Imaging Pearls ❯ Adrenal ❯ Pheochromocytoma
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- “Multiple prior studies have shown that between 17% and 67% of pheochromocytomas demonstrate an absolute washout of greater than or equal to 60% and a relative washout of greater than or equal to 40%. A nonenhanced CT attenuation of less than or equal to 10 HU in the solid portion of the tumor is highly specific for adenoma, rarely occurring in pheochromocytoma. In addition, pheochromocytoma is characteristically hypervascular, manifesting as hyperenhancement during the portal venous phase.”
Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards
Ryan Chung et al.
RadioGraphics 2023; 43(7):e220191 July 2023 - “In the absence of the above imaging features, long-term (≥12 months) stability of a solid adrenal mass or slow growth (≤3 mm/year) is most suggestive of a benign tumor, most commonly adenoma. The diagnosis of an adrenal adenoma can be challenging when typical imaging features are absent, and stability cannot be established. Atypical imaging features of adenomas include lipid-poor adenoma, macroscopic fat, hemorrhage, iron, heterogeneity, large size, and growth.”
Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards
Ryan Chung et al.
RadioGraphics 2023; 43(7):e220191 July 2023 - “Identifying enhancing soft tissue can be challenging in the acute setting. Furthermore, rapid or marked enlargement of an adrenal mass due to hemorrhage can be difficult to distinguish from growth of a malignant mass. There are no established guidelines for follow-up to assess for an underlying mass after resolution of hemorrhage; however, follow-up imaging is often warranted, and 6–12 weeks after resolution of the hemorrhage is reasonable. Of note, mild elevation of plasma normetanephrine levels can occur secondary to hemorrhage and irritation of medullary cells.”
Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards
Ryan Chung et al.
RadioGraphics 2023; 43(7):e220191 July 2023 - Pheochromocytoma Pearl
Perform biochemical evaluation for adrenal mass <4 cm with cystic and/or necrotic change and hyperenhancement, even if absolute washout is ≥ 60%, because these features are common in pheochromocytoma; look for a thickened rind of enhancing soft tissue to distinguish cyst from cystic and/or necrotic change
- “Pheochromocytoma is a neuroendocrine tumor arising in the adrenal medulla with varied imaging appearances and associated risk of serious cardiovascular complications if left undiagnosed and untreated. It is discovered incidentally in up to 70% of cases due to the increase in use of CT in clinical practice. Biopsy can have life-threatening consequences, so imaging is crucial for diagnosis and surgical planning. The purpose of this review is to demonstrate unusual CT appearances of pheochromocytoma and enhance diagnostic confidence in cases discovered incidentally. High level of suspicion for pheochromocytoma based on CT findings, along with urinary metanephrine levels, can obviate the need for additional expensive imaging.”
The good, the bad, and the ugly: uncommon CT appearances of pheochromocytoma
Renu Berry· Kiran Busireddy · Linda C. Chu · Pamela T. Johnson · Elliot K. Fishman
Abdominal Radiology (2022) 47:1406–1413 
The good, the bad, and the ugly: uncommon CT appearances of pheochromocytoma
Renu Berry· Kiran Busireddy · Linda C. Chu · Pamela T. Johnson · Elliot K. Fishman
Abdominal Radiology (2022) 47:1406–1413- “As pheochromocytomas enlarge, the masses tend to undergo ischemia and necrosis, which accounts for central degeneration and fibrosis, reflected as heterogeneous enhancement on CT. Predominantly cystic pheochromocytoma is rare but is the result of the same pathophysiology of hemorrhagic degeneration and/ or necrosis. The “ring sign,” defined as a hyperenhancing rim, is fairly characteristic of a cystic pheochromocytoma and was observed in more than 40% of cases in one series. A cystic pheochromocytoma can be distinguished from other cystic adrenal masses (pseudocysts, lymphangiomas) due to variable degrees of complexity, such as a thick enhancing wall. In contradistinction, adrenal pseudocysts resulting from prior hemorrhage demonstrate a thin uniform wall that can be calcified. Pheochromocytoma may also present as a multiloculated cystic mass with septations.”
The good, the bad, and the ugly: uncommon CT appearances of pheochromocytoma
Renu Berry· Kiran Busireddy · Linda C. Chu · Pamela T. Johnson · Elliot K. Fishman
Abdominal Radiology (2022) 47:1406–1413 - “Paragangliomas that originate from the chromaffin tissue of the sympathetic nervous system are termed pheochromocytomas (PCCs). Urinary bladder PCCs are rare tumors that account for only 0.06% of all bladder tumors and 1% of all PCCs. Bladder PCCs were first reported in 1953 by Zimmerman et al., and since 2015, about 270 bladder PCCs have been reported worldwide. These tumors typically occur in the second to fifth decades of life with a preponderance toward females. Although most bladder PCCs are sporadic, they can be familial or occur as parts of syndromes such as neurofibromatosis type I and von Hippel-Lindau syndrome. These tumors are usually functional, meaning they secrete excess catecholamines that lead to clinical manifestations, including paroxysmal hypertension, headaches, palpitations, and sweating.”
Magnetic resonance imaging of bladder pheochromocytomas: a review
Yanni Zulia et al.
Abdominal Radiology (2022) 47:4032–4041 - “Bladder PCCs can be functional or nonfunctional, depending on whether catecholamines are oversecreted. Most bladder PCCs (83%) are functional, which means they secrete excess catecholamines that lead to adverse effects, including persistent or paroxysmal hypertension, headaches, palpitations, syncope and sweating. These symptoms often occur during micturition, which leads to increased bladder pressure and contraction, triggering catecholamine release (“micturition attacks”). Other symptoms include gross hematuria or obstructive symptoms such as frequency, urgency, and dysuria. In the case of nonfunctional bladder PCCs, gross hematuria and obstructive issues are often the only symptoms present .”
