Malignant Adrenal Disease Research Articles

PSUN13 Transcriptional and epigenetic landscapes of adrenocortical tumors

Abstract Historically, our knowledge of adrenocortical tumorigenesis has been limited to clinical observations of genetic syndromes featuring benign and malignant adrenal disease. In the last two decades, the enormous boom in high-throughput approaches has transformed our understanding of adrenal pathophysiology. While benign adrenocortical tumors may be cured by surgery, adrenocortical carcinoma (ACC) continues to be associated with dismal clinical outcomes. Understanding the molecular pathogenesis of adrenocortical tumors and the programs that facilitate benign versus malignant trajectories is crucial for developing curative therapeutic approaches. Although numerous transcriptome, epigenome, and single cell datasets profiling physiologic adrenal cortex and adrenal tumors are publicly available, there is no analysis integrating the spectrum of physiologic to malignant disease. Through analysis of these datasets, including single center datasets and those published by ENCODE, ENSAT, and TCGA, we demonstrate that biologic processes involved in tissue differentiation are recurrently disrupted across tumorigenesis. While the dominant programs supporting benign tumors include intracellular signaling programs that stabilize steroidogenic identity, ACC is characterized by activation of proliferation, immune, and imprinting programs that restrict access to adrenocortical differentiation states. Taken together, these studies identify that loss of differentiation fidelity within the confines of putative cell of origin is the core determinant of benign versus malignant tumorigenesis in the adrenal cortex. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

O093 The adrenal incidentaloma clinic: a novel and streamlined approach

Abstract Introduction An incidental adrenal nodule is present in 1–3% of abdominal cross-sectional imaging and pose a diagnostic dilemma for the investigating clinician. Adrenal nodules can be functional or pose a cancer risk, hence a complete adrenal hormone profile investigation is necessary. Methods We piloted a streamlined clinic within the endocrine surgery department for assessing adrenal incidentalomas by trained surgical care practitioners. Data was collected retrospectively for patients reviewed from March 2020 to September 2021 to evaluate its efficacy and the completion of investigations. Results 98 new patients were seen, with an average age of 64.97 (±13.91) years. The mean time from referral to review was 37.61 (±26.07) days. The mean nodule size was 21.74 (±9.93) mm (range: 6.00–73.00 mm) and were most commonly identified on CT virtual colonoscopy (28.6%), CT abdomen and pelvis (20.4%) and Trauma CT (10.2%), with over two-thirds of referrals from colorectal services (38.9%) and Emergency Medicine (29.5%). 82.7% of patients had metanephrines tested, 79.6% for aldosterone-renin ratio and 75.5% for overnight dexamethasone suppression test following clinic attendance. 8.6% of patients had raised metanephrines, with 25.6% for aldosterone-renin ratio and 37.8% for overnight dexamethasone suppression test. 27.8% were referred on for further assessment with an adrenal CT. Three patients were operated on, one for phaeochromocytoma and two patients for metastases. Conclusion Preliminary results suggest this clinic provides efficient services with good completion of investigations and follow-up. It offers clinicians unfamiliar with or unable to organise adrenal investigations, a dedicated clinic, to ensure appropriate clinical assessments. Take-home message This dedicated incidentaloma clinic contributes to the effective use of resources in doing hormonal profiling for patients and identification of patients at risk of functional and malignant adrenal disease.

Integration of molecular imaging in the personalized approach of patients with adrenal masses.

