Absent nocturnal cortisol decline in Pheochromocytoma: A retrospective study

Pheochromocytoma is a catecholamine-producing tumor that may exhibit atypical hormonal profiles. Emerging evidence suggests an association with cortisol dysregulation in the absence of overt Cushing syndrome; however, systematic cortisol evaluation is not routinely performed. This study investigated the prevalence and clinical characteristics of absent nocturnal cortisol decline in pheochromocytoma. This retrospective study included 53 patients with histologically confirmed pheochromocytoma treated between 2011 and 2024. All eligible patients diagnosed during the study period were included. Among them, 22 had paired morning (8:00 AM) and midnight serum cortisol measurements for analysis of nocturnal cortisol decline. Adrenocorticotropic hormone (ACTH) and the 1-mg dexamethasone suppression test (DST) were assessed when available. Patients were stratified by midnight cortisol level (≥1.8 µg/dL vs < 1.8 µg/dL). Among the 22 patients, 18 (82%) had elevated midnight cortisol, indicating absent nocturnal decline (mean midnight, 5.1 µg/dL; mean morning, 13.7 µg/dL). The elevated group (n = 18) was older than the normal group (n = 4) (median, 64 vs 43 years). Metabolic comorbidities were more frequent in the elevated group, including diabetes (50% vs. 25%), dyslipidemia (61% vs. 25%), and cardiovascular disease (44% vs. 0%). DST was performed in 10 patients and showed adequate suppression in 7 of 8 patients with paired cortisol measurements, arguing against autonomous cortisol secretion. No patients had clinical features of overt Cushing syndrome. Absent nocturnal cortisol decline was common and may reflect a pseudo-Cushing state associated with catecholamine excess. These findings support further evaluation of cortisol regulation and its clinical implications.