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Introduction: The aim of this publication is to review the initial management procedure for adrenal incidentalomas, and where appropriate, to establish a carcinological management procedure for malignant adrenal tumours., Materials and Methods: The multidisciplinary working group updated the CCAFU 2022 recommendations for the carcinological management of adrenal incidentalomas on the basis of a comprehensive PubMed review of the literature., Results: Although the majority of adrenal masses are benign and nonfunctional, it is important to investigate them because of their serious endocrine potential, and because of certain cancers. Malignant adrenal tumours (MCTs) are essentially adrenocortical carcinomas (ACCs), malignant pheochromocytomas (MPCs), and adrenal metastases (AMs). The work-up for the malignancy of an adrenal incidentaloma includes a full history, physical examination, and a biochemical/hormonal assessment to look for subclinical hormone secretion. Diagnostic hypotheses are sometimes available at this stage, but morphological and functional imaging and histological analysis enable the malignancy assessment to be completed, and a carcinological diagnosis to be made., Conclusions: SCC and MCC are mostly sporadic, but a hereditary origin is always possible. SCC is suspected preoperatively, but a diagnosis of certainty is histological. The diagnosis of PCM is more delicate and is based on clinical, biological, and imaging findings. The definitive diagnosis of MS requires a percutaneous biopsy. All cases must then be discussed within the COMETE adrenal cancer network., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype-phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET , NF1 , VHL , and SDHD . Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype-phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies.

Paediatric phaeochromocytomas and paragangliomas (PPGLs), though rare tumours, are associated with significant disability and death in the most vulnerable of patients early in their lives. However, unlike cryptogenic and insidious disease states, the clinical presentation of paediatric patients with PPGLs can be rather overt, allowing early diagnosis, granted that salient findings are recognized. Additionally, with prompt and effective intervention, prognosis is favourable if timely intervention is implemented. For this reason, this review focuses on four exemplary paediatric cases, succinctly emphasizing the now state-of-the-art concepts in paediatric PPGL management., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Background: Mild autonomous cortisol secretion (MACS) accounts for a significant proportion of adrenal incidentaloma. Current endocrinological screening tests for MACS are complex, particularly in areas with limited medical resources. This study aimed to develop a diagnostic tool based on leukocyte-related parameters to differentiate between MACS and non-functioning adrenal adenoma (NFA)., Methods: Inthis retrospective case-control study, propensity score-matching was used to select 567 patients from a cohort of 1108 patients (201 MACS, 907 NFA). External validation cohort included 52MACS and 48 NFA from two hospitals, which did not overlap with the modeling cohort patients. Leukocyte-related parameters were evaluated, and the diagnostic efficacy of each parameter was assessed by calculating Youden's J index (J) and the area under the curve (AUC). The study population was divided into training and testing samples using a 10-fold cross-validation method. Machine learning (ML) and classification and regression tree (CART) model were established., Results: After propensity score matching, 567 patients were enrolled, including 197 MACS and 370 NFA. With the exception of basophil percentage, all other parameters differed significantly between the two groups. Lymphocyte count, lymphocyte percentage, eosinophils count, eosinophils percentage, and basophil percentage were lower in the MACS group compared to the NFA group. Eosinophils percentage demonstrated the highest AUC (0.650), with a sensitivity of 51.3% and specificity of 73.2%. The ML model, based on multiple parameters,exhibited better performance in diagnosing MACS (sensitivity 76%, specificity 77.4%, and AUC 0.818). A clinically usable CART model achieved an AUC of 0.872, with a sensitivity of 95% and a specificity of 75.7%.  In the validation cohort, the prediction accuracy of the ML model and the CART model were 0.784 and 0.798, respectively., Conclusion: TheCART diagnostic model, constructed based on leukocyte-related parameters, could assist clinicians in distinguishing between MACS and NFA., (© 2024. The Author(s).)