Adrenal masses are a frequent finding in clinical practice. Many of them are incidentally discovered with a prevalence of 4% in patients undergoing abdominal anatomic imaging and require a differential diagnosis. Biochemical tests, evaluating hormonal production of both adrenal cortex and medulla (in particular, mineralocorticoids, glucocorticoids and catecholamines), have a primary importance in distinguishing functional or non-functional lesions. Conventional imaging techniques, in particular computerized tomography (CT) and magnetic resonance imaging (MRI), are required to differentiate between benign and malignant lesions according to their appearance (size stability, contrast enhanced CT and/or chemical shift on MRI). In selected patients, functional imaging is a non-invasive tool able to explore the metabolic pathways involved thus providing additional diagnostic information. Several single photon emission tomography (SPET) and positron emission tomography (PET) radiopharmaceuticals have been developed and are available, each of them suitable for studying specific pathological conditions. In functional masses causing hypersecreting diseases (mainly adrenal hypercortisolism, primary hyperaldosteronism and pheochromocytoma), functional imaging can lateralize the involvement and guide the therapeutic strategy in both unilateral and bilateral lesions. In non-functioning adrenal masses with inconclusive imaging findings at CT/MR, [18F]-FDG evaluation of tumor metabolism can be helpful to characterize them by distinguishing between benign nodules and primary malignant adrenal disease (mainly adrenocortical carcinoma), thus modulating the surgical approach. In oncologic patients, [18F]-FDG uptake can differentiate between benign nodule and adrenal metastasis from extra-adrenal primary malignancies.

Health-Related Quality of Life in Adrenocortical Carcinoma.

Insight into the health-related quality of life (HRQoL) impact of adrenocortical carcinoma (ACC) is important. The disease and its treatment options potentially have an impact on HRQoL. For patients with limited survival, HRQoL research is of utmost importance. We will therefore provide an overview of HRQoL studies in patients with ACC. We found six studies that measured HRQoL in 323 patients with ACC (3 cross-sectional, 1 cohort, 2 trials), all indicating a reduced HRQoL compared to the general population. The FIRMACT trial found that HRQoL of patients with ACC was reduced compared to the general population, and that chemotherapy-mitotane further reduced HRQoL even though survival improved. Clinical aspects of the disease, including cortisol and aldosterone production and adrenal insufficiency have shown great impact on HRQoL in benign disease, even after the recovery of hormonal status. However, the impact of malignant adrenal disease and treatment options on HRQoL including adrenalectomy, radiotherapy, mitotane therapy, and chemotherapy have not been sufficiently studied in patients with ACC. Although the number of HRQoL studies in patients with ACC is limited, the existing literature does indicate that ACC has a large impact on patients’ HRQoL, with disease specific aspects. Further HRQoL research in patients with ACC is essential to improve patient-centered care, preferably by using an ACC-specific HRQoL questionnaire.

Outcomes of surgery for benign and malignant adrenal disease from the British Association of Endocrine and Thyroid Surgeons' national registry.

This study investigated the indications, procedures and outcomes for adrenal surgery from the UK Registry of Endocrine and Thyroid Surgery database from 2005 to 2017, and compared outcomes between benign and malignant disease. Data on adrenalectomies were extracted from a national surgeon-reported registry. Preoperative diagnosis, surgical technique, length of hospital stay, morbidity and in-hospital mortality were examined. Some 3994 adrenalectomies were registered among patients with a median age of 54 (i.q.r. 43-65) years (55·9 per cent female). Surgery was performed for benign disease in 81·5 per cent. Tumour size was significantly greater in malignant disease: 60 (i.q.r. 34-100) versus 40 (24-55) mm (P < 0·001). A minimally invasive approach was employed in 90·2 per cent of operations for benign disease and 48·2 per cent for cancer (P < 0·001). The conversion rate was 3·5-fold higher in malignant disease (17·3 versus 4·7 per cent; P < 0·001). The length of hospital stay was 3 (i.q.r. 2-5) days for benign disease and 5 (3-8) days for malignant disease (P < 0·050). In multivariable analysis, risk factors for morbidity were malignant disease (odds ratio (OR) 1·69, 1·22 to 2·36; P=0·002), tumour size larger than 60 mm (OR 1·43, 1·04 to 1·98; P =0·028) and conversion to open surgery (OR 3·48, 2·16 to 5·61; P < 0·001). The in-hospital mortality rate was below 0·5 per cent overall, but significantly higher in the setting of malignant disease (1·2 versus 0·2 per cent; P < 0·001). Malignant disease (OR 4·88, 1·17 to 20·34; P =0·029) and tumour size (OR 7·47, 1·52 to 39·61; P =0·014) were independently associated with mortality in multivariable analysis. Adrenalectomy is a safe procedure but the higher incidence of open surgery for malignant disease appears to influence postoperative outcomes.

