Work-up of the Incidental Adrenal Mass

EUROPEAN UROLOGY FOCUS 1 (2016) 217–222

available at www.sciencedirect.com journal homepage: www.europeanurology.com/eufocus

Review – Adrenal Glands

Work-up of the Incidental Adrenal Mass Pascal Baltzer a,*, Paola Clauser a, Tobias Klatte b, Jochen Walz c a

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; b Department of

Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; c Institut Paoli-Calmettes, Service de chirurgie urologique, Marseille, France

Article info

Abstract

Article history: Accepted December 7, 2015

Context: Incidental adrenal masses (or adrenal incidentalomas [AI]) are a common finding during imaging and are present in up to 5% of the computed tomography (CT) scans performed on the general population. The best way to manage these lesions is still under discussion. Objective: To evaluate recent literature and available guidelines regarding the work-up of AIs. Evidence acquisition: We used a medical search engine to identify studies published in the past 5 yr regarding AIs. We also evaluated current guidelines and the most relevant papers published before 2010. Evidence synthesis: Unenhanced and contrast-enhanced CT, with laboratory tests to exclude functional lesions, are the most sensitive and specific methods currently available for the characterisation of adrenal masses. Magnetic resonance imaging, positron emission tomography–CT and fine-needle aspiration biopsy can be used as adjunct diagnostic tools in indeterminate lesions but are rarely indicated. In a relatively high number of indeterminate nodules, follow-up or surgery is suggested, although most of these lesions turn out to be benign. Conclusions: Various imaging modalities, with CT being most important, are available to diagnose malignant and functional lesions in AIs. An improved identification of benign lesions is warranted to reduce the number of unnecessary surgeries and follow-up examinations in patients with benign lesions. Patient summary: We performed a review of the literature on and guidelines for the management of incidental adrenal masses. It is possible to detect the presence of lesions that require surgery in the majority of cases. Follow-up is required for lesions that are not treated surgically. # 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Associate Editor: James Catto Keywords: Adrenal Imaging Pheochromocytoma Carcinoma Metanephrines MRI PET

* Corresponding author. Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna/Vienna General Hospital, Wa¨hringer Guertel 18-20, Floor 7F, 1090 Vienna, Austria. Tel. +43 1 40400 48180; Fax:. E-mail address: [email protected] (P. Baltzer).

1.

Introduction

An incidental adrenal mass (or adrenal incidentaloma [AI]) is defined as an adrenal lesion >1 cm identified in an imaging examination performed as a result of a clinical question neither related to nor suspicious for adrenal disease in patients who have no clinical suggestion of

adrenal disease [1]. By this definition, adrenal masses in patients with a known malignancy and those showing clinical signs or symptoms hinting at an underlying adrenal disorder discovered before or after imaging are not called AIs [2]. AIs are discovered during thoracic or abdominal cross-sectional imaging in 0.8–5.0% of examinations [3–5]. Their incidence tends to increase with age, increasing

http://dx.doi.org/10.1016/j.euf.2015.12.003 2405-4569/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

218

EUROPEAN UROLOGY FOCUS 1 (2016) 217–222

the prevalence of AIs up to 10% in computed tomography (CT) scans performed in the elderly population [4,6]. The majority of AIs, even if present in cancer patients, are nonfunctional, benign lesions that account for 82.5% of cases. These nonfunctional benign lesions comprise adenomas (61%), myelolipomas (10%), adrenal cysts (6%), and ganglioneuromas (5.5%) [3,6,7]. The remaining adrenal pathologies of AI include cortisol-secreting adenomas (5.3%), pheochromocytomas (5.1%), adrenocortical carcinomas (4.7%), metastatic lesions (2.5%), and aldosteronomas (1%) [3,6,7]. When an AI lesion is detected, a clinical examination checking for subtle signs and symptoms of adrenal dysfunction and a laboratory work-up to exclude functional lesions are mandatory. Functional lesions, such as cortisolsecreting lesions or pheochromocytomas, are associated with higher morbidity and mortality [8,9]. Currently, in spite of several limitations, CT is considered the most useful imaging technique in the differential diagnosis of adrenal masses; magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT appear to have an ancillary role for indeterminate lesions. The majority of the evidence on AIs stems from retrospective studies only; as a consequence, indications given in the currently available guidelines vary [2,10,11]. 2.

