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The definition of adrenal incidentaloma encompasses a heterogeneous spectrum of pathologic entities, including primary adrenocortical and medullary tumors, benign or malignant lesions, hormonally active or inactive lesions, metastases, and infections. This article provides an overview of the diagnostic clinical approach and management of the incidentally discovered adrenal masses. Approaches are based on data collected in more than 1000 cases of the Collaborative Study Group on Adrenal Incidentaloma of the Italian Society of Endocrinology and the authors' experience.
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PMID:Management approaches to adrenal incidentalomas. A view from Ancona, Italy. 1073 67

Incidentally discovered adrenal masses, or adrenal incidentalomas, have become a common clinical problem owing to wide application of radiologic imaging techniques. This definition encompasses a heterogeneous spectrum of pathologic entities, including primary adrenocortical and medullary tumors, benign or malignant lesions, hormonally active or inactive lesions, metastases, and infections. Once an adrenal mass is detected, the clinician needs to address two crucial questions: is the mass malignant, and is it hormonally active? This article provides an overview of the diagnostic clinical approach and management of the adrenal incidentaloma. Mass size is the most reliable variable to distinguish benign and malignant adrenal masses. Adrenalectomy should be recommended for masses greater than 4.0 cm because of the increased risk of malignancy. Adrenal scintigraphy has proved useful in discriminating between benign and malignant lesions. Finally, fine-needle aspiration biopsy is an important tool in the evaluation of oncological patients and it may be useful in establishing the presence of metastatic disease. The majority of adrenal incidentalomas are non-hypersecretory cortical adenomas but an endocrine evaluation can lead to the identification of a significant number of cases with subclinical Cushing's syndrome (5-15%), pheochromocytoma (1.5-13%) and aldosteronoma (0-7%). The first step of hormonal screening should include an overnight low dose dexamethasone suppression test, the measure of urinary catecholamines or metanephrines, serum potassium and, in hypertensive patients, upright plasma aldosterone/plasma renin activity ratio. Dehydroepiandrosterone sulfate measurement may show evidence of adrenal androgen excess.
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PMID:Adrenal incidentaloma. 1100 18

Adrenal epithelioid angiosarcoma is an extremely rare tumor. Even if such tumors are very aggressive, a long survival may occasionally be observed after an adrenal ectomy. A 70-year-old woman suffering from persistent right flank pain showed a 5-cm right adrenal mass plus a 2-cm liver mass at the radiologic workup, and both were suspected of being malignant. No adrenal hypersecretion was demonstrated. During an explorative median laparotomy the right adrenal gland with the whole periadrenal tissue and locoregional lymph nodes was removed. A histological examination revealed an adrenal angiosarcoma. The resection margin was tumor-free with no lymph node infiltration. The liver mass turned out to be a cistobiliary adenoma. Since no distant metastases were observed, no adjuvant chemotherapy was performed. After an 18-month follow-up the patient is still well with no sign of a relapse. When this rare adrenal tumor is encountered and curative treatment is attempted initially extensive surgical procedures are essential.
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PMID:Adrenal angiosarcoma: report of a case. 1210 88

Megestrol acetate (MA) has glucocorticoid activity and can induce significant secondary adrenal suppression. We designed this study to determine the extent of adrenal insufficiency in cancer patients receiving MA by utilising a sensitive low-dose adrenocorticotropin (ACTH) stimulation test. Adrenal function was assessed by a low-dose (0.625 microg) ACTH (1-24) stimulation test in 30 patients receiving MA for metastatic cancer. 10 of the patients who failed this test underwent a standard (250 microg) test on another day. Adrenal function was also evaluated in 15 of the patients by measuring the excretion of free cortisol in 24-h urine samples. Peak serum cortisol levels following stimulation with low-dose (0.625 microg) ACTH (1-24) were <18 microg/dl in 16 of 30 (53%) patients, of whom 9 had a basal serum cortisol level of <5 microg/dl. Five of 16 poor responders to the low-dose test showed normal stimulation with the standard (250 microg) ACTH (1-24) test. Thus, adrenal insufficiency would fail to be detected by the standard high dose test in these patients. Patients who failed the low-dose ACTH (1-24) test had lower 24-h urinary free cortisol excretion (8.7+/-10.3 microg/24 h) than normal responders (35+/-12.7 microg/24 h). Impaired adrenal function is common in cancer patients receiving MA. The low-dose ACTH (1-24) test is apparently capable of revealing adrenal insufficiency undetected by the standard high-dose ACTH test. Patients receiving MA might have inadequate adrenal function during episodes of infection or after withdrawal of MA therapy and this may require prompt corticosteroid treatment.
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PMID:A low-dose adrenocorticotropin test reveals impaired adrenal function in cancer patients receiving megestrol acetate therapy. 1455 38