A Retrospective Review of CyberKnife Stereotactic Body Radiotherapy for Adrenal Tumors (Primary and Metastatic): Winthrop University Hospital Experience.

The adrenal gland is a common site of cancer metastasis. Surgery remains a mainstay of treatment for solitary adrenal metastasis. For patients who cannot undergo surgery, radiation is an alternative option. Stereotactic body radiotherapy (SBRT) is an ablative treatment option allowing larger doses to be delivered over a shorter period of time. In this study, we report on our experience with the use of SBRT to treat adrenal metastases using CyberKnife technology. We retrospectively reviewed the Winthrop University radiation oncology data base to identify 14 patients for whom SBRT was administered to treat malignant adrenal disease. Of the factors examined, the biological equivalent dose (BED) of radiation delivered was found to be the most important predictor of local adrenal tumor control. We conclude that CyberKnife-based SBRT is a safe, non-invasive modality that has broadened the therapeutic options for the treatment of isolated adrenal metastases.

Time to recovery of adrenal function after curative surgery for Cushing's syndrome depends on etiology.

Successful tumor resection in endogenous Cushing's syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy. The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing's disease (CD), adrenal CS, and ectopic CS. We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983-2014. The mean follow-up time was 8 years. We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease. The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03-1.1 y) in ectopic CS, 1.4 years (IQR, 0.9-3.4 y) in CD, and 2.5 years (IQR, 1.6-5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822-0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses. Time to recovery of adrenal function is dependent on the underlying etiology of CS.

Characterization of Adrenal Masses by Using FDG PET: A Systematic Review and Meta-Analysis of Diagnostic Test Performance

To perform a systematic review and meta-analysis of published data to determine the diagnostic utility of adrenal fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing benign from malignant adrenal disease. Data on FDG PET assessment in MEDLINE and other electronic databases (from inception to November 2009) and in subject matter-specific journals were evaluated and compared with histologic diagnoses and/or established clinical and imaging follow-up results. Methodologic quality was assessed by using Quality Assessment of Diagnostic Accuracy Studies criteria. Bivariate random-effects meta-analytical methods were used to estimate summary and subgroup-specific sensitivity, specificity, and receiver operating characteristic curves and to investigate the effects of study design characteristics and imaging procedure elements on diagnostic accuracy. A total of 1391 lesions (824 benign, 567 malignant) in 1217 patients from 21 eligible studies were evaluated. Qualitative (visual) analysis of 841 lesions (in 14 reports) and quantitative analyses based on standardized uptake values (SUVs) for 824 lesions (in 13 reports) and standardized uptake ratios (SURs) for 562 lesions (in eight reports) were performed. Resultant data were highly heterogeneous, with a model-based inconsistency index of 88% (95% confidence interval [CI]: 79%, 98%). Mean sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio values for differentiating between benign and malignant adrenal disease were 0.97 (95% CI: 0.93, 0.98), 0.91 (95% CI: 0.87, 0.94), 11.1 (95% CI: 7.5, 16.3), 0.04 (95% CI: 0.02, 0.08), and 294 (95% CI: 107, 805), respectively, with no significant differences in accuracy among the visual, SUV, and SUR analyses. Meta-analysis of combination PET-computed tomography (CT) reports revealed that FDG PET was highly sensitive and specific for differentiating malignant from benign adrenal disease. Diagnostic accuracy was not influenced by the type of imaging device (PET vs PET/CT), but specificity was dependent on the clinical status (cancer vs no cancer).

