Radiomics in the characterization of lipid-poor adrenal adenomas at unenhanced CT: time to look beyond usual density metrics.

OBJECTIVES: In this study, we developed a radiomic signature for the classification of benign lipid-poor adenomas, which may potentially help clinicians limit the number of unnecessary investigations in clinical practice. Indeterminate adrenal lesions of benign and malignant nature may exhibit different values of key radiomics features. METHODS: Patients who had available histopathology reports and a non-contrast-enhanced CT scan were included in the study. Radiomics feature extraction was done after the adrenal lesions were contoured. The primary feature selection and prediction performance scores were calculated using the least absolute shrinkage and selection operator (LASSO). To eliminate redundancy, the best-performing features were further examined using the Pearson correlation coefficient, and new predictive models were created. RESULTS: This investigation covered 50 lesions in 48 patients. After LASSO-based radiomics feature selection, the test dataset's 30 iterations of logistic regression models produced an average performance of 0.72. The model with the best performance, made up of 13 radiomics features, had an AUC of 0.99 in the training phase and 1.00 in the test phase. The number of features was lowered to 5 after performing Pearson's correlation to prevent overfitting. The final radiomic signature trained a number of machine learning classifiers, with an average AUC of 0.93. CONCLUSIONS: Including more radiomics features in the identification of adenomas may improve the accuracy of NECT and reduce the need for additional imaging procedures and clinical workup, according to this and other recent radiomics studies that have clear points of contact with current clinical practice. CLINICAL RELEVANCE STATEMENT: The study developed a radiomic signature using unenhanced CT scans for classifying lipid-poor adenomas, potentially reducing unnecessary investigations that scored a final accuracy of 93%. KEY POINTS: • Radiomics has potential for differentiating lipid-poor adenomas and avoiding unnecessary further investigations. • Quadratic mean, strength, maximum 3D diameter, volume density, and area density are promising predictors for adenomas. • Radiomics models reach high performance with average AUC of 0.95 in the training phase and 0.72 in the test phase.

Follow-up of non-palpable testicular incidentalomas under 1 cm: does growth rate differentiate malignant and non-malignant lesions?

OBJECTIVE: To determine whether small, incidentally detected testicular lesions can be safely followed up, by assessing growth rate and volume threshold for benign vs. malignant lesions. METHODS: This retrospective observational study includes a consecutive series of 130 testicular incidentalomas < 1 cm and with negative tumour markers identified from October 2001 to November 2022, which were initially followed up with ultrasound. A total of 39 cases proceeded to surgery during the study period, either due to lesion growth (n = 28) or patient preference/recommendation by the referring urologist (n = 11). For the lesions that were growing, specific growth rate (SGR) and doubling time (DT) were calculated assuming an exponential growth pattern. In addition, the velocity of increase of the average diameter (∆Dav) and of the maximum diameter (∆Dmax) were calculated. RESULTS: Of the 130 nodules that were initially followed up, six disappeared, eight were reduced in size, eighty-eight were stable, and twenty-eight increased in size. For operated nodules all 18 malignant tumours, 8/9 benign tumours, and 2/12 surgically proved non-neoplastic lesions were growing. The best cut-off values of the growth indicators to differentiate between malignant and non-malignant histology were 3.47 × 10-3%volume/day, ≤ 179 days, > 10 × 10-3 mm/day, and > 5 × 10-3 mm/day for SGR, DT, ∆Dmax, ∆Dav, respectively. CONCLUSIONS: Malignant and non-malignant small incidentalomas can be effectively differentiated based on growing parameters, even though overlap exists. An increase of the maximum diameter of about 1 mm and 2 mm in three months and in six months, respectively, suggests malignancy. CLINICAL RELEVANCE STATEMENT: Growing parameters allow an educated assessment of benign and malignant small testicular incidentalomas. Non-aggressive management is justified and safe when follow-up includes self-examination and tumour marker assessment to reduce the risk of interval tumour growth. KEY POINTS: Small, non-palpable and asymptomatic testicular nodules < 1 cm are unexpectedly discovered during scrotal ultrasound. Growth indicators estimate the potential malignancy, even though overlap with non-malignant lesions exists. Non-growing incidentalomas can be safely followed up.

Incidence, Presentation, and Natural History of Adrenal Hemorrhage: An Institutional Analysis.

