Blunted Cortisol Awakening Response in Patients with Inflammatory Bowel Disease: A Cross-Sectional Case-Control Study

Inflammatory bowel disease (IBD) involves chronic immune activation, yet alterations in the cortisol awakening response (CAR) remain poorly defined. We compared cortisol dynamics in patients with IBD and healthy controls and explored associations with phenotype, endoscopic activity, and inflammation.

This single-centre, cross-sectional case-control study enrolled 100 patients with IBD (51 with ulcerative colitis [UC] and 49 with Crohn's disease [CD]) and 78 frequency-matched controls. Salivary cortisol was measured at awakening (C0), 30-45 min later (C1), and bedtime (C2); 97 patients and 78 controls met timing criteria. The absolute post-awakening increment (ΔCAR) and area under the curve with respect to increase (AUCi) were calculated. Analyses included non-parametric tests, adjusted regression, mixed models, and multiplicity-corrected within-IBD comparisons and correlations.

Patients with IBD had lower C0 (median 0.478 vs. 1.067 µg/dL) and C1 (0.850 vs. 1.950 µg/dL; both p < 0.001), whereas C2 was comparable (p = 0.819). ΔCAR (0.130 vs. 0.461 µg/dL) and AUCi (2.080 vs. 7.770 min·µg/dL) were lower in IBD (both p < 0.001); adjusted analyses confirmed this pattern. Cortisol metrics did not differ consistently by IBD subtype or endoscopic activity. Higher high-sensitivity C-reactive protein (hs-CRP) correlated positively with C0 (ρ = 0.325; q = 0.041) and inversely with ΔCAR (ρ = -0.402; q = 0.002), AUCi (ρ = -0.408; q = 0.002), and relative CAR (ρ = -0.517; q < 0.001).

IBD was associated with attenuated CAR and lower morning cortisol output, with preserved bedtime concentrations. These cross-sectional findings support a relationship between systemic inflammation and altered early-morning HPA-axis dynamics but do not establish causality.