatment could be undertaken. The prognosis in patients with malignant disease was very poor. Patients in whom more than 5 yr had elapsed since initial surgery were studied separately, including a questionnaire on their perceived quality of health. In 45 patients with Cushing's disease who had been cured through transsphenoidal neurosurgery, only 1 had died (SMR, 0.31; CI, 0.01-1.72) compared with 6 of 20 patients with persistent hypercortisolism after initial neurosurgery (SMR, 5.06; CI, 1.86-11.0). In patients with adrenal adenoma, SMR was 3.95 (CI, 0.81-11.5). The perceived quality of health was significantly impaired only in patients with Cushing's disease and appeared independent of disease control or presence of hypopituitarism. It is concluded that 1) Cushing's syndrome is rare and is associated with increased mortality, in patients with no concurrent malignancy also; 2) the excess mortality was mainly observed during the first year of disease; and 3) the impaired quality of health in long-term survivors of Cushing's disease is not fully explained.

42 Reads
  • Source
    • "Obesity and diabetes are major factors in morbidity and mortality in Cushing's disease (Ntali et al. 2015). Cushing's disease is very rare, with an incidence of 1.2–2.4 per million (Lindholm et al. 2001), but iatrogenic Cushing's syndrome, caused by chronic glucocorticoid treatment, is very common and leads to similar clinical manifestations. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNA sequencing on subcutaneous adipose tissue from patients with Cushing's disease (n=5) compared to patients with non-functioning pituitary adenomas (n=11). We found higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in a model system, we subjected mice to dexamethasone treatment for 12 weeks and analyzed their inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the co-morbidities associated with chronic elevations of glucocorticoids.
    Journal of Molecular Endocrinology 07/2015; 55(2). DOI:10.1530/JME-15-0119 · 3.08 Impact Factor
  • Source
    • "1/100.000 population [1,2]. The symptoms and signs of CS like truncal obesity, moon face, diabetes mellitus, hypertension and muscle weakness result from chronic glucocorticoid excess. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Kaposi sarcoma (KS) is a malignant disease most commonly diagnosed in the setting of a human immunodeficiency virus (HIV) infection and in patients receiving immunosuppressive treatment. Pulmonary KS has never been reported in association with endogenous Cushing’s syndrome (CS). Case presentation A 60-year-old woman presented with symptoms and signs of CS. Adrenal CS was confirmed by standard biochemical evaluation. Imaging revealed a right adrenal lesion (diameter 3.5 cm) and multiple pulmonary nodules, suggesting a cortisol-secreting adrenal carcinoma with pulmonary metastases. The patient underwent right adrenalectomy with a pathohistological diagnosis of an adrenal adenoma. Subsequent thoracoscopic wedge resection of one lung lesion revealed pulmonary KS with positive immunostaining for human herpes virus 8 (HHV-8). HIV-serology was negative. Hydrocortisone replacement was initiated for secondary adrenal insufficiency after surgery. Post-operative follow up imaging showed complete remission of all KS-related pulmonary nodules solely after resolution of hypercortisolism. Conclusion KS may occur in the setting of endogenous CS and may go into remission after cure of hypercortisolism without further specific treatment.
    BMC Endocrine Disorders 07/2014; 14(1):63. DOI:10.1186/1472-6823-14-63 · 1.71 Impact Factor
  • Source
    • "Untreated or inadequately treated Cushing's disease is associated with cardiovascular disease, central obesity, skeletal fractures, insulin-resistant hyperglycaemia, arterial hypertension, limiting proximal muscle weakness, persistent cognitive defects and increased mortality (Lindholm et al., 2001; Schteingart, 2009; Arnaldi et al., 2003; Newell-Price et al., 2006; Plotz et al., 1952). However, when eucortisolemia is achieved, the observed mortality rate returns to normal over a 10–20 year follow-up period (Clayton, 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cushing's disease, a hypercortisolemic state induced by an ACTH overexpressing pituitary adenoma, causes increased morbidity and mortality. Selective antagonism of the melanocortin type 2 receptor (MC2R) may be a novel treatment modality. Five structurally related peptides with modified HFRW sites but intact putative MC2R binding sites were tested for antagonistic activity at MC1R, MC2R/MRAP, MC3R, MC4R and MC5R. Two of these peptides (GPS1573 and GPS1574) dose-dependently antagonized ACTH-stimulated MC2R activity (IC50s of 66 ±23 nM and 260±1 nM, respectively). GPS1573 and 1574 suppressed the Rmax but not EC50 of ACTH on MC2R, indicating non-competitive antagonism. These peptides did not antagonize α-MSH stimulation of MC1R and antagonized MC3, 4 and 5R at markedly lower potency. GP1573 and GPS1574 antagonize MC4R with IC50s of 950 nM and 3.7 μM, respectively. In conclusion, two peptide antagonists were developed with selectivity for MC2R, forming a platform for development of a medical treatment for Cushing's disease.
    Molecular and Cellular Endocrinology 07/2014; 394(1-2). DOI:10.1016/j.mce.2014.07.003 · 4.41 Impact Factor
Show more