Background: Medullary thyroid cancer (MTC) is one of the rare neuroendocrine malignancies. This cancer is hereditary in approximately 20% of cases. Although lymph node (LN) metastasis is prevalent in MTC, distant metastasis is not commonly seen in these patients. The most common locations for metastasis are the lungs, liver, and bones. This study presents an extremely rare MTC metastasis to bone marrow (BM) and adrenal gland, which has not been reported before., Case: The patient was a 50-year-old man with a diagnosis of MTC and total thyroidectomy 2 months before his presentation. He came to the emergency department (ED) complaining of dyspnea, diffuse bone pain, nonbloody diarrhea, and abdominal cramps starting in the last month before. Initial treatment with intravenous fluid infusion and loperamide, due to the provisional diagnosis of infectious diarrhea, was ineffective. Further assessments revealed severe pancytopenia and a massive tumor above the left kidney. Bone marrow aspiration (BMA) and biopsy (BMB) led to the diagnosis of invasive metastasis of the MTC to the BM and the left adrenal gland. In the initial evaluations, his COVID-19 test became positive, and despite all efforts, his condition deteriorated, and he died 5 days after admission due to respiratory distress., Conclusion: Most MTC cases present with thyroid nodules in the initial steps and are confined to the thyroid gland or the adjacent LNs. These cases are mostly cured by thyroidectomy and LN dissection. This neuroendocrine cancer infrequently becomes aggressive and involves other parts of the body. However, involving BM or adrenal gland has been scarcely reported. Due to ineffective red and white blood cell production, BM metastasis can cause pancytopenia and, consequently, pallor, fatigue, dyspnea, and susceptibility to infections. High calcitonin levels can also cause diarrhea. The initial diagnosis is mostly with neck ultrasound (US) and fine needle aspiration (FNA). Total thyroidectomy is the main therapeutic option for these patients. Calcitonin and carcinoembryonic antigen (CEA) are sensitive indicators of recurrence or remaining tumors, which might be helpful for the initial diagnosis and postoperation follow-up. Although extremely rare, invasive metastasis of MTC might involve unusual body organs such as the BM or adrenal glands. In cases of unjustifiable pancytopenia or adrenal dysfunction in MTC-positive patients, these possibilities should be considered and ruled out by some specific evaluations, such as bone marrow biopsy and contrast-enhanced imaging., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

The urinary normetanephrine to creatinine ratio (uNMN/Cr) and urinary metanephrine to creatinine ratio (uMN/Cr) are commonly evaluated for the diagnosis of pheochromocytomas (PCC) in dogs. This study aimed to establish reference intervals for uNMN/Cr and uMN/Cr in 56 healthy dogs in Japan and to investigate the effect of urine collection methods on these measurements in 15 non-PCC dogs. The upper limits of reference intervals for uNMN/Cr and uMN/Cr were 124.4 nmol/mmol (90% confidence interval [CI] 107.7-137.0) and 121.1 nmol/mmol (90% CI 102.8-145.1), respectively. Both uNMN/Cr and uMN/Cr were significantly higher when urine was collected in the hospital compared to at home. Several factors, including the method of urine collection, should be considered when utilizing these reference intervals.

