Indeterminate Adrenal Masses Research Articles

8097 A Rare Case of a Renal Cell Carcinoma and Pheochromocytoma Collision Tumor

Abstract Disclosure: R. Daas: None. S. Logan: None. W. Sexton: None. V. Chumbalkar: None. M. McGettigan: None. C. Veloski: None. Background: Collision tumors are neoplasms comprised of two or more distinct tumors. A collision tumor consisting of a renal cell carcinoma and pheochromocytoma is extremely rare with less than five cases reported in the literature. Clinical Case: A 64-year-old male with a history of hypertension and type 2 diabetes presented with hematuria. The patient was on 4 anti-hypertensive medications at the time. He noted increased road rage, anxiety, tremors, and insomnia. A CT abdomen/pelvis revealed an exophytic 8.6 x 7.9 cm left upper pole renal mass and a 7.5 x 6.2 cm left adrenal mass. Contrast-enhanced MRI abdomen showed a left upper/interpolar renal mass with heterogenous peripheral enhancement, restricted diffusion, and areas of central necrosis along with a heterogenous, enhancing left adrenal mass with associated restricted diffusion and areas of cystic necrosis. Both masses had associated areas of hyperintense signal on T1 fat-suppressed MRI suggestive of hemorrhage. Lab work revealed ACTH 26.6 pg/mL (7.2-63.3), cortisol 13 ug/dL (3.7-19.4), aldosterone 23.1 ng/dL (4-31), renin 4 ng/mL/hr (0.5-4), dopamine 136 pmol/L (<240), epinephrine 121 pmol/L (<330), norepinephrine 23,666 pmol/L (1050-4800), plasma normetanephrines 12.3 nmol/L (0-0.89), plasma metanephrines <0.10 nmol/L (0-0.49), 24-hour urine normetanephrines 4,178 mcg (122-676) and 24-hour urine metanephrines 4,233mcg (224-832). The patient was treated with alpha blockade prior to left radical nephrectomy, left adrenalectomy and infrahilar paraaortic lymph node dissection. Despite aggressive preoperative alpha blockade with maximal doses of doxazosin, addition of metyrosine and other anti-hypertensives, he developed acute hypertension with adrenal mass manipulation during the procedure and then hypotension following removal. He was admitted to the ICU for management of hypotension with pressors and fluid resuscitation and did well. Post-operative labs showed plasma normetanephrines 0.98 nmol/L (0.00-0.89) and plasma metanephrines 0.11 nmol/L (0.00-0.49). Pathology revealed clear cell renal cell carcinoma (RCC) of the kidney. The adrenal gland showed 2 tumors; one consistent with pheochromocytoma and another intimately associated with the former consistent with metastatic RCC, morphology diagnostic of a collision tumor. Following surgical resection, the patient was referred for genetic testing, surveillance imaging and lab testing, and treated with pembrolizumab adjuvant therapy for stage IV RCC. Conclusion: Although collision tumors are rare, biochemical testing to rule out a pheochromocytoma must be performed for all indeterminate adrenal masses and presumed adrenal metastases of active malignancies. Presentation: 6/2/2024

Comparative Analysis of FSE T2 Weighted, Chemical Shift and Dynamic Contrast-Enhanced MR Imaging in the Characterization of Adrenal Masses Based on Qualitative and Quantitative Parameters.

