Update on clinical characteristics in the evaluation of phaeochromocytoma and paraganglioma.

Pheochromocytomas and sympathetic paragangliomas (PPGL) are rare neuroendocrine tumors originating from chromaffin tissue of the adrenal medulla and extra-adrenal sympathetic paraganglia. Historically, many of these tumors were diagnosed postmortem, earning pheochromocytomas the moniker "great mimic" due to their diverse clinical manifestations that can resemble various other conditions. Over time, the clinical presentation of PPGL has evolved, with a shift from symptomatic or postmortem diagnoses to more frequent incidental discoveries or diagnoses through screening, with postmortem identification now being rare. The development of a clinical scoring system has improved the identification of patients at increased risk for PPGL. Notably, the proportion of PPGL patients with normal blood pressure ranges from 15 % to 40 %, varying based on the clinical context. Despite the tumor's reputation, PPGL is an exceedingly rare cause of resistant hypertension. Management of a pheochromocytoma crisis has advanced, with several classes of drugs available for treatment. However, PPGL during pregnancy remains a significant concern, associated with substantial maternal and fetal mortality rates. Additionally, PPGL can present as rare disorders, including catecholamine-induced cardiomyopathy, Cushing syndrome, and urinary bladder PGL. Given these varied presentations, heightened awareness and prompt recognition of PPGL are crucial for timely diagnosis and treatment, ultimately improving patient outcomes. In this article, we offer an in-depth analysis of the diverse clinical presentations of PPGL, highlighting their complexity and the associated diagnostic and treatment strategies.

The Influence of Remnant Cholesterol on Cardiovascular Risk and Mortality in Patients with Non-Functional Adrenal Incidentalomas and Mild Autonomous Cortisol Secretion: A Retrospective Cohort Study.

Background: Increased cardiovascular risk has been described in individuals with adrenal incidentalomas. The aim of the present study is to assess the effect of remnant cholesterol (RC) on the cardiovascular risk and mortality of patients with adrenal incidentalomas. Methods: A retrospective cohort study was conducted with patients with adrenal incidentalomas between 2001 and 2024. One hundred thirty-seven patients (mean age of 61.2 ± 11.5 years; 56.6% women) with non-functioning adrenal incidentalomas and with mild autonomous cortisol secretion (MACS) (cortisol post-dexamethasone suppression test ≥1.8 µg/mL) were included. The patients were divided into two groups using 30 mg/dL as the cut-off for RC. Logistic regression models were used to study the impact of RC on major adverse cardiovascular events and mortality (MACEs). Results: Patients with RC ≥ 30 mg/dL exhibited a higher prevalence of type 2 diabetes mellitus (T2D) (p < 0.001), lower HDL-C (p < 0.001) and LDL-C (p = 0.025) levels, a higher frequency of treatment with statins (p = 0.032), and a higher rate of non-fatal major cardiovascular events (p = 0.038) and MACEs (p = 0.038). Patients with MACS showed no differences in RC or complications during the follow-up. The relative risk of high RC was 2.65 (1.04-6.77) for cardiovascular events and 2.27 (1.05-4.92) for MACEs, with p < 0.05 in both cases. The only variables independently affecting MACEs were age ([odds ratio] OR = 1.13 [p = 0.004]), female sex (OR = 0.20; p = 0.016), LDL-C (OR = 1.02; p = 0.029), and RC (OR = 1.06; p = 0.014). T2D and HDL-C were not independently associated with MACEs. Conclusions: RC ≥30 mg/dL in patients with adrenal incidentalomas was associated with a higher prevalence of T2D, lower HDL-C levels, and a higher risk of MACEs. MACS was not associated with RC or MACEs during the follow-up.

The Spectrum of Adrenal Lesions in a Tertiary Referral Center.