INTRODUCTION: Adrenal hemorrhage (AH) can occur due to multiple etiologies with variable radiographic appearance, often indistinguishable from underlying adrenal neoplasms. There is a lack of AH literature and evidence-based guidelines. Our study aimed to understand the prevalence and etiology of AH, follow-up, and incidence of underlying neoplasm. METHODS: An institutional database was queried from January 2006 to October 2021 for patients with AH on imaging, excluding patients with known malignancies, adrenal masses, or prior adrenal surgery. Demographics, medical history, hematoma size, laterality, biochemical evaluation, intervention, and additional imaging were reviewed. RESULTS: Of 490,301 imaging reports queried, 530 (0.11%) with AH met inclusion criteria. Most imaging (n = 485, 91.5%) was performed during trauma evaluation. Two patients underwent dedicated intervention at presentation. Interval imaging was performed in 114 (21.5%) patients at a median of 2.6 (interquartile range 0.99-13.4) mo, with resolution (n = 84, 73.7%) or decreased size of AH (n = 21, 18.4%) in most patients. Only 10 patients (1.9%) saw an outpatient provider in our system to address AH or evaluate for underlying mass, and 9 (1.7%) underwent biochemical screening. Thirteen patients (11% of 118 patients with any follow-up) had evidence of an adrenal mass, confirmed on serial imaging (n = 10) or adrenalectomy (n = 3). Scans performed for nontrauma indications were significantly more likely to have an underlying mass (n = 6/26 [23.1%]) than those performed for trauma evaluation (n = 7/92 [7.6%], P = 0.04). CONCLUSIONS: AH is a rare finding associated with an increased rate of underlying adrenal mass, particularly when unrelated to trauma. Most AH resolves spontaneously without intervention. Follow-up imaging at 6 mo can help distinguish mass-associated AH from simple hemorrhage.

Adrenal Referral Pattern: Management of Patients With an Adrenal Incidentaloma.

INTRODUCTION: Adrenal incidentalomas (AIs) are found in 3%-4% of abdominal computed tomography scans. Timely evaluation of their functional status and malignant potential is necessary to guide nonoperative surveillance or surgery. This study aims to evaluate the adherence of referring service patterns to the American Association of Endocrine Surgeons and American Association of Clinical Endocrinologists guidelines for the biochemical workup of AIs at a tertiary surgical clinic. METHODS: We conducted a retrospective study of 125 patients evaluated for AIs at the endocrine surgery clinic between 2017 and 2022. Information on patient demographics, referral source, and reasons for referral was collected. The appropriateness of the biochemical workup for AIs by referring physicians was assessed. Statistical analyses included chi-square and Kruskal-Wallis tests. RESULTS: Referrals came from endocrinologists (44.8%), other subspecialists (31.2%), and primary care physicians (PCPs) (19.2%). Among 125 patients, diagnoses included benign adrenal masses (52.8%), aldosteronomas (10.4%), cortisol-secreting tumors (15.2%), pheochromocytomas (12.8%), and metastatic masses (4.0%). Endocrinologists were more likely to conduct a complete biochemical workup compared to other subspecialties and PCPs (P < 0.001). Eighty-three (66.4%) patients underwent adrenalectomy, with those referred by endocrinologists more likely to undergo surgery than those referred by other subspecialties and PCPs (P < 0.001). There was no significant difference in the time from the initial clinic visit to surgery by referral source (P > 0.05). CONCLUSIONS: Over half of AIs referrals to the endocrine surgery clinic came from subspecialists and PCPs rather than endocrinologists. Familiarizing all referring physicians with American Association of Endocrine Surgeons/Association of Clinical Endocrinologists guidelines may reduce undiagnosed functional AI cases and facilitate timely surgical management.

The improvement of postoperative blood pressure and associated factors in patients with hormone-negative adrenal adenoma and hypertension.