The purpose of our study was to investigate the role of different magnetic resonance imaging (MRI) parameters in the characterization of adrenal masses. A total of 150 patients who presented with 186 adrenal tumors were retrospectively evaluated in this study. Final patient cohort consisted of 17 pheochromocytomas, 3 adrenocortical carcinomas, 24 metastases, 31 lipid-poor adenomas and 111 lipid-rich adenomas. We carried out a visual assessment on FSE (Fast spin echo)T2 weighted images and also calculated T2 signal intensity ratio of all adrenal masses and also performed a qualitative assessment on chemical shift imaging (CSI) together with quantitative calculation using Adrenal to spleen signal intensity (si) ratio and Adrenal si index formulas. On dynamic contrast-enhanced sequences, visual assessment based on enhancement patterns on late-arterial phase images was performed and also mean signal intensity measurements were carried out. All examinations were interpreted by two abdominal radiologists in consensus who were blinded to the clinical and pathological findings. Statistical analysis was performed. On FSE T2 weighted imaging, isointense to liver and slightly hyperintense than liver was found higher in benign cases, however, in malignant cases moderately and strikingly hyperintense than liver was higher than in benign cases (p=0.001, p<0.01). There was a statistically significant difference between the T2 signal intensity ratio values of adrenal tumor groups (p=0.001, p<0.01). In lipid-rich and lipid-poor adenoma groups, T2 signal intensity ratio values was significantly lower than in pheochromocytoma and metastasis cases. In malignant group, T2 signal intensity ratio values were found statistically significantly higher than in the benign group (p=0.001, p<0.01). There was a statistically significant difference between CSI visual assessment of adrenal tumor groups (p=0.001, p<0.01). Although moderate and significant signal intensity loss was usually detected in lipid-rich adenoma group, never detected in other tumor groups. There was also a statistically significant difference between benign and malignant adrenal tumor groups (p=0.001, p<0.01). In the malignant group, Adrenal to spleen si ratio values were found significantly higher whereas, Adrenal si index values were significantly lower compared to benign tumors (p=0.001, p<0.01). Based on malignancy, there was a statistically significant difference between adrenal tumor groups (p=0.001, p<0.01). Although capillary blush and homogenous type enhancement were more common in benign cases than in malignant ones, peripheral-patchy and strikingly capillary blush type enhancement was more frequent in malignant tumors. Based on malignancy, mean arterial signal intensity values of malignant tumors were statistically higher than benign tumors (p=0.001; p<0.01). Dynamic contrast-enhanced MRI protocol including CSI aids in the characterization of indeterminate adrenal masses. Herein, the combined use of qualitative and quantitative parameters enables more tumors to be recognized that otherwise would be indeterminate.

Pheochromocytomas Most Commonly Present As Adrenal Incidentalomas: A Large Tertiary Center Experience.

Pheochromocytomas are increasingly diagnosed in incidentally detected adrenal masses. However, the characteristics of incidental pheochromocytomas are unclear. We aimed to assess the proportion and clinical, biochemical, radiological, genetic, histopathological, and follow-up characteristics of incidental pheochromocytomas. A retrospective review was conducted of patients with pheochromocytoma seen between January 2010 and October 2022 at a large UK tertiary care center. The diagnosis was confirmed histologically or by the combined presence of increased plasma and/or urinary metanephrines (MN), indeterminate adrenal mass on cross-sectional imaging, and metaiodobenzylguanidine avidity. We identified 167 patients with pheochromocytoma; 144 (86.2%) underwent adrenalectomy, for 23 (13.8%) surgery was either awaited, deemed unsuitable due to frailty or other metastatic malignancy, or declined by the patients. Excluding pheochromocytomas diagnosed via screening genetically predisposed individuals (N = 20), 37 of 132 (28.0%) presented with adrenergic symptoms and/or uncontrolled hypertension, while 91 of 132 (69.0%) patients presented with an incidentally detected adrenal mass. Incidentally detected patients were older (median age 62 years) than those detected due to clinical suspicion (aged 42 years) or after genetic screening (aged 33 years) (all P < .05). Incidentally detected pheochromocytomas were smaller (median 42 mm) than tumors detected due to adrenergic symptoms/uncontrolled hypertension (60 mm), but larger than tumors identified by genetic screening (30 mm) (all P < .05). Increased MN excretion showed a similar pattern (symptomatic/uncontrolled hypertension > incidental > genetic screening) (all P < .05). Hereditary predisposition was detected in 20.4% of patients (incidental, 15.3%; symptomatic/uncontrolled hypertension, 42.9%). The majority of pheochromocytomas are diagnosed incidentally and have distinct clinical, radiological, biochemical, and genetic features. Their detection at older age but smaller size may point to a different underlying tumor biology.

Prediction of 2-[18F]FDG PET-CT SUVmax for Adrenal Mass Characterization: A CT Radiomics Feasibility Study