BACKGROUND: Adrenal tumors are a common finding in clinical practice, and only detailed evaluation may reveal secretory and metabolic abnormalities or their malignant character. We aimed to highlight epidemiological data, rates of malignancy, clinical or secretory characteristics, and the cardiometabolic implications of adrenal masses. METHODS: We conducted a retrospective analysis using data from the medical files of 474 patients with adrenal pathology hospitalized between January 2007 and January 2020, before the COVID-19 pandemic, using the ICD-10 codes. After applying inclusion and exclusion criteria, a total of 264 patients with adrenal tumors were enrolled in the study. Patients underwent clinical examination, abdominal imaging, and hormonal evaluation, and some of them underwent a pathological exam after adrenalectomy. RESULTS: Median age at diagnosis was 56 (17) years, with 81.06% of patients being female. The median follow-up period was 41.5 (70) months, ranging from 6 months to 13 years. Adrenal tumors were most frequently seen in older female patients, with 83.47% of them being over 40 years old. The malignancy rate was 4.54%. Hormonally nonfunctioning tumors (71.95%) predominated, and overt hypercortisolism was present in 10.61% of patients, as was mild autonomous cortisol secretion in 5.31% of patients, primary hyperaldosteronism in 8.71% of patients, and adrenal paraganglioma in 3.41% of patients. Cardiometabolic comorbid conditions were similar in patients with functioning and nonfunctioning tumors. CONCLUSIONS: All patients with adrenal tumors should receive a complete hormonal workup and detailed malignancy risk assessment. Even though a hormonally active tumor predisposes to cardiometabolic comorbid conditions, a nonfunctioning lesion may also be associated with such disorders and needs thorough assessment.

Presentation and management of patients with adrenal masses: a large tertiary centre experience.

BACKGROUND: Adrenal masses are found in up to 5%-7% of adults. The 2016 European guidelines on the management of adrenal incidentalomas have standardised the workup of these patients, but evidence of their impact on clinical practice is lacking. METHODS: Retrospective review of clinical presentation, radiological characteristics, and final diagnosis of a large cohort of patients with adrenal masses referred to a tertiary care centre 1998-2022. Sub-analysis compares outcomes before and after implementing the 2016 guidelines. RESULTS: A total of 1397 patients (55.7% women; median age 60 years [interquartile range {IQR}, 49-70]) were included. Incidental discovery was the most frequent mode of presentation (63.7%) and 30.6% of patients had masses ≥ 4 cm (median 2.9 cm [IQR, 1.9-4.7]). Unenhanced computed tomography Hounsfield units (HU) were available for 763 patients; of these, 32.9% had heterogeneous masses or >20 HU. The most common diagnoses were adrenocortical adenoma (56.0%), phaeochromocytoma (12.7%), adrenocortical carcinoma (10.6%), and metastases (5.7%). At multivariable analysis, significant predictors of malignancy included >20 HU or heterogeneous density (odds ratio [OR] 28.40), androgen excess (OR 27.67), detection during cancer surveillance (OR 11.34), size ≥ 4 cm (OR 6.11), and male sex (OR 3.06). After implementing the 2016 guidelines, the number of adrenalectomies decreased (6.1% pre-2016 vs 4.5% post-2016) and the number of patients discharged increased (4.4% pre-2016 vs 25.3% post-2016) for benign non-functioning adrenal masses. CONCLUSION: Implementing the 2016 guidelines positively impacted clinical practice, reducing unnecessary surgeries and increasing the discharge rate for benign adrenal masses, thereby preserving healthcare resources and patient burden.

Changes in nonfunctional adrenal incidentaloma after COVID-19 infection and a model for predicting benign and malignant adrenal incidentaloma.

