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Adrenal Incidentaloma: An Overview of Clinical and Epidemiological Data from the National Italian Study Group
Abstract
BACKGROUND: The incidental discovery of an adrenal mass raises the problem of distinguishing the frequent benign masses from the infrequent malignant ones that require surgery. At present, univocal guidelines to approach this problem are not available. The aim of the present study was to perform a multicentric retrospective analysis of adrenal masses incidentally discovered (adrenal incidentalomas). PATIENTS AND METHODS: Hospital records of adrenal incidentalomas diagnosed over a 15-year period in 29 surgical and medical centers in Italy were scrutinized. Collected cases were 1,013, and 887 were analyzed. RESULTS: The majority of patients were in the 5th and 6th decade and females were predominantly affected. The frequency of adrenocortical cancer was 12% among operated patients (316 cases). The tumor diameter was highly correlated with the risk of malignancy, as well as the CT characteristics such as density, shape and margins. The frequency of pheochromocytoma was 10% among operated patients. CONCLUSIONS: The occurrence of incidentally discovered adrenocortical carcinomas and pheochromocytomas is not rare. Evaluation of the mass size and CT characteristics are simple and effective methods to differentiate malignant lesions. Biochemical screening for pheochromocytoma is mandatory before surgery.
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“Although the majority of AIs are unilateral, bilateral AIs may be found in 10% to 15% of cases (169).”
From Adrenal incidentaloma (2020) · cites this paper as [169]
In the citing paper
“Two large studies (169,170) found that the most common causes of bilateral AI were metastasis, primary bilateral macronodular adrenal hyperplasia (PBMAH), and bilateral cortical adenomas.”
From Adrenal incidentaloma (2020) · cites this paper as [169]
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Telomerase activity in the differentiation of benign and malignant adrenal tumors
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“Size is thought to be the most important predictor for malignancy, and a size of > 4cm is a crucial feature (86).”
BackgroundDifferentiation of Adrenal Adenomas From Metastases With Unenhanced Computed Tomography
Gufler, H., Eichner, G., Großmann, A., Krentz, H., Schulze, C. G., Sauer, S., & Grau, G. (2004) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-200411000-00015 · Cited by 17
Federal clinical practice guidelines on the diagnostics and treatment of adrenocortical cancer
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“При изучении итальянского регистра [30, 31] лишь 25% опухолей надпочечников более 4 см оказались злокачественными.”
Primary aldosteronism and hypercortisolism due to bilateral functioning adrenocortical adenomas
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“Adrenal adenomas are detected as an incidental finding in 1–4% of radiological imaging analyses of the abdomen [1, 2].”
BackgroundAssociation between Tumor Size and Malignancy Risk in Hormonally Inactive Adrenal Incidentalomas
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“However, the sensitivity of ultrasound and CT to detect adrenal masses is reported to be 87% and 93% respectively, and a close correlation is also found between the sizes measured by both imaging procedures (12, 13 ).”
MethodPreclinical Cushing’s Syndrome Resulting from Black Adrenal Adenoma
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Adrenal Incidentaloma Controversial Size Recommendations
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Panizzo, V., Rubino, B., Piozzi, G. N., Ubiali, P., Morandi, A., Nencioni, M., & Micheletto, G. (2018) · American Journal of Case Reports · doi:10.12659/ajcr.910259 · Cited by 16
“In a report on 887 patients who had adrenal incidentalomas, a diameter greater than 4 cm was shown to have a 90% sensitivity for the detection of AC, but a low specificity (only 24% of the lesions were malignant) [72].”
BackgroundSubclinical Cushing’s Syndrome
Beuschlein, F., & Reincke, M. (2005) · Springer eBooks · doi:10.1007/3-540-26861-8_7 · Cited by 15
Incidental Adrenal Nodules and Masses: The Imaging Approach
Willatt, J., Chong, S. T., Ruma, J. A., & Kuriakose, J. W. (2015) · International Journal of Endocrinology · doi:10.1155/2015/410185 · Cited by 14
“A cutoff of 4 cm can be used to decide if an adrenal mass is benign or malignant with greater than 90% sensitivity [13, 47, 48].”