Context: Adrenal incidentalomas (AIs) are relatively uncommon neoplasms in 2% of apparently healthy individuals requiring evaluation for functionality and malignancy., Aim: We aimed to study the clinical, biochemical, and radiological profiles of patients presenting with AI and histopathological outcomes of those undergoing adrenalectomy. Materials and Methods: This retrospective study enrolled 62 AI patients attending a tertiary care center in South India between January 2016 and October 2023. Demographic details, radiological features, functionality, and histopathological data were analyzed., Results: Out of 62 patients, total masses evaluated were 65 indicating bilaterality in 3 patients. The female: male ratio was 1.69, with a median age of 55 years (interquartile range: 44-64 years). 45.1% of individuals were >60 years. The most common indication for imaging was pain abdomen in 43 (69.4%). The median size was 3.2 cm. Fifty-five (88.7%) were assessed for functionality and 27 (49.1%) were functional. Among the 62 individuals, 14 (20.2%) had hypercortisolism, 11 (15.9%) had pheochromocytoma, 5 (7.24%) had primary hyperaldosteronism (PA), and 4 (5.7%) had hyperandrogenism including plurihormonal in 7. A mass size of 3.2 cm was of great value in distinguishing functional tumors with a sensitivity of 72% and specificity of 66% with an area under the curve of 0.682. A total of 34 (54.8%) patients underwent adrenalectomy. On histopathological examination, Adenoma (44.1%) was the most common followed pheochromocytoma (26.5%), adrenal cysts (8.8%), and Myelolipoma (5.9%). Two (5.9%) incidentalomas were adrenocortical carcinoma (ACC). Eight (53.3%) adenomas were functional with 6 having hypercortisolism (including 1 with hyperandrogenism) and 2 with PA., Conclusion: In our experience, the incidence of pheochromocytoma was second most common after adenoma. Since most functional tumors (60%) and all ACCs were ≥4 cm, a thorough biochemical evaluation for hormonal excess and evaluation for malignancy followed by surgery should be considered for lesions, especially ≥4 cm. Thus, we report the baseline demographic and clinical characteristics of patients with AI from a single center in South India., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Objective: This white paper provides practical guidance for clinicians encountering bilateral adrenal masses., Methods: A case-based approach to the evaluation and management of bilateral adrenal masses. Specific clinical scenarios presented here include cases of bilateral adrenal adenomas, hemorrhage, pheochromocytomas, metastatic disease, myelolipomas, as well as primary bilateral macronodular adrenal hyperplasia., Results: Bilateral adrenal masses represent approximately 10% to 20% of incidentally discovered adrenal masses. The general approach to the evaluation and management of bilateral adrenal masses follows the same protocol as the evaluation of unilateral adrenal masses, determined based on the patient's clinical history and examination as well as the imaging characteristics of each lesion, whether the lesions could represent a malignancy, demonstrate hormone excess, or possibly represent a familial syndrome. Furthermore, there are features unique to bilateral adrenal masses that must be considered, including the differential diagnosis, the evaluation, and the management depending on the etiology. Therefore, considerations for the optimal imaging modality, treatment (medical vs surgical therapy), and surveillance are included. These recommendations were developed through careful examination of existing published studies as well as expert clinical opinion consensus., Conclusion: The evaluation and management of bilateral adrenal masses require a comprehensive systematic approach which includes the assessment and interpretation of the patient's clinical history, physical examination, dynamic hormone evaluation, and imaging modalities to determine the key radiographic features of each adrenal nodule. In addition, familial syndromes should be considered. Any final treatment options and approaches should always be considered individually., Competing Interests: Disclosure I.B. reports consulting/advisory board/data safety monitoring board fees to institution from HRA Pharma, Recordati, Corcept, Sparrow, Xeris, NovoNordisk, AstraZeneca, Crinetics, Neurocrine, Diurnal, Adrenas, Spruce, and Adrenas and funding for investigator-initiated research from HRA Pharma and Recordati all unrelated to the current paper. A.V. reports consulting fees from Corcept, Mineralys, and HRA Pharma, all unrelated to the current work. A.H. reports research funding from Corcept, AstraZeneca, and Spruce Biosciences consulting and advisory board fees from Corcept, all unrelated to the current paper. O.H. reports advisory board participation with Corcept Therapeutics, Neurocrine Biosciences, Recordati Rare Diseases, Xeris Pharma, Amryt Pharma, and Lantheus. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. All rights reserved.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pheochromocytomas are rare neuroendocrine tumors that can present as hypertensive crises or serious cardiac and cerebrovascular complications that endanger the patient's life. Two unusual cases of adrenergic crises induced by pheochromocytoma with cardiovascular manifestations are presented, one with multiple complications/multiorgan failure, fatal outcome and definitive diagnosis in the post mortem autopsy, and another with a satisfactory evolution after diagnosis and appropriate treatment., (Copyright © 2024 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Pheochromocytomas are rare neuroendocrine tumors that derive from the chromaffin cells of the adrenal medulla and secrete catecholamines. The measurement of plasma or fractionated urine metanephrines is the hormonal determination of choice for the biochemical diagnosis. Once the biochemical diagnosis is confirmed, the next step is the localization study. It is recommended to request a genetic study in all patients with pheochromocytomas since 40% of cases are hereditary. Once the diagnostic study is completed, preoperative treatment with alpha blockers should be instituted at least 7-14 days before adrenalectomy. However, in low-risk patients, the omission of presurgical treatment could be considered if the surgery is performed in centers with experience and a strict monitoring of the patient is carried out during the perioperative period. This document offers a practical guide on the diagnosis and perioperative approach in patients with pheochromocytomas., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

