title: Proinflammatory cytokines remain elevated despite long-term remission in Cushing's disease: a prospective study.
abstract: BACKGROUND
  Inflammation contributes to the development of metabolic and cardiovascular disease. Cushing's disease (CD), a state of chronic glucocorticoid (GC) excess characterized by visceral obesity and insulin resistance, may be associated with increased systemic inflammation. Cardiovascular mortality in CD remains elevated even after successful remission. It is unclear whether a chronic low-grade inflammatory state persists even after remission of CD, which may account for the increased CVD mortality.
  
  
  OBJECTIVE
  (1) To assess circulating proinflammatory cytokines in patients with active CD and BMI-matched controls; (2) to prospectively follow plasma cytokine concentrations in patients with CD before and after surgical remission; and (3) to assess whether plasma cytokine concentrations correlate with adipose tissue distribution and ectopic lipid content in liver and muscle.
  
  
  METHODS
  Plasma cytokines from prospectively enrolled patients with CD (N = 31) were quantified during active disease (v1) vs controls (N = 18) and 19·5 ± 12·9 months after surgical remission (v2). Fasting plasma IL-6, IL-1β, TNF-α, IL-8, IL-17 and IL-10 were quantified using a multiplex assay. Total and regional fat masses were measured by whole-body MRI.
  
  
  RESULTS
  Circulating IL-6 and IL-1β were elevated in patients with active CD vs controls (P < 0·05) and remained elevated in CD after surgical remission, despite decreases in BMI (P < 0·001), HOMA-IR (P < 0·001), and visceral, hepatic and intermuscular fat (P < 0·001, <0·001 and 0·03, respectively).
  
  
  CONCLUSIONS
  Despite long-term remission and improvements in fat distribution and insulin sensitivity, patients with CD may suffer from a state of chronic low-grade inflammation, which could contribute to increased cardiovascular mortality.
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Nirali
authors.initials: N
authors.lastname: Shah
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Henry H
authors.initials: HH
authors.lastname: Ruiz
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Usman
authors.initials: U
authors.lastname: Zafar
authors.affiliation: Department of Neurosurgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Kalmon D
authors.initials: KD
authors.lastname: Post
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Buettner
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Neurosurgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Eliza B
authors.initials: EB
authors.lastname: Geer
mesh_terms: D050154:Adiposity; D000328:Adult; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000097:blood* / Q000601:surgery; D011446:Prospective Studies; D012044:Regression Analysis; D012074:Remission Induction
chemical_list: D016207:Cytokines; D002097:C-Reactive Protein