A Comparison of Near-Infrared Autofluorescence Findings in Benign Versus Malignant Adrenal Tumors.

BACKGROUND: Many adrenal tumors are deemed radiologically indeterminate and surgically removed. Adrenal tissue, like parathyroid glands, exhibits near-infrared autofluorescence (NIRAF) properties. This study was designed to investigate the potential of NIRAF to differentiate benign versus malignant adrenal tumors. METHODS: Patients undergoing adrenalectomy between October 2021 and May 2023 were prospectively studied. Adrenalectomy specimens were inspected with NIRAF imaging. Specimen autofluorescence (AF) characteristics were recorded. Comparisons were made between different tumor types and a logistic regression model was constructed to differentiate benign versus malignant tumors. A receiver operating characteristic curve was used to identify an optimal AF threshold differentiating benign versus malignant tumors. RESULTS: A total of 108 adrenal specimens were examined: adrenocortical adenomas/other benign lesions (n = 72), pheochromocytomas (n = 18), adrenocortical neoplasms of uncertain behavior (n = 4), and malignant tumors (n = 14). A significant difference in normalized AF intensity was identified when comparing adrenocortical adenomas (3.08 times background) with pheochromocytomas (1.95, p = 0.001) and malignant tumors (1.11, p < 0.0001). The Area Under the Curve differentiating benign vs malignant tumors was 0.87, with an optimal normalized AF threshold at 1.93. CONCLUSIONS: Different adrenal pathologies exhibit diverse AF properties. These findings suggest a potential intraoperative utility of NIRAF in predicting benign versus malignant nature for radiologically indeterminate adrenal tumors.

Using CT radiomic features based on machine learning models to subtype adrenal adenoma.

BACKGROUND: Functioning and non-functioning adrenocortical adenoma are two subtypes of benign adrenal adenoma, and their differential diagnosis is crucial. Current diagnostic procedures use an invasive method, adrenal venous sampling, for endocrinologic assessment. METHODS: This study proposes establishing an accurate differential model for subtyping adrenal adenoma using computed tomography (CT) radiomic features and machine learning (ML) methods. Dataset 1 (289 patients with adrenal adenoma) was collected to develop the models, and Dataset 2 (54 patients) was utilized for external validation. Cuboids containing the lesion were cropped from the non-contrast, arterial, and venous phase CT images, and 1,967 features were extracted from each cuboid. Ten discriminative features were selected from each phase or the combined phases. Random forest, support vector machine, logistic regression (LR), Gradient Boosting Machine, and eXtreme Gradient Boosting were used to establish prediction models. RESULTS: The highest accuracies were 72.7%, 72.7%, and 76.1% in the arterial, venous, and non-contrast phases, respectively, when using radiomic features alone with the ML classifier of LR. When features from the three CT phases were combined, the accuracy of LR reached 83.0%. After adding clinical information, the area under the receiver operating characteristic curve increased for all the machine learning methods except for LR. In Dataset 2, the accuracy of LR was the highest, reaching 77.8%. CONCLUSION: The radiomic features of the lesion in three-phase CT images can potentially suggest the functioning or non-functioning nature of adrenal adenoma. The resulting radiomic models can be a non-invasive, low-cost, and rapid method of minimizing unnecessary testing in asymptomatic patients with incidentally discovered adrenal adenoma.

Dual Energy-Derived Metrics for Differentiating Adrenal Adenomas From Nonadenomas on Single-Phase Contrast-Enhanced CT.