Aims: To compare nonfunctional adrenal incidentalomas (NFAI) in individuals with and without a history of COVID-19 infection, while also establishing predictive models for distinguishing between benign and malignant adrenal incidentalomas (AI). Methods: A retrospective collection of data from patients with AI who underwent surgery and were verified in our hospital between April 2022 and June 2023 was conducted. A total of 121 patients were included in the study. Demographic information, tumor characteristics, functional indicators, and complications were compared among the patients. Statistical analyses utilized the t-test for continuous variables and Pearson chi-square test or Fisher's exact test for categorical variables. Results: Patients with COVID-19 exhibited a higher prevalence of obesity (84.2% vs. 63.3%, P=0.048) and elevated direct bilirubin (DBIL) levels (44.1% vs. 19.2%, P=0.043) compared to those without COVID-19. Moreover, patients with Malignant AI, in contrast to Benign AI, showed higher normal total protein (TP) levels (28.8% vs. 57.1%, P=0.016) and larger tumor sizes (20 vs. 32.5mm, P=0.009). Univariate analysis identified low TP (OR=0.303, 95% CI=0.111-0.825, P=0.020) and tumor size (OR=1.045, 95% CI=1.011-1.080, P=0.009) as potential risk factors for multivariate analysis. A predictive model comprising clinical risk factors (tumor size and low TP) demonstrated an AUC of 0.754 (95% CI, 0.603-0.904) with a sensitivity of 0.75 and specificity of 0.775. The calibration curve revealed a bias-corrected AUC of 0.77. Conclusion: No discernible differences in the clinical manifestations of adrenal incidentalomas were observed between cases with and without a history of COVID-19 infection. However, AI with larger tumor diameters and lower than normal levels of total protein exhibited a more pronounced malignant potential.

The Incidence of Cancers in Patients With Nonfunctional Adrenal Tumors: A Swedish Population-Based National Cohort Study.

Context: It is unclear if nonfunctional adrenal tumors (NFAT) are associated with higher cancer incidence. Objective: To analyze the cancer incidence in patients with NFAT. Methods: In this national register-based retrospective cohort study, consecutive patients with NFAT identified in Sweden 2005-2019 and matched control individuals without adrenal tumors were followed up to 15 years. Outcome data were collected from national registers and adjusted for confounders. Both cases and controls were followed until newly diagnosed malignancy, death, or until 2019. Individuals with adrenal hormonal excess or prior malignancy were excluded. Results: Among 17 726 cases, 10 777 (60.8%) were women, and the median age was 65 (IQR, 57-73) years. Among 124 366 controls, 69 514 (55.9%) were women, and the median age was 66 (IQR, 58-73) years. The incidence of any cancer was higher in patients with NFAT compared to controls (hazard ratio [HR] 1.35 95% CI 1.29-1.40; adjusted HR 1.31, 95% CI 1.26-1.37). NFAT was associated with a higher incidence of adrenal, thyroid, lung, stomach and small intestine, kidney, pancreatic, breast, and colorectal cancer. Sensitivity analyses did not change the overall results, but associations were not significantly increased after adjustment in patients with NFAT and appendicitis or gallbladder/biliary tract/pancreas disorders. Cancer incidence may have been underestimated by adjusting for unclear and benign tumors. Conclusion: The incidence of cancer was increased in patients with NFAT. Long-term follow-up may be indicated.

Serum steroid profiling in the diagnosis of adrenocortical carcinoma: a prospective cohort study.

CONTEXT: Guidelines suggest performing urine steroid profiling in patients with indeterminate adrenal tumors to make a noninvasive diagnosis of adrenocortical carcinoma (ACC). However, urine steroid profiling is not widely available. OBJECTIVE: To determine the accuracy of clinically available serum 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone in diagnosing ACC. METHODS: We conducted a prospective single-center cohort study of patients with adrenal masses evaluated between 2015-2023. Serum was analyzed by liquid chromatography-mass spectrometry for 17OH-pregnenolone, 17OH-progesterone, 11-deoxycortisol. Reference standard for adrenal mass included histopathology, imaging characteristics, imaging follow up of 2 years, or clinical follow up of 5 years. Localized Generalized Matrix Learning Vector Quantization (LGMLVQ) analysis was used to develop serum steroid score and assessed with area under receiver operating curve (AUROC). RESULTS: Of 263 patients with adrenal masses, 44 (16.7%) were diagnosed with ACC, 161 (61%) with adrenocortical adenomas (ACAs), 27 (10%) with other adrenal malignancies, and 31 (12%) with other. Hounsfield unit (HU) ≥ 20 was demonstrated in all ACCs, in all but one other adrenal malignancy, and in 58 (31%) ACAs. All 3 steroids were higher in patients with ACCs vs non-ACCs, including when comparing ACCs with functioning ACAs, and with ACAs with HU ≥ 20 (P<0.0001 for all). LGMLVQ analysis yielded a serum steroid score that discriminated between ACC and non-ACC groups with a mean threshold fixed AUROC of 0.823. CONCLUSIONS: We showed that measurements of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone could be valuable in diagnosing ACC. After appropriate validation, serum steroid score could be integrated in clinical practice.