OBJECTIVE: To investigate the effect of adrenal surgery on blood pressure (BP) improvements in patients with hormone-negative adrenal adenoma (HNA) concomitant with hypertension and analyze associated prognostic factors. METHODS: We retrospectively reviewed the clinical data of patients with HNA and hypertension and patients with aldosterone-producing adenoma (APA) and hypertension who underwent adrenal surgery at our center between 2019 and 2022. Hypertension outcomes were evaluated in all patients and subjects were divided into three groups according to follow-up BP and the administration of anti-hypertensive agents: a clinical curation group, an improvement group, and a no-improvement group. Logistic regression analysis was performed to predict factors associated with clinical curation in patients with HNA post-surgery. RESULTS: Of the 182 patients with HNA, clinical curation was achieved in 58 patients (31.9%), improvement in 72 (39.5%), and no improvement in 52 (28.6%). The clinical curation, improvement and no improvement rates in patients with APA were 64.8% (n = 118), 15.9% (n = 29), and 19.2% (n = 35). Multivariate logistic regression analysis indicated that a duration of hypertension ≤6 years and a plasma aldosterone level >160 pg/ml were both independent factors for the clinical curation of hypertension in patients with HNA after adrenal surgery. CONCLUSION: Adrenal surgery can cure or improve hypertension in most patients with HNA, especially in a short duration of hypertension and high plasma levels of aldosterone.

Plasma Steroid Profiling Combined With Machine Learning for the Differential Diagnosis in Mild Autonomous Cortisol Secretion From Nonfunctioning Adenoma in Patients With Adrenal Incidentalomas.

OBJECTIVE: To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas. METHODS: The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model. RESULTS: Seventy-six patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among 5 ML models evaluated, eXtreme Gradient Boosting demonstrated superior performance with an area under the curve of 0.77 using 24 steroid hormones. The SHAP method identified 5 steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone, 11-deoxycortisol, 11ß-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate. Upon incorporating clinical features into the model, the area under the curve increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, dehydroepiandrosterone, low-density lipoprotein cholesterol, body mass index, and adrenocorticotropic hormone along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model. CONCLUSIONS: We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these 2 entities through a single blood collection.

Relationship Between Dexamethasone Suppression Test Cortisol Level >0.9 µg/dL and Depression and Quality of Life in Adrenal Incidentalomas: A Single Center Observational Case-Control Study.

OBJECTIVE: There has been increasing evidence that patients with adrenal incidentalomas (AIs) who have 1-mg dexamethasone suppression test (DST) cortisol levels >0.9 µg/dL may be exposed to the adverse consequences of hypercortisolaemia. We aim to evaluate whether there is a difference in Beck Depression Inventory-II (BDI-II) and quality of life (QoL) score in patients with AI based on the threshold of a DST cortisol level >0.9 µg/dL. METHODS: This case-control study included 42 nonfunctional adrenal incidentaloma (NFAI), 53 mild autonomic cortisol secretion (MACS) and 42 healthy controls (HCs). In addition, patients were categorized as ≤0.9 and >0.9 µg/dL according to their DST cortisol results. RESULTS: There was no difference in the QoL and BDI-II scores of MACS compared to NFAI. The BDI-II score was higher and QoL was lower in MACS and NFAI compared to HCs. The difference in QoL and BDI-II scores between MACS and NFAI remained insignificant when the DST cortisol levels threshold was graded upward (5.0 µg/dL). The prevalence of depression was higher in the AI >0.9 µg/dL group than the AI ≤0.9 µg/dL group (respectively, 16.7% and 55.8%, P = .003), BDI-II scores were higher in the AI >0.9 µg/dL group than in the AI ≤0.9 µg/dL group and HCs. The DST was an independent factor affecting the frequency of depression (odds ratio: 1.39, P = .037). CONCLUSION: MACS and patients with NFAI had similar QoL and depression scores according to the 1.8 µg/dL and above, whereas, had lower QoL and higher depression scores according to the 0.9 µg/dL.

Tumor enlargement in adrenal incidentaloma is related to glaucoma: a new prognostic feature?

PURPOSE: The uncertainty on the management of small adrenal incidentalomas (AIs) still represents a challenge in real clinical practice. Considering the lack of knowledge on risk factors implicated in tumour enlargement, the aim of this study was to identify risk factors for morphological changes during follow-up of adrenal incidentalomas (AIs). METHODS: We retrospectively evaluated demographic, clinical, radiological and biochemical parameters of 153 AIs (2007-2021). Patients with histological diagnosis of metastases or pheochromocytoma were excluded. To detect risk factors for tumor enlargement, diseases associated with AIs were included if their prevalence was higher than 2%. Patients were divided into two groups (A: radiological stability; B: tumor enlargement defined as > 5 mm/year in the main diameter). RESULTS: Group A: 89.5% and group B: 10.5%, mean follow-up 38.6 ± 6.9 months (range 6-240). Tumor enlargement when occurred was within 36 months of follow-up. In group B high body weight (p < 0.03), dehydroepiandrosterone sulfate (DHEAS) (p < 0.05) and direct renin concentration (DRC) (p < 0.04) were higher than group A, while aldosterone levels were lower; moreover, considering comorbidities, glaucoma and dysglycemia (p < 0.01 for both) had higher prevalence in group B. Glaucoma and dysglycemia were independent predictors of enlargement. Patients affected by glaucoma, atrial fibrillation, dysglycemia had a lower dimensional change-free survival than non-affected. CONCLUSIONS: Glaucoma might be a novel risk factor for AI enlargement. If subtle undetectable cortisol hypersecretion has a role is a topic for further research.