BACKGROUND. Adrenal masses are often indeterminate on single-phase postcontrast CT. Dual-energy CT (DECT) with three-material decomposition algorithms may aid characterization. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of metrics derived from portal venous phase DECT, including virtual noncontrast (VNC) attenuation, fat fraction, iodine density, and relative enhancement ratio, for characterizing adrenal masses. METHODS. This retrospective study included 128 patients (82 women, 46 men; mean age, 64.6 ± 12.7 [SD] years) who between January 2016 and December 2019 underwent portal venous phase abdominopelvic DECT that showed a total of 139 adrenal lesions with an available reference standard based on all imaging, clinical, and pathologic records (87 adenomas, 52 nonadenomas [48 metastases, two adrenal cortical carcinomas, one ganglioneuroma, one hematoma]). Two radiologists placed ROIs to determine the following characteristics of the masses: VNC attenuation, fat fraction, iodine density normalized to portal vein, and for masses with VNC greater than 10 HU, relative enhancement ratio (ratio of portal venous phase attenuation to VNC attenuation). Readers' mean measurements were used for ROC analyses, and clinically optimal thresholds were derived as thresholds yielding the highest sensitivity at 100% specificity. RESULTS. Adenomas and nonadenomas were significantly different (all p < .001) in VNC attenuation (mean ± SD, 18.5 ± 12.9 vs 34.1 ± 8.9 HU), fat fraction (mean ± SD, 24.3% ± 8.2% vs 14.2% ± 5.6%), normalized iodine density (mean ± SD, 0.34 ± 0.15 vs 0.17 ± 0.17), and relative enhancement ratio (mean ± SD, 186% ± 96% vs 58% ± 59%). AUCs for all metrics ranged from 0.81 through 0.91. The metric with highest sensitivity for adenoma at the clinically optimal threshold (i.e., 100% specificity) was fat fraction (threshold, ≥ 23.8%; sensitivity, 59% [95% CI, 48-69%]) followed by VNC attenuation (≤ 15.2 HU; sensitivity, 39% [95% CI, 29-50%]), relative enhancement ratio (≥ 214%; sensitivity, 37% [95% CI, 25-50%]), and normalized iodine density (≥ 0.90; sensitivity, 1% (95% CI, 0-60%]). VNC attenuation at the traditional true noncontrast attenuation threshold of 10 HU or lower had sensitivity of 28% (95% CI, 19-38%) and 100% specificity. Presence of fat fraction 23.8% or greater or relative enhancement ratio 214% or greater yielded sensitivity of 68% (95% CI, 57-77%) with 100% specificity. CONCLUSION. For adrenal lesions evaluated with single-phase DECT, fat fraction had higher sensitivity than VNC attenuation at both the clinically optimal threshold and the traditional threshold of 10 HU or lower. CLINICAL IMPACT. By helping to definitively diagnose adenomas, DECT-derived metrics can help avoid downstream imaging for incidental adrenal lesions.

Evaluation of the T2-weighted (T2W) adrenal MRI calculator to differentiate adrenal pheochromocytoma from lipid-poor adrenal adenoma.

OBJECTIVES: To evaluate the T2-weighted (T2W) MRI calculator to differentiate adrenal pheochromocytoma from lipid-poor adrenal adenoma. METHODS: Twenty-nine consecutive pheochromocytomas resected between 2010 and 2019 were compared to 23 consecutive lipid-poor adrenal adenomas. Three blinded radiologists (R1, R2, R3) subjectively evaluated T2W signal intensity and heterogeneity and extracted T2W signal intensity ratio (SIR) and entropy. These values were imputed into a quantitative and qualitative T2W adrenal MRI calculator (logistic regression model encompassing T2W SIR + entropy and subjective SI [relative to renal cortex] and heterogeneity) using a predefined threshold to differentiate metastases from adenoma and accuracy derived by a 2 × 2 table analysis. RESULTS: Subjectively, pheochromocytomas were brighter (p < 0.001) and more heterogeneous (p < 0.001) for all three radiologists. Inter-observer agreement was fair-to-moderate for T2W signal intensity (K = 0.37-0.46) and fair for heterogeneity (K = 0.24-0.32). Pheochromocytoma had higher T2W-SI-ratio (p < 0.001) and entropy (p < 0.001) for all three readers. The quantitative calculator differentiated pheochromocytoma from adenoma with high sensitivity, specificity, and accuracy (100% [95% confidence intervals 88-100%], 87% [66-97%], and 94% [86-100%] R1; 93% [77-99%], 96% [78-100%], and 94% [88-100%] R2; 97% [82-100%], 96% [78-100%], and 96% [91-100% R3]). The qualitative calculator was specific with lower sensitivity and overall accuracy (48% [29-68%], 100% [85-100%], and 74% [65-83%] R1; 45% [26-64%], 100% [85-100%], and 72% [63-82%] R2; 59% [39-77%], 100% [85-100%], and 79% [70-88% R3]). CONCLUSIONS: T2W signal intensity and heterogeneity differ, subjectively and quantitatively, in pheochromocytoma compared to adenoma. Use of a quantitative T2W adrenal calculator which combines T2W signal intensity ratio and entropy was highly accurate to diagnose pheochromocytoma outperforming subjective analysis. KEY POINTS: • Pheochromocytomas have higher T2-weighted signal intensity and are more heterogeneous compared to lipid-poor adrenal adenomas evaluated subjectively and quantitatively. • The quantitative T2-weighted adrenal MRI calculator, a logistic regression model combining T2-weighted signal intensity ratio and entropy, is highly accurate for diagnosis of pheochromocytoma. • The qualitative T2-weighed adrenal MRI calculator had high specificity but lower sensitivity and overall accuracy compared to quantitative assessment and agreement was only fair-to-moderate.