Evidence acquisition

We performed a qualitative literature search of studies published in English using the terms incidental adrenal mass and adrenal incidentaloma. We searched Medline for the period January 2010 to September 2015, considering both original research and review papers. We examined only peer-reviewed articles. We considered further literature, including works published before 2010, by screening the references of the identified articles. 3.

Evidence synthesis

When an AI is discovered, the main task is to exclude functional or malignant disease. Functional adrenal lesions are commonly related to a subclinical Cushing syndrome, symptoms associated with pheochromocytoma or hyperaldosteronism. Primary malignant adrenal tumours and metastases should be ruled out, particularly in patients who have a known or suspected primary tumour. Imaging studies and a laboratory work-up are necessary to exclude these entities [12]. 3.1.

Role of computed tomography

CT is currently the imaging modality of choice according to all guidelines for the work-up of adrenal masses. A literature overview demonstrates that size is a risk factor both for functional and malignant adrenal lesions, with a general cut-off for increased risk at 4 cm [13]. With this cutoff, the sensitivity of CT is about 93%, but the specificity is fairly low (42%) because of the relative rarity of malignant adrenal lesions [14]. Precontrast CT is usually sufficient to

accurately diagnose a lipid-rich benign adenoma irrespective of its size [15]. In the case of non–lipid-containing lesions or incidental masses in the absence of a precontrast scan, delayed enhanced scans are diagnostically helpful because they identify an absolute or relative wash-out of the contrast medium that is typical for benign lesions. Further evaluation of nonfunctional lesions using PET or fine-needle aspiration (FNA) is recommended only in selected cases. According to a meta-analysis of 10 studies that included 495 adrenal lesions (223 malignant), the recommended threshold for CT density measurements to identify benign lipid-rich adenomas correctly is 10 Hounsfield units (HU). At this threshold, pooled sensitivity and specificity were 71% and 98%, respectively. HU 2 were reported as always benign. Although specific for diagnosis of benign lesions, these results imply that, given the low prevalence of malignancy [13,16], a large number of benign adenomas are nonlipid-containing (lipid-poor) adenomas, and further tests are necessary to exclude malignancy in these lesions. Bae and co-workers [17] suggested a histogram analysis of unenhanced CT density values to identify lipid-containing adenomas not evident in simple density analysis. An improved characterisation of lipid-poor adenomas as benign in up to 52% of cases using this method has been described [18]. Both lipid-rich and lipid-poor benign adenomas show a faster wash-out of contrast medium than other adrenal masses. This feature can be exploited diagnostically, leading to high performance indices. Washout is measured as either absolute (calculated as [portal venous HU delayed phase HU] / [portal venous HU precontrast HU]) or relative (calculated as [portal venous HU delayed phase HU] / portal venous HU) wash-out. Although absolute wash-out may be more exact when taking into account precontrast lesion density [19], the diagnostic performance of both methods seems to be largely equivalent [15]. The relative method is also applicable if no precontrast scan is performed, as done in the majority of abdominal CT examinations. Short CT protocols are needed in clinical practice. Although abbreviated, 10-min–delay CT protocols seem to provide high specificity [20], more recent results indicate that sensitivity is not as high as prior research had indicated [21]. According to initial research, a 5-min delay may be sufficient to determine a diagnostic degree of wash-out compared to a 10-min delay, allowing clinicians to further tailor CT protocols to address the needs of clinical practice [19]. Of note, there is no consistent definition of absolute and relative wash-out. The reproducibility of CT measurements in terms of inter- and intrareader agreement is underinvestigated in the literature. Although the agreement appears generally to be good, various factors related to patients’ characteristics, acquisition parameters, and observer characteristics could influence the quantitative evaluation of adrenal masses [22]. Consequently, great caution has been advised when using specific attenuation threshold values for diagnosis of adrenal lesions [22]. Besides these quantitative approaches, qualitative criteria such as irregular borders; thickened enhancing rim;