BackgroundMethodAdrenal Imaging: Magnetic Resonance Imaging and Computed Tomography
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Histopathologic Features of Adrenal Cortical Carcinoma
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“The prevalence rate of cortical adenomas in a series of surgically resected incidental tumors is of 53% (Angeli et al., 1997) whereas the incidence for ACC is between 4 to 12 new cases per million in adults (Grumbach et al.”
BackgroundDisseminated Nocardia Farcinica Pneumonia with Left Adrenal Gland Abscess
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“Rarely, adrenal masses can come from infectious causes, especially if bilateral abscesses are present [3].”
BackgroundAdrenal Imaging Features Predict Malignancy Better than Tumor Size
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Adrenal bilateral incidentaloma by reactivated histoplasmosis
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Hypertension and Cushing’s syndrome: hunt for the red flag
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Radiographic Evaluation of Nonfunctioning Adrenal Neoplasms
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“The National Italian Study Group on Adrenal Tumors found that a 4 cm adrenal lesion had a 93% sensitivity but only 24% specificity for ACC.(16)”
BackgroundInfluentialIs the Adrenal Incidentaloma Functionally Active? An Approach-To-The-Patient-Based Review
Bernardi, S., Calabrò, V., Cavallaro, M., Lovriha, S., Eramo, R., Fabris, B., de Manzini, N., & Dobrinja, C. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11144064 · Cited by 12
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“Although controversy persists about the likely identification of adrenal masses 4 to 6 cm in diameter,(8) recent studies suggested that a cut‐off adrenal mass size > 4 cm in diameter was a surgical indicator due to concerns about adrenocortical carcinoma.(34-36) These results were based on the characteristics of tumor…”
BackgroundReidelberger, K., & Fingeret, A. L. (2021) · Surgical Clinics of North America · doi:10.1016/j.suc.2021.06.006 · Cited by 12
Clinical Review: The Approach to the Evaluation and Management of Bilateral Adrenal Masses
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Adrenal incidentaloma: differential diagnosis and management strategies
Morelli, V., & Palmieri, S. (2018) · Minerva Endocrinology · doi:10.23736/s0391-1977.18.02868-7 · Cited by 12
CT sensitivity for adrenal adenoma according to lesion size
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Zufallsbefunde in der Abdomensonographie
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Bilateral primary adrenal non-Hodgkin′s lymphoma without adrenal insufficiency
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“in their study have reported that the maximum diameter of a mass is predictive of both malignancy and overall prognosis, with 90% of adrenocortical carcinomas being >4 cm.[2] Therefore, any mass >4 cm should be treated like a malignancy until proven otherwise.”
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“Epidemiological data from Italy [34] showed that the majority of patients with adrenal incidentalomas were in the 5th and 6th decades and females were predominantly affected.”
BackgroundBeuschlein, F., Borgemeister, M., Schirra, J. R. J., Göke, B., Faßnacht, M., Arlt, W., Allolio, B., & Reincke, M. (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01006.x · Cited by 10
“Patients with subclinical Cushing's syndrome due to adrenal incidentaloma presented with hypertension, obesity and diabetes to an even higher degree (Angeli et al., 1997).”
Bilateral adrenal incidentaloma with subclinical hypercortisolemia: indications for surgery
Papierska, L., Ćwikła, J. B., Rabijewski, M., Glinicki, P., Otto, M., & Kasperlik-Zaluska, A. A. (2014) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.2347 · Cited by 10
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Cavallaro, G., Polistena, A., D’Ermo, G., et al. (2011) · European surgery. Supplement/European surgery · doi:10.1007/s10353-011-0034-y · Cited by 9
“larger than 4 cm [10].”