Background: Indeterminate adrenal masses (AM) pose a diagnostic challenge, and 2-[18F]FDG PET-CT serves as a problem-solving tool. Aim of this study was to investigate whether CT radiomics features could be used to predict the 2-[18F]FDG SUVmax of AM. Methods: Patients with AM on 2-[18F]FDG PET-CT scan were grouped based on iodine contrast injection as CT contrast-enhanced (CE) or CT unenhanced (NCE). Two-dimensional segmentations of AM were manually obtained by multiple operators on CT images. Image resampling and discretization (bin number = 16) were performed. 919 features were calculated using PyRadiomics. After scaling, unstable, redundant, and low variance features were discarded. Using linear regression and the Uniform Manifold Approximation and Projection technique, a CT radiomics synthetic value (RadSV) was obtained. The correlation between CT RadSV and 2-[18F]FDG SUVmax was assessed with Pearson test. Results: A total of 725 patients underwent PET-CT from April 2020 to April 2021. In 150 (21%) patients, a total of 179 AM (29 bilateral) were detected. Group CE consisted of 84 patients with 108 AM (size = 18.1 ± 4.9 mm) and Group NCE of 66 patients with 71 AM (size = 18.5 ± 3.8 mm). In both groups, 39 features were selected. No statisticallyf significant correlation between CT RadSV and 2-[18F]FDG SUVmax was found (Group CE, r = 0.18 and p = 0.058; Group NCE, r = 0.13 and p = 0.27). Conclusions: It might not be feasible to predict 2-[18F]FDG SUVmax of AM using CT RadSV. Its role as a problem-solving tool for indeterminate AM remains fundamental.

Deep learning approach for differentiating indeterminate adrenal masses using CT imaging.

Distinguishing stage 1-2 adrenocortical carcinoma (ACC) and large, lipid poor adrenal adenoma (LPAA) via imaging is challenging due to overlapping imaging characteristics. This study investigated the ability of deep learning to distinguish ACC and LPAA on single time-point CT images. Retrospective cohort study from 1994 to 2022. Imaging studies of patients with adrenal masses who had available adequate CT studies and histology as the reference standard by method of adrenal biopsy and/or adrenalectomy were included as well as four patients with LPAA determined by stability or regression on follow-up imaging. Forty-eight (48) subjects with pathology-proven, stage 1-2 ACC and 43 subjects with adrenal adenoma >3 cm in size demonstrating a mean non-contrast CT attenuation >20 Hounsfield Units centrally were included. We used annotated single time-point contrast-enhanced CT images of these adrenal masses as input to a 3D Densenet121 model for classifying as ACC or LPAA with five-fold cross-validation. For each fold, two checkpoints were reported, highest accuracy with highest sensitivity (accuracy focused) and highest sensitivity with the highest accuracy (sensitivity focused). We trained a deep learning model (3D Densenet121) to predict ACC versus LPAA. The sensitivity-focused model achieved mean accuracy: 87.2% and mean sensitivity: 100%. The accuracy-focused model achieved mean accuracy: 91% and mean sensitivity: 96%. Deep learning demonstrates promising results distinguishing between ACC and large LPAA using single time-point CT images. Before being widely adopted in clinical practice, multicentric and external validation are needed.

Prevalence of 'Fat-Poor' Adrenal Adenomas at Chemical-Shift MRI.

: To determine the prevalence of 'fat-poor' adrenal adenomas at chemical-shift-MRI. : This prospective IRB approved study identified 104 consecutive patients with 127 indeterminate adrenal masses that underwent 1.5-T chemical-shift-MRI between 2021-2023. Two blinded radiologists independently measured: 1) 2-Dimensionsal (2D) chemical-shift signal intensity (SI)-index on 2D Chemical-shift-MRI (SI-index >16.5% diagnosed presence of microscopic fat), 2) unenhanced CT attenuation (in cases where unenhanced CT was available). : From 127 adrenal masses, there were 94% (119/127) adenomas and 6% (8/127) other masses (2 pheochromocytoma, 5 metastases, 1 lymphoma). 98% (117/119) adenomas had SI-Index >16.5%, only 2% (2/119) adenomas were 'fat-poor' by MRI. SI-Index >16.5% was 100% specific for adenoma, all other masses had SI-Index <16.5%. Unenhanced CT was available in 43% (55/127) lesions (50 adenomas, 5 other masses). 34% (17/50) adenomas were lipid-poor (>10 HU). Percentage of adenomas with SI-Index >16.5% were: 1) ≤10 HU, 100% (33/33), 2) 11-29 HU, 100% (12/12), 3) ≥30 HU, 60% (3/5). No other masses had attenuation ≤10 HU (0/5). : Fat-poor adrenal adenomas are uncommon using 2D chemical-shift signal intensity index >16.5% at 1.5-T, occurring in approximately 2% of adenomas in this large prospective series.

Clinical utility of nuclear imaging in the evaluation of pediatric adrenal neoplasms.