Magnetic resonance imaging of bladder pheochromocytomas: a review
Yanni Zulia et al.
Abdominal Radiology (2022) 47:4032–4041 - “While the exact mechanism of bleeding and rupture in a pheochromocytoma is unknown, it is believed to be associated with an increase in intracapsular pressure, due to various factors, such as trauma. Additional causes include rapid tumor growth, which can result in the tumor outgrowing its blood supply, leading to central necrosis and hemorrhage. In addition, systemic hypertension due to the elevated catecholamines secreted by the tumor leads to vasoconstriction in the central vessels of the tumor, resulting in necrosis.”
The good, the bad, and the ugly: uncommon CT appearances of pheochromocytoma
Renu Berry· Kiran Busireddy · Linda C. Chu · Pamela T. Johnson · Elliot K. Fishman
Abdominal Radiology (2022) 47:1406–1413
- “Pheochromocytomas and Paragangliomas (PCC/PGL) are rare endocrine tumors that are mostly benign, but often hormone producing, causing significant morbidity and mortality due to excess catecholamine secretion and cardiovascular crises. It is estimated that 30% of PCC/PGL are due to germline mutations, including Neurofibromatosis type 1 (NF1).”
Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening.
Petr, E.J., Else, T.
Clin Diabetes Endocrinol 4, 15 (2018). - "Catecholamine excess and resultant cardiovascular crises. A significant percentage (~ 30%) of those affected with PCC/PGL tumors harbor a germline mutation that predisposes them both to the development of PCC/PGL and also to other tumors unique to each particular inherited syndrome [1–5]. The most common known hereditary tumor syndromes that increase risk for PCC/PGL are Hereditary Paraganglioma Syndrome (SDHx), Neurofibromatosis Type 1 (NF1), von Hippel Lindau disease (VHL), Multiple Endocrine Neoplasia type 2 (MEN2, RET), TMEM127- and MAX-related hereditary pheochromocytoma, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC, FH) [6–8]. For MEN2 and VHL, there are recommendations to screen for PCC/PGL in mutation carriers (ie. annual metanephrine levels in MEN2 and annual metanephrine levels and review of adrenal glands on abdominal imaging in VHL)
Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening.
Petr, E.J., Else, T.
Clin Diabetes Endocrinol 4, 15 (2018). - “The most common known hereditary tumor syndromes that increase risk for PCC/PGL are Hereditary Paraganglioma Syndrome (SDHx), Neurofibromatosis Type 1 (NF1), von Hippel Lindau disease (VHL), Multiple Endocrine Neoplasia type 2 (MEN2, RET), TMEM127- and MAX-related hereditary pheochromocytoma, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC, FH) [6–8]. For MEN2 and VHL, there are recommendations to screen for PCC/PGL in mutation carriers (ie. annual metanephrine levels in MEN2 and annual metanephrine levels and review of adrenal glands on abdominal imaging in VHL.”
Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening.
Petr, E.J., Else, T.
Clin Diabetes Endocrinol 4, 15 (2018). - “Since almost all NF1-associated PCC/PGL appear to be biochemically active, screening with plasma or urine free fractionated metanephrine levels in the setting of a high pre-test probability should capture most cases. Most PCC/PGL were located in the adrenal gland, were amenable to complete surgical resection, and did not recur or progress to metastatic disease.”
Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening.
Petr, E.J., Else, T.
Clin Diabetes Endocrinol 4, 15 (2018).
- “Pheochromocytoma is a rare neuroendocrine tumor arising in the adrenal medulla, which accounts for elevated blood pressure in a small minority of adults with hypertension and is benign in 90% of cases. Nonethe- less, identification is important because uncontrolled catecholamine secretion increases the risk of serious cardiovascular complications. Approximately 11–21% of patients are asymptomatic, while others may present with symptoms mistaken for underlying cardiovascular conditions (e.g., palpitations) .”
The good, the bad, and the ugly: uncommon CT appearances of pheochromocytoma
Renu Berry · Kiran Busireddy · Linda C. Chu · Pamela T. Johnson· Elliot K. Fishman
Abdominal Radiology https://doi.org/10.1007/s00261-022-03447-y - "The classic pheochromocytoma is a round or oval, hypervascular, heterogeneously enhancing mass. The early intense enhancement is reportedly due to its capillary-rich framework. Vascular pheochromocytomas can exceed washout thresholds on adrenal protocol CT and be mistaken for a lipid-poor adenoma. Accordingly, adrenal protocol CT washout is not reliable for distinguishing these two pathologies. If the venous enhancement level exceeds 130 HU, the lesion is more likely a pheochromocytoma. If the adrenal mass is detected incidentally on arterial phase CT, arterial phase attenuation of 110 HU or higher is not typical of adenoma but is characteristic of pheochromocytoma. Arterial phase enhancement of > 110 HU was 58% sensitive and 100% specific for pheochromocytomas in one study.”
The good, the bad, and the ugly: uncommon CT appearances of pheochromocytoma
Renu Berry · Kiran Busireddy · Linda C. Chu · Pamela T. Johnson· Elliot K. Fishman
Abdominal Radiology (2022) https://doi.org/10.1007/s00261-022-03447-y - "Pheochromocytomas have the highest heritability among all endocrine tumors, with nearly 35–40% being hereditary in origin. The occurrence of bilateral pheochromocytomas is 10% in sporadic cases, 50–80% in multiple endocrine neoplasia type II (MEN2), and 40–80% in Von Hippel–Lindau (VHL). In patients with bilateral pheochromocytoma, a syndromic cause should be considered, most common being MEN2A or MEN2B, neurofibromatosis type 1 (NF-1), and hereditary pheochromocytoma paraganglioma (HPP) syndrome.”