EUROPEAN UROLOGY FOCUS 1 (2016) 217–222

internal lesion heterogeneity; and the presence of haemorrhage, calcifications, and necrosis show varying associations with malignancy, as similar features also may be present in large, degenerated adrenal adenomas [23,24]. Recently, the possible role of dual-energy CT has been increasingly investigated. In one of the first studies, Kim and co-workers [25] evaluated 49 patients using unenhanced images, early and delayed virtual unenhanced images, and early (60 s) and delayed contrast-enhanced CT (15 min). They tested the diagnostic value of absolute and relative wash-out as suggested previously. Although lipid-poor adenomas could be accurately classified by considering wash-out, virtual unenhanced images proved diagnostically inferior to true unenhanced CT images [25]. Glazer et al. suggested a possible role for both virtual monochromatic spectral images and virtual unenhanced images, although for a limited number of patients [26]. In contrast to Kim et al, Mileto and co-workers found an improved performance of dual-energy CT density analysis compared with unenhanced CT for characterisation of AIs [27]. At present, the variability of the investigated CT features and study protocols and the lack of prospective validation studies do not allow final conclusions regarding the role of dual-energy CT. 3.2.

Role of magnetic resonance imaging

MRI is an additional imaging modality that has been suggested both as a substitute for unenhanced CT in the diagnosis of lipid-rich adenomas and as an adjunctive tool to differentiate lipid-poor adenomas from other, more aggressive lesions. The technique most used in adrenal evaluation is chemical shift imaging (CS-MRI). In analogy to density evaluation in unenhanced CT, CS-MRI is used to identify the presence of intralesional lipids. The MRI sequence used is a dual-echo breath-hold gradient echo acquisition that takes advantage of the phase periodicity or chemical shift between fat and water to characterise the relative water and fat content of the examined tissue. By choosing appropriate echo times, the signal from water and fat will be on the same phase during one acquisition (in phase), while they will oppose during another acquisition and thereby cancel each other out (out of phase). At least two image sets need to be acquired. In the out-of-phase image, a signal drop (as compared to the in-phase image) indicates the presence of intracellular lipids. Several studies compared CS-MRI to unenhanced CT, suggesting that MRI is able to correctly reclassify adenoma lesions with a CT density >10 HU [28,29]. Besides the decreased performance of CS-MRI in lesions >20 HU, a lack of incremental diagnostic information has been shown when using both techniques for detection of benign, lipid-rich lesions [29,30]. It has been suggested that quantitative measurements increase the diagnostic performance of MRI. These methods are based on the calculation of ratios, comparing the signal intensity of the adenoma in in-phase and out-of-phase images with that of the spleen, kidney, or muscles. However, improved diagnostic performance could not be demonstrated [31–36].

219

Furthermore, direct comparisons of CS-MRI with contrast-enhanced CT are in favour of the latter [37,38]. Although the rapid contrast wash-out characteristics of adenomas were first described with gadolinium-enhanced MRI [39], subsequent studies did not validate these findings for clinical use [4,35]. 3.3.

Role of positron emission tomography

PET/CT is designed to evaluate metabolic activity in tissue. The most commonly used radiotracer is 18-fluorodeoxyglucose (18F-FDG), which can quantify glucose metabolism in the investigated tissue. PET/CT has mainly been used to differentiate benign from malignant lesions, in particular, to identify metastasis in cancer patients. When adding the information of unenhanced CT to those of PET/CT, studies have shown high diagnostic performance in differentiating benign from malignant adrenal masses, with high sensitivities and specificities exceeding 95% and 90%, respectively [40]. It should be noted that sensitivity for lesions <1 cm is low. Furthermore, false-positive 18F-FDG uptake is regularly observed in certain adenomas, inflammatory processes, and postsurgical situations. Because of cost, availability, and radiation exposure, PET/CT should be reserved for patients with a known primary tumour or if the adrenal lesion is highly suspicious of being a metastasis of an unknown cancer. 3.4.

Role of biopsy

FNA is indicated only in cases that remain indeterminate after a complete work-up and for which short-term followup is not an option. This may be the case in patients who have unknown primary malignancy, where immediate diagnosis alters patient management. Furthermore, equivocal lesions are considered a relative indication for adrenal biopsy [41]. Prior to invasive tissue sampling, the presence of pheochromocytoma and adrenocortical carcinoma should be excluded through imaging and laboratory evaluation. On the one hand, FNA of a pheochromocytoma might lead to a hypertensive crisis [42]; on the other hand, FNA results in cases of adrenal cortical carcinoma may remain indeterminate, but FNA has a considerable risk of tumour seeding [41]. Relative contraindications are uncorrectable coagulopathy or an unsafe needle approach. Using careful planning and hydrodissection, most targets can be reached safely [41,43]. Complications include a low risk of pneumothorax and haemorrhage that require intervention. Abscesses, pancreatitis, and tumour seeding have been sporadically reported [44]. 3.5.