Partial Adrenalectomy Carries a Considerable Risk of Incomplete Cure in Primary Aldosteronism.

PURPOSE: Laparoscopic adrenalectomy is standard treatment for patients with unilateral aldosterone-producing adenomas, but surgeons are increasingly tempted to perform partial adrenalectomy, disregarding potential multinodularity of the adrenal. We assess the diagnostic value of endoscopic ultrasound for differentiating solitary adenomas from multinodularity by examining in-depth adrenal pathology with ex vivo 11.7 T magnetic resonance imaging and immunohistochemistry. MATERIALS AND METHODS: In 15 primary aldosteronism patients, we performed intraoperative endoscopic ultrasound, ex vivo magnetic resonance imaging and histopathological examination. Every adrenal was intraoperatively and postoperatively assessed for solitary adenomas or multinodular hyperplasia. After unblinding for ex vivo magnetic resonance imaging results a second detailed histopathological examination, including immunohistochemistry analysis with CYP11B2 (aldosterone synthase) and chemokine receptor 4 (CXCR4), a new marker for aldosterone-producing adenomas, was performed. Finally, presence of somatic mutations linked to aldosterone-producing adenomas was assessed. RESULTS: The sensitivity and specificity of endoscopic ultrasound to identify multinodularity were 46% and 50%, respectively. We found multinodular hyperplasia in 87% of adrenals with ex vivo magnetic resonance imaging combined with detailed histopathology, and 6 adrenals contained multiple CYP11B2-producing nodules. Every CYP11B2 positive nodule and 61% of CYP11B2 negative nodules showed CXCR4 staining. Finally, in 4 adrenals (27%) we found somatic mutations. In multinodular glands, only 1 nodule harbored this mutation. CONCLUSIONS: Intraoperative endoscopic ultrasound in primary aldosteronism patients has low accuracy to identify multinodularity. Ex vivo magnetic resonance imaging can serve as a tool to direct detailed histopathological examination, which frequently shows CYP11B2 production in multiple nodules. Therefore, partial adrenalectomy is inappropriate in primary aldosteronism as multiple aldosterone-producing nodules easily stay behind.

A case of adrenocortical adenoma harboring venous thrombus mimicking adrenal malignancy.

Advances in imaging technology and its widespread use have increased the number of identified patients with bilateral adrenal incidentalomas. The pathology of bilateral adrenal incidentalomas is gradually elucidated by its increased frequency. Although there is no consensus regarding the optimal management of bilateral adrenal lesions, adrenal lesions that are a suspected adrenocortical carcinoma on the basis of radiological imaging require surgical resection. We report a clinically interesting case of a 59-year-old female with adrenocortical adenoma harboring venous thrombus that mimicked adrenal malignancy. She was referred for evaluation of asymptomatic asymmetric lesions on both adrenal glands. Abdominal computed tomography and magnetic resonance imaging showed a 4.7-cm-diameter heterogenous lesion with peripheral enhancement in the right adrenal gland and a 2.0-cm-diameter homogenous lesion in the left adrenal gland. Adrenal scintigraphy with 131I-adosterol exhibited marked accumulation in the left lesion and slight accumulation in the middle inferior portion of the right lesion. Endocrine data revealed subclinical Cushing syndrome, and the patient underwent right laparoscopic adrenalectomy. The serum cortisol level was not suppressed on an overnight dexamethasone suppression test after the adrenalectomy. The resected tumor revealed a cortisol-producing adrenocortical adenoma harboring an organized and re-canalized venous thrombus, which was associated with focal papillary endothelial hyperplasia. This case illustrates the difficulty with preoperatively diagnosing this heterogeneously enhanced large benign adrenal lesion and differentiating it from adrenocortical carcinoma or angiosarcoma.

Pregnancy-induced Cushing's syndrome with an adrenocortical adenoma overexpressing LH/hCG receptors: a case report.