The good, the bad, and the ugly: uncommon CT appearances of pheochromocytoma
Renu Berry · Kiran Busireddy · Linda C. Chu · Pamela T. Johnson· Elliot K. Fishman
Abdominal Radiology (2022) https://doi.org/10.1007/s00261-022-03447-y - "Bleeding and rupture of a pheochromocytoma is rare, with approximately 50 reported cases between 1950 and 2000. While the exact mechanism of bleeding and rupture in a pheochromocytoma is unknown, it is believed to be associated with an increase in intracapsular pressure, due to various factors, such as trauma. Additional causes include rapid tumor growth, which can result in the tumor outgrowing its blood supply, leading to central necrosis and hemorrhage.”
The good, the bad, and the ugly: uncommon CT appearances of pheochromocytoma
Renu Berry · Kiran Busireddy · Linda C. Chu · Pamela T. Johnson· Elliot K. Fishman
Abdominal Radiology (2022) https://doi.org/10.1007/s00261-022-03447-y
- “Pheochromocytomas are neoplasms of the chromaffin cells of the adrenal medulla in 80%–90% of cases. Ectopic/extra-adrenal pheochromocytomas that arise from sympathetic and para-aortic sympathetic ganglia are called paragangliomas. Pheochromocytomas and paragangliomas occur in 0.05%–0.1% of hypertensive patients, and their combined annual incidence in the United States is estimated to be between 500 and 1,600 cases. Approximately 10%–15% of pheochromocytomas and paragangliomas are malignant, but it could be up to 40%. Pheochromocytomas release catecholamines (epinephrine and norepinephrine) and their metabolites metanephrine and normetanephrine, resulting in hypertension, arrhythmia, and/or hyperglycemia. About 40% of paragangliomas secrete catecholamines. Head and neck paragangliomas only secrete catecholamines about 5% of the time and often it is dopamine.”
Neuroendocrine and Adrenal Tumors, Version 2.2021
Manisha H. Shah et al.
J Natl Compr Canc Netw 2021;19(7):839–868 - "The peak incidence of occurrence for pheochromocytomas is between the third and fifth decades of life, but they generally occur at a younger age and are more likely to be bilateral in patients with familial disease. Paragangliomas are more likely to be malignant than pheochromocytomas in the adrenal medulla (about 40% vs 10%). Pheochromocytomas and paragangliomas associated with a familial syndrome tend to be more aggressive and more likely to metastasize than sporadic tumors. In fact, a study showed that 87.5% of patients presenting with these tumors prior to age 20 harbored a germline mutation in one of several genes tested if they also had metastatic disease. For those without metastases, the rate of identification of these mutations was still high, at 64.7%.”
Neuroendocrine and Adrenal Tumors, Version 2.2021
Manisha H. Shah et al.
J Natl Compr Canc Netw 2021;19(7):839–868
- Bilateral Adrenal Masses: Pheochromocytoma
- Approximately 10% of pheochromocytomas are extra-adrenal, bilateral, multifocal, malignant, found in children, or associated with a hereditary or familial syndrome. Pediatric pheochromocytomas account for 10% of all pheochromocytomas; these are characterized by a slight male predominance and are less likely malignant than adult tumors. Approximately 30% of pediatric pheochromocytomas are bilateral, extra-adrenal, multiple, or familial. - Pheochromocytoma: Familial Data
- Approximately 10% of pheochromocytomas are familial, associated with neuroectodermal disorders (von Hippel-Lindau disease, von Recklinghausen's disease, tuberous sclerosis, Sturge-Weber syndrome or Carney's syndrome) or as a part of hereditary multiple endocrine neoplasia (MEN) 2A and 2B. - Pheochromocytoma: Familial Data
- In MEN-2, bilateral adrenal medullary hyperplesia (diffuse or nodular) is almost always present and precedes pheochromocytoma, which develops in 30–50% of patients. Pheochromocytomas are usually multicentric and bilateral in up to 50–80% of cases with long term follow-up. They are rarely extra-adrenal or malignant. - Pheochromocytoma: Familial Data
- Pheochromocytomas associated with neuroectodermal disorders are most common in von Hippel-Lindau disease, occurring in approximately 25% of patients. They are often bilateral and rarely extra-adrenal except in Carney's syndrome, which is associated with functioning extra-adrenal paraganglioma. All patients with “sporadic” pheochromocytoma should be screened for MEN-2 and van Hippel-Lindau disease. - “Cystic appearance was present in 12/22 (55%, 95% CI 32-76%) pheochromocytomas (mean size 5.3 cm), 15/34 (44%, 95% CI 27-62%) malignant masses (mean size 5.8 cm), and 2/36 (5.6%, 95% CI 0.7-9%) adenomas (mean size 3.2 cm). Sensitivity and specificity of cystic appearance for distinguishing pheochromocytoma or malignant masses from adenomas were 48.2% (95% CI 34.7-62.0%) and 94.4% (95% CI 81.3-99.3%), respectively. Cystic appearance was a significant predictor of tumor type (p = 0.015) even after controlling for tumor size. Reader agreement for cystic appearance was almost perfect with a kappa of 0.85.”
Accuracy of focal cystic appearance within adrenal nodules on contrast-enhanced CT to distinguish pheochromocytoma and malignant adrenal tumors from adenomas.
Corwin MT et al.
Abdom Radiol (NY). 2021 Jan 8. doi: 10.1007/s00261-020-02925-5. - “An indeterminate adrenal lesion that enhances greater than 130 HU on multidetector CT cannot be assumed to be an adenoma. Hypervascular pheochromocytoma (>130 HU) mimics adenoma washout pattern; absolute venous phase enhancement level must be considered.”
