Elliot K. Fishman M.D.
Johns Hopkins Hospital

Click here to view this module as a video lecture.

“Incidental adrenal nodules are quite common, occurring in 6% of the population in a large autopsy series and approximately 4% of all abdominal CT exams. The prevalence of incidental adrenal nodules increases with patient age, ranging from < 1% in patients in their 20’s to 7% in patients older than 70. Despite adrenal nodules being a very common finding, the vast majority of all incidentally detected adrenal nodules are benign.” 
Management of incidental adrenal masses: an update 
Daniel I. Glazer, William W. Mayo‐Smith 
Abdom Radiol (NY). 2020 Apr;45(4):892-900 https://doi.org/10.1007/s00261-019-02149-2

”Despite adrenal nodules being a very common finding, the vast majority of all incidentally detected adrenal nodules are benign. The challenge is determining which incidentally detected nodules can safely be left alone (nonhyperfunctioning mass, myelolipoma, hemorrhage, cyst) and which require further work-up to be certain that they are not clinically significant neoplasms (adrenocortical carcinoma (ACC), pheochromocytoma, or metastases).”
Management of incidental adrenal masses: an update 
Daniel I. Glazer, William W. Mayo‐Smith 
Abdom Radiol (NY). 2020 Apr;45(4):892-900 https://doi.org/10.1007/s00261-019-02149-2

“When an incidental adrenal mass is discovered at imaging, three important items to determine are a history of malignancy, presence of prior abdominal imaging, and symptoms of a hyperfunctioning mass, as this will guide subsequent management. First, if the patient has a history of malignancy, then an incidental mass has a higher chance of being a metastasis although the risk is still only 26–36%. Second, if prior imaging is available, greater than 1 year of stability is indicative of benignity. Third, if the patient presents with signs or symptoms of adrenal hyperfunction (including hypertension or Cushing’s features) this is suggestive of a biochemically active neoplasm that would require further investigation.”
Management of incidental adrenal masses: an update 
Daniel I. Glazer, William W. Mayo‐Smith 
Abdom Radiol (NY). 2020 Apr;45(4):892-900

”Adrenal protocol CT is the modality of choice for evaluating adrenal masses as it can characterize a nodule using both density measurements and contrast washout. An adrenal protocol CT consists of a dose reduced unenhanced CT followed by measurement of the attenuation of the nodule in question. If the attenuation of the adrenal mass is ≤ 10 HU (Hounsfield Units), then no further imaging is necessary. If attenuation is > 10 HU, then intravenous contrast is administered, and the patient imaged at 70 s and 15 min to calculate contrast washout. Attenuation based diagnosis of adrenal nodules relies on the presence of lipid within an adenoma which reduces mean attenuation within the entire nodule.”
Management of incidental adrenal masses: an update 
Daniel I. Glazer, William W. Mayo‐Smith 
Abdom Radiol (NY). 2020 Apr;45(4):892-900

“Using a threshold of 10 HU on unenhanced images, a diagnosis of benign lipid-rich adenoma can be made with 98% specificity. However, lipid-poor benign adrenal nodules (approximately 20% of adenomas) measure greater than 10 HU on unenhanced CT but can be confidently diagnosed using contrast washout . Masses that have an absolute washout of ≥ 60% [(enhanced HU—delayed HU)/(enhanced HU—unenhanced HU)] or relative washout of ≥ 40% [(enhanced HU—delayed HU)/enhanced HU] are lipid- poor adenomas. Masses that have absolute washout of < 60% or relative washout of < 40% remain indeterminant and require further work-up.”
Management of incidental adrenal masses: an update 
Daniel I. Glazer, William W. Mayo‐Smith 
Abdom Radiol (NY). 2020 Apr;45(4):892-900

“Chemical shift MRI has been shown to have a sensitivity of 67% and specificity of 89–100%, similar to CT. However, subgroup analysis shows that chemical shift MRI is inferior to CT at diagnosing adenomas when a nodule measures > 20 HU at unenhanced CT. For this reason, adrenal protocol CT is favored over MRI unless there are patient specific factors which render CT undesirable such as history of iodinated contrast allergy.”
Management of incidental adrenal masses: an update 
Daniel I. Glazer, William W. Mayo‐Smith 
Abdom Radiol (NY). 2020 Apr;45(4):892-900