Recent guidelines for diagnostic and therapeutic management of accidentally detected adrenal tumours (incidentaloma) in adults.

At the end of 2023, the European Journal of Endocrinology published the latest guidelines of the European Society of Endocrinology (ESE) on the management of accidentally detected adrenal tumours (incidentalomas) in adults. Comparing them with the previous version of the ESE recommendations from 2016, a tendency towards far-reaching individualisation of the therapeutic and diagnostic approach in patients with adrenal incidentaloma can be seen - it is reflected by changes in the initial assessment of the malignancy of the lesion, in the scope of the proposed hormonal assessment, and qualification for surgery. The latest version of the guidelines includes 9 completely new recommendations, and 5 more recommendations have been significantly changed. Among the most important changes, the introduction of the term "mild autonomous cortisol secretion" (MACS) instead of the previously used term "autonomous cortisol secretion (ACS)" along with more precise recommendations regarding its management should be emphasised. An important novelty is also the modification of the criteria for benign adrenal adenoma, which does not require further imaging observation - due to the results of recent clinical studies, the authors have removed the criteria of size below 4 cm from the definition. Among others, the guidelines also encourage more proactive surgical treatment of indeterminate adrenal incidentaloma in people < 40 years of age and pregnant women. The authors of the recommendations repeatedly accentuate the importance of a multidisciplinary approach in making decisions regarding further management of patients with an unspecified adrenal tumour. Despite a few significant differences compared to the previous version of guidelines, the authors emphasise the presence of gaps in the current scientific evidence, which would not allow for the formulation of more unambiguous recommendations. The need to optimise ordered diagnostic tests, which generate additional socio-economic burdens without negative impact on patients' health, is also an important aspect of the latest guidelines.

Fragility Fractures and Cortisol Secretion in Patients With Nonfunctioning Adrenal Incidentalomas.

Context: The risk of vertebral fractures (VFx) in patients with nonfunctioning adrenal incidentalomas (NFAI) is unknown. Objective: This work aimed to assess in NFAI patients the prevalence and incidence of VFx and a hormonal marker to identify patients at risk. Methods: A retrospective, cross-sectional, and longitudinal study of outpatients was conducted. A total of 306 NFAI patients (cross-sectional arm) and 213 controls were evaluated for VFx prevalence; 85 NFAI patients (longitudinal arm, follow-up 30.3 ± 17.5 months) were evaluated for VFx incidence. Main outcome measures included serum cortisol after 1 mg-dexamethasone test (F-1mgDST), lumbar spinal (LS), and femoral neck (FN) bone mineral density (BMD) and VFx presence, by radiograph of the spine. Results: Cross-sectional arm: prevalent VFx associated with F-1mgDST with a cutoff of 1.2 µg/dL (33 nmol/L, area under the curve 0.620 ± 0.39; P = .002). Compared with controls and NFAI patients with F-1mgDST less than 1.2 µg/dL (group A), NFAI patients with F-1mgDST greater than or equal to 1.2 µg/dL (group B) showed a higher VFx prevalence (10.8%, 12.6%, and 29.5%, respectively; P < .001 all comparisons), which was associated with F-1mgDST greater than or equal to 1.2 µg/dL (odds ratio 3.02; 95% CI, 1.63-5.58; P < .001) accounting to confounders. Longitudinal arm: the VFx incidence was higher in group B than in group A (19.3% vs 3.6%; P = .05). In group B, all incident VFx occurred in patients without low BMD. The F-1mgDST cutoff for predicting an incident VFx was 1.2 µg/dL, although statistical significance was not reached after adjustment for confounders (P = .061). Conclusion: In NFAI patients, F-1mgDST levels greater than or equal to 1.2 µg/L (33 nmol/L) are associated with prevalent VFx and may identify patients at risk of incident VFx.

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.

Predictors of malignancy for treatment direction in patients with nonfunctioning adrenal incidentaloma.