Adrenal Adenoma and Pheochromocytoma: Comparison of Multidetector CT Venous Enhancement Levels and Washout Characteristics.
Northcutt BG, Trakhtenbroit MA, Gomez EN, Fishman EK, Johnson PT.
J Comput Assist Tomogr. 2016 Mar-Apr;40(2):194-200. - Objective: To evaluate the proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT and the diagnostic performance of adrenal washout CT for differentiating adenoma from pheochromocytoma.
Conclusions: There was a non-negligible proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT. Although overall diagnostic performance was excellent for differentiating adenoma from pheochromocytoma, specificity was relatively low.
Pheochromocytoma as a frequent false-positive in adrenal washout CT: A systematic review and meta-analysis.
Woo S, Suh CH, Kim SY, Cho JY, Kim SH.
Eur Radiol. 2018 Mar;28(3):1027-1036. - Key points:
• Non-negligible proportion of pheochromocytomas can be mistaken for adenoma.
• Adrenal washout CT showed good sensitivity (97%) but relatively low specificity (67%).
• Findings other than washout percentage should be used when diagnosing pheochromocytomas.
Pheochromocytoma as a frequent false-positive in adrenal washout CT: A systematic review and meta-analysis.
Woo S, Suh CH, Kim SY, Cho JY, Kim SH.
Eur Radiol. 2018 Mar;28(3):1027-1036. - “The majority of LATs were still benign, but they had a higher probability to be malignant. Benign LATs made up 68.13% of all cases, mainly adrenal cysts (19.52%), pheochromocytoma (18.73%), benign adenoma (16.73%), and myelolipoma (7.17%). Malignant LATs accounted for 28.69% of cases, mainly including adrenocortical carcinoma (8.76%) and metastases (17.13%). Laparoscopic surgery was found to involve less trauma than open surgery. It was also safer and postoperative recovery was faster, but it had drawbacks and could not completely replace open surgery. CT features had obvious specificity for the diagnosis of benign and malignant tumors.”
Clinical analysis of adrenal lesions larger than 5 cm in diameter (an analysis of 251 cases).
Zhang Z et al.
World J Surg Oncol. 2019 Dec 16;17(1):220. - "CT features had obvious specificity for the diagnosis of benign and malignant tumors. For example, benign adenomas had a smaller pre-contrast (< 10 Hu) whereas malignant adrenal tumors had, on the contrary, higher attenuation. Regarding adrenal malignant carcinoma, adrenal primary malignant tumors showed a better prognosis than adrenal metastases (mean survival of 19.17 months vs 9.49 months). Primary adrenal cortical carcinoma without metastasis had a better prognosis than primary adrenal cortical carcinoma metastasis (mean survival of 23.71 months vs 12.75 months), and adrenal solitary metastasis had a better prognosis than general multiple metastatic carcinoma (mean survival of 14.95 months vs 5.17 months).”
Clinical analysis of adrenal lesions larger than 5 cm in diameter (an analysis of 251 cases).
Zhang Z et al.
World J Surg Oncol. 2019 Dec 16;17(1):220. - “Although in general PCC/PGL are rare tumors, NF1 is a common condition (prevalence of 1:3000 live births), and an estimated 5–7% of patients with NF1 will develop PCC/PGL in their lifetime. NF1 has a high rate of de novo mutations (~ 50%), is inherited in autosomal dominant fashion, and has a variable clinical presentation. The diagnosis of NF1 is made clinically in those who meet at least two of the following criteria: 6 or more café-au-lait macules, axillary or inguinal freckling, 2 or more neurofibromas or 1 plexiform neurofibroma, 2 or more Lisch nodules, an optic glioma, sphenoid or tibial bone dysplasia, or a first-degree relative with NF1.”
Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening.
Petr, E.J., Else, T.
Clin Diabetes Endocrinol 4, 15 (2018). - "Pheochromocytomas (PCC) and Paragangliomas (PGL) are rare endocrine tumors, occurring with an incidence of 0.8 per 100,000. Most of these tumors are benign, rather than malignant, however they can cause significant morbidity and mortality via catecholamine excess and resultant cardiovascular crises. A significant percentage (~ 30%) of those affected with PCC/PGL tumors harbor a germline mutation that predisposes them both to the development of PCC/PGL and also to other tumors unique to each particular inherited syndrome.”
Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening.
Petr, E.J., Else, T.
Clin Diabetes Endocrinol 4, 15 (2018). - “The most common known hereditary tumor syndromes that increase risk for PCC/PGL are Hereditary Paraganglioma Syndrome (SDHx), Neurofibromatosis Type 1 (NF1), von Hippel Lindau disease (VHL), Multiple Endocrine Neoplasia type 2 (MEN2, RET), TMEM127- and MAX-related hereditary pheochromocytoma, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC, FH).”
Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening.
Petr, E.J., Else, T.
Clin Diabetes Endocrinol 4, 15 (2018). - “In summary, NF1-associated PCC/PGL presented at a similar age as reported for sporadic cases of PCC/PGL. The majority of NF1-associated PCC/PGL were benign unilateral adrenal tumors, which were biochemically active and positive on MIBG scans. Most patients had hypertension or tachycardia or both at the time of diagnosis. Although almost half of the PCC/PGL in this cohort (n = 8) were discovered incidentally on imaging, upon further investigation three of these patients had suggestive symptoms of PCC/PGL (tachycardia, palpitations, HTN urgency) and one had a preexisting adrenal nodule that had not been evaluated.”
Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening.
Petr, E.J., Else, T.
