Surgical Management of Primary Aldosteronism.

Hypertension leads to multiple comorbidities and increased risk for mortality. Endocrine disorders contribute to the development of hypertension, including primary aldosteronism (PA). This article discusses the evaluation and management of PA.

Adrenal schwannoma can be FDG-Avid on PET/CT: case report and review of historic institutional pathology.

Schwannomas are benign, generally indolent tumors of neural crest origin and comprise the most common histologic tumor of peripheral nerves. Schwannomas are a rare histology for retroperitoneal tumors and very rare histologic findings for tumors of the adrenal gland with fewer than 50 cases in the reported literature. Here we present a case report of a non-hormonally functional but metabolically active adrenal tumor with indeterminate imaging characteristics with final pathology showing a 6.1 cm adrenal schwannoma as well as historical institutional pathology review revealing two additional cases.

Allelic Variant of Armadillo Repeat Containing Protein 5 (ARMC5) in Myelolipoma Mimicking Pheochromocytoma: A Case Report.

Adrenal myelolipomas are benign adrenocortical tumors composed of adipose tissue mixed with hematopoietic precursor cells. An association of myelolipoma with adrenal cortical adenoma is rare and the pathogenesis of these tumors remains unclear. Here we present a case of an incidentally discovered adrenal tumor with radiologic characteristics of a myelolipoma who underwent adrenalectomy due to biochemical suspicion for pheochromocytoma. The final pathology, however, revealed a myelolipoma with a co-existing adrenal cortical adenoma without evidence of pheochromocytoma. Genetic analysis revealed the presence of a hitherto unreported heterozygous variant, c.329C>A (p.Ala110Asp), of the armadillo repeat-containing protein 5 (ARMC5) gene which when inactivated is commonly associated with bilateral adrenal nodularity.

Lexicon for adrenal terms at CT and MRI: a consensus of the Society of Abdominal Radiology adrenal neoplasm disease-focused panel.

PURPOSE: Substantial variation in imaging terms used to describe the adrenal gland and adrenal findings leads to ambiguity and uncertainty in radiology reports and subsequently their understanding by referring clinicians. The purpose of this study was to develop a standardized lexicon to describe adrenal imaging findings at CT and MRI. METHODS: Fourteen members of the Society of Abdominal Radiology adrenal neoplasm disease-focused panel (SAR-DFP) including one endocrine surgeon participated to develop an adrenal lexicon using a modified Delphi process to reach consensus. Five radiologists prepared a preliminary list of 35 imaging terms that was sent to the full group as an online survey (19 general imaging terms, 9 specific to CT, and 7 specific to MRI). In the first round, members voted on terms to be included and proposed definitions; subsequent two rounds were used to achieve consensus on definitions (defined as ≥ 80% agreement). RESULTS: Consensus for inclusion was reached on 33/35 terms with two terms excluded (anterior limb and normal adrenal size measurements). Greater than 80% consensus was reached on the definitions for 15 terms following the first round, with subsequent consensus achieved for the definitions of the remaining 18 terms following two additional rounds. No included term had remaining disagreement. CONCLUSION: Expert consensus produced a standardized lexicon for reporting adrenal findings at CT and MRI. The use of this consensus lexicon should improve radiology report clarity, standardize clinical and research terminology, and reduce uncertainty for referring providers when adrenal findings are present.

Adrenal nodules for the non-specialist: What to look out for and when to refer.

Almost all medical specialities utilise cross-sectional imaging of the abdomen to evaluate many different medical conditions. This ever-increasing use of cross-sectional imaging has led to a dramatic increase in the detection rate of adrenal nodules. Following appropriate biochemical and radiological evaluation, the vast majority of these are shown to be benign adrenal adenomas. A small minority are diagnosed with a functional or malignant lesion that may result in significant morbidity and mortality requiring specialist management.

Computer-assisted Reporting and Decision Support Increases Compliance with Follow-up Imaging and Hormonal Screening of Adrenal Incidentalomas.

