Clinically inapparent adrenal masses are incidentally detected after imaging studies conducted for reasons other than the evaluation of the adrenal glands. They have frequently been referred to as adrenal incidentalomas. In preparation for a National Institutes of Health State-of-the-Science Conference on this topic, extensive literature research, including Medline, BIOSIS, and Embase between 1966 and July 2002, as well as references of published metaanalyses and selected review articles identified more than 5400 citations. Based on 699 articles that were retrieved for further examination, we provide a comprehensive update of the diagnostic and therapeutic approaches focusing on endocrine and radiological features as well as surgical options. In addition, we present recent developments in the discovery of tumor markers, endocrine testing for subclinical disease including autonomous glucocorticoid hypersecretion and silent pheochromocytoma, novel imaging techniques, and minimally invasive surgery. Based on the statements of the conference, the available literature, and ongoing studies, our aim is to provide practical recommendations for the management of this common entity and to highlight areas for future studies and research.

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The Clinically Inapparent Adrenal Mass: Update in Diagnosis and Management

Adrenal cortical carcinoma is a rare endocrine tumor for which complete surgical resection is the only potentially curative treatment. Accurate preoperative evaluation (biochemical and radiographic) of the patient who presents with an adrenal mass maximizes the opportunity for the patient to undergo a complete, margin-negative resection of the primary tumor, which is the most powerful prognostic variable for long-term survival. The response to chemotherapy or mitotane is modest in patients with advanced disease. Hopefully, an improved understanding of the molecular pathogenesis of this challenging tumor will lead to the development of more effective therapies in the future.

Adrenal cortical carcinoma

Positron emission tomography (PET) is a diagnostic imaging technique that allows identification of biochemical and physiologic alterations in tumors. Use of PET performed with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) significantly improves the accuracy of tumor imaging. In terms of oncologic applications, FDG PET has already gained widespread acceptance in the initial staging of cancer, management of recurrent cancer, and monitoring the response to therapy. With conventional imaging modalities, size criteria are used to distinguish between benign and malignant disease in lymph nodes; conversely, FDG PET is based on identification of fundamental aspects of tumor metabolism. FDG uptake in tumors is proportional to the metabolic rate of viable tumor cells, which have an increased demand for glucose. The high sensitivity and high negative predictive value of FDG PET in most malignant tumors enable this technique to play an even greater role in tumor management at initial staging and follow-up.

https://pubs.rsna.org/doi/pdf/10.1148/rg.232025705

Clinical Role of FDG PET in Evaluation of Cancer Patients

The purpose of this study was to analyze the CT contrast enhancement washout curves of adrenal masses and to determine the earliest time after initial enhancement that differentiation of adenomas from nonadenomas is possible.Contrast enhancement washout curves were generated after delayed contrast-enhanced CT scans of 52 adrenal adenomas and 24 nonadenomas. The optimal threshold value and corresponding sensitivity and specificity for the diagnosis of adenoma were determined according to attenuation values. Also, we calculated the percentage and relative percentage of enhancement washout at time delays from 5 to 45 min after initial enhancement.The mean percentage of enhancement washout for adrenal adenomas was 51% at 5 min and 70% at 15 min, compared with 8% and 20%, respectively, for nonadenomas. The sensitivity and specificity for the diagnosis of adenoma were both 96% at a threshold attenuation value of 37 H on the 15-min delayed enhanced scan.On CT, adrenal adenomas show a much earlier and more rapid ...

https://www.ajronline.org/doi/pdfplus/10.2214/ajr.170.3.9490968

CT time-attenuation washout curves of adrenal adenomas and nonadenomas.

Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in “incidentalomas” have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 pg/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol-producing tumors, and the findings in these patients were compared with those of overt Cushina’s syndrome in 8 uatients (8 females. awd 26-50 yr) suffering from coriisoi-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test. (J Clin Endocrinol Metab 75: 826-832, 1992)

https://epub.ub.uni-muenchen.de/7006/2/Reincke_Martin_7006.pdf

Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome.

Fast gradient-echo magnetic resonance (MR) imaging of 38 adrenal masses with proved diagnosis was performed during suspended respiration with various repetition times (TRs), echo times (TEs), and flip angles. Dynamic perfusion studies after gadolinium diethylenetriamine-pentaacetic acid (DTPA) administration were performed by repeated imaging at short time intervals. With more T2 weighting (TR = 60 msec, TE = 30 msec, and flip angle = 15 degrees), malignant tumors and pheochromocytomas had a significantly higher relative signal intensity than adenomas; overlap of signal intensity led to equivocal findings in nine cases. After administration of Gd-DTPA, adenomas showed only mild enhancement and quick washout; malignant tumors and pheochromocytomas showed strong enhancement and slower washout. Five of the nine cases that were equivocal in precontrast images could thus be correctly classified. In addition to this improved classification of adrenal masses, fast, dynamic contrast material-enhanced MR imaging resulted in a reduction in total examination time.

Adrenal masses: evaluation with fast gradient-echo MR imaging and Gd-DTPA-enhanced dynamic studies.

During an 18-month period, a prospective study comparing the findings at computed tomography (CT) and magnetic resonance (MR) imaging was conducted on 35 patients who satisfied the following criteria: prior surgery for rectal cancer (11 curative resections, 24 rectal amputations), perineal pain and/or elevated carcinoembryonic antigen (CEA) level, and a soft-tissue mass in the presacral fossa demonstrated at CT. Twenty-two patients had tumor recurrence; 13 patients had only inflammatory changes or radiation fibrosis. At a single examination of each patient (with no reference to prior baseline studies), MR imaging was more accurate than CT, largely because MR imaging was more successful in the distinction of recurrence from fibrosis based on the differences in signal intensity on T2-weighted images.

W Steinbrich

Papers

Adrenal masses: evaluation with fast gradient-echo MR imaging and Gd-DTPA-enhanced dynamic studies.

Recurrent rectal cancer: diagnosis with MR imaging versus CT.