Pro-inflammatory cytokines remain elevated despite long-term remission in Cushing's disease: a prospective study

Abstract

Context

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 if a chronic low grade inflammatory state persists even after remission of CD, which may account for the increased CVD mortality.

Purpose

1) To assess circulating pro-inflammatory cytokines in active CD patients and BMI-matched controls; 2) to prospectively follow plasma cytokine concentrations in CD patients before and after surgical remission; and 3) to assess if plasma cytokine concentrations correlate with adipose tissue distribution and ectopic lipid content in liver and muscle.

Methods

Plasma cytokines from prospectively enrolled CD patients (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 active CD patients 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 inter-muscular 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.

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