BACKGROUND: Pregnancy-induced Cushing's syndrome (CS) with an adrenocortical adenoma overexpressing luteinizing hormone (LH)/human choriogonadotropin (hCG) receptors (LHCGR) has been rarely reported in the literatures. This peculiar condition challenges the canonical diagnosis and management of CS. CASE PRESENTATION: A 27-year-old woman (G2P0A1) presented at 20 weeks gestational age (GA) with overt Cushingoid clinical features. Adrenocorticotropic hormone (ACTH)-independent CS was diagnosed based on undetectable ACTH and unsuppressed cortisol levels by dexamethasone. Magnetic resonance imaging (MRI) scanning without contrast revealed a left adrenal nodule while pituitary MRI scanning was normal. A conservative treatment strategy of controlling Cushingoid comorbidities was conducted. At 36 weeks GA, a caesarean operation was performed and a live female infant was delivered. At 8 weeks after parturition, our patient achieved normalization of blood pressure, blood glucose, serum potassium, and urinary cortisol level spontaneously. During non-pregnancy period, stimulation testing with exogenous hCG significantly evoked a cortisol increase. The woman underwent resection of the adrenal tumor at 6 months after parturition. Immunohistochemistry (IHC) showed the tumor tissue that stained positive for luteinizing hormone (LH)/human choriogonadotropin (hCG) receptor (LHCGR), whereas negative for both melanocortin 2 receptor (MC2R) and G protein-coupled receptor-1 (GPER-1). CONCLUSIONS: Stimulation test with exogenous hCG after parturition is necessary for the diagnosis of pregnancy-induced CS. LHCGR plays an essential role in the pathogenesis of this rare condition.

Chemical shift imaging for evaluation of adrenal masses: a systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis of published data to evaluate the utility of chemical shift imaging (CSI) for differentiating between adrenal adenomas and non-adenomas. METHODS: A systematic search of the MEDLINE, Web of Science Core Collection, EMBASE and Cochrane Central Register of Controlled Trials electronic databases was performed. The methodological quality of the included studies was assessed by using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. A bivariate random effect model was used to determine summary and subgroup sensitivity and specificity and calculate summary receiver operating characteristic curves (SROC). RESULTS: Eighteen studies with 1138 patients and 1280 lesions (859 adenomas, 421 non-adenomas) in total were included. In addition to summary analysis, quantitative analyses of the adrenal signal intensity index (SII, 978 lesions, 14 studies), adrenal-to-spleen ratio (ASR; 394 lesions, 7 studies) and visual analysis (560 lesions, 5 studies) were performed. The resultant data showed considerable heterogeneity (inconsistency index I2 of 94%, based on the diagnostic odds ratio, DOR). The pooled sensitivity of CSI for adenoma was 0.94 [95% confidence interval (CI) 0.88-0.97] and pooled specificity was 0.95 (95% CI 0.89-0.97). The area (AUC) under the SROC curve was 0.98 (95% CI 0.96-0.99). The corresponding AUCs were 0.98, 0.99 and 0.95 for SII, ASR and visual evaluation, respectively. CONCLUSION: CSI has high sensitivity, specificity and accuracy for adrenal adenoma. Diagnostic performance does not improve when quantitative indices are used. KEY POINTS: • Inclusion of CSI in abdominal MRI protocols provides an effective solution for classifying adrenal masses discovered on MR exams • Visual evaluation of adrenal CSI is sufficient; use of quantitative indices does not improve diagnostic accuracy.

Differences in Growth Rate on CT of Adrenal Adenomas and Malignant Adrenal Nodules.

OBJECTIVE. The purpose of this study is to determine the differences in growth rate of adrenal adenomas and malignant adrenal nodules. MATERIALS AND METHODS. This was a retrospective review of adults with an adrenal nodule seen at two different abdominal or chest CT examinations or PET/CT examinations. Patients in the adenoma group were included if they had a CT, MRI, or pathologic diagnosis of an adrenal adenoma. Patients in the malignant group were included if they had a pathologically proven malignant adrenal nodule. Nodule growth was defined as a change in the largest axial diameter greater than or equal to 3 mm. Growth rate was calculated by dividing the change in the longest axial diameter by the time between the first and last imaging examination. RESULTS. There were 105 adenomas and 26 malignant nodules. Of the 105 adenomas, 34 (32.4%; 95% CI, 23.6-42.2%) grew, three (2.9%; 95% CI, 0.6-8.1%) became smaller, and 68 (64.8%; 95% CI, 54.8-73.8%), were unchanged in size. All 26 (100%; 95% CI, 89.1-100%) malignant nodules grew. The mean (± SD) growth rate of adenomas was 1.0 ± 0.67 mm/year (range, 0.3-2.8 mm/year), compared with 58.4 ± 78.5 mm/year (range, 5.8-395.4 mm/year) for malignant nodules (p < 0.001). A growth rate of 3 mm/year distinguished adenomas from malignant nodules with a sensitivity of 100% (95% CI, 86.8-100%) and a specificity of 100% (95% CI, 96.6-100%). CONCLUSION. Approximately one-third of radiologically proven adrenal adenomas grew, all of which grew at a rate less than 3 mm/year. All malignant adrenal nodules grew, and all at a rate greater than 5 mm/year.