Laboratory work-up

Regardless of its characteristics on CT or MRI, all patients must undergo laboratory tests to exclude a functional adrenal lesion (Table 1). Subclinical hypercortisolism, defined as a biochemical cortisol excess without signs of overt hypercortisolism (Cushing syndrome), is not a rare finding in functional adrenal incidentalomas, with a

220

EUROPEAN UROLOGY FOCUS 1 (2016) 217–222

Table 1 – Laboratory test for diagnosis of functional adrenal lesions Diagnosis Subclinical Cushing syndrome

Pheochromocytoma

Primary hyperaldosteronism

Available tests  1 mg overnight dexamethasone suppression test  2-day low-dose dexamethasone suppression test  Plasma-free metanephrines  (24-h total urinary metanephrines and fractionated catecholamines)  Plasma aldosterone concentration  Plasma renin activity  Plasma/serum electrolytes (sodium, potassium)  Blood pH level

reported prevalence of 5% to 30% in different series [45]. Subclinical hypercortisolism has been associated with an increased risk of cardiovascular disease, diabetes, and osteoporosis and thus increased morbidity and mortality. Early treatment is especially effective for recovery (eg, from hypertension and diabetes) [8,9,45]. Subclinical hypercortisolism can be detected with the 1-mg dexamethasone suppression test. After dexamethasone administration, the majority of healthy individuals suppress their serum cortisol concentration to <5 mg/dl [1]. Pheochromocytoma is found in 1.1% to 11% of AIs, even in normotensive patients [46–48]. A preoperative diagnosis is important, considering the potential risk and complications of a hypertensive crisis. Pheochromocytoma usually appears as a hyperdense (>30 HU) lesion on CT. A recent study concluded that the risk of pheochromocytoma is close to 0% if the lesion is hypodense on CT (<10 HU). Consequently, laboratory testing cam be avoided in these cases [49]. The sensitivity and specificity of the 24-h urine test for catecholamines are fairly high but less sensitive than the free metanephrines. Measuring plasmafree metanephrines (normetanephrine, metanephrine) yields a high diagnostic sensitivity (99%) and specificity (89%) and is the recommended test for diagnosing or excluding pheochromocytoma [1]. Primary hyperaldosteronism is rarely diagnosed in patients who have an AI, with a prevalence <2% [46,47], but it considered an important cause of hypertension that poorly responds to treatment. The symptoms are caused by arterial hypertension (eg, headache) and hypokalemia (eg, fatigue, numbness, muscle cramps, weakness). The lesions are usually small, and hypokalemia and metabolic alkalosis are not necessarily present.

higher in lesions exceeding a diameter of 3 cm [9]. The majority of experts agree on the need for tailored follow-up intervals that consider both lesions’ and patients’ characteristics as risk factors. 4.

Conclusions

In incidentally detected adrenal masses, the available imaging and laboratory test are able to identify functional and malignant lesions with high diagnostic accuracy. Despite this fact, many benign lesions still undergo surgery or follow-up because of equivocal imaging findings. In addition, diagnosis of asymptomatic functional adrenal masses or adrenocortical carcinoma has not lead to an increased survival nor to a better prognosis for the patients diagnosed with such lesions [8,57,58]. Prospective studies are needed to evaluate the usefulness of new imaging modalities in improving lesion characterisation and reducing unnecessary surgeries and follow-up. Author contributions: Pascal Baltzer had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Baltzer, Clauser, Klatte, Walz. Acquisition of data: Baltzer. Analysis and interpretation of data: Baltzer. Drafting of the manuscript: Baltzer, Clauser. Critical revision of the manuscript for important intellectual content: Baltzer, Clauser, Klatte, Walz. Statistical analysis: Baltzer. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: Baltzer. Other (specify): None. Financial disclosures: Pascal Baltzer certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None.

