Natural history of large adrenal tumors

Magdalena Macech¹Maciej Stępień¹Joanna Podgórska²Sadegh Toutounchi³Łukasz Koperski⁴Joanna Barankiewicz⁵Malgorzata Bobrowicz¹Agnieszka Kondracka¹Urszula Ambroziak^1*

• ¹Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland
• ²Second Department of Clinical Radiology, Medical University of Warsaw, Warsaw, Poland
• ³Department of General, Vascular, Endocrine and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland
• ⁴Department of Pathology, Medical University of Warsaw, Warsaw, Poland
• ⁵Laboratory of Cellular and Genetic Therapies, Center for Preclinical Research, Medical University of Warsaw, Warsaw, Poland

Objective: The aim of this study was to characterize large adrenal tumors (LATs), assess the diagnostic accuracy of imaging modalities in detecting malignant LATs, and determine whether further follow-up of seemingly benign LATs is necessary. Patients and Methods: We retrospectively analyzed the clinical, biochemical, and imaging characteristics at presentation and during follow-up in a single-center cohort of patients with adrenal tumors ≥4 cm in diameter evaluated between June 2013 and June 2023. Results: Of 1473 patients with adrenal tumors, 269 (18.3%) had lesions measuring ≥4 cm in diameter, of whom 220 were included in the study. Among LATs, 34.6% were adrenocortical adenomas, 27.3% other benign adrenal tumors, 17.3% adrenocortical carcinomas, 11.4% other malignant tumors, and 9.6% pheochromocytomas. Overall, 44.7% of tumors were non-functioning, while 37.8% secreted corticosteroids. Sensitivity of unenhanced computed tomography attenuation values in detecting malignancy was 100% using the threshold >10 Hounsfield units (HU) and 89.5% for >20 HU (with specificity 66.1% and 81.4% respectively). Magnetic resonance with chemical shift analysis demonstrated high sensitivity (94.4%), but low specificity (56.8%). 18F-fluorodeoxyglucose-positron emission tomography integrated with computed tomography showed 100% sensitivity using adrenal liver ratio >1, when the maximum standardized uptake value >5 cutoff was applied, sensitivity remained 100%, while specificity improved (100% vs 82.1%). Eighty-seven tumors were managed with follow-up, with a mean duration of 30.1 months. Significant tumor growth occurred in four cases (4.6%): three myelolipomas and one indeterminate lesion in a patient with extra-adrenal malignancy. Adrenalectomy was performed in six patients (6.9%). Although these tumors were initially classified as adrenocortical adenomas, histopathology revealed benign lesions in five cases and adrenocortical carcinoma in one. The risk of developing mild autonomous cortisol secretion among non-functioning tumors was 6.7%. No progression to overt Cushing's syndrome was observed. Conclusion: Although the risk of malignancy increases with tumor size, most large adrenal tumors are benign. Imaging modalities demonstrate high sensitivity for detecting malignancy in LATs. No malignancies were identified in homogeneous lesions with attenuation <10 HU. LATs that do not meet these benign imaging criteria should undergo multidisciplinary evaluation and continued follow-up.