“In addition to imaging tests which are useful in determining if a mass is benign or malignant, biochemical screening is necessary to determine if a mass is hyperfunctioning. Recommendations regarding biochemical screening are somewhat varied, but both the ACR and the American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons recommend biochemical screening of most if not all patients presenting with an incidentally discovered adrenal mass.”
Management of incidental adrenal masses: an update 
Daniel I. Glazer, William W. Mayo‐Smith 
Abdom Radiol (NY). 2020 Apr;45(4):892-900

First, a subset of pheochromocytomas may demonstrate greater than 60% washout on adrenal protocol CT and could potentially be misdiagnosed as lipid-poor adenomas. It is for this reason that bio- chemical evaluation is recommended by the American Association of Clinical Endocrinologists and the American Asso- ciation of Endocrine Surgeons even for masses with benign imaging features.

Finally, both benign and malignant adrenal lesions may show uptake at FDG- 18 PET/CT. Although most benign conditions that can mimic adrenal malignancy are typically bilateral (adrenal hyperplasia, tuberculosis), it is possible for adenomas to demonstrate mild FDG avidity although it is typically less than liver.

“ Pheochromocytomas are often considered the great mimicker of other adrenal tumors. Because of their varied clinical, imaging, and pathologic appearances, accurate diagnosis can be challenging.”
Pheochromocytoma: The Range of Appearances on Ultrasound, CT, MRI, and Functional Imaging
Leung K et al.
AJR 2013; 200:370-378

90% are sporadic and 10% are part of syndromes

• von Hippel-Lindau syndrome (10-26%)
• MEN Type II (50%)
• Neurofibromatosis Type 1 (1%)
• Pheochromocytoma-Paraganglioma Syndromes Associated with SDHB and SDHD Mutation

“In a 7-year period at a single institution, 40 patients, 70% of new cases of surgically proven pheochromocytoma, were initially detected by serendipity.”
Serendipity in the diagnosis of pheochromocytoma.
Oshmyansky AR et al
J Comput Assist Tomogr. 2013 Sep-Oct;37(5):820-3

“Approximately 5% of adrenal incidentalomas are pheochromocytomas. Although initial reports found that 11% of pheochromocytomas were found incidentally, due to the increased use of CT, more recent studies have reported an incidental adrenal pheochromocytomas rate of 44–58%. The incidental rate of discovery in those studies did not differ with the incidental rate of 58.9% (23 of 39 cases) in this study.”
Assessment of clinical and radiologic differences between small and large adrenal pheochromocytomas
Kim DW et al.
Clin Imaging. 2017 May-Jun;43:153-157. 

“ Pheochromocytomas are typically round or oval masses that range in size from 1 to 10 cm or more. CT imaging usually shows avid enhancement and washout. These tumors may be complicated by varying degrees of degeneration, hemorrhage, necrosis, fibrosis, or cystic changes. Their various imaging features have earned these tumors the nickname of an “imaging chameleon”. Pheochromocytomas may mimic adrenal adenoma, adrenal cortical carcinoma, or metastasis, and are not usually diagnosed by CT alone.”
Assessment of clinical and radiologic differences between small and large adrenal pheochromocytomas
Kim DW et al.
Clin Imaging. 2017 May-Jun;43:153-157

OBJECTIVE: To characterize large adrenal tumors (≥4 cm in diameter) and to identify features associated with malignancy.
CONCLUSION: The prevalence of malignancy in patients with adrenal tumors of 4 cm or more in diameter was 31%. Older age, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were associated with an increased risk for malignancy. Clinical context should guide management in patients with adrenal tumors of 4 cm or more in diameter.
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors.
Iñiguez-Ariza NM et al. 
Mayo Clin Proc Innov Qual Outcomes. 2017 Dec 21;2(1):30-39.

“We suggest that clinical context, hormonal assessment, and image phenotype can together determine the need for adrenalectomy in patients with adrenal tumors of at least 4 cm in diameter. Patients with large adrenal tumors should be managed by an expert multidisciplinary team that includes endocrinologists, radiologists, and adrenal surgeons.”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors.
Iñiguez-Ariza NM et al. 
Mayo Clin Proc Innov Qual Outcomes. 2017 Dec 21;2(1):30-39.

