Cortisol Excess May Predict Poor Outcomes in Adrenal Cancer

TOPLINE Higher urinary free cortisol (UFC) levels at diagnosis were associated with an increased risk for tumor recurrence or progression in patients with Cushing syndrome (CS) secondary to adrenocortical carcinoma (ACC), according to a multicenter international cohort study of 101 patients. Both tumor size and UFC levels independently predicted metastatic disease at diagnosis. METHODOLOGY - ACC is a rare, aggressive cancer, with cortisol excess as its most common endocrine manifestation. Higher cortisol levels may contribute to worse outcomes, but data on the prognostic impact of the degree of hypercortisolism remained limited. - Researchers conducted a retrospective cohort study to assess whether more severe hypercortisolism at diagnosis was linked to worse survival among 101 patients (median age at diagnosis, 51.1 years; 76.2% women) with overt CS due to ACC. - Patients were categorized according to the severity of hypercortisolism at the time of diagnosis, measured as UFC levels above the upper limit of normal (ULN): mild (< 2x ULN), moderate (2-5x ULN), and severe (> 5x ULN). UFC levels at diagnosis were available for 90 of the 101 patients. - The primary outcomes were progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS). DFS was assessed only in patients with European Network for the Study of Adrenal Tumors stage I-III disease who underwent complete (R0) resection (n = 34); PFS only in those with stage IV disease (n = 54). - Median follow-up from diagnosis was 18.8 months. TAKEAWAY - At diagnosis, the median UFC level was 6.4 times the ULN; 53.5% of the patients had metastatic ACC at presentation. Both UFC levels and adrenal tumor diameter independently distinguished metastatic from localized disease at diagnosis. - Median OS was 19.4 months; median DFS was 12.3 months for patients with localized disease who achieved R0 resection, and PFS was 5.6 months for patients with metastatic disease. Patients presenting with metastatic disease had markedly worse OS compared with those diagnosed at a localized stage (median, 10.38 months vs 30.0 months). - In a combined analysis of recurrence among patients with localized disease and progression among patients with metastatic disease, the risk for tumor recurrence or progression increased with hypercortisolism severity — 21% in mild, 52% in moderate, and 57% in severe CS groups (P = .035 for trend). - For this composite endpoint, multivariate analysis pointed to some independent risk factors including older age, elevated UFC, hypokalemia, and higher Ki-67 index. IN PRACTICE "These findings support the concept that hormonal activity should be considered alongside established clinicopathological factors when stratifying patients according to recurrence or progression risk," the authors wrote. SOURCE This study was led by Marta Araujo-Castro, Hospital Universitario Ramón y Cajal, Madrid, Spain. It was published online in The Journal of Clinical Endocrinology & Metabolism. LIMITATIONS The retrospective design of the study may have introduced selection bias. Hormonal data were missing for a small proportion of cases. In addition, a relatively short follow-up duration for some patients may have limited the assessment of long-term survival outcomes. DISCLOSURES The Spanish Cushing syndrome registry that contributed cases to this study is supported by the Spanish Society of Endocrinology & Nutrition, Esteve, and Recordati Rare Diseases. Some authors reported receiving consulting fees, honoraria, research grants, or being involved in clinical research with various pharmaceutical companies. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.