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Bilateral Adrenal Incidentalomas: A Case Report and Review of Diagnostic Challenges
Carlson, A. L., Marney, A. M., Anderson, S. R., & Gilbert, M. P. (2013) · Case Reports in Endocrinology · doi:10.1155/2013/953052 · Cited by 8
“Speci�c attention should be paid to the unique clinical situation of the bilateral pheochromocytoma, which account for approximately 10% of pheochromocytomas [4, 5].”
BackgroundIncidentalomas suprarrenales: experiencia clínica en los hospitales de Castilla-La Mancha
Lamas, C., Palma, M., Martín, D., de Frutos, V. Á., López, M., & Marco, A. (2009) · Endocrinología y Nutrición · doi:10.1016/s1575-0922(09)72708-1 · Cited by 8
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Presacral myelolipoma, case report and literature review
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Evaluation of Adrenal Vein Sampling Use and Outcomes in Patients With Primary Aldosteronism
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Large idiopathic unilateral adrenal hematoma in a young woman
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“sodic secondary hypertension along with headaches, sweating, and palpitations [4-6].”
BackgroundInfluentialDIAGNOSIS AND MANAGEMENT OF ADRENAL INCIDENTALOMAS
Barzon, L., & Boscaro, M. (2000) · The Journal of Urology · doi:10.1097/00005392-200002000-00003 · Cited by 6
Illuminati, G., Pasqua, R., D’Ermo, G., Girolami, M., Cerbelli, B., d’Amati, G., Carboni, F., & Fiori, E. (2021) · Frontiers in Surgery · doi:10.3389/fsurg.2021.671424 · Cited by 5
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“…of malignancy, and a study by the National Italian Study Group on Adrenal Tumors, which included 887 AIs, showed that adrenocortical carcinoma was significantly correlated with the size of the mass, and the sensitivity of detecting adrenocortical carcinoma with a threshold of 4 cm was 93% [11].”
BackgroundLee, J.-M., Kim, M. K., Ko, S., Koh, J., Kim, B., Kim, S.-W., Kim, S., Kim, H. J., Ryu, O., Park, J., et al. (2017) · Korean Journal of Medicine · doi:10.3904/kjm.2017.92.1.4 · Cited by 5
Hormonal Evaluation of Incidental Adrenal Masses: The Exception, Not the Rule
Kirsch, M. J., Hsu, K., Lee, M. H., Pickhardt, P. J., Kim, D. H., Sippel, R. S., & Dedhia, P. H. (2020) · World Journal of Surgery · doi:10.1007/s00268-020-05679-9 · Cited by 5
Naffouje, S. A., Sabesan, A. C., Johnson, J. E. H., Kirtane, K., Gonzalez, R. J., & Mullinax, J. E. (2021) · Journal of Surgical Oncology · doi:10.1002/jso.26639 · Cited by 5
“Eight hundred and thirty patients had T1/T2, 365 had T3, and 162 had T4 ACC.”
BackgroundInfluentialAdrenal masses: A urological perspective
Fergany, A. F. (2016) · Arab Journal of Urology · doi:10.1016/j.aju.2016.09.001 · Cited by 5
“The prevalence of adrenal incidentaloma increases with age from <1% in patients younger than 30 years to 7% in patients older than 70 years, and is bilateral in 10% of cases [1].”
BackgroundAssessment of clinical and radiologic differences between small and large adrenal pheochromocytomas
Kim, D. W., Yoon, S. K., Kim, S., Kang, E. J., & Kwon, H. J. (2017) · Clinical Imaging · doi:10.1016/j.clinimag.2017.03.002 · Cited by 5
Guidelines for the management of the incidentally discovered adrenal mass
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Adrenal Cortex Tumors and Hyperplasias
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“…be considered as rare, in spite of being dependant on the size of the tumor (above 4 cm the probability of an incidentaloma being malignant is 24% (Angeli et al., 1997); however, due to the importance of such a situation the initial major concern in evaluating an adrenal incidentaloma is the…”
BackgroundInfluentialManejo de la masa suprarrenal: lo que el urólogo debe saber
Suárez, M. H., Junquera, J. M. A., Boix, P., Dieguez, M., Delgado, E., García, J. M. A., & García, R. A. (2010) · Actas Urológicas Españolas · doi:10.1016/j.acuro.2009.11.010 · Cited by 4
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“• Lesions <4 cm have a risk of ACC of <2 % [ 26 ].”