OBJECTIVE: To assess the impact of using a computer-assisted reporting and decision support (CAR/DS) tool at the radiologist point-of-care on ordering provider compliance with recommendations for adrenal incidentaloma workup. METHOD: Abdominal CT reports describing adrenal incidentalomas (2014 - 2016) were retrospectively extracted from the radiology database. Exclusion criteria were history of cancer, suspected functioning adrenal tumor, dominant nodule size < 1 cm or ≥ 4 cm, myelolipomas, cysts, and hematomas. Multivariable logistic regression models were employed to predict follow-up imaging (FUI) and hormonal screening orders as a function of patient age and sex, nodule size, and CAR/DS use. CAR/DS reports were compared to conventional reports regarding ordering provider compliance with, frequency, and completeness of, guideline-warranted recommendations for FUI and hormonal screening of adrenal incidentalomas using Chi-square test. RESULT: Of 174 patients (mean age 62.4; 51.1% women) with adrenal incidentalomas, 62% (108/174) received CAR/DS-based recommendations versus 38% (66/174) unassisted recommendations. CAR/DS use was an independent predictor of provider compliance both with FUI (Odds Ratio [OR]=2.47, p = 0.02) and hormonal screening (OR=2.38, p = 0.04). CAR/DS reports recommended FUI (97.2%,105/108) and hormonal screening (87.0%,94/108) more often than conventional reports (respectively, 69.7% [46/66], 3.0% [2/66], both p <0.0001). CAR/DS recommendations more frequently included instructions for FUI time, protocol, and modality than conventional reports (all p <0.001). CONCLUSION: Ordering providers were at least twice as likely to comply with report recommendations for FUI and hormonal evaluation of adrenal incidentalomas generated using CAR/DS versus unassisted reporting. CAR/DS-directed recommendations were more adherent to guidelines than those generated without.

ACR Appropriateness Criteria® Adrenal Mass Evaluation: 2021 Update.

The appropriate evaluation of adrenal masses is strongly dependent on the clinical circumstances in which it is discovered. Adrenal incidentalomas are masses that are discovered on imaging studies that have been obtained for purposes other than adrenal disease. Although the vast majority of adrenal incidentalomas are benign, further radiological and biochemical evaluation of these lesions is important to arrive at a specific diagnosis. Patients with a history of malignancy or symptoms of excess hormone require different imaging evaluations than patients with incidentalomas. This document reviews imaging approaches to adrenal masses and the various modalities utilized in evaluation of adrenal lesions. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

An Adrenocortical Carcinoma Evolving After Nine Years of Latency From a Small Adrenal Incidentaloma.

Adrenal incidentalomas (AIs) are common incidental findings in medical practice with clinical significance. Although most AIs are nonsecretory and nonmalignant, they require a short course of follow-up over one to two years to rule out malignancy or hormonal secretion according to clinical practice guidelines. However, this can result in some adrenocortical carcinomas (ACCs) being missed if they transform at a later stage or evolve slowly. Here, we report one such case of an AI, which although remained indolent, eventually transformed into an ACC many years after the initial detection.

Incidental Adrenal Nodules.

Incidentally detected adrenal nodules are common, and prevalence increases with patient age. Although most are benign, it is important for the radiologist to be able to accurately determine which nodules require further testing and which are safely left alone. The American College of Radiology incidental adrenal White Paper provides a structured algorithm based on expert consensus for management of incidental adrenal nodules. If further diagnostic testing is indicated, adrenal computed tomography is the most appropriate test in patients for nodules less than 4 cm. In addition to imaging, biochemical testing and endocrinology referral is warranted to exclude a functioning mass.

Comparison of Histogram-Based Gaussian Analysis With and Without Noise Correction for the Characterization of Indeterminate Adrenal Nodules.

OBJECTIVE. The purpose of this study is to determine whether gaussian-based histogram analysis without and with noise correction can characterize indeterminate adrenal nodules (those with attenuation greater than 10 HU on unenhanced CT) as lipid-poor adenomas. MATERIALS AND METHODS. This retrospective study evaluated adrenal nodules larger than 1 cm on unenhanced CT using gaussian analysis without and with noise correction on intralesional ROIs. Two independent readers who were blinded to the final diagnoses evaluated the nodules. The final diagnosis for each nodule was determined on the basis of pathologic findings or accepted imaging criteria. Interreader agreement was assessed using the intraclass correlation coefficient. Algorithm performance was summarized using sensitivity, specificity, and the AUC. RESULTS. Ninety-four adrenal nodules in 85 patients were analyzed; 36 of these were metastases (34 of which were pathologically confirmed), and 58 were presumed adenomas. Interreader agreement was excellent for nodule size, mean attenuation, SD of attenuation, and the gaussian index. Noise-corrected gaussian analysis had significantly higher specificity (81.9% vs 55.6%; p < 0.001) and lower sensitivity (36.2% vs 56.9%; p < 0.001) for identifying adenomas than did the uncorrected gaussian analysis. The AUC of corrected gaussian analysis was 0.72, which is significantly greater than that of uncorrected gaussian analysis (0.51; p ≤ 0.001) and similar to that of mean attenuation (0.77). CONCLUSION. Noise correction is necessary when using a gaussian analysis characterization of indeterminate adrenal nodules on modern unenhanced CT examinations. This method may be able to discriminate between adenomas and nonadenomas.

