The incidental detection of adrenal lesions has become increasingly common due to the widespread use of cross-sectional abdominal imaging modalities.

Indeterminate Adrenal Lesions

Indeterminate adrenal lesions refer to adrenal masses that do not exhibit clear imaging features allowing for definitive classification as benign or malignant. These lesions often lack the homogeneous, lipid-rich appearance (<10 HU on Non-Contrast CT) typical of benign adenomas and may demonstrate intermediate attenuation, heterogeneous enhancement, atypical imaging characteristics and a size < 1 cm. They pose a diagnostic challenge for radiologists, as some of them elude clear identification and remain uncertain in diagnosis.

Imaging Modalities and Their Role in Characterization

Computed Tomography (CT)

CT is the first-line imaging modality for evaluating adrenal lesions.

• Attenuation on NCCT: Benign lesions typically exhibit attenuation of <10 HU and may contain calcifications or macroscopic fat, like lipid-rich adenomas, whereas indeterminate lesions often have higher attenuation.
• Contrast Washout Analysis: A dedicated adrenal washout CT protocol includes a non-contrast, a contrast-enhanced scan with a delay of 60 sec and a delayed scan at 15 minutes. If an adrenal lesion is detected during an enhanced scan, a follow-up adrenal scan can be performed 15 minutes after contrast injection to determine the relative washout. Absolute washout >60% and Relative washout >40% are suggestive of adenomas, both lipid-rich and lipid-poor. False-positive washout findings can occur in hypervascular regions, adrenal hyperplasia, and pheochromocytomas. If the density exceeds 120 HU in the portal phase, further investigation is necessary to rule out pheochromocytoma, rather than assuming it to be an adenoma. Lack of washout or slower washout suggests malignancy.
  

  Fig 1: Contrast Washout Analysis: Absolute washout >60% and Relative washout >40% are suggestive of adenomas, both lipid-rich and lipid-poor.
• Calcifications and necrosis: Present in pheochromocytomas, ACC, and metastases.
• Size and growth rate: Lesions >4 cm, heterogeneous enhancement, and rapid growth raise suspicion for malignancy.

Magnetic Resonance Imaging (MRI)

MRI is useful when CT findings remain inconclusive.

• Chemical Shift Imaging (CSI): In-phase and opposed-phase sequence to detect microscopic intracellular fat. Most radiologists rely on visual assessment to determine if there is a signal drop in out-of-phase images. An alternative approach involves quantifying the change in signal intensity in the OP image and comparing it to the IP image, using the spleen as an internal reference. This method allows for the calculation of either the adrenal-to-spleen ratio (ASR) or the adrenal signal intensity index (SI-index) using the Adrenal MRI calculator. An ASR of less than 0.71 and an SI-index greater than 16.5% suggest the presence of an adrenal adenoma. Lipid-poor adenomas show no significant signal drop on OP images, whereas lipid-rich adenomas demonstrate significant signal loss. CSI is less effective than washout CT for detecting lipid-poor adenomas.
  

  Fig 2: Chemical Shift Imaging: An ASR of less than 0.71 and an SI-index greater than 16.5% suggest the presence of an adrenal adenoma.
• Fat-suppression Imaging: Detects macroscopic fat.
• T2-Weighted Imaging: To diagnose a cyst or cystic component. Pheochromocytomas appear with the classic 'light bulb' sign. ACC and metastases often appear hyperintense.
• Dynamic gadolinium-enhanced MRI: To differentiate adenomas from non-adenomas. Malignant lesions are often characterized by strong contrast enhancement.
• Diffusion-Weighted Imaging (DWI): Restricted diffusion may suggest malignancy, though overlap exists.

Positron Emission Tomography-Computed Tomography (PET-CT)

PET-CT, particularly using 18F-FDG, detects malignancy, especially in metastatic disease, as malignant tumors excibit higher glucose metabolism and elevated FDG uptake (>3.5 SUV). PET is useful in adrenal imaging, helping to detect metastases in ACC and identify the primary tumor in metastatic adrenal lesions. FDG is not specific to any adrenal tumor but is useful in distinguishing malignant from benign tumors. False-positive results can occur due to certain adenomas, pheochromocytomas, as well as inflammatory and infectious lesions.

18F-DOPA and 68Ga-DOTATATE PET

For PET-CT imaging, 18F-dihydroxyphenylalanine (DOPA) and 18F-fluorodopamine (DA) serve as 18F-labeled tracers specifically targeting pheochromocytomas. Additionally, these tumors express somatostatin receptors, allowing imaging through somatostatin analogues. The traditional somatostatin receptor scan (Octreoscan) is increasingly being replaced by PET-CT imaging using 68Ga-labeled somatostatin analogues such as DOTA-TOC, DOTA-NOC, and DOTA-TATE.

Clinical Management

Management of indeterminate adrenal lesions depends on imaging findings, lesion size, growth rate, and functional status. Current clinical guidelines, including those from the European Society of Endocrinology and the American College of Radiology, recommend a structured approach to adrenal lesion evaluation.

• Observation and Follow-Up: Recommended for lesions <4 cm with benign imaging characteristics.
  

  Fig 3: 42-year-old woman presenting with right flank pain. (A) Non-contrast-enhanced CT shows a large right adrenal cystic lesion with peripheral calcifications and attenuation values <10 HU. (B) Contrast-enhanced CT obtained 60 seconds after intravenous contrast administration reveals no enhancement of the right adrenal lesion. (C) Axial Fat-Saturation T2 and (D) T2-weighted images demonstrate a homogeneously high signal intensity within the right adrenal lesion. These findings are consistent with a benign lesion, specifically an adrenal cyst, and no further investigation is required.
• Hormonal Workup: Essential for ruling out functional tumors, including pheochromocytomas, ACCs, Cushing’s syndrome, or primary aldosteronism.
• Surgical Resection: Lesions greater than 4 cm, those demonstrating rapid growth, and those with imaging features concerning for malignancy—such as irregular margins, necrosis, or heterogeneous enhancement—warrant surgical intervention.
  

  Fig 4: 68-year-old man with left adrenal gland incidentaloma. (A) Non-contrast-enhanced CT demonstrating a 4,5 cm heterogenous left adrenal mass with an attenuation value of 33 HU. (B) Non-contrast-enhanced Ct obtained a year after the initial demonstrating an enlargement of ~3 cm regarding the diameter of the lesion. Consequently left adrenalectomy was performed. The histological report described a benign adrenal cortical neoplasm, indicating an adenoma, with diffuse hemorrhage. A 2,5 cm right adrenal gland lesion with an attenuation value <10 HU and no change regarding the size between the two exams, is also noticed, indicating an adenoma.
• Biopsy: Avoided for suspected pheochromocytomas due to the risk of catecholamine crisis. Reserved for cases where metastatic disease is suspected, and tissue confirmation is required.