Background: Adrenal composite pheochromocytoma-ganglioneuroma is uncommon. The aim of this study is to investigate the characteristics of patients with this tumor. Methods: Histologic features of 46 pheochromocytomas diagnosed over a 28-year period (1971-1998) were reviewed. The clinical records, pathologic features, and ploidy patterns of patients with composite pheochromocytoma-ganglioneuroma were studied. Cases reported in the literature were also reviewed and compared with typical pheochromocytomas. Results: Four patients (two men; two women) with composite pheochromocytoma-ganglioneuromas were found. The tumors comprised 8.7% of pheochromocytomas. The two male patients with composite tumors were younger than the two female patients (age = 32, 52 vs 73, 75, respectively). The radiologic, gross, and microscopic appearances of the tumors were heterogeneous. One patient had malignant tumor with distant metastases. Flow cytometric analysis showed that the pheochromocytoma component was aneuploid and the ganglioneuroma portion was diploid. A review of the literature showed 31 adrenal composite pheochromocytoma-ganglioneuromas. Composite tumors were seen in older patients and were bigger than typical pheochromocytomas. Conclusion: Composite pheochromocytoma-ganglioneuromas had distinctive clinicopathologic features. Life-long clinical and biochemical follow-up of these patients is essential in view of the non-diploid DNA pattern.
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PMID:Composite Pheochromocytoma-Ganglioneuroma of the Adrenal Gland: An Uncommon Entity with Distinctive Clinicopathologic Features. 1211 71

The aim of this retrospective study was to evaluate the diagnostic accuracy of nor-cholesterol and meta-iodobenzylguanidine radionuclide imaging in two separate groups of patients with adrenal tumours to characterize lesions as adenoma or pheochromocytoma. We studied 75 patients (22 male and 53 female, mean age 47 +/- 15 years) with hypersecreting (n = 32) or non-hypersecreting (n = 43) unilateral adrenal tumours detected by computerized tomography or magnetic resonance scans. 131I nor-cholesterol adrenal scintigraphy was performed in 41 patients. Meta-[131I]iodobenzylguanidine (131I-MIBG) imaging was acquired in the other 34 patients. Pathology examinations (n = 58) or computerized tomography follow-up studies (n = 17) were obtained. Adrenal lesions were represented by 44 adenomas, four cysts, one myelolipoma, one pseudotumour, one ganglioneuroma, 16 pheochromocytomas, three carcinomas, four metastases and one sarcoma. Radionuclide studies were qualitatively evaluated and the corresponding results were classified as true positive, true negative, false positive and false negative. Diagnostic sensitivity, specificity and accuracy as well as positive and negative predictive values were calculated. The diagnostic values of nor-cholesterol scintigraphy in identifying adrenal adenomas were sensitivity 100%, specificity 71%, accuracy 95%, positive predictive value 94% and negative predictive value 100%; of note, two false positive cases were observed represented by a pheochromocytoma and a myelolipoma. The diagnostic values of MIBG scintigraphy in recognizing pheochromocytoma were sensitivity 100%, specificity 95%, accuracy 97%, positive predictive value 94% and negative predictive value 100%; only one false positive case occurred consisting of a carcinoma. It is concluded that, in the large majority of cases, adrenal scintigraphy using nor-cholesterol or MIBG is able to characterize specific lesions such as adenoma and pheochromocytoma, respectively. These findings show relevant clinical impact, particularly in patients with non-hypersecreting adrenal lasions. Radiotracer selection depends on clinical patient history and department availability; since benign adenomas are the most common cause of non-hypersecreting tumours, nor-cholesterol should be the first choice followed by MIBG if nor-cholesterol shows normal images. However, rare as well as unusual findings may be observed; nor-cholesterol uptake may occasionally be also found in non-adenoma tumours such as myelolipoma and pheochromocytoma. Similarly, MIBG accumulation may occur not only in lesions arising from medullary chromaffin tissue, but also rarely in cortical adrenal carcinoma.
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PMID:Diagnostic accuracy of radionuclide imaging using 131I nor-cholesterol or meta-iodobenzylguanidine in patients with hypersecreting or non-hypersecreting adrenal tumours. 1235 93

The incidental finding of an unsuspected adrenal mass ranges from 0.5% to 5% in abdominal CT series. The optimal diagnostic approach to such masses is to diagnose malignant or secretory tumors requiring excision and to otherwise avoid unnecessary surgery. Physical examination generally contributes little. A standard biochemical evaluation should include the measurement of 24 hour urinary catecholamines and metanephrine, urinary free cortisol and plasma cortisol levels at 8 a.m. and 8 p.m. combined with an overnight low-dose dexamethasone suppression test, serum potassium assay, and determination of upright plasma aldosterone to plasma renin activity. These tests will serve to screen for pheochromocytoma, subclinical Cushing's syndrome, and primary hyperaldosteronism respectively. Imaging characteristics suggestive of malignancy include: size greater than 4 cm., heterogeneous lesion and/or density greater than 20 Hounsfield Units on CT scan, slow enhancement with delayed washout after intravenous contrast injection on CT scan, and slightly decreased signal intensity in out of phase (fat suppressed) MR acquisition. Fine-needle aspiration biopsy should be performed only if metastatic disease is suspected. Adrenal scintigraphy with iodocholesterol may be useful where adenoma with subclinical Cushing's syndrome or solid tumor is suspected. In summary, the following strategy is recommended for the management of adrenal incidentalomas : mass lesions larger than 4 cm. and hormone-secreting tumors should be removed. All non-secreting adrenal incidentalomas smaller than 4 cm. in diameter should be followed by serial imaging at regular intervals (6, 12, and 36 months) and by endocrine reevaluation at one year.
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PMID:[Diagnostic and therapeutic strategy for an incidental finding of an adrenal mass]. 1241 Jan 36