Efectividad diagnóstica de la tomografía por emisión de positrones con 18fluorodeoxiglucosa asociada a tomografía axial en la discriminación de benignidad o malignidad de las lesiones suprarrenales

Introduction The usefulness of 18fluorodeoxyglucose positron emission tomography combined with axial tomography (PET-CT) in diagnosing whether adrenal tumours are benign or malignant is assessed. Material and methods A retrospective study conducted between June 2005 and May 2009 on a consecutive series of patients on whom a PET-CT scan was performed to study suspected malignant adrenal disease. Focal uptakes were assessed, along with the maximum standard uptake value (SUV), and the ratio of the maximum adrenal/hepatic value. The sensitivity, specificity, positive and negative predictive value of the test, the maximum adrenal uptake values and the ratio for those where the diagnostic yield was maximum. Results Fifteen patients were included. The final diagnosis showed malignancy in eight and seven were benign. Ten patients had adrenal uptake: three in benign lesions and seven in neoplasias, with a mean uptake value of 6.3 (3.2 in benign lesions and 9.0 in malignant lesions). The mean adrenal/hepatic ratio was 1.8 (0.9 in benign and 2.6 in malignant lesions). When the presence of adrenal uptake is associated with a final diagnosis of malignancy, we obtained a sensitivity of 87.5%, a specificity of 57.1%, and a positive and negative predictive value of 70% and 80%, respectively. An SUV cut-off value of 6, or an adrenal/hepatic uptake ratio of 2, gave a sensitivity of 75%, a specificity of 100%, and a positive and negative predictive value of 100% and 77.7%, respectively. Conclusions PET-CT has a high ability to discriminate between benign and malignant lesions in the adrenal disease studied.

Diagnostic efficacy and discriminatory capacity of positron emission tomography combined with axial tomography of adrenal lesions

IntroductionThe usefulness of 18fluorodeoxyglucose positron emission tomography combined with axial tomography (PET-CT) in diagnosing whether adrenal tumours are benign or malignant is assessed. Material and methodsA retrospective study conducted between June 2005 and May 2009 on a consecutive series of patients on whom a PET-CT scan was performed to study suspected malignant adrenal disease. Focal uptakes were assessed, along with the maximum standard uptake value (SUV), and the ratio of the maximum adrenal/hepatic value. The sensitivity, specificity, positive and negative predictive value of the test, the maximum adrenal uptake values and the ratio for those where the diagnostic yield was maximum. ResultsFifteen patients were included. The final diagnosis showed malignancy in eight and seven were benign. Ten patients had adrenal uptake: three in benign lesions and seven in neoplasias, with a mean uptake value of 6.3 (3.2 in benign lesions and 9.0 in malignant lesions). The mean adrenal/hepatic ratio was 1.8 (0.9 in benign and 2.6 in malignant lesions). When the presence of adrenal uptake is associated with a final diagnosis of malignancy, we obtained a sensitivity of 87.5%, a specificity of 57.1%, and a positive and negative predictive value of 70% and 80%, respectively. An SUV cut-off value of 6, or an adrenal/hepatic uptake ratio of 2, gave a sensitivity of 75%, a specificity of 100%, and a positive and negative predictive value of 100% and 77.7%, respectively. ConclusionsPET-CT has a high ability to discriminate between benign and malignant lesions in the adrenal disease studied.

Improved Detection and Characterization of Adrenal Disease with PET-CT

Positron emission tomography (PET)-computed tomography (CT) combines complementary modalities, thereby providing useful structural and functional information for the detection and characterization of a variety of conditions affecting the adrenal gland. The coregistered information provided by PET-CT is often superior to that provided by CT or PET owing to a variety of pitfalls inherent in the use of either modality alone. In addition, PET-CT can prove invaluable in the differentiation between benign and malignant adrenal disease. However, this combined modality also has certain limitations. Benign entities such as lipid-poor adenomas may demonstrate increased uptake at 2-[fluorine 18]fluoro-2-deoxy-d-glucose PET while being indeterminate at standard CT. Moreover, the combined information from PET-CT will not always obviate additional studies or biopsy. Nevertheless, radiologists and nuclear physicians should be familiar with the common as well as the atypical manifestations of adrenal disease at PET and CT. They should also be meticulous in the performance and interpretation of PET-CT, which is crucial for optimal diagnosis and treatment.