Adrenal neoplasms rarely occur in children. They can be diagnosed in the presence of endocrine, metabolic or neurological problems, an abdominal mass, more rarely an adrenal incidentaloma, or in the context of an adrenal mass discovered in the evaluation of childhood cancer including hematologic malignancy. According to standard medical practice, pediatric malignancies are almost always evaluated by 18F-fluorodeoxyglucose positron emission tomography with computed tomography ([18F]FDG PET/CT). Nuclear imaging using specific radiotracers is also an important tool for diagnosing and staging neuroblastoma, pheochromocytoma, hormone hypersecretion, or indeterminate adrenal masses. The Hippocratic oath "primum non nocere" encourages limitation of radiation in children per the ALARA concept (as low as reasonably achievable) but should not lead to the under-use of nuclear imaging because of the potential risk of inaccurate diagnosis or underestimation of the extent of disease. As in adults, nuclear imaging in children should be performed in conjunction with hormone evaluation and morphological imaging.

A case of unilateral post-COVID-19 adrenal haemorrhage and follow-up during pregnancies.

The spectrum of endocrine-related complications of COVID-19 infection is expanding; one of the most concerning of which is adrenal haemorrhage due to the risk of catastrophic adrenal crisis. In this study, we present a case that highlights the challenging management of a large, indeterminate unilateral adrenal mass during pregnancy and draws attention to a rare yet probably underestimated complication of COVID-19. During hospitalization for severe COVID-19 pneumonia, a 26-year-old woman was incidentally found to have a 12.5 cm heterogeneous left adrenal mass. Soon after the discovery, she became pregnant and upon referral, she was in the seventh week of gestation, without clinical or biochemical features of hormonal excess. The uncertainty of the diagnosis and the risks of malignancy and surgical intervention were discussed with the patient, and a period of radiological surveillance was agreed upon. An MRI scan performed 3 months later showed a size reduction of the adrenal lesion to 7.9 cm, which was against malignancy. A Doppler ultrasound showed a non-vascular, well-defined round lesion consistent with an adrenal haematoma, likely a complication of the recent COVID-19 infection. The multidisciplinary team recommended further radiological follow-up. The patient then spontaneously had miscarriage at 12 weeks gestation. Subsequent radiological surveillance showed a further size reduction of the adrenal lesion to 5.5 cm. The patient conceived again during follow-up, and the repeated Doppler ultrasound showed stable appearances of the adrenal mass, and thus, it was agreed to continue radiological monitoring after delivery. The pregnancy was uneventful, and the patient delivered a healthy baby. An MRI scan performed after delivery showed a stable but persistent lesion consistent with a likely underlying adrenal lesion. Unilateral adrenal haemorrhage can occur as a complication of COVID-19 and should be considered in the differential diagnosis of heterogeneous adrenal masses if there is a history of recent infection. Management of large indeterminate adrenal masses during pregnancy poses several challenges and should be led by an experienced multidisciplinary team. Underlying adrenal tumours may trigger non-traumatic haemorrhages, especially if exacerbated by stressful illness.

Imaging incidental adrenal lesions.

Incidental adrenal masses are among the most common incidental lesions detected on cross-sectional imaging. The majority are benign lesions, adenomas and myelolipomas being the most common. Simple cross-sectional imaging techniques using CT and MRI permit the characterization of over 80%, thereby requiring no further imaging. The remaining lesions are considered indeterminate. These lesions consist of benign and malignant lesions sharing imaging features. Further imaging and management of these indeterminate lesions should be guided by close collaboration between different specialists in an MDT setting. Advanced imaging options include dedicated adrenal scintigraphy, positron emission tomography CT, biopsy and surveillance. Biochemical and hormonal evaluation is also important to identify hyperfunctioning adrenal lesions. This review focuses on imaging features of benign and malignant adrenal masses used for characterization and suggests an imaging pathway for indeterminate adrenal masses.

Inter-individual comparison of diagnostic accuracy of adrenal washout CT compared to chemical shift MRI plus the T2-weighted (T2W) adrenal MRI calculator in indeterminate adrenal masses: a retrospective non-inferiority study.