Clin Diabetes Endocrinol 4, 15 (2018). - “In summary, undiagnosed NF1-associated PCC/PGL poses a dangerous risk to patients, including cardiovascular crises such as labile intra-operative blood pressures, pregnancy and delivery complications, and severe complications including MI and cardiac arrest. Most NF1-associated PCC/PGL are detectable by biochemical evaluation. Therefore, we suggest consideration of screening adults with NF1 for PCC/PGL with plasma or urine free fractionated metanephrines every 1–2 years starting at age 18, especially in any NF1 patient with hypertension or tachycardia, and most importantly prior to any surgical procedures and pregnancy or delivery as these are times of increased risk for cardiovascular crisis. This approach has the potential to reduce the PCC/PGL-associated morbidity and mortality in the population of patients with NF1.”
Pheochromocytoma and Paraganglioma in Neurofibromatosis type 1: frequent surgeries and cardiovascular crises indicate the need for screening.
Petr, E.J., Else, T.
Clin Diabetes Endocrinol 4, 15 (2018).
- Purpose: To investigate the performance of modified criteria to distinguish pheochromocytoma from adrenal adenoma by using adrenal protocol computed tomography (CT).
Methods: We retrospectively included consecutive 199 patients who underwent adrenal CT and surgically proven pheochromocytoma (n = 66) or adenoma (n = 133). Two independent radiologists analyzed two CT criteria for pheochromocytoma. Conventional criteria were as follows: (a) lesion attenuation on unenhanced CT > 10 Hounsfield unit (HU); (b) absolute percentage washout < 60%; and (c) relative percentage washout < 40%. Modified criteria were as follows: (a) conventional criteria or (b) one of the following findings: (i) lesion attenuation on unenhanced CT ≥ 40 HU, (ii) 1-min enhanced CT ≥ 160 HU, (iii) 15-min enhanced CT ≥ 70 HU, , or (iv) intralesional cystic degeneration seen on both 1-min and 15-min enhanced CT. We analyzed area under the curve (AUC) and inter-reader agreement.
Distinguishing pheochromocytoma from adrenal adenoma by using modified computed tomography criteria
Sohi Kang et al
Abdominal Radiology (2020) https://doi.org/10.1007/s00261-020-02764-4 - Results: Proportion of pheochromocytoma was 33.2% (66/199). AUC of modified criteria was consistently higher than that of conventional criteria for distinguishing pheochromocytoma from adenoma (reader 1, 0.864 versus 0.746 for raw data set and 0.865 versus 0.746 for internal validation set; reader 2, 0.872 versus 0.758 for raw data set and 0.872 versus 0.757 for internal validation set) (p < 0.05 for all comparisons). Inter-reader agreement was excellent in interpreting any criteria (weighted kappa > 0.800).
Conclusion: Our modified criteria seem to improve diagnostic performance of adrenal CT in distinguishing pheochromocytoma from adrenal adenoma.
Distinguishing pheochromocytoma from adrenal adenoma by using modified computed tomography criteria
Sohi Kang et al
Abdominal Radiology (2020) https://doi.org/10.1007/s00261-020-02764-4 - “Thus, our modified criteria for pheochromocytoma (i.e., criteria 2) were as follows: (a) conventional criteria; OR (b) one of following findings: (i) lesion attenuation on UCT ≥ 40 HU, (ii) 1-min CECT ≥ 160 HU, (iii) 15-min CECT ≥ 70 HU, OR (iv) intralesional cystic degeneration seen on both 1-min and 15-min CECT.”
Distinguishing pheochromocytoma from adrenal adenoma by using modified computed tomography criteria
Sohi Kang et al
Abdominal Radiology (2020) https://doi.org/10.1007/s00261-020-02764-4
- “Adrenal pheochromocytomas may develop in 25%–30% of VHL cases The mean age of onset is 27 years (range, 5–58 years). VHL- associated pheochromocytomas manifest more commonly in boys , and 20%–50% may be bilateral.The risk of developing a second tumor increases with age, with studies reporting a 50% risk of a second tumor at 30 years after the initial diagnosis; 1%–5% of these tumors are malignant.”
Tumors in von Hippel–Lindau Syndrome: From Head to Toe—Comprehensive State-of-the-Art Review Ganeshan D et al. RadioGraphics 2018 (in press) - “Extra-adrenal pheochromocytomas/paragangliomas may be seen in 15% of VHL cases at various sites along the sympathetic chain in the abdomen, thorax, or head and neck. Patients may be asymptomatic or experience classic symptoms such as paroxysmal or refractory hypertension, palpitations, headaches, sweating, and hypertensive crises. A diagnosis of a pheochromocytoma is usually confirmed on the basis of biochemical abnormalities, including elevated plasma metanephrine and 24-hour urinary catecholamine levels.”
Tumors in von Hippel–Lindau Syndrome: From Head to Toe—Comprehensive State-of-the-Art Review Ganeshan D et al. RadioGraphics 2018 (in press) - “A significant subset of pheochromocytomas mimics adenomas on absolute or relative percentage washout calculations. However, nodules with venous phase enhancement of 85 HU or more are much more likely to be pheochromocytomas than adenomas, regardless of whether the lesion shows absolute or relative percentage washout compatible with a lipid-poor adenoma. The typical values of absolute and relative percentage washout of adrenal adenoma should be interpreted along with the venous phase enhancement value to avoid potential misdiagnoses.”
Pheochromocytomas Versus Adenoma: Role of Venous Phase CT Enhancement Mohammed MF et al. AJR 2018; 210:1073–1078 - “As such, we suggest a cutoff of 85 HU to recommend further investigation to exclude pheochromocytoma even if an incidental, clinically silent adrenal nodule meets the washout criteria of adenoma. This process would in turn help avoid duplicative imaging and decrease costs, waiting times, and additional follow-up adrenal protocol imaging.”