Predicting postoperative hypocortisolism in patients with non-aldosterone-producing adrenocortical adenoma: a retrospective single-centre study.

BACKGROUND: Limited information exists on postoperative hypocortisolism and hypothalamus-pituitary-adrenal axis recovery in patients with adrenal incidentaloma following unilateral adrenalectomy. We evaluated frequency of postoperative hypocortisolism and predictors for recovery in non-aldosterone-producing adrenocortical adenoma patients after unilateral adrenalectomy. METHODS: A retrospective analysis of 32 adrenal incidentaloma patients originally included in the ITACA trial (NCT04127552) with confirmed non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy from September 2019 to April 2023 was conducted. Preoperative assessments included adrenal MRI, anthropometrics, evaluation of comorbidities, adrenal function assessed via ACTH, urinary free cortisol, and 1 mg dexamethasone suppression test. ACTH and serum cortisol or Short Synacthen test were performed within 6 days, 6 weeks, 6 months, and a year after surgery. RESULTS: Six days postoperative, 18.8% of patients had normal adrenal function. Among those with postoperative hypocortisolism, 53.8% recovered by 6 weeks. Patients with earlier adrenal recovery (6 weeks) had lower preoperative 1 mg dexamethasone suppression test (median 1 mg dexamethasone suppression test 76.2 [61.8-111.0] nmol/L vs 260.0 [113.0-288.5] nmol/L, p < 0.001). Univariate analysis showed preoperative 1 mg dexamethasone suppression test negatively related with baseline ACTH levels (r = - 0.376; p = 0.041) and negatively associated with the 6-week baseline (r = - 0.395, p = 0.034) and 30-min cortisol levels during Short Synacthen test (r = - 0.534, p = 0.023). Logistic regression analysis demonstrated preoperative 1 mg dexamethasone suppression test as the only biochemical predictor for 6-week adrenal recovery: ROC curve identified a 1 mg dexamethasone suppression test threshold of 131 nmol/L predicting 6-week recovery with 89.5% sensitivity and 72.7% specificity (AUC 0.87; 95% CI 66.9-98.7, p < 0.001). Other preoperative assessments (tumor size, ACTH levels and anthropometrics) were not associated with postoperative hypothalamus-pituitary-adrenal axis function, but the presence of diabetes was associated with a lower probability of recovery (OR = 24.55, p = 0.036). ACTH levels increased postoperatively in all patients but did not predict hypothalamus-pituitary-adrenal axis recovery. CONCLUSIONS: The preoperative 1 mg dexamethasone suppression test cortisol value and presence of diabetes are the only relevant predictor of hypothalamus-pituitary-adrenal axis recovery in patients with non-aldosterone- producing adrenocortical adenoma undergoing surgery, regardless other clinical and biochemical variables. Notably, pre- and postoperative ACTH levels did not predict hypothalamus-pituitary-adrenal axis recovery. These findings point towards the potential for saving resources by optimizing their allocation during follow-up assessments for patients with non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy.

Development and validation of a model predicting adrenal lipid-poor adenoma based on the minimum attenuation value from non-contrast CT: a dual-center retrospective study.