Impact of hypercortisolism on skeletal muscle mass and adipose tissue mass in patients with adrenal adenomas.

CONTEXT: Abdominal visceral adiposity and central sarcopenia are markers of increased cardiovascular risk and mortality. OBJECTIVE: To assess whether central sarcopenia and adiposity can serve as a marker of disease severity in patients with adrenal adenomas and glucocorticoid secretory autonomy. DESIGN: Retrospective cohort study. PATIENTS: Twenty-five patients with overt Cushing's syndrome (CS), 48 patients with mild autonomous cortisol excess (MACE) and 32 patients with a nonfunctioning adrenal tumour (NFAT) were included. METHODS: Medical records were reviewed, and body composition measurements (visceral fat [VAT], subcutaneous fat [SAT], visceral/total fat [V/T], visceral/subcutaneous [V/S] and total abdominal muscle mass) were calculated based on abdominal computed tomography (CT). RESULTS: In patients with overt CS, when compared to patients with NFAT, the V/T fat and the V/S ratio were increased by 0.08 (P < .001) and by 0.3 (P < .001); however, these measurements were decreased by 0.04 (P = .007) and 0.2 (P = .01), respectively, in patients with MACE. Total muscle mass was decreased by -10 cm2 (P = .02) in patients with overt CS compared to patients with NFAT. Correlation with morning serum cortisol concentrations after dexamethasone suppression testing revealed that for every 28 nmol/L cortisol increase there was a 0.008 increase in V/T (P < .001), 0.02 increase in the V/S fat ratio (P < .001) and a 1.2 cm2 decrease in mean total muscle mass (P = .002). CONCLUSIONS: The severity of hypercortisolism was correlated with lower muscle mass and higher visceral adiposity. These CT-based markers may allow for a more reliable and objective assessment of glucocorticoid-related disease severity in patients with adrenal adenomas.

Retrolaparoscopic adrenalectomy assisted by three-dimensional reconstructed digital model in a patient with situs inversus totalis.

BACKGROUND: Situs inversus totalis is a relatively rare congenital anomaly. Performing the retrolaparoscopic adrenalectomy for the patient with situs inversus totalis is a skill-demanding and challenging surgical task, which has been even more rarely reported. CASE PRESENTATION: We present a case with a large right adrenal mass (10.2 × 9.4 × 7.9 cm) complicated by situs inversus totalis. This 59-year-old female patient underwent the retrolaparoscopic adrenalectomy in our department. In order to facilitate the surgical orientation and improve the manipulating accuracy, the data from computed tomography images was extracted and the three-dimensional digital model was reconstructed. Under the assistance of preoperative planning and intraoperative navigation by the three-dimensional digital model, the retrolaparoscopic adrenalectomy was technically precise and successful. The targeted adrenal tumor was excised completely with final pathological diagnosis of adrenocortical adenoma. CONCLUSIONS: Retrolaparoscopic adrenalectomy can be performed safely in patients with situs inversus totalis. The assistance of preoperative planning and intraoperative navigation by the reconstructed three-dimensional digital model can facilitate the operation and lead to more precise vessel manipulation and accurate excision of tumor that is both effective and safe.

Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism.

INTRODUCTION: The correct differentiation between unilateral and bilateral adrenal involvement in patients with primary aldosteronism (PA) is of utmost importance to justify surgical treatment. The aim of this study was to determine the accuracy of adrenal imaging compared to adrenal venous sampling (AVS), histopathology and postoperative outcome. METHODS: The data of all patients with unequivocal AVS who underwent unilateral laparoscopic adrenalectomy for primary aldosteronism between May 2004 and April 2015 were entered in this retrospective study. We compared computed tomography (CT) and magnetic resonance imaging (MRI) results with corresponding AVS data, histopathology findings and postoperative outcome. RESULTS: A total of 175 patients underwent unilateral laparoscopic adrenalectomy for primary aldosteronism. AVS was successful in 152 patients and postoperative outcome available in 148 patients. Despite unilateral disease according to AVS results, bilateral normal glands were seen in 15 MRI (17·2%) and 7 CT scans (8·5%), respectively. Unilateral enlargement of the nonhypersecreting adrenal gland was found in three MRI (3·5%) and 10 CT scans (12·2%) of patients who showed aldosterone hypersecretion deriving from the contralateral gland. Fifteen MRI (17·2%) and 18 CT scans (22·0%) revealed bilateral adrenal pathology despite unilateral aldosterone hypersecretion. CONCLUSION: The accuracy of CT and magnetic resonance imaging in predicting unilateral disease is poor. AVS appears to be an essential diagnostic step to identify those patients who may benefit from unilateral adrenalectomy.

