Two Suspects, One Culprit: Dexamethasone-Suppressed Adrenal Venous Sampling in Mild Autonomous Cortisol Secretion (#438)
Background
Management of mild autonomous cortisol secretion (MACS) in patients with bilateral adrenal adenomas remains challenging because no validated imaging modality can reliably localise cortisol secretion. While computed tomography defines adrenal anatomy, it cannot distinguish unilateral cortisol-producing adenoma from bilateral disease, including bilateral cortisol-producing adenomas, primary bilateral macronodular adrenal hyperplasia (PBMAH) and primary pigmented nodular adrenocortical disease (PPNAD). Although NP-59 scintigraphy was historically used for functional adrenal imaging, it is no longer routinely available, leaving an important diagnostic gap. Dexamethasone-suppressed adrenal venous sampling (AVS) has recently emerged as a promising technique for functional localisation.
Case
A 73-year-old woman was referred following incidental detection of bilateral lipid-rich adrenal adenomas (39 mm left; 8 mm right). She had biochemically confirmed MACS, with three elevated 24-hour urinary free cortisol collections, two abnormal 1-mg overnight dexamethasone suppression tests (post-DST cortisol 141–235 nmol/L), suppressed ACTH (<5 ng/L) and low DHEAS, but no classical Cushingoid features. As she wished to pursue surgery, determining whether cortisol excess was unilateral or bilateral became critical. The differential diagnosis included unilateral cortisol-producing adenoma with a contralateral incidentaloma, bilateral cortisol-producing adenomas, PBMAH and PPNAD. Dexamethasone-suppressed AVS demonstrated successful bilateral adrenal vein cannulation, marked left-sided cortisol predominance (cortisol-to-metanephrine lateralisation ratio 6.5), and contralateral suppression, consistent with unilateral cortisol hypersecretion. She subsequently proceeded to left adrenalectomy.
Conclusion
This case highlights an important unmet need in the management of MACS: there is currently no clinically available imaging modality capable of functionally localising cortisol secretion. Bilateral adrenal nodules do not necessarily indicate bilateral cortisol production, and anatomical imaging alone cannot guide operative management. Dexamethasone-suppressed AVS resolved the diagnostic uncertainty, differentiated unilateral from bilateral disease, and enabled targeted adrenalectomy. As evidence evolves, cortisol AVS may become an important adjunct in selected patients with MACS and bilateral adrenal lesions.
- Fassnacht M, Tsagarakis S, Terzolo M, et al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023;189(1):G1-G42. doi:10.1093/ejendo/lvad045
- Prete A, Bancos I. Mild autonomous cortisol secretion: pathophysiology, diagnosis and management. Nat Rev Endocrinol. 2024;20(2):97-112. doi:10.1038/s41574-023-00930-1
- Deutschbein T, Reimondo G, Di Dalmazi G, et al. Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: results of the NAPACA Outcome Study. Lancet Diabetes Endocrinol. 2022;10(7):499-508. doi:10.1016/S2213-8587(22)00109-6
- Kjellbom A, Lindgren O, Puvaneswaralingam S, et al. Association between mortality and degree of autonomous cortisol secretion in adrenal incidentalomas. Ann Intern Med. 2021;174(8):1041-1049. doi:10.7326/M20-7578
- Young WF Jr, du Plessis H, Thompson GB, et al. The clinical conundrum of corticotropin-independent autonomous cortisol secretion in patients with bilateral adrenal masses. World J Surg. 2008;32(5):856-862. doi:10.1007/s00268-007-9457-4
- Ueland GÅ, Methlie P, Kellmann R, et al. Adrenal venous sampling for assessment of autonomous cortisol secretion. J Clin Endocrinol Metab. 2018;103(12):4553-4560. doi:10.1210/jc.2018-00970
- Johnson PC, Bancos I, Young WF Jr, et al. Adrenal venous sampling in patients with ACTH-independent autonomous cortisol secretion and bilateral adrenal masses. Clin Endocrinol (Oxf). 2023;98(2):177-189. doi:10.1111/cen.14860
- Bouys L, Gaujoux S, Bertherat J, et al. Primary bilateral macronodular adrenal hyperplasia: recent insights into pathophysiology, genetics, and management. Endocrine. 2021;71(3):595-603. doi:10.1007/s12020-020-02579-9
- Tang P, Li X, Chen Y, et al. Clinical characteristics and management of primary bilateral macronodular adrenal hyperplasia: a contemporary review. BMC Endocr Disord. 2023;23(1):77. doi:10.1186/s12902-023-01327-8
- Chan SL, Chatterjea R, Cheah WK, Oh HB. Functional imaging and adrenal venous sampling in ACTH-independent Cushing syndrome: current evidence and future directions. JCEM Case Rep. 2025;3(10):luaf192. doi:10.1210/jcemcr/luaf192