To compare diagnostic accuracy of washout (WO)-CT to chemical shift (CS)-MRI + T2W adrenal MRI Calculator (T2W-Calculator) to diagnose adrenal adenoma in indeterminate adrenal masses. This retrospective, cross-sectional, non-inferiority study evaluated 40 consecutive indeterminate adrenal masses; each with WO-CT and MRI. Two blinded radiologists independently evaluated in mixed order: pre-contrast attenuation (Hounsfield Units, HU) and absolute WO ([Peak.HU-Delay.HU]/[Peak.HU-Pre.HU] × 100%), Chemical Shift Signal Intensity (CS-SI) Index, T2W SI ratio, and Entropy (which were imputed into the T2W-Calculator). Diagnostic accuracy for adrenal adenoma was tabulated using 2 × 2 tables. True -positive diagnoses of adenoma were CT = Pre-HU < 10 or absolute WO ≥ 60%, MRI = SI index ≥ 16.5% or T2W-Calculator < 0.631. There were 73% (29/40) adenomas and 27% (11/40) other masses (5 pheochromocytoma, 3 solitary fibrous tumor, 1 metastasis, 1 cavernous hemangioma, and 1 adrenocortical carcinoma). Sensitivity, specificity, and accuracy for diagnosis of adenoma using CT-WO were 78% (95% confidence intervals [CI] 56-93%), 35% (14-62%), and 57% (42-71%) Reader 1 and 72% (53-87%), 46% (17-77%), and 59% (41-76%) Reader 2. Sensitivity, specificity, and accuracy for diagnosis of adenoma using MRI were 100% (88-100%), 64% (34-90%), and 82% (67-97%) Reader 1 and 86% (68-96%), 73% (39-94%), and 80% (64-95%) Reader 2. MRI had higher overall accuracy (p = 0.02 Reader 1, 0.05 Reader 2) compared to CT-WO. Chemical shift MRI combined with the T2W adrenal MRI calculator is not inferior to CT Washout for diagnosis of adrenal adenoma among indeterminate adrenal masses.

Concomitant Pheochromocytoma and Primary Aldosteronism: A Case Series and Literature Review.

ContextThe detection and management of concomitant pheochromocytoma (PHEO) and primary aldosteronism (PA) is not well understood.ObjectiveTo investigate varying presentations and outcomes of cases with coexisting PHEO and PA to provide an approach to its diagnosis and management.MethodsWe conducted a retrospective case series of adult patients with concomitant PHEO and PA at Mayo Clinic from 2000-2020 and an additional review of cases before 2000 and from the medical literature. Clinical, biochemical, radiologic, and histologic parameters were measured.ResultsFifteen patients (53% men, median age 53 years) were diagnosed with concomitant PHEO and PA. The majority presented with hypertension (13, 87%) and hypokalemia (13, 87%), and 6 (40%) presented with symptoms suggestive of catecholamine excess. All patients who underwent preoperative workup for catecholamine excess (14, 93%) were found to have biochemical levels above the upper limits of normal. Adrenal vein sampling (AVS) was performed in 9 patients (60%), where 5 (56%) were diagnosed with bilateral PA, and 4 (44%) with unilateral PA. Patients underwent either unilateral (12, 80%) or bilateral (3, 20%) adrenalectomy. Biochemical improvement or resolution of catecholamine excess was confirmed in all cases with documented measurements. Recurrence of PHEO was not observed. Six patients (40%) displayed persistent PA postoperatively.ConclusionConcomitant PHEO and PA is a rare but likely underreported condition. Hypertension with or without hypokalemia should prompt evaluation for PA, while any indeterminate adrenal mass should be assessed for PHEO. Coexisting disease warrants consideration of AVS to determine the laterality of PA to ensure appropriate management.