Diagnostic accuracy of virtual non-contrast enhanced dual-energy CT for diagnosis of adrenal adenoma: A systematic review and meta-analysis.

OBJECTIVE: To compare the diagnostic accuracy of dual-energy (DE) virtual non-contrast computed tomography (vNCT) to non-contrast CT (NCT) for the diagnosis of adrenal adenomas. METHODS: Search of multiple databases and grey literature was performed. Two reviewers independently applied inclusion criteria and extracted data. Risk of bias was assessed using QUADAS-2. Summary estimates of diagnostic accuracy were generated and sources of heterogeneity were assessed. RESULTS: Five studies (170 patients; 192 adrenal masses) were included for diagnostic accuracy assessment; all used dual-source dual-energy CT. Pooled sensitivity for adrenal adenoma on vNCT was 54% (95% CI: 47-62%). Pooled sensitivity for NCT was 57% (95% CI: 45-69%). Pooling of specificity was not performed since no false positives were reported. There was a trend for overestimation of HU density on vNCT as compared to NCT which appeared related to contrast timing. Potential sources of bias were seen regarding the index test and reference standard for the included studies. Potential sources of heterogeneity between studies were seen in adenoma prevalence and intravenous contrast timing. CONCLUSIONS: vNCT images generated from dual-energy CT demonstrated comparable sensitivity to NCT for the diagnosis of adenomas; however the included studies are heterogeneous and at high risk for some types of bias. KEY POINTS: • Similar sensitivity of vNCT to NCT for diagnosis of adenoma • Heterogeneity could be related to vNCT from early (<=60 sec) CECT studies • Could not pool specificity as there were no false positives • Small number of heterogeneous studies at high risk of bias.

Can Imaging Predict Subclinical Cortisol Secretion in Patients With Adrenal Adenomas? A CT Predictive Score.

OBJECTIVE: The aim of this study is to determine whether any correlation between CT findings and functional parameters exists to predict subclinical glucocorticoid secretion. MATERIALS AND METHODS: This is a retrospective database study of 55 patients with incidentally discovered adenomas, investigated through CT with an adrenal protocol, assessing diameters and attenuation values on the unenhanced and contrast-enhanced phases. Patients underwent blood cortisol and corticotropin evaluation and overnight dexamethasone suppression test (DST), in accordance with clinical recommendations. Cortisol levels higher than 50 nmol/L after DST identified subclinical cortisol secretion. We identified 28 subjects with lipid-rich nonsecreting adenomas, nine with lipid-rich secreting adenomas, 11 with lipid-poor nonsecreting adenomas, and seven with lipid-poor secreting adenoma. RESULTS: Cortisol levels after DST were significantly and positively related to mass diameters. At univariate analysis, maximum and minimum diameters and attenuation in the delayed phase were significantly related to the presence of secreting or nonsecreting adenoma; at multivariate analysis, only the minimum diameter and the attenuation in the venous phase entered the stepwise logistic regression. Similarly, minimum diameter and attenuation in the venous phase emerged also at the multivariate stepwise regression between radiologic parameters and cortisol levels after DST. The formula of the radiologic score computed by using the coefficients of the multivariate regression was as follows: (0.1914 × minimum diameter) + (0.0308 × enhanced attenuation). The diagnostic accuracy of this discriminatory score in differentiating secreting from nonsecreting adenomas was 84.9%, the sensitivity was 81.3%, and the specificity was 87.2%. Adenomas with scores greater than 7.59 were considered as secreting adenomas, and adenomas with scores less than 7.36 were considered as nonsecreting adenomas. CONCLUSION: This study shows that imaging parameters can predict subclinical cortisol hypersecretion in patients with adrenal adenomas.

Utility of MRI to Differentiate Clear Cell Renal Cell Carcinoma Adrenal Metastases From Adrenal Adenomas.