Utility of the 10 Hounsfield unit threshold for identifying adrenal adenomas: Can we improve?

BACKGROUND: Current recommendations using Hounsfield units (HU) ≤ 10 to identify adrenal adenomas on unenhanced computed tomography (CT) miss 10-40% of benign adenomas. We sought to determine if changing HU threshold and adding absolute percent contrast washout (APW) criteria would identify adrenal adenomas better than current recommendations. METHODS: Imaging characteristics were compared between patients with adenomas (n = 128) and those with non-adenomas (n = 54) after unilateral adrenalectomy. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated. RESULTS: Using HU ≤ 10 to identify adenomas had a sensitivity of 47.6%, specificity of 93.3% (AUC = 0.71, p < 0.001), PPV of 95.3%, and NPV of 58.1% for identifying adrenal adenomas. Applying HU ≤ 16 improved sensitivity (65.4%) without reducing specificity (93.3%) (AUC = 0.79, p < 0.001), PPV increased to 96.3%, and NPV decreased to 47.6%. Applying HU ≤ 16 as the initial criterion followed by APW > 60% for lesions exceeding 16 HU, sensitivity increased to 93.4%, specificity was 93.3% and PPV 96.6%, and NPV improved to 85.7% (AUC = 0.96, p < 0.001). CONCLUSIONS: Criteria of initial threshold of HU ≤ 16 followed by APW > 60% for lesions exceeding 16 HU yielded improved sensitivity and specificity in identification of adrenal adenomas.

Hyperaldosteronism from a large adrenal adenoma in a patient with bilateral adrenal nodules.

Primary aldosteronism (PA) is a potentially reversible cause of uncontrolled hypertension. Early diagnosis and timely management of PA can prevent end-organ damage. Aldosteronoma Resolution Score (ARS) is a useful tool to predict cure rates and resolution of hypertension after adrenalectomy.

Evaluation of diagnostic accuracy: multidetector CT image noise correction improves specificity of a Gaussian model-based algorithm used for characterization of incidental adrenal nodules.

OBJECTIVES: To investigate whether the histogram analysis method of characterizing adrenal nodules as adenomas is affected by increased noise with modern CT technique, and if an extension that allows for noise correction will improve diagnostic performance. MATERIALS AND METHODS: This is a HIPAA-compliant, IRB-approved retrospective study performed on 58 total patients. The first group of 29 patients had 33 adrenal lesions that were pathology-proven non-adenomas. The second group had 29 patients with 33 pathology-proven or presumed adenomas based on established imaging criteria. The nodules were evaluated using the histogram method, mean attenuation method, and a Gaussian model-based algorithm without (uncorrected Gaussian algorithm) and with correction (corrected Gaussian algorithm) for image noise. Sensitivity, specificity, and accuracy for identifying adenoma were derived. RESULTS: There were no significant differences in identifying adenoma from non-adenoma when using the histogram analysis method and the uncorrected Gaussian algorithm, both of which had low specificities of 42.4% and 47.0%, respectively (p = 0.30). Adding noise correction to the Gaussian algorithm resulted in a statistically significant increase in specificity relative to the histogram method (86.4% vs. 42.4%, p < 0.001). The corrected Gaussian algorithm improved sensitivity compared to the mean attenuation method (71.2% vs. 54.5%, p < 0.001), but had lower specificity (86.4% vs. 100%, p < 0.001), and similar overall accuracy (78.8% vs. 77.3%, p = 0.74). CONCLUSION: With modern low-dose CT technique, the specificity scores of the histogram method for discrimination of adrenal adenomas and non-adenomas are lower than with previous higher dose scans. The specificity and accuracy of a histogram-equivalent method can be increased mathematically through image noise correction, and the corrected Gaussian algorithm has improved sensitivity to the mean attenuation with similar accuracy albeit with lower specificity. Although this suggests limited utility for histogram analysis in adrenal nodule characterization, our study demonstrates the potential mathematical application for other noise-dependent CT characterization methods.

