Annexin A1 as a diagnostic biomarker for cyclic Cushing disease.

Cyclic Cushing syndrome, a rare endocrine disorder marked by periodic fluctuations of cortisol secretion and clinical manifestations, is diagnostically challenging. This study integrates clinical and multi-omics data to advance early diagnosis. We analyzed four patients with pituitary cyclic Cushing syndrome and fifty-six patients with conventional Cushing disease. Proteomics profiling identified differentially expressed proteins; Annexin A1 expression was validated via immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay. Single-cell RNA sequencing mapped its cellular origin. Annexin A1 expression was significantly elevated in pituitary tumors and serum of patients with cyclic Cushing syndrome. Serum Annexin A1 measured during the remission phase in patients with cyclic Cushing syndrome demonstrated promising diagnostic ability, and a related diagnostic approach was proposed. Single-cell transcriptomics revealed a distinct Annexin A1-enriched tumor subpopulation, predominantly in patients with cyclic Cushing syndrome. Multi-omics and clinical integration identify Annexin A1 as a diagnostic biomarker for cyclic Cushing disease.