Severe Cushing Syndrome Due to Ectopic ACTH Secretion by Pheochromocytoma

Introduction: Ectopic ACTH production is a very unusual cause of Cushing Syndrome (CS). When it occurs, lung cancer is the main cause. Very rarely, this ectopic source of ACTH can arise from a Pheochromocytoma (Pheo). A recent literature review identified less than 100 cases described. We present a case of 28 years old woman who was referred for adrenalectomy for CS with notorious adrenal mass. However, during the investigation, ectopic ACTH due a Pheo was identified. Case Report: A 28-year-old woman required emergency care for ecchymosis and asymptomatic hypertension (BP: 230x130mmHg). Hyperpigmentation of the skin was evident on physical examination. Severe hypokalemia (K: 2.5mEq/liter) was detected. She denied taking any medication and was unaware of any previous illness. She always had normal BP measurements as well as laboratory tests. No family history of adrenal disease or secondary hypertension causes. During hospitalization, the hypothesis of CS was made and confirmed after: cortisol after 1mg dexamethasone: 44.5mcg/dl (<1.8mcg/dl) and 24h urinary free cortisol: 6228 mcg/dl (28-213mcg/dl). Concomitantly, a CT scan of the abdomen exhibited a left adrenal mass (3.1x2.8x3.5cm) of uncertain etiology and ACTH: 352pg/ml (<46pg/ml). Additionally, the patient presented hyperglycemia during hospitalization. After confirmation of the ACTH dependent CS, pituitary MRI was performed with normal results and a chest CT scan ruled out lung masses. As there was still no etiological confirmation and due to clinical deterioration, it was decided to start Ketoconazole 200mg/day, rising until 600mg and spironolactone with doses up to 250mg/day with a significant improvement in hypokalemia, decreased cortisol levels and optimal BP control. Due to the extremely high levels of ACTH and indeterminate adrenal mass, the hypothesis of ACTH ectopic due Pheo was postulated. Patient underwent abdomen MRI with left adrenal mass with hypersignal at T2 and urinary metanephrines levels: 6132mcg/24h (<289mcg/24h), urinary normetanephrines: 1808mcg/24h (<732mcg/24h). Once the diagnosis was elucidated, she received preoperative preparation with alpha blocker (Doxazosin) and underwent adrenalectomy without complications. After discharge, she received prednisone 10mg/day. The patient presented normalization of BP levels, as well as glycemic control with a slight improvement in skin hyperpigmentation. The pathology department confirmed Pheo and an ACTH expression was observed in immunohistochemistry. A genetic panel for Pheo is running with no results so far. Conclusion: Despite an extremely rare cause of CS, the ectopic production of ACTH by a Pheo has extremely high mortality rates, especially when not diagnosed or managed correctly. The clinicians must always remain alert and suspect this syndrome when the patient has a confirmed ACTH dependent CS associated with adrenal masses.

Concomitant Pheochromocytoma and Primary Aldosteronism: A Case Series and Literature Review

Objective: The detection and management of concomitant pheochromocytoma (PHEO) and primary aldosteronism (PA) is not well understood. Our objectives were to investigate varying presentations and outcomes of cases with coexisting PHEO and PA to provide an approach to its diagnosis and management. Design: Retrospective case series from 2000–2020 at a single institution tertiary center; additional review of previously known cases before 2000 and from the medical literature. Patients and Measurements: Adult patients with concomitant PHEO and PA. Clinical, biochemical, radiologic, and histologic parameters were reviewed. Results: Fifteen patients (53% men, median age 53 years) were diagnosed with concomitant PHEO and PA. The majority presented with hypertension (13, 87%) and hypokalemia (13, 87%), but only 6 (40%) presented with symptoms suggestive of catecholamine excess. All patients with preoperative work-up for catecholamine excess (14, 93%) were found to have elevated plasma or urinary metanephrines/catecholamines above the upper limit of normal. Adrenal vein sampling (AVS) was performed in 9 (60%) patients, where 5 (56%) were diagnosed with bilateral PA, and 4 (44%) with unilateral PA. All patients underwent either unilateral (12, 80%) or bilateral (3, 20%) adrenalectomy to treat their PHEO and/or PA. Postoperative catecholamines and/or catecholamine breakdown products normalized or improved in 13 (87%) patients and were not measured in 2. Recurrence of PHEO was not observed. Six (40%) displayed persistent PA postoperatively, where 4 required long-term mineralocorticoid blockade. Conclusions: Concomitant PHEO and PA is a rare but likely under-reported condition. Hypertension with or without hypokalemia should prompt evaluation for PA, while any indeterminate adrenal mass should be worked up for PHEO. Coexisting disease warrants consideration of AVS to determine the laterality of PA to ensure appropriate management.

18F-FDG-PET/CT Evaluation of Indeterminate Adrenal Masses in Noncancer Patients.

Adrenal tumors in noncancer patients are common. Evaluate performance of 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) in distinguishing between benign and malignant adrenal tumors. Retrospective chart review 2010-2019. Academic institution. One hundred and seventeen noncancer patients, defined as having no history of cancer or with cancer in remission for ≥5 years, completed 18F-FDG-PET/CT to evaluate adrenal masses, with pathologic diagnoses or imaging follow-up (≥12 months). 18F-FDG-PET/CT of 117 indeterminate adrenal masses. Receiver operator characteristic curve of the ratios of adrenal lesion standardized uptake value (SUV)max to liver SUVmean and of adrenal lesion SUVmax to aortic arch blood pool SUVmean were constructed. Seventy benign and 47 malignant masses (35 adrenocortical carcinomas [ACCs], 12 adrenal metastases) were identified. Malignant masses had higher median liver SUV and blood pool SUV ratios than benign masses (6.2 and 7.4 vs 1.4 and 2.0, P < .001). Median liver and blood pool SUV ratios of ACC (6.1 and 7.3, respectively) and metastases (6.7 and 7.7, respectively) were higher than those of than adenomas (1.4 and 2.2, P < .05 for all comparisons). Optimal liver SUV ratio to discern between benign and malignant masses was 2.5, yielding 85% sensitivity, 90% specificity, and 7 false negative results (including 3 ACCs). Optimal blood pool SUV ratio was 3.4, yielding 83% sensitivity, 90% specificity, and 8 false negative results (including 4 ACCs). When used in conjunction with other clinical assessments, 18F-FDG-PET/CT can be a valuable tool in evaluating adrenal masses in noncancer patients.