OBJECTIVE: The early differentiation of adrenal lipid-poor adenomas from non-adenomas is a crucial step in reducing excessive examinations and treatments. This study seeks to construct an eXtreme Gradient Boosting (XGBoost) predictive model utilizing the minimum attenuation values (minAVs) from non-contrast CT (NCCT) scans to identify lipid-poor adenomas. MATERIALS AND METHODS: Retrospective analysis encompassed clinical data, minAVs, CT histogram (CTh), mean attenuation values (meanAVs), and lesion diameter from patients with pathologically or clinically confirmed adrenal lipid-poor adenomas across two medical institutions, juxtaposed with non-adenomas. Variable selection transpired in Institution A (training set), with XGBoost models established based on minAVs and CTh separately. Institution B (validation set) corroborated the diagnostic efficacy of the two models. Receiver operator characteristic (ROC) curve analysis, calibration curves, and Brier scores assessed the diagnostic performance and calibration of the models, with the Delong test gauging differences in the area under the curve (AUC) between models. SHapley Additive exPlanations (SHAP) values elucidated and visualized the models. RESULTS: The training set comprised 136 adrenal lipid-poor adenomas and 126 non-adenomas, while the validation set included 46 and 40 instances, respectively. In the training set, there were substantial inter-group differences in minAVs, CTh, meanAVs, diameter, and body mass index (BMI) (p < 0.05 for all). The AUC for the minAV and CTh models were 0.912 (95% confidence interval [CI]: 0.866-0.957) and 0.916 (95% CI: 0.873-0.958), respectively. Both models exhibited good calibration, with Brier scores of 0.141 and 0.136. In the validation set, the AUCs were 0.871 (95% CI: 0.792-0.951) and 0.878 (95% CI: 0.794-0.962), with Brier scores of 0.156 and 0.165, respectively. The Delong test revealed no statistically significant differences in AUC between the models (p > 0.05 for both). SHAP value analysis for the minAV model suggested that minAVs had the highest absolute weight (AW) and negative contribution. CONCLUSION: The XGBoost predictive model based on minAVs demonstrates effective discrimination between adrenal lipid-poor adenomas and non-adenomas. The minAV variable is easily obtainable, and its diagnostic performance is comparable to that of the CTh model. This provides a basis for patient diagnosis and treatment plan selection.

Clinical features and treatment options for pediatric adrenal incidentalomas: a retrospective single center study.

BACKGROUND: The aim of this study was to investigate the clinical features and treatment options for pediatric adrenal incidentalomas(AIs) to guide the diagnosis and treatment of these tumors. METHODS: The clinical data of AI patients admitted to our hospital between December 2016 and December 2022 were collected and retrospectively analyzed. All patients were divided into neonatal and nonneonatal groups according to their age at the time of the initial consultation. RESULTS: In the neonatal group, 13 patients were observed and followed up, and the masses completely disappeared in 8 patients and were significantly reduced in size in 5 patients compared with the previous findings. Four patients ultimately underwent surgery, and the postoperative pathological diagnosis was neuroblastoma in three patients and teratoma in one patient. In the nonneonatal group, there were 18 cases of benign tumors, including 9 cases of ganglioneuroma, 2 cases of adrenocortical adenoma, 2 cases of adrenal cyst, 2 cases of teratoma, 1 case of pheochromocytoma, 1 case of nerve sheath tumor, and 1 case of adrenal hemorrhage; and 20 cases of malignant tumors, including 10 cases of neuroblastoma, 9 cases of ganglioneuroblastoma, and 1 case of adrenocortical carcinoma. CONCLUSIONS: Neuroblastoma is the most common type of nonneonatal AI, and detailed laboratory investigations and imaging studies are recommended for aggressive evaluation and treatment in this population. The rate of spontaneous regression of AI is high in neonates, and close observation is feasible if the tumor is small, confined to the adrenal gland and has no distant metastasis.

Incidental Renal Cysts Found by Point-of-Care Ultrasound: A Retrospective Chart Review.

BACKGROUND: Incidental findings are unrelated to a patient's complaint, found on diagnostic imaging, such as point-of-care ultrasound (POCUS). Incidental findings represent potential harms to patients and may lead to increased patient anxiety and health care costs related to downstream testing and surveillance. STUDY OBJECTIVES: In this study, we aimed to calculate the rate of incidental renal cysts found by POCUS. Further, we hoped to describe how emergency physicians relay the findings to patients. Lastly, we hoped to examine if patients suffered harms in the 12 months following identification of an incidental renal cyst. METHODS: From our single-center, academic emergency department (ED), we reviewed renal POCUS images from 1000 consecutive adult ED patients to determine if there was a renal cyst. Next, we performed manual chart review to determine if patients were informed of the incidental renal cyst or suffered any patient harms. RESULTS: We found the prevalence of renal cysts to be 6.5% (95% confidence interval: 4.9%-8.4%). Those with cysts were more likely to be older compared to those without (63 ± 14 vs. 49 ± 15 years of age). Only 8% of patients had evidence that they were informed of their incidental renal cyst. No patients received a biopsy or were diagnosed with renal cell carcinoma or polycystic kidney disease. CONCLUSION: Incidental renal cysts are common and are more likely to be found in older adults. In our study, physicians infrequently informed patients of their incidental finding.