OBJECTIVE: The purpose of this study is to compare MRI features of clear cell renal cell carcinoma (RCC) adrenal metastases and adenomas. MATERIALS AND METHODS: Fifteen clear cell RCC adrenal metastases imaged with MRI were compared to 29 consecutive adenomas between 2006 and 2015. Two blinded radiologists assessed homogeneity (homogeneous vs heterogeneous), signal intensity (SI) decrease on chemical-shift MRI, and T2-weighted SI (isointense, mildly hyperintense, or markedly hyperintense) relative to muscle. A third blinded radiologist measured the chemical-shift SI index, adrenal-to-spleen SI ratio, T2-weighted SI ratio, AUC for contrast-enhanced MRI, and histogram analysis. Analyses were performed using chi-square, linear regression, ROC, and logistic regression modeling. RESULTS: Clear cell RCC metastases were larger than adenomas (mean [± SD], 5.0 ± 4.2 cm [range, 1.1-15 cm] vs 2.0 ± 0.7 cm [range, 1.2-3.7 cm]; p < 0.0001). Subjectively, 33.3% (5/15) of metastases and 68.9% (20/29) of adenomas showed an SI decrease on chemical-shift MRI (p = 0.0421; κ = 0.76). Chemical-shift SI index (mean, 9.2% ± 20.6%; range, -30.0% to 57.9%) and adrenal-to-spleen SI ratio (0.94 ± 0.23 [range, 0.44-1.33]) for metastases differed significantly from those for adenomas (47.3% ± 27.8% [range, -9.4% to 86%] and 0.52 ± 0.28 [range, 0.13-1.11], respectively) (p < 0.0001). Twenty percent (3/15) of metastases had chemical-shift SI index in the adenoma range (> 16.5%). Metastases had higher T2-weighted SI than did adenomas, both quantitatively (5.1 ± 3.0 [range, 1.5-10.6] vs 1.8 ± 0.8 [range, 0.5-3.8]; p < 0.0001) and subjectively (p < 0.0001; κ = 0.89). Metastases had higher entropy than did adenomas (6.76 ± 0.61 vs 6.1 ± 0.74; p = 0.0051) and were subjectively more heterogeneous (p < 0.0001; κ = 0.86). The contrast-enhanced MRI AUC, skewness, and kurtosis did not differ between groups (p > 0.05). The ROC AUCs were 0.91 (95% CI, 0.79-1.0) for T2-weighted SI ratio and 0.85 (95% CI, 0.68-1.0) for entropy. The logistic regression model of T2-weighted SI ratio plus entropy improved accuracy (ROC AUC, 0.97; 95% CI, 0.93-1.0]) compared with either feature alone (p = 0.0215). CONCLUSION: Increased T2-weighted SI and heterogeneity are features that can differentiate clear cell RCC adrenal metastases from adenomas using quantitative and subjective analysis.

Pheochromocytoma with Synchronous Ipsilateral Adrenal Cortical Adenoma.

BACKGROUND: Pheochromocytoma with synchronous ipsilateral adrenal cortical adenoma (PSCA) may present with mixed clinical, biochemical, and radiological features characteristic to each neoplasm subtype. METHODS: All patients with a pathological diagnosis of pheochromocytoma were evaluated for an ipsilateral cortical adenoma from 1994 through 2015. Retrospectively extracted data included indications for adrenalectomy, diagnostic workup (biochemical and radiographic), operative characteristics, pathological findings, and postoperative complications. RESULTS: Sixteen of 413 patients (4%) undergoing adrenalectomy for pheochromocytoma had a PSCA. Median patient age was 57.7 years (IQR 50.1, 63.1); 50% were male. On imaging, 75% of the adrenal neoplasms were found incidentally and only 50% were reported to have a synchronous ipsilateral neoplasm based on imaging findings. Clinically important cortical hormone secretion was diagnosed in 38% of these patients; 25% had glucocorticoid secretory autonomy; and 13% had primary aldosteronism. CONCLUSION: Physicians should be aware that adrenal neoplasms with mixed diagnostic findings may represent PSCA. Evaluation should be performed on this co-occurrence to prevent perioperative complications from resection of an unexpected secretory cortical neoplasm.

Spinal adrenal cortical adenoma associated with Beckwith-Wiedemann syndrome: case report and review of the literature.