Pheochromocytomas Versus Adenoma: Role of Venous Phase CT Enhancement Mohammed MF et al. AJR 2018; 210:1073–1078 - “In our study, a venous phase enhancement value of 85 HU or more was detected in 30 pheochromocytomas (88.2%) and seven ad- enomas (16.3%). By contrast, a venous phase enhancement value below 85 HU was detect- ed in four pheochromocytomas (11.8%) and 36 adenomas (83.7%) .A threshold of 85 HU identi fied pheochromocytoma with 88.2% sensitivity and 83.7% specificity.”
Pheochromocytomas Versus Adenoma: Role of Venous Phase CT Enhancement Mohammed MF et al. AJR 2018; 210:1073–1078 - “On assessment of peak venous enhancement, a cutoff of 85 HU provides a highly sensitive and specific threshold in evaluation of incidental adrenal nodules. Exceeding this threshold favors the diagnosis of pheochromocytoma rather than adenoma but is not a threshold for exclusion of adenoma or definitive diagnosis of pheochromocytoma.”
Pheochromocytomas Versus Adenoma: Role of Venous Phase CT Enhancement Mohammed MF et al. AJR 2018; 210:1073–1078
- “Hereditary syndromes associated with pheochromocytomas and EAPs include multiple endocrine neoplasia (MEN) syndrome types 2A and 2B, neurofibromatosis type 1 (NF-1), von Hippel–Lindau disease (VHL), and familial paraganglioma syndrome (PGL), as outlined in the Table. These syndromes are associated with germline mutations that activate the RET gene (MEN), inactivate the NF-1gene (NF-1), inactivate the VHL gene (VHL), and inactivate the genes for succinate dehydrogenase (SDH) subunits B, C, or D (PGL). Problematically, the well-recognized syndromes associated with these mutations may be clinically silent. Thus, many neuroendocrine tumors previously thought to be sporadic (due to an absence of syndromic stigmata) harbor underlying mutations.”
From the Radiologic Pathology Archives: Adrenal Tumors and Tumor-like Conditions in the Adult: Radiologic-Pathologic Correlation Grant E. Lattin, Jr et al. RadioGraphics 2014 34:3, 805-829
- “Pheochromocytomas tend to have different CT imaging features mimicking other tumors according to the size of the tumors. However, clinical features, CT imaging characteristics, and radioisotope activity are not different between small and large pheochromocytomas.”
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. Clinical Imaging (in press) - “Reinig, et al. noted that smaller pheochromocytomas tend to be homogeneous, while larger masses tend to be heterogeneous due to hemorrhage and necrosis. However, differences in clinical features and other radiologic features between small and large pheochromocytomas have not been well studied.”
Assessment of clinical and radiologic differences between small and large adrenal pheochromocytomas Kim DW et al. Clinical Imaging (in press) - “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. Clinical Imaging (in press) - “There was a trend for smaller pheochromocytomas (6 of 10, 60%) to meet CT washout criteria for adenomas compared with larger pheochromocytomas (9 or 29, 31%), although this difference was not significant. Pheochromocytomas appearing as small and homogeneous adrenal masses with adenoma-like washout values by only adrenal protocol CT would be falsely diagnosed as adenoma and may be not be worked up further. In our study, five cases with small pheochromocystomas were falsely diagnosed as adenomas. However, these five cases had positive biochemical test results. Therefore, clinical features and biochemical tests should also be considered when diagnosing adrenal masses.”
Assessment of clinical and radiologic differences between small and large adrenal pheochromocytomas Kim DW et al. Clinical Imaging (in press) - “In conclusion, clinical features, CT imaging characteristics, and radioisotope activity are not significantly different between large and small pheochromocytomas. However, smaller pheochromocytomas were more likely to meet CT washout criteria for adenomas compared with larger pheochromocytomas, although this difference was not statistically significant.”
Assessment of clinical and radiologic differences between small and large adrenal pheochromocytomas Kim DW et al. Clinical Imaging (in press)
- “In 40 (70.2%) of the 57 patients, an adrenal pheochromocytoma was detected in an imaging study performed without suspicion of an adrenal lesion. There were 13 chest computed tomography studies-8 to evaluate for possible pulmonary emboli. Other indications included abdominal pain or discomfort (n = 8), trauma (n = 3), abnormal liver function tests (n = 3), suspect renal artery stenosis (n = 3), hematuria (n = 2), colitis (n = 2), and 4 miscellaneous indications.”
Serendipity in the diagnosis of pheochromocytoma. Oshmyansky AR et al J Comput Assist Tomogr. 2013 Sep-Oct;37(5):820-3 - “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
- “The aim of the study was to evaluate the prevalence of pheochromocytoma (PHEO) in patients with neurofibromatosis type 1 (NF1), and to analyze the behavior of some anthropometric and cardiovascular parameters. In 48 consecutive NF1 patients, urinary metanephrines and vanillylmandelic acid excretion were assessed. The body mass index (BMI), waist circumference (WC), ambulatory blood pressure monitoring (ABPM), echocardiography and ultrasound carotid arterial wall evaluation were performed. In NF1 patients, 11 (29.3%) had arterial hypertension, 7 (14.6%) had a PHEO. Four (57%) NF1 patients with PHEO were symptomatic at the diagnosis. In PHEO-NF1 patients, we revealed a lower BMI and WC values with respect to NF1 patients without PHEO and normal subjects (NSs) (p < 0.05), respectively. The nocturnal non-dipping pattern at the ABPM was present in 40.4% of NF1 patients, and in particular this phenomenon was present in PHEO-NF1 patients (71.4%). Left ventricular mass index and intima media thickness were significantly higher in NF1 patients as compared to NS (p < 0.05), particularly in NF1-PHEO patients (p < 0.05). In conclusions, these findings revealed high prevalence of PHEO in NF1 patients and suggest that, in addition to blood pressure, humoral factors (increased sympathetic activity or neurofibromin), influence the pathogenesis of remodeling of cardiovascular system.”