Clinical, radiological, and surgical outcomes of 431 patients with adrenal incidentalomas: retrospective study of a 10-year single-center experience.

Background/aim: The incidence of adrenal tumors is increasing due to the widespread utilization of radiographic imaging techniques. Factors such as tumor size, radiological characteristics, and functionality of adrenal adenomas play crucial roles in diagnosis and subsequent management. In this retrospective study, we investigated the clinical, radiological, and surgical features of patients with adrenal incidentalomas (AIs) and evaluated their follow-up results. Materials and methods: We analyzed data from 431 patients diagnosed with AIs (130 males, 301 females) who underwent adrenal hormone evaluation at our center. We compared nonfunctioning and functioning AIs in terms of radiological features. We also compared baseline and follow-up characteristics in nonfunctioning AIs. Results: The mean age of the patients was 55.4 ± 11.5 years, with a mean tumor size of 25.9 ± 14.3 mm. Mean follow-up duration was 3.17 ± 2.07 years. Adenoma localization revealed 165 (38.3%) right-sided, 185 (42.9%) left-sided, and 81 (18.8%) bilateral cases. Most patients (76.6%) had nonfunctioning AIs. During follow-up, nonfunctioning AIs exhibited increased fasting blood glucose, fasting insulin and HOMA-IR values (p = 0.002, <0.001 and 0.004, respectively). Among the functioning AIs cases (23.4%), autonomous cortisol secretion, Cushing's syndrome, pheochromocytoma, and primary aldosteronism were observed in 10.4%, 5.1%, 3.9%, and 3.9% of cases, respectively. Receiver operating characteristic curve analysis determined an adrenal adenoma size of 26.5 mm as the optimal cut-off for distinguishing between functioning and nonfunctioning AIs, with a sensitivity and specificity of 61.4% and 70.0%, respectively. Conclusion: Although the majority of AIs are nonfunctioning, the prevalence of functioning adrenal adenomas is not rare. Our findings suggest that adenoma size emerges as a valuable predictor for early detection of functioning adenomas. In addition, smaller masses appear to carry a lower risk of malignancy.

Diagnosis, Management, and Follow-Up of the Incidentally Discovered Adrenal Mass: CUA Guideline Endorsed by the AUA.

PURPOSE: Incidental adrenal masses are common and require a multidisciplinary approach to evaluation and management that includes family physicians, urologists, endocrinologists, and radiologists. The purpose of this guideline is to provide an updated approach to the diagnosis, management, and follow-up of adrenal incidentalomas, with a special focus on the areas of discrepancy/controversy existing among the published guidelines from other associations. MATERIALS AND METHODS: This guideline was developed by the Canadian Urological Association (CUA) through a working group comprised of urologists, endocrinologists, and radiologists and subsequently endorsed by the American Urological Association (AUA). A systematic review utilizing the GRADE approach served as the basis for evidence-based recommendations with consensus statements provided in the absence of evidence. For each guideline statement, the strength of recommendation was reported as weak or strong, and the quality of evidence was evaluated as low, medium, or high. RESULTS: The CUA working group provided evidence- and consensus-based recommendations based on an updated systematic review and subject matter expertise. Important updates on evidence-based radiological evaluation and hormonal testing are included in the recommendations. This guideline clarifies which patients may benefit from surgery and highlights where short term surveillance is appropriate. CONCLUSION: Incidentally detected adrenal masses require a comprehensive assessment of hormonal function and oncologic risk. This guideline provides a contemporary approach to the appropriate clinical, radiographic, and endocrine assessments required for the evaluation, management, and follow-up of patients with such lesions.

Consensus statement on the management of incidentally discovered FDG avid thyroid nodules in patients being investigated for other cancers.

With the widespread use of 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) in the investigation and staging of cancers, incidental discovery of FDG-avid thyroid nodules is becoming increasingly common, with a reported incidence in the range 1%-4% of FDG PET/CT scans. The risk of malignancy in an incidentally discovered FDG avid thyroid nodule is not clear due to selection bias in reported retrospective series but is likely to be less than 15%. Even in cases where the nodule is found to be malignant, the majority will be differentiated thyroid cancers with an excellent prognosis even without treatment. If, due to index cancer diagnosis, age and co-morbidities, it is unlikely that the patient will survive 5 years, further investigation of an incidental FDG avid thyroid nodule is unlikely to be warranted. We provide a consensus statement on the circumstances in which further investigation of FDG avid thyroid nodules with ultrasound and fine needle aspiration might be appropriate.