BACKGROUND: Adrenal incidentalomas (AI) are predominantly nonfunctional and benign, and their detection and differential diagnosis are aided by computed tomography (CT). A nonfunctioning adrenal incidentaloma (NFAI) usually requires regular follow-up; however, adrenalectomy may be necessary in certain patients. This study aimed to evaluate prognostic predictors to guide the treatment approach for AIs. METHODS: This retrospective, single-center study involved patients diagnosed with NFAI from January 2000 to December 2020. Patients were divided into surgery and observation groups. A subgroup analysis compared malignant and benign adenoma within the surgery group. RESULTS: A total of 307 patients were included, with 127 in the surgery group and 180 in the observation group. The surgery group displayed distinct morphological and malignant potential features in CT scans more frequently than the observational group did. The malignant subgroup exhibited more irregular borders on CT, and a higher number of patients with absolute washout under 60 % and relative washout under 40 % compared with the benign adenoma subgroup. Interestingly, within the surgery group, the mean tumor size was <4 cm for the both malignant and benign adenoma subgroups. CONCLUSIONS: Characterizing NFAI is important for appropriate treatment, as not all AIs have a favorable prognosis. CT findings associated with malignant potential, such as Hounsfield unit and washout values, were useful in determining the need for surgical treatment. However, the conventional criterion of a 4-cm size threshold for surgery was not a reliable malignancy predictor. Surgical resection should be considered for specific patient groups to ensure proper treatment over mere observation.

Lymphoid Structure Presenting as a Hypermetabolic Adrenal Incidentaloma.

Adrenal incidentalomas are a frequent cause for consultation in endocrinology. Current guidelines provide an algorithm for their evaluation to determinate the risk of hormonally active or malignant condition. We report a unique case of benign adrenal incidentaloma in a 53-year-old woman with multiple malignancy criteria on contrast-free computed tomography and [18F]fluorodeoxyglucose positron emission tomography-computed tomography, leading to a left adrenalectomy. Histopathologic analysis showed a 15-mm intra-adrenal lymphoid organ localized in the medulla, without any cellular atypia and organized with a capsule and multiple germinal centers. The surrounding adrenal tissue was unremarkable, and the patient did not develop any inflammatory, infectious, or neoplastic disease during the 2 following years. This is the first described case of a well-organized intra-adrenal ectopic lymphoid organ in the absence of any evident stimulus.

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.

Evaluating the efficacy of surgical and conservative approaches in mild autonomous cortisol secretion: a meta-analysis.

Introduction: The management of Mild Autonomous Cortisol Secretion (MACS) remains a topic of debate among clinicians, with differing opinions on the effectiveness of surgical intervention compared to conservative treatment methods. This meta-analysis provides a comprehensive assessment of available literature to determine the most effective approach for treating this condition. Methods: On December 1, 2023, an exhaustive literature search of English databases Embase, PubMed, the Cochrane Library, Scopus, Web of Science, as well as the Chinese databases China HowNet, Wanfang Database, SinoMed Database, and Weipu Database using the keywords "Mild Autonomous Cortisol Secretion", "Subclinical Cushing's Syndrome", "Subclinical Hypercortisolism", "Mild Cortisol Autonomous Secretion", "Adrenal Incidentaloma", "Surgical Treatment" and "Adrenalectomy". The data were statistically analyzed using STATA version 15.0. Results: In this comprehensive analysis involving 629 patients with MACS, the therapeutic efficacy of adrenalectomy was evident. The meta-analysis results indicate that compared to conservative treatment, surgical intervention more effectively improves obesity indicators in patients: waist circumference (SMD=-0.62, 95% CI: -1.06 to -0.18), BMI (SMD=-0.41, 95% CI: -0.62 to -0.20), enhances glycemic control: fasting blood glucose (SMD=-0.47, 95% CI: -0.68 to -0.26), glycated hemoglobin (SMD=-0.66, 95% CI: -0.95 to -0.38), improves lipid metabolism: triglycerides (SMD=-0.45, 95% CI: -0.73 to -0.16), lowers blood pressure: systolic blood pressure (SMD=-1.04, 95% CI: -1.25 to -0.83), diastolic blood pressure (SMD=-0.89, 95% CI: -1.12 to -0.65), and ameliorates hormonal metabolic disorder: 24h urinary free cortisol (SMD=-1.10, 95% CI: -1.33 to -0.87), ACTH (SMD=2.30, 95% CI: 1.63 to 2.97). All these differences are statistically significant. Conclusion: This meta-analysis shows that, compared to conservative treatment, surgical treatment is more effective in improving obesity indicators, glycemic control, lipid metabolism, reducing blood pressure, and ameliorating hormonal metabolic disorders in patients with MACS. These statistically significant results highlight the importance of considering surgical intervention in the management of patients with MACS. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023492527.