Neurofibromatosis type 1 (NF1) and pheochromocytoma: prevalence, clinical and cardiovascular aspects. Zinnamosca L et al. Arch Dermatol Res. 2011 Jul;303(5):317-25. - “The aim of the study was to evaluate the prevalence of pheochromocytoma (PHEO) in patients with neurofibromatosis type 1 (NF1), and to analyze the behavior of some anthropometric and cardiovascular parameters. In 48 consecutive NF1 patients, urinary metanephrines and vanillylmandelic acid excretion were assessed. The body mass index (BMI), waist circumference (WC), ambulatory blood pressure monitoring (ABPM), echocardiography and ultrasound carotid arterial wall evaluation were performed. In NF1 patients, 11 (29.3%) had arterial hypertension, 7 (14.6%) had a PHEO. Four (57%) NF1 patients with PHEO were symptomatic at the diagnosis. In PHEO-NF1 patients, we revealed a lower BMI and WC values with respect to NF1 patients without PHEO and normal subjects (NSs) (p < 0.05), respectively.”
Neurofibromatosis type 1 (NF1) and pheochromocytoma: prevalence, clinical and cardiovascular aspects. Zinnamosca L et al. Arch Dermatol Res. 2011 Jul;303(5):317-25. - “The aim of the study was to evaluate the prevalence of pheochromocytoma (PHEO) in patients with neurofibromatosis type 1 (NF1), and to analyze the behavior of some anthropometric and cardiovascular parameters. In 48 consecutive NF1 patients, urinary metanephrines and vanillylmandelic acid excretion were assessed. The body mass index (BMI), waist circumference (WC), ambulatory blood pressure monitoring (ABPM), echocardiography and ultrasound carotid arterial wall evaluation were performed. In NF1 patients, 11 (29.3%) had arterial hypertension, 7 (14.6%) had a PHEO. Four (57%) NF1 patients with PHEO were symptomatic at the diagnosis. In PHEO-NF1 patients, we revealed a lower BMI and”
Neurofibromatosis type 1 (NF1) and pheochromocytoma: prevalence, clinical and cardiovascular aspects. Zinnamosca L et al. Arch Dermatol Res. 2011 Jul;303(5):317-25. - “Neurofibromatosis Type 1(NF-1) has autosomal dominant inheritance with complete penetrance, variable expression and a high rate of new mutation. Pheochromocytoma occurs in 0.1%-5.7% of patients with NF-1.”
Pheochromocytoma associated with neurofibromatosis type 1: concepts and current trends Zografos GN et al. World Journal of Surgical Oncology 2010, 8:14 - “Pheochromocytoma occurs in 0.1%-5.7% of patients with NF-1, and in 20%-50% of NF-1 patients with hypertension, compared to 0.1% of all hypertensive individuals. The mean age at diagnosis of pheochrocytoma in patients with NF-1 is 42 years. Persons with NF-1 are at increased risk for malignant conditions, especially malignant peripheral nerve sheath tumor (MPNST), leukemia and rhabdomyosarcoma.”
Pheochromocytoma associated with neurofibromatosis type 1: concepts and current trends Zografos GN et al. World Journal of Surgical Oncology 2010, 8:14 - “Pheochromocytoma occurs in 0.1%-5.7% of patients with NF-1, and in 20%-50% of NF-1 patients with hypertension, compared to 0.1% of all hypertensive individuals. The mean age at diagnosis of pheochrocytoma in patients with NF-1 is 42 years. Persons with NF-1 are at increased risk for malignant conditions, especially malignant peripheral nerve sheath tumor (MPNST), leukemia and rhabdomyosarcoma.”
Pheochromocytoma associated with neurofibromatosis type 1: concepts and current trends Zografos GN et al. World Journal of Surgical Oncology 2010, 8:14 - Von Hippel-Lindau (VHL) disease, an autosomal dominant syndrome, is clinically subdivided into two types: those without Pheo (VHL type 1) and those with Pheo (VHL type 2). Type 2 VHL disease, where pheochromocytoma develops, accounts for 10% of VHL disease cases. The largest series of VHL patients with pheochromocytomas was described by Walther et al . The mean age at diagnosis was 29.9 year, which was statistically significantly younger than the mean age at diagnosis in a control group of patients with sporadic pheochromocytoma (39.7 years). However, there may be bias due to routine screening in the VHL group.”
Pheochromocytoma associated with neurofibromatosis type 1: concepts and current trends Zografos GN et al. World Journal of Surgical Oncology 2010, 8:14
- “ 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 et al.
AJR 2013; 201:834-839 - “ Greater enhancement of pheochromocytomas was variable: 25% greater in the arterial phase, 25% equal across phases, and 50% greater in the venous phase.”
MDCT of Adrenal Masses: Can Dual-Phase Enhancement Patterns Be Used to Differentiate Adenoma and Pheochromocytoma-
Northcutt BG et al.
AJR 2013; 201:834-839 - “ First, adenomas usually are more enhancing in the venous than in the arterial phase or have equivalent enhancement across phases. Second, a mass that is greater than 110-HU enhancing in the arterial phase, particularly with higher enhancement in the arterial phase, is most likely a pheochromocytoma. Third a pheochromocytoma are more likely to be heterogeneous than are adenomas.”
MDCT of Adrenal Masses: Can Dual-Phase Enhancement Patterns Be Used to Differentiate Adenoma and Pheochromocytoma-
Northcutt BG et al.