PURPOSE: Ectopic adrenal cortical adenoma in the spinal region is extremely rare. The majority of cases of ectopic adrenocortical tissue are found along the path of embryonic migration within the urogenital tract. Beckwith-Wiedemann syndrome (BWS) is a pediatric overgrowth disorder involving a predisposition to tumor development, including adrenal lesions. To date, only eight spinal cases have been reported. This is the third reported case in pediatric population, the first one associated with genetic syndrome and the first benign to recur. We review the current literature on this topic. CASE DESCRIPTION: We present a 2-year-old boy affected by Beckwith-Wiedemann syndrome who developed a tumor at L4-L5 level. He underwent a gross total resection with MRI post-surgery demonstrating non-residual tumor. Histology disclosed an ectopic adrenal cortical adenoma with oncocytic features. Immunohistochemically was positive for inhibin-alpha, synaptophysin, and melan-A. It was negative for chromogranin A, GFAP, S-100, and other markers. One year later, he developed a recurrence at the same level being necessary a second surgery leaving a small sheet of residual tumor. CONCLUSION: Spinal adrenocortical adenomas are exceptional, and its behavior could be related to other conditions such as BWS. Gross total resection can be curative but a tight follow-up is needed. Immunohistochemical studies that include inhibin-alpha, synaptophysin, and melan-A can be useful in differential diagnosis as ultrastructural study. The decision on how to treat these patients is difficult given the low number of cases.

[Fortuitous discovery of an adrenal mass following spontaneous retroperitoneal hemorrhage]. / Découverte fortuite d'une masse surrénalienne suite a une hémorragie rétroperitonéale spontanée.

We report a case of spontaneous retroperitoneal haemorrhage by bleeding of an adrenal adenoma. Retroperitoneal haemorrhages are rarely encountered in practice, but must be rapidly diagnosed due to the life threatening risk. The etiologies, clinical assessment, management and differential diagnosis of spontaneous retroperitoneal haemorrhages are discussed.

Nous rapportons un cas d'hémorragie rétro-péritonéale spontanée sur saignement d'un adénome surrénalien. Les hémorragies rétro-péritonéales sont rarement rencontrées en pratique, mais doivent être rapidement diagnostiquées en raison du risque vital pour le patient. Les étiologies, la mise au point clinique, la prise en charge et le diagnostic différentiel des hémorragies rétro-péritonéales spontanées sont discutés.

Primary Hyperaldosteronism Due to Adrenocortical Adenoma: a Case Report.

Primary hyperaldosteronism is an adrenal abnormality in which there is some degree of autonomy of aldosterone secretion. We report a case of thirty three years old Javanese female presented with uncontrolled hypertension, muscular weakness, cramps  and progressing shortness of breath during working for 6 years. She had history of hypertension since age 20. Her serum potassium level was always low that associated with inappropriate kaliuresis. Blood gas analysis revealed metabolic alkalosis. Sonography of the adrenal gland showed right hipoechoic architecture; CT scan of the abdomen confirmed an right adrenal tumor measured 4 cm in its greatest dimension. Endocrine evaluation revealed high plasma aldosterone concentration, suppressed plasma renin activity, aldosterone/renin ratio of 112 and confirmed the diagnosis of primary aldosteronism. She underwent unilateral adrenalectomy. Histopathological report from excised adrenal tumor were compatible to benign adrenocortical adenoma. The patient discharge home with well controlled blood pressure and normokalemia. No clinical symptoms was reported in follow-up.

Contralateral adrenal suppression on adrenocortical scintigraphy provides good evidence showing subclinical cortisol overproduction from unilateral adenomas.

Unilateral and/or predominant uptake on adrenocortical scintigraphy (ACS) may be related to autonomous cortisol overproduction in patients with subclinical Cushing's syndrome (SCS). However, there is no information regarding whether increased tracer uptake on the tumor side or decreased uptake on the contralateral side on ACS is more greatly associated with inappropriate cortisol production. Therefore, we evaluated the relationship between quantitative 131I-6ß-iodomethyl-norcholesterol (131I-NP-59) uptake in both adrenal glands and parameters of autonomic cortisol secretion and attempted to set a cut off for SCS detection. The study included 90 patients with unilateral adrenal adenoma who fulfilled strict criteria. The diagnosis of SCS was based on serum cortisol ≥3.0 µg/dL after 1-mg dexamethasone suppression test (DST) with at least 1 other hypothalamus-pituitary-adrenal axis function abnormality. Twenty-two (27.7%) subjects were diagnosed with SCS. The uptake rate on the affected side in the SCS group was comparable to that in the non-functioning adenoma group. In contrast, the uptake rate on the contralateral side was lower and the laterality ratio significantly higher in the SCS group. The two ACS indices were correlated with serum cortisol levels after a 1-mg DST, but uptake on the tumor side was not. Tumor size was also important for the functional statuses of adrenal tumors and NP-59 imaging patterns. The best cut-off point for the laterality ratio to detect SCS was 3.07. These results clearly indicate that contralateral adrenal suppression in ACS is good evidence showing subclinical cortisol overproduction.