Unexpected discrepancies between steroid intra-tissular content in adrenal tumors and clinical diagnosis of steroid excess

OBJECTIVE: Adrenocortical tumor (ACT) morbidity is associated with steroid secretion, depending on tumor type. Indeed, adrenal steroidogenesis is a finely regulated process, altered in ACT. These alterations are usually characterized by blood steroid assays, also depending on steroid gonadal production and metabolism. Our aim was to determine steroid content directly in ACT tissues and to compare it with clinical diagnosis of steroid excess. METHODS: A profile of 13 steroids was analyzed in ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (Thermo Fisher Scientific®) in frozen tissue samples from 75 ACT, 7 Cushing's disease, and 9 normal adrenals. RESULTS: Steroid levels were 10-1000 times higher in tissue from normal adrenal than normal concentrations expected in blood. Concentration ratios between tissue from normal adrenal and blood reference values were lower for distal products than for steroid precursors. In adrenocortical cancers, intra-tissular steroid content was lower than in unilateral benign tumors despite clear clinical steroid excess. Unexpectedly, in overt-Cushing adenomas, intra-tissular cortisol levels were not higher and androstenedione levels were not lower than in non-functioning adenomas. Adrenal differentiation score based on transcriptome was well correlated with intra-tissular cortisol levels. CONCLUSION: Discrepancies observed between steroid levels measured in ACT tissue and clinical diagnosis of steroid excess suggest a dysregulation of steroid export depending on tumor type, opening new perspectives for diagnosis and treatment of steroid excess.