“Of 4085 patients with adrenal tumors, 705 (17%) had adrenal masses measuring 4 cm or more in diameter; of these, 373 (53%) were women, with a median age of 59 years (range, 18-91 years) and median tumor size of 5.2 cm (range, 4.0-24.4 cm). Underlying diagnoses were adrenocortical adenomas (n=216 [31%]), pheochromocytomas (n=158 [22%]), other benign adrenal tumors (n=116 [16%]), adrenocortical carcinomas (n=88 [13%]), and other malignant tumors (n=127 [18%]).”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors.
Iñiguez-Ariza NM et al. 
Mayo Clin Proc Innov Qual Outcomes. 2017 Dec 21;2(1):30-39.

“Compared with benign tumors, malignant tumors were less frequently diagnosed incidentally (45.5% vs 86.7%), were larger (7 cm [range, 4-24.4 cm] vs 5 cm [range, 4-20 cm]), and had higher unenhanced computed tomographic (CT) attenuation (34.5 Hounsfield units [HU] [range, 14.1-75.5 HU] vs 11.5 HU [range, -110 to 71.3 HU]; P<.001).”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors.
Iñiguez-Ariza NM et al. 
Mayo Clin Proc Innov Qual Outcomes. 2017 Dec 21;2(1):30-39.

“On multivariate analysis, older age at diagnosis, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were all found to be statistically significant predictors of malignancy.”
Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors.
Iñiguez-Ariza NM et al. 
Mayo Clin Proc Innov Qual Outcomes. 2017 Dec 21;2(1):30-39.

OBJECTIVE. The purpose of this study is to determine the differences in growth rate of adrenal adenomas and malignant adrenal nodules. RESULTS. A growth rate of 3 mm/year distinguished adenomas from malignant nodules with a sensitivity of 100% (95% CI, 86.8–100%) and a specificity of 100% (95% CI, 96.6–100%). 
CONCLUSION. Approximately one-third of radiologically proven adrenal adenomas grew, all of which grew at a rate less than 3 mm/year. All malignant adrenal nodules grew, and all at a rate greater than 5 mm/year.
Differences in Growth Rate on CT of Adrenal Adenomas and Malignant Adrenal Nodules 
Corwin MT et al.
AJR 2019; 213:1–5

“Growth or stability over time are important factors in distinguishing benign from malignant adrenal nodules with indeterminate imaging features. However, a spe- cific growth rate to reliably distinguish between the two has not been established, to our knowledge. This is because benign nodules can grow. The results of our study show that approximately one-third of radiologically proven adrenal adenomas grow over time, and all adenomas that grew did so at a rate less than 3 mm/year, whereas all malignant adrenal nodules grew faster than 5 mm/year.”
Differences in Growth Rate on CT of Adrenal Adenomas and Malignant Adrenal Nodules 
Corwin MT et al.
AJR 2019; 213:1–5

”In conclusion, approximately one-third of radiologically proven adrenal adenomas in our retrospective single-institution study grew over time, at a rate of 3 mm/year or less, whereas malignant adrenal nodules grew at a faster rate, greater than 5 mm/year. If confirmed by larger multiinstitutional studies, a growth rate of 3 mm/year may be a useful threshold to distinguish benign from malignant adrenal nodules.”
Differences in Growth Rate on CT of Adrenal Adenomas and Malignant Adrenal Nodules 
Corwin MT et al.
AJR 2019; 213:1–5

“ For indeterminate adrenal masses identified at dual-phase IV contrast-enhanced CT, higher enhancement during the arterial phase, arterial phase enhancement levels greater than 110HU, and lesion heterogeneity should prompt consideration of pheochromocytoma.”
MDCT of Adrenal Masses: Can Dual-Phase Enhancement Patterns Be Used to Differentiate Adenoma and Pheochromocytoma?
Northcutt BG, Raman SP, Long C, Oshmyansky AR, Siegelman SS, Fishman EK, Johnson PT
AJR 2013; 201:834-839

“In a 7-year period at a single institution, 40 patients, 70% of new cases of surgically proven pheochromocytoma, were initially detected by serendipity.”
Serendipity in the diagnosis of pheochromocytoma.
Oshmyansky AR et al
J Comput Assist Tomogr. 2013 Sep-Oct;37(5):820-3