A Pilot Study on Serum Lipidomic Alterations in Patients with Adrenal Tumors

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy posing significant diagnostic challenges, particularly in distinguishing it from other adrenal tumors, such as adenoma and pheochromocytoma, due to overlapping imaging and biochemical features. Improved non-invasive tools are critically needed for earlier, more accurate classification of this rare cancer. This pilot study analyzed serum lipidomic profiles in ACC, pheochromocytoma, and adenoma patients versus healthy volunteers. The most significant alterations occurred in sphingomyelins (SM) and diacylglycerols (DG). All tumor samples showed reduced very-long odd-chain SM (e.g., SM 39:1, SM 41:1, SM 41:2) and elevated DG (e.g., DG 34:1, DG 34:2, DG 36:2). These abnormalities were most pronounced in malignant tumors: ACC and metastases (AUC = 0.933), followed by pheochromocytoma (AUC = 0.800) and adenoma (AUC = 0.711). ACC patients also exhibited specific lipid signatures with decreased alkyl/alkenyl phospholipids (e.g., PE O-38:5) and lysophosphatidylcholines (e.g., LPC 20:5, LPC 18:2) versus healthy volunteers, not observed in pheochromocytoma or adenomas. Ceramide species (e.g., Cer 42:2;O2, Cer 34:1;O2) were increased in ACC compared to the other tumor types. Incorporating lipid-to-lipid ratios (Cer/SM, Cer/DG) further improved statistical model accuracy. Compared to clinical biochemistry/oxidative stress (OS) parameters, lipidomic profiling showed superior discriminatory power in adrenal tumor diagnosis. The presented study shows the serum lipidomic profiling as a promising non-invasive method for distinguishing adrenal tumor subtypes (ACC, pheochromocytoma, and adenoma) from healthy individuals, with strong diagnostic potential for ACC.