SUN-373 Small Adrenal Incidentaloma Stable in Size Becoming a Stage IV Adrenocortical Carcinoma 10 Years Later in a Young Patient Carrying a Germline APC Variant of Uncertain Significance (VUS)

Recent guidelines on adrenal incidentalomas suggested that patients with an indeterminate adrenal mass on imaging choosing not to undergo adrenalectomy to repeat imaging with either unenhanced computed tomography (CT) or Magnetic resonance imaging with chemical shift analysis in 6 to 12 months. If the adrenal mass is non-functioning and stable in size, patients may not require any additional monitoring.We report here a case of a young woman known for a small adrenal mass, stable in size for 4 years who was ultimately diagnosed with a Stage IV adrenal cortical carcinoma (ACC) 10 years later. Case report. In 2006, a 32-year-old French Canadian woman was referred in endocrinology for evaluation of a left 2.7 x 2.0 cm incidentally discovered adrenal mass. On presentation, her hormonal work up included a normal 1mg overnight dexamethasone suppression test (DST) and dehydroepiandrosterone sulfate (DHEA-S) within normal limits. On unenhanced computed tomography (CT), the radiodensity of the adrenal mass was 23 Hounsfield units (HU). The patient was followed with adrenal imaging and hormonal investigation yearly for 4 years and the adrenal mass demonstrated no growth in 4 years. Ten years after initial presentation, in 2016, after five years lost to follow up the patient presented with renal colic. Urological CT has unexpectedly revealed that the left adrenal mass had significantly progressed measuring 9 x 8.2 cm and 2 new hepatic lesions were identified. Biochemical work up demonstrated hypercortisolism and hyperandrogenemia: plasma cortisol after 1 mg overnight DST was 486 nmol/L and DHEA-S was 14.0 mmol/L (N 0.9-6.5). Twenty-four-hour urine steroid profiling was consistent with an ACC co-secreting cortisol, androgens and glucocorticoid precursors. The diagnosis of ACC with hepatic ACC metastases was confirmed by histology. Following genetic analysis, germline heterozygous variant of uncertain significance (VUS) was identified in the exon 16 of the APC gene NM_000038.5:c.2414G>A,(p.Arg805Gln) (rs200593940). The patient had no clinical manifestations of familial adenomatous polyposis. Immunohistochemical staining of the ACC were positive for IGF-2 and cytoplasmic/nuclear β-catenin, however, no somatic APC or beta-catenin mutations were found. This case illustrates that 1) small adrenal incidentaloma stable in size may progress to ACC 2) better genetic characterization of these patients may eventually give clues to this unusual evolution.

Influence of slice thickness on result of CT histogram analysis in indeterminate adrenal masses

PurposeThe aim was to determine the optimal slice thickness of CT images and the optimal threshold of negative voxels for CT histogram analysis to distinguish adrenal adenomas from non-adenomas with a mean attenuation more than 10 Hounsfield units (HU).MethodsVolume CT histogram analysis of 83 lipid-poor adenomas and 80 non-adenomas was performed retrospectively. The volume of interest was extracted from each adrenal lesion, and the mean attenuation, standard deviation (SD), and percentage of voxels with a negative CT value were recorded using reconstructions with different slice thicknesses (5 mm, 2.5 mm, 1.25 mm). The percentage of negative voxels was correlated with SD as a measure of image noise and with the reference splenic tissue values. The sensitivity, specificity, and positive predictive value (PPV) for the identification of adenomas were calculated using reconstructions with different slice thicknesses and three different thresholds of negative voxels (1%, 5%, 10%).ResultsThe percentage of negative voxels increased with a thinner slice thickness and correlated with increasing CT image noise in adenomas, non-adenomas, and spleen. Using a threshold of 10% negative voxels and a slice thickness of 5 mm, we reached a sensitivity of 53.0%, specificity of 98.8% and the highest PPV, and thus we propose this combination for clinical use. Other combinations achieved a clearly lower specificity and PPV as a result of the increasing noise in CT images.ConclusionThe CT slice thickness significantly affects the result and diagnostic value of histogram analysis. Thin CT slice reconstructions are inappropriate for histogram analysis.