Pheochromocytoma-induced diffuse alveolar hemorrhage after cholecystectomy: A case report and literature review.

Diffuse alveolar hemorrhage (DAH) can be caused by various conditions, categorized as autoimmune and non-autoimmune. Immunofactor-mediated vasculitis, such as Wegener granulomatosis, microscopic polyangiitis, Goodpasture syndrome, connective tissue disorders, and antiphospholipid antibody syndrome, are common autoimmune causes. Non-autoimmune factors include infectious or toxic exposures and neoplastic conditions. The diagnosis of DAH, resulting from excessive catecholamine release from an adrenal pheochromocytoma or extra-adrenal paraganglioma, can present diagnostic challenges and necessitate prompt treatment. In this report, we present a case of pheochromocytoma that manifested as an adrenal incidentaloma (diagnosed during the management of sudden-onset DAH after cholecystectomy). Case report: A 39-year-old female patient with adrenal incidentaloma developed DAH following a cholecystectomy procedure, presenting with sudden-onset hemoptysis and dyspnea. Administration of glucocorticoids, known to precipitate pheochromocytoma crisis (PCC), was required before the cause was determined. Intubation and mechanical ventilation were necessary due to persistent hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). The patient in this case experienced two epidoses of PCC while she was on mechanical ventilation. Subsequent work-up revealed a 26 × 25 mm left adrenal adenoma with hormonal confirmation of catecholamine hypersecretion. A laparoscopic adrenalectomy was done eight months later to excise the left adrenal gland. Subsequent examination of the tissue revealed pheochromocytoma, thereby validating the initial diagnosis. Conclusion: Adrenal incidentalomas may be pheochromocytomas (adrenal incidentalomas can manifest as pheochromocytomas), even without adrenergic symptoms. It is recommended that adrenal incidentalomas undergo evaluation for pheochromocytoma before undergoing invasive surgery or receiving corticosteroid treatment. When considering potential causes of DAH without further elucidation, including a pheochromocytoma or paraganglioma (PPGLs) in the differential diagnosis is important.

Clinical Evaluation of Adrenal Incidentaloma: The Experience of a Referral Center.

The number of adrenal incidentaloma (AI) cases has increased in the last few years due to the widespread use of imaging diagnostics. Management requires evaluation of the malignant nature and hormonal activity. The aim of the present study is to assess possible clinical abnormalities in 132 AI patients both at baseline and during follow-up (mean 48.6 ± 12.5 months). In all patients, demographic, anthropometric data, biochemical, metabolic and hormonal data, and 24-h ambulatory blood pressure monitoring were assessed. Mild autonomous cortisol secretions (MACS) were diagnosed in patients without signs and symptoms of overt Cushing's syndrome and post dexamethasone (DXM) plasma cortisol concentration > 50 nmol/L (>1.8 µg/dL). Patients with overnight DXM-1 mg test positive showed higher values of diastolic blood pressure, glycemia and uric acid levels compared to patients with negative DXM test at baseline. During follow-up, the potential development of MACS in patients with nonfunctional AI showed a prevalence of 29%, though the cardiovascular and metabolic alterations were less pronounced compared to those diagnosed with MACS at baseline. Therefore, follow-ups with AI patients are useful for observing changes in clinical features.

Increased cardiometabolic risk and prevalence of ascending aorta dilation in patients with nonfunctioning adrenal incidentaloma: a retrospective propensity score-matched study.