Adrenal incidentaloma: Do patients with apparently nonfunctioning mass or autonomous cortisol secretion have similar or different clinical and metabolic features?

OBJECTIVE: Although there is growing evidence associating nonfunctioning adrenal incidentalomas (NFAI) with cardiovascular risk factors, there are limited data whether NFAI and autonomous cortisol secretion (ACS) groups have similar or different clinical and metabolic features. The aim of this study is to compare cardiometabolic clinic parameters among patients with ACS and NFAI, as well as controls. DESIGN: Cross-sectional study. PATIENTS: Eighty nine NFAI, 58 ACS and 64 controls were evaluated. MEASUREMENTS: Diagnosis of NFAI (1 mg dexamethasone suppression test [1 mg-DST] ≤50 nmol/L [≤1.8 µg/dl]) and ACS (1 mg-DST > 50 nmol/L [> 1.8 µg/dl]) was established according to current guidelines. The control group was selected based on a normal adrenal imaging exam. RESULTS: There were no differences between groups regarding age, gender, ethnicity, menopause or body mass index. Patients with adrenal incidentaloma presented higher frequency of hypertension (74.1 vs. 57.8%; p = .02), resistant hypertension (45.4 vs. 9.4%; p < .001), dyslipidemia (80.1 vs. 63.9%; p = .01), as well as metabolic syndrome (84.2 vs. 61.7%; p = .001) compared to the controls, respectively. NFAI and ACS patients presented similar frequency of arterial hypertension (70.8 vs. 79.3%) and resistant hypertension (41.3 vs. 51.1%), dyslipidemia (79.3 vs. 81.5%) and metabolic syndrome (83.3 vs. 85.7%); also, levels of HbA1c were similar between the groups. Binary logistic regression showed that NFAI (p = .004) and ACS (p = .001) were independent predictors for resistant hypertension (p = .003); also, ACS was an independent predictor for metabolic syndrome (p = .04). CONCLUSIONS: NFAI and ACS presented a higher frequency of cardiometabolic morbidities in comparison with individuals with normal adrenal glands. Additionally, we demonstrated that both ACS and NFAI groups have similar cardiometabolic conditions.

An unusual cause of adrenal insufficiency with elevation of 17-hydroxyprogesterone: case report.

BACKGROUND: We present an intriguing case of primary adrenal lymphoma, with associated primary adrenal insufficiency (PAI), in a patient presenting a transitory partial 21-hydroxylase deficiency during the active phase of the adrenal disease. CASE PRESENTATION: An 85-years old woman was referred because of worsening asthenia, lumbar pain, generalized myalgia and arthralgia. During investigations a computed tomography (CT) scan evidenced two large bilateral adrenal masses, highly suspicious for primary adrenal tumor. The hormonal assessment revealed very low levels of morning plasma cortisol and 24-h urinary cortisol, elevated ACTH levels with low plasma concentration of aldosterone, pointing to the diagnosis of PAI. After diagnosis of PAI our patient started glucocorticoid and mineralcorticoid replacement therapy with clinical benefit. In order to further characterize the adrenal lesions, adrenal biopsy, was performed. The histology revealed a high grade non-Hodgkin lymphoma with an immunophenotype consistent with intermediate aspects between diffuse large B-cell and Burkitt lymphoma, with a high proliferation index (KI-67 > 90%). The patient received chemotherapy with epirubicin, vincristine, cyclophosphamide, and rituximab, associated with methylprednisolone that resulted in a complete clinical and radiological remission within one year. After 2 years from the diagnosis and a total of 6 cycles of rituximab, the patient was in good clinical condition and was taking only the replacement therapy for PAI. The patient initially presented also a slight increase of 17-hydroxyprogesterone (17-OHP) for age that normalize after resolution of lymphoproliferative disease. CONCLUSIONS: In the presence of bilateral adrenal disease and/or in the presence of signs and symptoms of PAI clinicians must exclude the presence of PAL. The evidence of elevated ACTH-stimulated 17-OHP levels also in patients with other adrenal masses, together with the detection of elevated basal 17-OHP levels in our patient make it more plausible, in our view, an effect of the lesion on the "healthy" adrenal tissue residue than a direct secretory activity by the adrenal tumor.