Caveat regarding CMS Merit-based Incentive Payment Systems incidental adrenal nodule measure.

Current Medicare MIP measures encourage radiologists not to recommend follow-up for ≤ 1 cm adrenal nodules. However, a radiologist may be the first to discover a small, subclinical pheochromocytoma. As such, recognition of the enhancement pattern of pheochromocytoma is important to ensure detection and properly guide management, which begins with clinical and laboratory assessment for elevated catecholamines.

Incidentally Detected Bilateral Adrenal Nodules in Patients Without Cancer: Is Further Workup Necessary?

OBJECTIVE: The purpose of this study was to determine the rate of malignancy in incidentally detected bilateral adrenal masses in patients with no known history of cancer. MATERIALS AND METHODS: A retrospective search of CT reports of patients with incidentally detected bilateral adrenal nodules was performed from January 1, 2002, to January 1, 2014. Patients were excluded if they had a known cancer or suspected functioning adrenal tumor; 161 patients were included. Nodules were characterized as benign or malignant on the basis of imaging features at the index CT examination, imaging features at subsequent adrenal protocol CT or MRI, imaging stability for a minimum of 1 year, or clinical follow-up of a minimum of 2 years. RESULTS: Mean nodule size was 1.8 cm (range, 0.7-4.9 cm). There were no cases of primary or secondary adrenal malignancy (95% CI, 0.00-0.023). The nodules diagnosed on index CT scans were 73 adrenal adenomas and two myelolipomas. Seventy-four nodules were subsequently characterized as adrenal adenomas on the basis of imaging findings. Of the 113 indeterminate nodules that had imaging follow-up, 111 were stable at the latest follow-up examination. One nodule grew 26% over 8.1 years, and the other grew 59% over 12.4 years. Clinical follow-up of patients with 60 indeterminate nodules revealed no evidence of adrenal malignancy. CONCLUSION: No case of malignancy was found in 322 incidentally detected bilateral adrenal nodules at CT of patients without known cancer. Imaging follow-up of such lesions may be unnecessary.

Diagnostic performance of unenhanced computed tomography and 18 F-fluorodeoxyglucose positron emission tomography in indeterminate adrenal tumours.

OBJECTIVE: Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18 F-fluorodeoxyglucose (18 FDG) positron emission tomography (PET)/CT imaging in a high-risk population for adrenal malignancy using an optimal reference standard. DESIGN: Retrospective cohort study. METHODS: Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy. RESULTS: Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (-21-78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%. 18 FDG-PET/CT was performed in 89 patients; median tumour size was 2.1 (0.7-9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3-29.4] vs 3.7 [1.4-24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74-13.4] vs 1.2 [0.5-6.6], respectively, P<.0001). 18 FDG-PET/CT ALR >1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%. CONCLUSION: Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high-risk population. For indeterminate adrenal lesions, given a superior specificity, 18 FDG-PET/CT could be considered as a second stage imaging study.

Management of Incidental Adrenal Masses: A White Paper of the ACR Incidental Findings Committee.

The ACR Incidental Findings Committee presents recommendations for managing adrenal masses that are incidentally detected on CT or MRI. These recommendations represent an update to the adrenal component of the JACR 2010 white paper on managing incidental findings in the adrenal glands, kidneys, liver, and pancreas. The Adrenal Subcommittee, constituted by abdominal radiologists and an endocrine surgeon, developed this algorithm. The algorithm draws from published evidence coupled with expert subspecialist opinion and was finalized by a process of iterative consensus. Algorithm branches categorize incidental adrenal masses on the basis of patient characteristics and imaging features. For each specified combination, the algorithm concludes with characterization of benignity or indolence (sufficient to discontinue follow-up) and/or a subsequent management recommendation. The algorithm addresses many, but not all, possible pathologies and clinical scenarios. Our goal is to improve the quality of patient care by providing guidance on how to manage incidentally detected adrenal masses.