Incidentally detected adrenal tumors are a common finding during abdominal ultrasonography, computed tomography, and magnetic resonance imaging. Although most of these lesions are benign adenomas, adrenocortical carcinomas and metastases constitute 5% to 10% of all tumors. Adrenal biopsy may be helpful, but its diagnostic value is controversial and disputed, and prospective studies have not yet been performed. Therefore, the diagnostic accuracy of adrenal core biopsy was evaluated in a prospective multicenter study involving 8 surgical centers in Germany and Austria. A total of 220 biopsies from surgical specimens of the adrenal gland were punctured in an ex vivo approach and processed for pathohistologic diagnosis using paraffin sections, routine staining, and immunohistochemistry (keratin KL1, vimentin, S100 protein, chromogranin A, synaptophysin, neuron-specific enolase, D11, MiB-1, and p53 protein). The evaluating pathologist was blinded for clinical data from the patients. A total of 89 adrenal adenomas (40.5%), 22 adrenal carcinomas (10.0%), 55 pheochromocytomas (25.0%), 15 metastases (6.8%), 16 adrenal hyperplasias (7.2%), and 23 other tumors (10.5%) were studied. Nine cases were excluded due to incomplete data (n = 2) or insufficient biopsy specimen (n = 7). In the remaining 211 tumors, compared with the final diagnoses of the surgical specimen, bioptic diagnoses were absolutely correct in 76.8% of the cases, nearly correct in 13.2% of the cases, and incorrect in 10% of the cases. Pheochromocytomas were correctly diagnosed in 96% of the cases, cortical adenomas were correctly or nearly correctly reported in 91% of the cases, cortical carcinomas were correctly or nearly correctly reported in 76% of the cases, and metastases were correctly or nearly correctly reported in 77% of the cases. Of the 39 malignant lesions, only 4 were misclassified, 2 as benign and 2 as possibly malignant. This resulted in an overall sensitivity for malignancy of 94.6% and specificity of 95.3%. Our findings suggest that adrenal core biopsy is a useful method for identifying and classifying adrenal tumorous lesions if sufficient biopsy specimens can be obtained. However, in clinical practice it remains to be shown whether the benefits of biopsy outweigh the risks of the procedure.
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PMID:High diagnostic accuracy of adrenal core biopsy: results of the German and Austrian adrenal network multicenter trial in 220 consecutive patients. 1261 87

We report a case of bilateral adrenal vein thrombosis in an adult female who had a history of breast cancer. The patient does not have clinical, serological or imaging evidence of metastatic disease 14 months from the initial diagnosis. Adrenal vein thrombosis is a rare entity. There have been no previous reports specifically stating an association between adrenal vein thrombosis and hypercoaguability, but there are many cases in the literature documenting venous thrombosis elsewhere within the body in patients with hypercoaguable states. Laboratory testing performed to exclude a hypercoaguable state, revealed heterozygosity for the Factor V Leiden mutation/activated protein C resistance and elevated factor VIII levels [3660 IU l(-1) (<1500)]. This is the first reported case of bilateral metachronous adrenal vein thrombosis in which MRI established the diagnosis.
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PMID:MRI diagnosis of bilateral adrenal vein thrombosis. 1289 1

Adrenocortical tumours have to be differentiated from cortical hyperplasias, medullary tumours and extra-adrenal tumours or metastases. These diagnoses are mostly possible using routine paraffin sections. In some cases, immunostaining for differing cortical and medullary tumours and metastases are necessary. Adrenal hyperplasias can be congenital or acquired. They are diffuse, micronodular or macronodular and may be inactive or induce a cortical hyperfunction. Very rarely, macronodular hyperplasias may transform into autonomous adenomas. Primary, pigmented adrenocortical disease is a rare, special type of primary adrenal Cushing's syndrome, showing many small tumours with pleomorphic cells and an atrophic surrounding cortical tissue. Adrenal adenomas are mostly unilateral and solitary tumours weighing less than 50 g. Adrenal cortical carcinomas are mostly larger. Like the adenomas, they may be inactive and may induce a hypercortisolism, a hyperandrogenism or (very rarely in carcinomas) a hyperaldosteronism. Differentiating cortical adenomas and carcinomas is difficult in some cases but is possible using a diagnostic algorithm. Myelolipomas are benign, inactive tumours composed of mature fat cells and bone marrow cells. They have to be differentiated from adenomas with myelolipomatous metaplasia. Further, rare primary cortical tumours are mentioned.
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PMID:[Adrenocortical tumours]. 1451 74


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