References [1] NIH state-of-the-science statement on management of the clinically unapparent adrenal mass (‘‘incidentaloma’’). NIH Consens State Sci Statements 2002;19:1–25. [2] Zeiger MA, Thompson GB, Duh Q-Y, et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Inci-

3.6.

Follow-up

dentalomas: executive summary of recommendations. Endocr Pract 2009;15:450–3.

The cost-effectiveness of follow-up in patients with adrenal masses characterised as benign or nonfunctional at initial work-up has recently been questioned. Empirical evidence has demonstrated mass enlargement during follow-up in only 4–6% of cases [50–52], while no evolution of hormonal activity was noted [53–55]. Other studies reported that up to 12% of the investigated cases developed hormonal dysfunction during follow-up [9,13,56], the risk being

[3] Davenport C, Liew A, Doherty B, et al. The prevalence of adrenal incidentaloma in routine clinical practice. Endocrine 2011;40:80–3. [4] Dunnick NR, Korobkin M. Imaging of adrenal incidentalomas: current status. AJR Am J Roentgenol 2002;179:559–68. [5] Gross MD, Korobkin M, Bou-Assaly W, Rubello D. Incidentallydiscovered adrenal masses. Discov Med 2010;9:24–33. [6] Androulakis II, Kaltsas G, Piaditis G, Grossman AB. The clinical significance of adrenal incidentalomas. Eur J Clin Invest 2011;41: 552–60.

EUROPEAN UROLOGY FOCUS 1 (2016) 217–222

[7] Bittner JG, Brunt LM. Evaluation and management of adrenal incidentaloma. J Surg Oncol 2012;106:557–64. [8] Debono M, Bradburn M, Bull M, Harrison B, Ross RJ, Newell-Price J. Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas. J Clin Endocrinol Metab 2014;99: 4462–70. [9] Morelli V, Palmieri S, Salcuni AS, et al. Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics. Eur J Endocrinol 2013;168:235–41. [10] Choyke PL, ACR Committee on Appropriateness Criteria. ACR appropriateness criteria on incidentally discovered adrenal mass. J Am Coll Radiol 2006;3:498–504. [11] Young Jr WF. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med 2007;356:601–10. [12] Zeiger MA, Siegelman SS, Hamrahian AH. Medical and surgical

221

[27] Mileto A, Nelson RC, Marin D, Roy Choudhury K, Ho LM. Dualenergy multidetector CT for the characterization of incidental adrenal nodules: diagnostic performance of contrast-enhanced material density analysis. Radiology 2015;274:445–54. [28] Israel GM, Korobkin M, Wang C, Hecht EN, Krinsky GA. Comparison of unenhanced CT and chemical shift MRI in evaluating lipid-rich adrenal adenomas. AJR Am J Roentgenol 2004;183:215–9. [29] Haider MA, Ghai S, Jhaveri K, Lockwood G. Chemical shift MR imaging of hyperattenuating (>10 HU) adrenal masses: does it still have a role? Radiology 2004;231:711–6. [30] Outwater EK, Siegelman ES, Huang AB, Birnbaum BA. Adrenal masses: correlation between CT attenuation value and chemical shift ratio at MR imaging with in-phase and opposed-phase sequences. Radiology 1996;200:749–52. [31] Mitchell DG, Crovello M, Matteucci T, Petersen RO, Miettinen MM.

evaluation and treatment of adrenal incidentalomas. J Clin Endo-

Benign adrenocortical masses: diagnosis with chemical shift MR

crinol Metab 2011;96:2004–15.

imaging. Radiology 1992;185:345–51.

[13] Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol 2003;149:273–85. [14] Mantero F, Terzolo M, Arnaldi G, et al. A survey on adrenal inci-

[32] Reinig JW, Stutley JE, Leonhardt CM, Spicer KM, Margolis M, Caldwell CB. Differentiation of adrenal masses with MR imaging: comparison of techniques. Radiology 1994;192:41–6.

dentaloma in Italy. Study Group on Adrenal Tumors of the Italian

[33] Tsushima Y, Ishizaka H, Matsumoto M. Adrenal masses: differenti-

Society of Endocrinology. J Clin Endocrinol Metab 2000;85:637–44.