BackgroundLau, S. K., & Weiss, L. M. (2005) · Pathology Case Reviews · doi:10.1097/01.pcr.0000175101.37448.90 · Cited by 5
Li, Y., & Zhang, B. (2019) · Revue Neurologique · doi:10.1016/j.neurol.2018.11.007 · Cited by 4
Management of the patient with incidental bilateral adrenal nodules
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Oncocytic Adrenocortical Neoplasm Diagnosed after Robot-Assisted Adrenalectomy
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“Size has been shown to be a highly sensitive criterion to rule out adrenocortical carcinoma (ACC); a cutoff of 4 cm was associated with a 90% sensitivity in one series [5].”
BackgroundNatural history of large adrenal tumors
Macech, M., Stępień, M., Podgórska, J., Toutounchi, S., Koperski, Ł., Barankiewicz, J., Bobrowicz, M., Kondracka, A., & Ambroziak, U. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1774131 · Cited by 3
“Previous studies reported a higher frequency of LATs, most likely due to limited availability and lower quality of imaging modalities (4, 9, 10).”
Suspected Primary Adrenal Lymphoma (PAL) Associated With Hemophagocytic Lymphohistiocytosis (HLH)
Kim, T. S., Cheng, K., Jaiswal, R., et al. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa156 · Cited by 3
“Bilateral masses are found in 10% to 15% of cases in an analysis of 2 large adrenal incidentaloma studies [3, 4].”
BackgroundDelaney, F. T., Chung, R., Blake, M. A., & Sweeney, A. T. (2025) · Endocrine Practice · doi:10.1016/j.eprac.2025.05.743 · Cited by 4
Adenomatoid Tumor of the Adrenal Gland
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Hermsen, I. G. C., Polak, M. P. J., & Haak, H. R. (2010) · Endocrine · doi:10.1007/s12020-010-9368-7 · Cited by 3
“An adrenal ‘incidentaloma’ is an adrenal mass, generally 1 cm or more in diameter, which is discovered coincidently during a radiological examination performed for indications other than an evaluation of adrenal disease [1].They are found in 4‐5% of the radiological investigations [2, 3]. 10‐15% of these adrenal incid…”
BackgroundCortical sparing adrenalectomy in sporadic and bilateral tumors
Colleselli, D., & Janetschek, G. (2019) · Laparoscopic Surgery · doi:10.21037/ls.2019.08.02 · Cited by 3
“A threshold of four centimeters was suggested to distinguish adrenal carcinomas from malignant entities with a sensitivity for adrenocortical carcinoma of 93% and a specificity of only 42% (8,9).”
BackgroundThe Etiological Profile of Adrenal Incidentalomas
Lahmamssi, F.-Z., Saadaoui, L., Aynaou, H., Salhi, H., & Ouahabi, H. E. (2022) · Cureus · doi:10.7759/cureus.32564 · Cited by 3
“The prevalence of adrenal incidentaloma (AI) increases with age, with a peak incidence between the fifth and seventh decade, which is similar to our series [2-4].”
ResultBilateral Adrenal Incidentalomas: A Rare Presentation of Lung Cancer
Diri, H., Kızıltepe, M., Karaburgu, S., Koc, M. S., Özaslan, E., & Tanrıverdi, F. (2015) · Case Reports in Endocrinology · doi:10.1155/2015/179472 · Cited by 3
“Bilateral adrenal masses account for 15% of adrenal incidentalomas [8, 9].”