Pitfalls in the management of indeterminate adrenal masses

Pitfalls in the management of indeterminate adrenal masses

Performance of 18F-FDG PET/CT in the Characterization of Adrenal Masses in Noncancer Patients: A Prospective Study.

Few prospective studies have evaluated the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the characterization of adrenal masses. To assess the performance of 18F-FDG PET/CT in the malignancy diagnosis of adrenal masses in noncancer patients. Prospective multicenter study. The study population consisted of 87 patients (87 adrenal masses) referred to endocrine surgeons: 56 with mass diameter ≥40 mm and 31 with a diameter <40 mm and of indeterminate nature based on unenhanced and washout CT attenuation densities. Fourteen patients had hypercortisolism. Adrenal masses were characterized by 18F-FDG PET/CT. Histology was the gold standard for the diagnosis of malignancy. In the absence of pathological proof (n = 23), the nature of the lesion was based on the 12-month imaging follow-up. Fifteen adrenal masses were classified as malignant (including 11 adrenocortical carcinomas) and 72 as benign. Compared with benign lesions, malignant lesions were larger in size (P = 0.003), had higher unenhanced densities (P = 0.002), lower relative washout values (P = 0.007), and higher 18F-FDG uptake parameters (P < 10-3). The optimal threshold value of (Tumor SUVmax:Liver SUVmax) the ratio for malignancy was >1.5 with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 86.7%, 86.1%, 56.5%, 96.9%, and 86.2%, respectively. Our results show that 18F-FDG PET/CT complements adrenal washout CT in the evaluation of adrenal masses and should be recommended in the evaluation of large and/or indeterminate adrenal masses.

Diffusion-weighted MRI in adrenal lesions: A warranted adjunct?

PurposeWe assessed the value of adding Diffusion-weighted (DW) sequences to conventional MR in the diagnostic adrenal algorithm, particularly in patients with indeterminate adrenal mass. We compared the predictive capabilities of apparent diffusion coefficient values (ADC), lesion size and signal drop on chemical shift MRI (CS MRI) for differentiating benign and malignant lesions. Materials and methodsFifty-five patients with 59adrenal lesions were evaluated. Lesion size, signal loss on CSMRI and ADCs were assessed. Sensitivity, specificity and accuracy were calculated for each parameter. We compared the predictive capability of ADC, CS signal drop, and lesion size for malignancy with receiver operating characteristic (ROC) curves. ResultsConsidering all lesion subtypes, ADC values showed overlap. Benign and malignant masses had statistically different mean ADCs, with greater mean ADC values in benign lesions (1.78±0.5 versus 0.97×10−3mm2/s±0.3). ADC had the lowest accuracy (71.2%) but highest specificity (100%). Lack of signal drop had the greatest sensitivity (100%); lesion size was the most accurate (88.1%). On ROC curves, ADC had the lowest prediction for malignancy. ConclusionLesion size and signal drop were stronger predictors of adrenal malignancy than ADC. ADC shows poor significance in individual cases due to overlapping values.

Value of 18-F-FDG PET/CT and CT in the Diagnosis of Indeterminate Adrenal Masses.

The purpose of this paper was to study the value of 18-FDG PET/CT and reassess the value of CT for the characterization of indeterminate adrenal masses. 66 patients with 67 indeterminate adrenal masses were included in our study. CT/MRI images and 18F-FDG PET/CT data were evaluated blindly for tumor morphology, enhancement features, apparent diffusion coefficient values, maximum standardized uptake values, and adrenal-to-liver maxSUV ratio. The study population comprised pathologically confirmed 16 adenomas, 19 metastases, and 32 adrenocortical carcinomas. Macroscopic fat was observed in 62.5% of the atypical adenomas at CT but not in malignant masses. On 18F-FDG PET/CT, SUVmax and adrenal-to-liver maxSUV ratio were significantly lower in adenomas than in malignant tumors. An SUVmax value of less than 3.7 or an adrenal-to-liver maxSUV ratio of less than 1.29 is highly predictive of benignity.