ACTH-cortisol dissociation in patients with Kawasaki disease: a retrospective study

Abstract

ACTH-cortisol dissociation is recognized in patients with critical illnesses. Cytokines, including tumor necrosis factor-α and interleukin-6 induce hypercortisolemia by enhancing the ACTH-independent synthesis and secretion of cortisol and by reducing cortisol breakdown. Subsequently, hypercortisolemia suppresses ACTH secretion by negative feedback inhibition. ACTH-cortisol dissociation in patients with systemic inflammatory diseases has not been reported. Here, we examined whether ACTH-cortisol dissociation is recognized in patients with Kawasaki disease (KD) associated with hypercytokinemia, as well as the possible cytokine involvement in ACTH-cortisol dissociation, retrospectively. The levels of serum cortisol, plasma ACTH, and cytokine-induced proteins, i.e., plasma C-reactive protein (CRP), serum ferritin, and urinary β2-microglobulin (U-β2MG), in 232 patients with KD were measured at diagnosis. Quartile groups based on cytokineinduced protein levels were formed (Q1, Q2, Q3, and Q4). We found a low median plasma ACTH [median (range): 8.9 (<2.0-332.0) pg/mL] but a high median serum cortisol level [median (range): 25.8 (1.4-99.8) μg/dL] in the entire study population. The median serum cortisol levels were significantly higher in the CRP-Q4, ferritin-Q4, and U-β2MG-Q4 groups than in the CRP-Q1, ferritin-Q2, and U-β2MG-Q1 groups, respectively (p < 0.01; p < 0.01; p < 0.001). The median plasma ACTH levels were significantly lower in the CRP-Q4 and ferritin-Q4 groups than in the CRP-Q1 and ferritin-Q1 groups, respectively (p < 0.001; p < 0.001). ACTH-cortisol dissociation was identified in patients with KD. Our findings suggest that inflammatory cytokines are involved in ACTH-independent hypercortisolemia in patients with KD. ACTH-cortisol dissociation in other systemic inflammatory diseases needs further investigation.

Single-Cell Analysis Reveals the Role of the Neuropeptide Receptor FPR2 in Monocytes in Kawasaki Disease: A Bioinformatic Study

“…Neuropeptides play an important role in the regulation of neuroendocrine processes and modulate many pathophysiological processes [ 11 , 12 ], including in cell-cell interactions [ 13 , 14 ]. The levels of various neuropeptides change during the course of KD [ 15 , 16 ]. Therefore, we speculated that neuropeptides may mediate monocyte interactions in KD.…”