BackgroundHypertension Associated With Large Bilateral Adrenal Masses
Handler, J. (2007) · Journal of Clinical Hypertension · doi:10.1111/j.1524-6175.2007.06307.x · Cited by 3
Minimally Invasive Adrenalectomy and Malignant Adrenal Tumours
Nies, C., & Langer, P. (2003) · European surgery. Supplement/European surgery · doi:10.1046/j.1682-4016.2003.03028.x · Cited by 3
Management of adrenal mass: What urologist should know
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Laparoscopic adrenalectomy for co-secreting aldosterone and cortisol adenomas
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A clinicopathological analysis of adrenal tumors in patients with history of extra-adrenal cancers
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Manejo clínico del incidentaloma suprarrenal: resultados de una encuesta
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“%) que se desarrolle hiper-producción hormonal, como la aparición de hipercorti-solismo 12-14 .”
Molecular genetics of adrenal cortical tumors
Kjellman, M., Roshani, L., Bäckdahl, M., & Larsson, C. (1999) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/00060793-199902000-00012 · Cited by 3
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Imaging Modalities for Adrenocortical Tumors
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Laparoscopic Adrenal-Sparing Surgery Case Series: Partial Adrenalectomy and Cyst Resection
Knežević, N. (2023) · Acta Clinica Croatica · doi:10.20471/acc.2023.62.s2.9 · Cited by 2
“One of the radiological criteria for malignant potential in incidentalomas is tumor size, and 4 cm was proposed as the appropriate cut-off 18 .”
BackgroundAlmuallem, S., Abualhamael, S. A., Hala, M., Hisham, M., & Murad, A. (2018) · International Archives of Urology and Complications · doi:10.23937/2469-5742/1510048 · Cited by 2
Pictorial essay: incidental findings on 18F-Fluciclovine PET/CT scan
Romagnolo, C., Cottignoli, C., Palucci, A., et al. (2021) · Clinical and Translational Imaging · doi:10.1007/s40336-021-00412-5 · Cited by 2
Management of adrenal incidentalomas: who, why and how?
Araujo-Castro, M., Iriarte-Durán, M. B., Ramírez, P. A. P., & Donato, S. (2025) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000917 · Cited by 1
Salam, S., Memon, N., Amini, M., & Sachmechi, I. (2025) · Open Journal of Endocrine and Metabolic Diseases · doi:10.4236/ojemd.2025.1511021 · Cited by 1
Suzuki, K., Imamura, A., & Funatsu, H. (2026) · Radiology Case Reports · doi:10.1016/j.radcr.2026.02.007 · Cited by 1
“The proportion of bilateral lesions among adrenal incidentalomas has also been reported to be low, with proportions of 10%, 11%, and 15% reported by Angeli et al. [ 3 ], Patrova et al. [ 4 ], and Barzon et al. [ 5 ], respectively.”
Draft of Russian Guidelines of Diagnosis and Treatment of Adrenal Cortical Cancer
Mel'nichenko, G. A., Stilidi, I. S., Горбунова, В. А., Alexeev, B. Y., Beltsevich, D. G., Райхман, А. О., Kuznetsov, N. S., Zhukov, N. V., & Bokhyan, V. Y. (2014) · Endocrine Surgery · doi:10.14341/serg201414-26 · Cited by 1
“При изучении итальянского регистра [31, 32] лишь 25% опухолей надпочечников более 4 см оказались злокачественными.”
The Evaluation and Follow-up of Adrenal Incidentaloma
Kim, S. G., & Choi, D. S. (2007) · Journal of Korean Endocrine Society · doi:10.3803/jkes.2007.22.4.257 · Cited by 1
“외국의 경우에는 국가적 차원에서 진행된 여러 전향적 다 기관 연구들이 보고되었다[10,11].”