UK practice on incidentally detected non-functioning pituitary microadenomas: analysis of two national surveys during a 12-year interval.

PURPOSE: The optimal management approach for presumed non-functioning pituitary microadenomas (microNFPAs) remains unclear. Our aim was to capture current UK practice and identify changes with time. METHODS: Two online surveys investigating clinicians' approaches were performed in 2009-2010 and 2021-2022 (advertised through Society for Endocrinology UK). RESULTS: 150 and 214 clinicians participated in the 2021 and 2009 survey, respectively (response rates 31.2% and 35.4%, respectively). At baseline, 2021 survey respondents were more likely to measure IGF-1 (96.0% vs 74.1%, p < 0.001) and morning cortisol (87.9% vs 62.6%, p < 0.001), and less likely GH (26.2% vs 42.6% p = 0.002), 24 h urine free cortisol (3.4% vs 23.2%, p < 0.0001) or dynamically assess adrenal reserve (11.4% vs 30.4%, p < 0.001). 47.2% of clinicians in 2021 would reassess pituitary function annually until discharge (in absence of tumour growth/symptoms). The 2021 survey respondents were more likely to stop imaging at or before 3 years (81.7% vs 44.3%, p < 0.001) and at or before 5 years (86.6.% vs 72.9%, p = 0.002), whilst 2009 survey respondents were more likely to continue imaging beyond 5 years (24% vs 7%, p < 0.001). Responses on imaging frequency/intervals showed notable variability in both surveys. CONCLUSIONS: Diagnostic and management approaches for microNFPAs have evolved in the UK. Biochemical investigations are performed in accord with consensus guidelines, though many clinicians perform annual biochemical surveillance without tumour growth/symptoms. A small number of clinicians request imaging beyond 5 years, but the frequency of imaging intervals until discharge remains variable. Robust evidence on the long-term natural history of microNFPAs is necessary to unify clinician approach.

Pituitary Incidentalomas: Best Practices and Looking Ahead.

Pituitary Incidentalomas (PI) are pituitary lesions serendipitously identified on imaging. PIs have become common in clinical practice because of increased use of imaging and radiologic advances. The most frequently incidentally detected lesions in adults are pituitary adenomas, followed by cystic lesions, and rarely other types of tumors and infiltrative and inflammatory disorders. Biochemical screening for hyperprolactinemia and acromegaly is needed in all patients with PI, whereas testing for hyposecretion is recommended for lesions larger than 6.0 mm. Most PIs are small nonfunctioning adenomas or cysts, which can be conservatively managed. For larger lesions, a multidisciplinary approach including endocrinology, neurosurgery, and neuro-ophthalmology is required. For incidentally detected lactotroph, somatotroph, and corticotroph adenomas, disease-specific management guidelines apply. Prospective studies are needed to enhance our understanding of the long-term course and response to treatment.

Congenital adrenal hyperplasia in patients with adrenal tumors: a population-based case-control study.

PURPOSE: Congenital adrenal hyperplasia (CAH) has been associated with adrenal tumors (ATs) but the relationship is still unclear. The aim was to investigate if CAH was more common in patients with adrenal tumors and their characteristics. METHODS: Using national registers all patients with an AT diagnosis (cases) and selected matched controls without AT diagnosis were included from 1st January 2005 to 31st December 2019. The patients with a CAH diagnosis were scrutinized in detail. RESULTS: ATs were diagnosed in 26,573 individuals and in none of 144,124 controls. In 20 patients with ATs and 1 control, a CAH diagnosis was present. The odds for having CAH in patients with ATs was 109 (95% CI 15-809; P < 0.0001). Among cases, 5 had a CAH diagnosis before the discovery of ATs and 15 afterwards. Half were females and two had been screened for CAH neonatally. The mean age when the ATs was discovered was 55.6 years. Adrenalectomy was performed in seven patients. Five patients had unilateral adrenalectomy before the CAH diagnosis and did not have any glucocorticoid protection. After the CAH diagnosis, 15 were initiated on glucocorticoids and 6 on mineralocorticoids. The majority diagnosed with CAH before index date had classic CAH. In individual diagnosed after index date, only three had classic CAH. The rest had nonclassical CAH. During the follow-up time of 9 years, six deceased, two of them in an adrenal crisis. CONCLUSIONS: The prevalence of CAH was greater in patients with ATs than in patients without. In all patients with ATs, CAH should be considered.