The cardiometabolic implications of Non-Functioning Adrenal Incidentaloma (NFAI) is still matter of debate. This study takes a novel approach to analyze this association, accounting for the influence of various confounding factors. We present the findings of a retrospective, cross-sectional, and case-control study. Data from all NFAI patients in primary prevention, referred to the University of Turin between 2000 and 2023, were collected and compared with subjects without adrenal disease, using propensity score matching analysis. A total of 1997 patients were included (906 patients with NFAI; 1091 controls). Adrenal tumor group was associated with high levels of cardiovascular risk scores in both univariate and multiple linear regression analyses (Progetto CUORE: EC 11.00, 95% CI 2.72-44.46, p = 0.001; SCORE: EC 1.97, 95% CI 1.01-3.81, p = 0.046). Regarding cardiometabolic complications, multivariable logistic regression revealed an independent association between NFAI and ascending aorta dilation (OR 4.64, 95% CI 2.24-9.63, p = 0.000), after adjusting for age, sex, smoking status, metabolic syndrome, number of antihypertensive drugs, estimated glomerular filtration rate (eGFR), and normetanephrine levels. Propensity score matching analysis (1:1 matching ratio), based on the same logistic regression model, confirmed the association of NFAI with aortic dilation (ß = 0.083, 95% CI 0.008-0.157, p = 0.030). No significant associations were found with metabolic syndrome, type II diabetes, eGFR <60 mL/min/1.73 m2, microalbuminuria, atrial fibrillation, or hypertensive heart disease. This study suggests that patients with NFAI face increased cardiometabolic risk and high prevalence of ascending aorta dilation. Routine evaluation of NFAI patients should include thorough cardiovascular assessment and consideration of treatments aimed at reducing cardiovascular risk.

From Adenoma to Carcinoma: the Unexpected Evolution of an Apparently Stable Adrenal Lesion.

BACKGROUND: There is a lack of solid long-term evidence with respect to the management over time of adrenal incidentalomas that miss clearly benign radiological features. We present the case of a 75-year-old man with a non-secreting adrenal mass, apparently stable in size (14 mm) and unchanged in features for 2 years, but subsequently diagnosed as adrenal carcinoma. CASE REPORT: The patient was referred to Grande Ospedale Metropolitano Niguarda in August 2022 due to the presence of a large lesion in the left adrenal site. In 2017, a 14 mm, 20 HU, round, regular-edged lesion was detected at a CT scan without contrast medium. Over the next two years, the patient was re-evaluated every 6 months with follow-up CT scans with no apparent densitometric or dimensional changes in the known lesion. In September 2022, 3 years after the last CT scan, the patient was hospitalised for pneumonia. An abdominal CT scan acquired during the hospitalisation showed an increase of the lesion to 14.5x10x12 cm. The patient subsequently underwent open nephrosurrenectomy, and histological examination confirmed the presence of an adrenal carcinoma (proliferation index 5%, Weiss score 7). No adjuvant therapy was administered, and the last CT scan in December 2022 was negative for the recurrence of the disease. CONCLUSION: Adrenal carcinoma usually presents as a clearly malignant lesion with rapid growth and a marked tendency to metastasise. This case highlights how an adrenal adenoma with indeterminate features is worthy of follow-up over time despite its apparent dimensional and radiological stability [1].

Adrenal cyst presenting with clinical features of a pheochromocytoma.

Benign adrenal cysts are relatively uncommon variants of all adrenal incidentalomas. When identified, most benign adrenal cysts are asymptomatic, which differentiates them from other functional adrenal lesions. There are various types of adrenal cysts, although the most common being an endothelial cyst. Ultimately, evaluation and management approaches are aimed at ruling out a functional adrenal mass and management of symptoms if present. We present a unique presentation of an otherwise healthy male with a large incidental adrenal cyst, later identified as a benign endothelial cyst, who presented with classic symptoms of catecholamine excess. The patient had a negative hormonal evaluation, and his episodic symptoms were resolved with surgical removal of the adrenal mass. This case report and brief review provides valuable insight into the evaluation and management of a unique clinical scenario, where a benign cystic mass led to compression-related symptoms of catecholamine excess that were resolved after removal of the nonfunctional, cystic, mass.

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.