AJR 2013; 201:834-839 - “The differential diagnosis of bilateral adrenal masses include infective aetiologies such as tuberculosis and histoplasmosis; infiltrative disorders such as metastasis from an unknown primary, non-Hodgkin’s lymphoma; amyloidosis and neoplasias such as bilateral pheochromocytoma and adrenocortical carcinoma. Rarely, longstanding untreated congenital adrenal hyperplasia and macronodular adrenal hyperplasia may also be associated with bilateral adrenal masses.”
Bilateral adrenal masses: varying aetiologies
Bhansali A et al.
BMJ Case Reports 2010; doi:10.1136/bcr.10.2009.2347
- “ A substantial minority of Pheochromocytomas have absolute or relative washout characteristics that overlap with those of lipid poor adenomas.”
Can Established CT Attenuation and Washout Criteria for Adrenal Adenoma Accurately Exclude Pheochromocytoma-
Patel J et al.
AJR 2013; 201:122-127 - “ In summary a substantial minority of Pheochromocytomas are both homogeneous and show absolute or relative washout profiles that meet established diagnostic criteria for lipid poor adrenal adenomas.”
Can Established CT Attenuation and Washout Criteria for Adrenal Adenoma Accurately Exclude Pheochromocytoma-
Patel J et al.
AJR 2013; 201:122-127
- “ 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 - Pheochromocytoma: Facts
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 - Pheochromocytoma: CT Findings
- Calcifications are found in 10% of Pheochromocytomas
- Pheochromocytomas typically are vascular on early phase CT scans
- Pheochromocytomas can have a 50% washout value and behave just like an adenoma
- In the absence of metastases it is hard to diagnosis whether or not a Pheochromocytoma is malignant
- Pheochromocytoma
- 0.1 – 0.2 % of adults with hypertension
- “new onset, refractory, paroxysmal or recently exacerbated”
- Palpitations, headache, diaphoresis, flushing
- May be asymptomatic - CT of Pheochromocytoma
- Highly variable imaging appearance
- Homogeneous or heterogeneous
- May be brightly enhancing
- Cystic degeneration
- Calcification in up to 1/3 - Pheochromocytoma Mimic
- Renal cell carcinoma metastases
- Hypervascular
- Can have central necrosis
- Can washout like an adenoma
- Hyperenhancing Adrenals
In the setting of shock
-Trauma
-Sepsis
-Pancreatitis
-Hemorrhage induced hypotension
Poor prognostic indicator - Adrenocortical Carcinoma
1st and 4th decades of life
55% are functional
-Cushing syndrome
-Feminization
-Virilization
-Mixed Cushing/virilization
Hypertension common with functional - CT of Pheochromocytoma
-Highly variable imaging appearance
-Homogeneous or heterogeneous
-May be brightly enhancing
-Cystic degeneration
-Calcification in up to 1/3 - Pheochromocytoma: Diagnosis
24-hour urine to assess for:
-Vanillylmandelic acid (VMA)
-Catecholamines
-Metanephrines - Pheochromocytoma
-0.1 – 0.2 % of adults with hypertension
-“new onset, refractory, paroxysmal or recently exacerbated”
-Palpitations, headache, diaphoresis, flushing
-May be asymptomatic - Adrenal: Extraadrenal Paragangliomas: CT Findings
- Homogeneous or heterogeneous hyperenhancing mass
- Range in size from 1 cm to over 20 cm
- Common locations are carotid body, jugular foramen, aorticopulmonary region, posterior mediastinum, abdominal paraaortic region including Organ of Zuckerkandl, and pelvis - Adrenal: Paraganglioma: Facts
- Neuroendocrine tumor which arises from the paraganglionic cells
- Pheochromocytoma is a paraganglioma of the adrenal gland
- Usually 4th and 5th decades of life
- 10% are clinically silent and picked up incidentally - Adrenal: Paraganglioma: Facts
- Familial Paragangliomas are 10% of cases
- 35-50% of familial cases are multicentric
- Occur with MEN IIA and IIB, tuberous sclerosis, neurofibromatosis, and von Hippel Lindau disease. Also part of Carney’s triad with gastric leiomyosarcoma, chondroma and extraadrenal paraganglioma - Adrenal: Paraganglioma "Although paragangliomas can occur in a variety of anatomic locations, the majority are seen in relatively predictable regions of the body." Extraadrenal Paragangliomas of the Body: imaging Features Lee KY et al. AJR 2006; 187:492-504
- "This case of an incidental pheochromocytoma showing contrast medium washout greater than 50% on delayed imaging reinterates the importance of performing a biochemical profile in any patient with an incidental discovered adrenal mass." Incidental Pheochromocytoma Mimicking Adrenal Adenoma Because of Rapid Contrast Enhancement Loss Yoon JK et al AJR 2006; 187:1309-1311.
- "Noncontrast 37 HU early phase (60 seconds) 127 HU delayed phase (15 minutes) 62 HU washout 72%" Incidental Pheochromocytoma Mimicking Adrenal Adenoma Because of Rapid Contrast Enhancement Loss Yoon JK et al AJR 2006; 187:1309-1311.
- Pheochromocytoma: Facts
- May result in life threatening hypertension or cardiac arrhythmias because of excessive catecholamine secretion
- Occurs in 0.1-0.9% of hypertensive patients
- 10% of patients asymptomatic - Pheochromocytoma: CT Findings
- Mass may be solid or cystic
- Most have attenuation value on noncontrast CT of >10 HU
- Fat may be seen in a pheo
- Variable washout curves - "On CT, pheochromocytomas may have attenuation values less than 10 HU and also may display more than 60% washout of contrast agents on delayed scanning.Adrenal pheochromocytoma should also be included with adenomas in the differential diagnosis both for masses with low attenuation on unenhanced CT and for lesions exhibiting a high percentage of contrast washout."
Low-Density Pheochromocytoma on CT: A Mimicker of Adrenal Adenoma Blake MA et al. AJR 2003;181:1663-1668