ation with chemical shift, fast low-angle shot MR imaging. Radiol-

[15] Terzolo M, Stigliano A, Chiodini I, et al. AME position statement on adrenal incidentaloma. Eur J Endocrinol 2011;164:851–70. [16] Song JH, Chaudhry FS, Mayo-Smith WW. The incidental adrenal mass on CT: prevalence of adrenal disease in 1,049 consecutive adrenal masses in patients with no known malignancy. AJR Am J Roentgenol 2008;190:1163–8. [17] Bae KT, Fuangtharnthip P, Prasad SR, Joe BN, Heiken JP. Adrenal masses: CT characterization with histogram analysis method. Radiology 2003;228:735–42. [18] Ho LM, Paulson EK, Brady MJ, Wong TZ, Schindera ST. Lipid-poor adenomas on unenhanced CT: does histogram analysis increase sensitivity compared with a mean attenuation threshold? AJR Am J Roentgenol 2008;191:234–8. [19] Kumagae Y, Fukukura Y, Takumi K, et al. Distinguishing adrenal adenomas from non-adenomas on dynamic enhanced CT: a com-

ogy 1993;186:705–9. [34] Bilbey JH, McLoughlin RF, Kurkjian PS, et al. MR imaging of adrenal masses: value of chemical-shift imaging for distinguishing adenomas from other tumors. AJR Am J Roentgenol 1995;164:637–42. [35] Korobkin M, Lombardi TJ, Aisen AM, et al. Characterization of adrenal masses with chemical shift and gadolinium-enhanced MR imaging. Radiology 1995;197:411–8. [36] Mayo-Smith WW, Lee MJ, McNicholas MM, Hahn PF, Boland GW, Saini S. Characterization of adrenal masses (< 5 cm) by use of chemical shift MR imaging: observer performance versus quantitative measures. AJR Am J Roentgenol 1995;165:91–5. [37] Park BK, Kim CK, Kim B, Lee JH. Comparison of delayed enhanced CT and chemical shift MR for evaluating hyperattenuating incidental adrenal masses. Radiology 2007;243:760–5. [38] Koo HJ, Choi HJ, Kim HJ, Kim S-O, Cho K-S. The value of 15-minute

parison of 5 and 10 min delays after intravenous contrast medium

delayed contrast-enhanced CT to differentiate hyperattenuating

injection. Clin Radiol 2013;68:696–703.

adrenal masses compared with chemical shift MR imaging. Eur

[20] Blake MA, Kalra MK, Sweeney AT, et al. Distinguishing benign from malignant adrenal masses: multi-detector row CT protocol with 10-minute delay. Radiology 2006;238:578–85. [21] Sangwaiya MJ, Boland GWL, Cronin CG, Blake MA, Halpern EF, Hahn PF. Incidental adrenal lesions: accuracy of characterization

Radiol 2014;24:1410–20. [39] Krestin GP, Steinbrich W, Friedmann G. Adrenal masses: evaluation with fast gradient-echo MR imaging and Gd-DTPA-enhanced dynamic studies. Radiology 1989;171:675–80. [40] Boland GWL, Dwamena BA, Jagtiani Sangwaiya M, et al. Character-

with contrast-enhanced washout multidetector CT—10-minute

ization of adrenal masses by using FDG PET: a systematic review

delayed imaging protocol revisited in a large patient cohort. Radi-

and meta-analysis of diagnostic test performance. Radiology

ology 2010;256:504–10. [22] Hammarstedt L, Thilander-Klang A, Muth A, Wa¨ngberg B, Ode´n A,

[41] Sharma KV, Venkatesan AM, Swerdlow D, et al. Image-Guided

2011;259:117–26.

Hellstro¨m M. Adrenal lesions: variability in attenuation over time,

Adrenal and Renal Biopsy. Tech Vasc Interv Radiol 2010;13:100–9.

between scanners, and between observers. Acta Radiol 2013;54:

[42] Vanderveen KA, Thompson SM, Callstrom MR, et al. Biopsy of

817–26. [23] Song JH, Grand DJ, Beland MD, Chang KJ, Machan JT, Mayo-Smith WW. Morphologic features of 211 adrenal masses at initial contrast-

pheochromocytomas and paragangliomas: potential for disaster. Surgery 2009;146:1158–66. [43] Tyng CJ, Bitencourt AG, Martins EB, Pinto PN, Chojniak R. Technical

enhanced CT: can we differentiate benign from malignant lesions

note: CT-guided paravertebral adrenal biopsy using hydrodissec-

using imaging features alone? AJR Am J Roentgenol 2013;201:

tion—a safe and technically easy approach. Br J Radiol 2012;85:

1248–53. [24] Ctvrtlı´k F, Herman M, Student V, Ticha´ V, Minarı´k J. Differential

[44] Harisinghani MG, Maher MM, Hahn PF, et al. Predictive value of

diagnosis of incidentally detected adrenal masses revealed on

benign percutaneous adrenal biopsies in oncology patients. Clin

routine abdominal CT. Eur J Radiol 2009;69:243–52. [25] Kim YK, Park BK, Kim CK, Park SY. Adenoma characterization: adrenal protocol with dual-energy CT. Radiology 2013;267:155–63.

e339–42.

Radiol 2002;57:898–901. [45] Chiodini I. Clinical review: diagnosis and treatment of subclinical

[26] Glazer DI, Maturen KE, Kaza RK, et al. Adrenal incidentaloma triage

hypercortisolism. J Clin Endocrinol Metab 2011;96:1223–36. [46] Bu¨low B, Ahre´n B. Adrenal incidentaloma—experience of a stan-

with single-source (fast-kilovoltage switch) dual-energy CT. AJR

dardized diagnostic programme in the Swedish prospective study.

Am J Roentgenol 2014;203:329–35.

J Intern Med 2002;252:239–46.

222

EUROPEAN UROLOGY FOCUS 1 (2016) 217–222

[47] Kasperlik-Załuska AA, Otto M, Cichocki A, et al. Incidentally discov-

[53] Grossrubatscher E, Vignati F, Possa M, Lohi P. The natural history of

ered adrenal tumors: a lesson from observation of 1,444 patients.

incidentally discovered adrenocortical adenomas: a retrospective

Horm Metab Res 2008;40:338–41. [48] Stenstro¨m G, Sva¨rdsudd K. Pheochromocytoma in Sweden 1958–

evaluation. J Endocrinol Invest 2001;24:846–55. [54] Sire´n J, Tervahartiala P, Sivula A, Haapiainen R. Natural course of

1981. An analysis of the National Cancer Registry Data. Acta Med

adrenal incidentalomas: seven-year follow-up study. World J Surg

Scand 1986;220:225–32.

2000;24:579–82.

[49] Sane T, Schalin-Ja¨ntti C, Raade M. Is biochemical screening for

[55] Tsvetov G, Shimon I, Benbassat C. Adrenal incidentaloma: clinical

pheochromocytoma in adrenal incidentalomas expressing low

characteristics and comparison between patients with and without

unenhanced attenuation on computed tomography necessary?

extraadrenal malignancy. J Endocrinol Invest 2007;30:647–52.

J Clin Endocrinol Metab 2012;97:2077–83. [50] Anagnostis P, Efstathiadou Z, Polyzos SA, et al. Long term follow-up

[56] Bernini GP, Moretti A, Oriandini C, Bardini M, Taurino C, Salvetti A. Long-term morphological and hormonal follow-up in a single unit on

of patients with adrenal incidentalomas—a single center experi-

115 patients with adrenal incidentalomas. Br J Cancer 2005;92:

ence and review of the literature. Exp Clin Endocrinol Diabetes

1104–9.

2010;118:610–6.

[57] Kutikov A, Mallin K, Canter D, Wong YN, Uzzo RG. Effects of

[51] Kastelan D, Kraljevic I, Dusek T, et al. The clinical course of patients

increased cross-sectional imaging on the diagnosis and prognosis

with adrenal incidentaloma: is it time to reconsider the current

of adrenocortical carcinoma: analysis of the National Cancer Data-

recommendations? Eur J Endocrinol 2015;173:275–82. [52] Muth A, Hammarstedt L, Hellstro¨m M, Sigurjo´nsdo´ttir HA´,

[58] Grogan RH, Mitmaker E, Vriens MR, et al. Adrenal incidentaloma:

Almqvist E, Wa¨ngberg B. Cohort study of patients with adrenal

does an adequate workup rule out surprises? Surgery 2010;148:

lesions discovered incidentally. Br J Surg 2011;98:1383–91.

392–7.

base. J Urol 2011;186:805–10.