Bilateral Pheochromocytoma and Medullary Thyroid Cancer
Земляной, В. П., Lisitsyn, A. A., Nakhumov, M. M., et al. (2017) · Journal of Experimental and Clinical Surgery · doi:10.18499/2070-478x-2017-10-3-201-206 · Cited by 1
Mileto, A., Marin, D., Ho, L. M., & Nelson, R. C. (2013) · Springer eBooks · doi:10.1007/978-88-470-5469-1_6 · Cited by 1
Adrenal Incidentalomas with Review of Literature
Puri, S., Mardi, K., Gupta, N., et al. (2016) · Journal of Cytology & Histology · doi:10.4172/2157-7099.1000426 · Cited by 1
“A study has shown size of 4 cm or greater to have greater chance of malignancy [4].”
BackgroundNixon, A. M., Aggeli, C., Parianos, C., et al. (2016) · Hellenic Journal of Surgery · doi:10.1007/s13126-016-0368-9 · Cited by 1
“had a diameter <4cm, characteristics associated with benign lesions [11,12].”
BackgroundEndocrine Surgery in Cirrhotic Patients
Zaidi, N., & Berber, E. (2017) · Springer eBooks · doi:10.1007/978-3-319-52396-5_22 · Cited by 1
Nonseminomatous Germ-Cell Tumor Presenting as Bilateral Adrenal Masses
Baral, N., Bansal, R., Basyal, B., Lee, W., Kulkarni, K., Kantorovich, V., & Sharma, M. (2020) · AACE Clinical Case Reports · doi:10.1016/j.aace.2020.11.011 · Cited by 1
Huge Adrenocortical Carcinoma: Case Report and Literature Review
Jasser, M., Mehdi, R., Nedhir, B. R., et al. (2022) · Acta Scientific Medical Sciences · doi:10.31080/asms.2022.06.1132 · Cited by 1
Antenatally Detected Functional Adrenocortical Adenoma
Singh, V. K., Khanna, C., Raman, V. S., et al. (2022) · Journal of Indian Association of Pediatric Surgeons · doi:10.4103/jiaps.jiaps_25_22 · Cited by 1
“[9] Clinical observation and follow‑up is recommended for lesions 4 cm and nonfunctional lesions with benign features on imaging.”
The Hormonal Status Comparison of Unilateral and Bilateral Adrenal Adenomas: Are They the Same?
Özbaş, B., Canpolat, A. G., Özbaş, C., Çorapçıoğlu, D., & Şahi̇n, M. (2023) · European Journal of Therapeutics · doi:10.58600/eurjther665
“In a few published articles, bilateral incidentalomas of adrenal glands were different from unilateral in terms of both functionality and etiology [3,7].”
Metadata
- Authors
- Angeli, A., Osella, G., Ali, A., & Terzolo, M.
- Affiliations
- University of Turin (IT)
- ORCID
- Terzolo, M.
- Venue
- Hormone Research
- Publisher
- S. Karger AG
- Published
- 1997
- Volume
- 47
- Issue
- 4-6
- Pages
- 279-283
- ISSN
- 0301-0163 (ISSN-L)
- 1423-0046
- OpenAlex
- W2023441974
- Cited by
- 259
- References
- 0
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 6 · 2023: 8 · 2022: 9 · 2021: 12 · 2020: 13 · 2019: 7 · 2018: 12 · 2017: 14 · 2016: 11 · 2015: 14 · 2014: 13 · 2013: 5 · 2012: 9
- FWCI
- 10.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormone Research (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac tumors and thrombi
- Keywords
- adrenal incidentaloma, adrenal mass, adrenocortical carcinoma, pheochromocytoma, tumor size, CT imaging characteristics, benign versus malignant differentiation, biochemical screening, surgical management
- MeSH terms
- Adolescent, Adrenal Gland Neoplasms, Adult, Aged, Aged, 80 and over, Female, Humans, Italy, Male, Middle Aged, Pheochromocytoma, Retrospective Studies
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