Transarterial embolization of a hyperfunctioning aldosteronoma in a patient with bilateral adrenal nodules.

Primary hyperaldosteronism often results in resistant hypertension and hypokalemia, which may lead to cardiovascular and cerebrovascular complications. Although surgery is first line treatment for unilateral functioning aldosteronomas, minimally invasive therapies may be first line for certain patients such as those who cannot tolerate surgery. We present a case of transarterial embolization (TAE) of an aldosteronoma. The patient presented with a cerebrovascular accident, and subsequently developed uncontrolled hypertension, hypokalemia, and a myocardial infarction. Following TAE, potassium returned to normal levels and blood pressure control was improved. There were no postoperative complications. TAE thus may be a safe and effective alternative to surgery.

Adrenal incidentalomas: are they being worked up appropriately?

INTRODUCTION: Adrenal incidentalomas are defined as masses picked up on imaging studies that were done for apparently different reasons. With frequent use of imaging modalities, incidental adrenal masses are commonly encountered in clinical practice. Guidelines are currently available for the diagnosis and management of adrenal incidentalomas, but the appropriateness of initial work-up and subsequent follow-up of incidental adrenal masses in the community hospital setting is unknown. OBJECTIVE: We studied the appropriateness of initial work-up and follow-up of incidental adrenal masses discovered on abdominal computerized tomography (CT). METHODS: In our retrospective study, we reviewed sequential CT scans of the abdomen performed in the month of January 2010 at a community hospital. Once patients with one or more adrenal masses were identified, outpatient charts for initial biochemical testing and follow-up imaging were obtained either through directly accessing the electronic medical records or through contacting primary care physician's offices. Patient charts were reviewed to assess the data for the next 2 years following the discovery of an adrenal abnormality. RESULTS: Twenty adrenal masses were incidentally discovered on 723 abdominal CTs performed within the month of January 2010 resulting in an overall incidence of 2.76%. Of the patients with incidentally discovered adrenal masses, appropriate biochemical and follow-up imaging were only performed in patients referred to an endocrinologist (2 of 20 patients). Thirty percent of patients with incidental masses received a repeat CT scan for non-adrenal reasons, and no change in the mass size was noted. CONCLUSION: Despite published guidelines, the initial work-up and follow-up of patients with an incidentally discovered adrenal mass is unsatisfactory. There is a desperate need for education of providers regarding appropriate work-up of incidental adrenal masses.

Do patients with incidentally discovered bilateral adrenal nodules represent an early form of ARMC5-mediated bilateral macronodular hyperplasia?

Bilateral adrenal macronodular hyperplasia (BMAH) is a rare form of Cushing's syndrome characterised by the presence of bilateral secretory adrenal nodules and hypercortisolism. Familial studies support a genetic basis for BMAH, and the disease has been linked to mutations in ARMC5, a gene shown to have a tumour suppressor-like action in the development of adrenal nodules. This study aimed to investigate whether ARMC5 mutations play a role in the development of incidentally discovered bilateral adrenal nodules. We investigated 39 patients with incidentally discovered bilateral adrenal nodules >0.8 cm in diameter who underwent extensive biochemical testing to look for signs of subclinical hypercortisolism. Genomic DNA was analysed by Sanger sequencing, using primers targeted to ARMC5 transcripts. Of the 39 patients included in our study, three were identified as having variants in ARMC5. Two of these are unlikely to be clinically significant, but there is evidence that the third mutation, Chr16:g.31476122;c.1778G>C (p.Arg593Pro), may be pathogenic. Another variant, affecting the same amino-acid residue c.1777C>T (p.Arg593Trp), has been identified previously in two studies of BMAH patients, where it has been shown to segregate with disease in one BMAH family. This patient had biochemical evidence of hypercortisolism in the absence of overt Cushing's syndrome, and underwent bilateral adrenalectomy separated in time. The presence of a probably clinically significant mutation in ARMC5 in one patient with bilateral adrenal incidentalomas adds to the growing body of evidence in support of ARMC5 as a critical mediator of adrenal nodule development. In addition, the absence of significant ARMC5 mutations in 38 of our patients represents an important negative finding, demonstrating the degree of variability within the pathogenesis of adrenal nodule development.