BACKGROUND Pheochromocytoma, a rare catecholamine-secreting tumor, often presents with paroxysmal or sustained hypertension, tachycardia, headache, and diaphoresis. Timely diagnosis is essential to prevent adverse complications. Less common presentations include pheochromocytoma crisis, with severe neurological and cardiac complications. CASE REPORT We report a unique case of a 25-year-old woman who initially presented with pheochromocytoma-induced hypertensive encephalopathy and acute coronary syndrome. Echocardiography revealed takotsubo-like cardiomyopathy, and magnetic resonance imaging of the brain revealed posterior reversible encephalopathy syndrome. Initial treatment focused on controlling her blood pressure and supporting cardiac function. Due to her recovering from immediate crisis and absence of further symptoms, the patient refused further follow-up. However, she eventually experienced another episode of hypertensive crisis 2 years later. Subsequent investigations with 24-h urine tests revealed elevated vanillylmandelic acid levels (7.93 mg/24 h), normetanephrine (2638.72 µg/24 h), and nor-metanephrine to creatinine ratio (3546.67) and normal urine metanephrine levels (195.92 µg/24 h) and metanephrine to creatinine ratio (263.33). Contrast-enhanced computed tomography of the abdomen revealed a 4.3×3.1×4-cm mass in the right adrenal gland. A DOTATATE positron emission tomography scan revealed a 3.9×4.3×2.7-cm localized right adrenal pheochromocytoma. Biochemical testing and adrenal imaging revealed a previously undiagnosed pheochromocytoma. Following targeted medical therapy and right adrenalectomy, the patient achieved complete resolution of her hypertension and associated symptoms. CONCLUSIONS Our case is a unique simultaneous presentation of posterior reversible encephalopathy syndrome and takotsubo-like cardiomyopathy, highlighting the importance to consider pheochromocytoma in acute neurological and cardiac presentations, even in the absence of typical symptoms.

BACKGROUND Pheochromocytomas, rare tumors arising from the adrenal medulla, can present with highly variable symptoms; therefore, pheochromocytomas frequently remain undiagnosed, leaving the potential for physiological complications. Acutely, these complications include pheochromocytoma crisis, in which high levels of catecholamines are released and cause a life-threatening hypertensive emergency. Over time, undiagnosed pheochromocytomas can lead to cardiovascular damage and end-organ disease related to chronic exposure to elevated blood pressure. CASE REPORT We share a case of pheochromocytoma in a 45-year-old woman who presented with gastrointestinal symptoms of intractable nausea, vomiting, and abdominal pain. Imaging revealed an adrenal mass that had radiographic features that were most consistent with myelolipoma. Before exposing the patient to anesthesia and endoscopy for further diagnostic workup of her gastrointestinal symptoms, which can trigger a catecholamine surge in individuals with a pheochromocytoma, further biochemical testing was performed. Testing of plasma and urine confirmed pheochromocytoma, and surgical resection was performed for definitive treatment. Ultimately, the patient had resolution of her symptoms following the removal of the tumor. CONCLUSIONS The resolution of symptoms following surgical resection suggests that symptoms may have been related to the mass effect of the tumor or as an atypical manifestation of increased catecholamine levels. Additionally, by screening for pheochromocytoma, the patient was able to avoid potential complications that can result from common gastroenterological diagnostic procedures. This case report highlights the potential benefit for screening for pheochromocytoma when faced with symptoms that may be non-specific or related to mass effect upon surrounding organs.

Pheochromocytoma crisis is rare but potentially fatal if not recognized early and properly managed. Here, a woman in her 20s with a paraganglioma-induced pheochromocytoma crisis, who was successfully treated by veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and interval tumor resection, is described. In July 2022, the patient was brought to hospital with a complaint of sudden-onset of palpitations with vomiting. The patient developed cardiorespiratory failure with hypoxia. Computed tomography scan showed pulmonary oedema and a mass anterior to the inferior vena cava. She was transferred to the intensive care unit and treated with VA-ECMO. The patient's ECMO was withdrawn after 6 days without any complications. After hemodynamic stabilization, the patient underwent tumor resection 4 months later. The postoperative course was uneventful and she was discharged on postoperative day 7. Histopathological analysis confirmed a paraganglioma. VA-ECMO may play a significant role in saving lives and providing time for accurate diagnosis and specific treatment of a patient with pheochromocytoma crisis. Appropriate individual management can help avoid the occurrence of ECMO complications., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Adrenal pathologies have variable clinical presentations and primary care providers should be aware of common and serious adrenal disorders. All adrenal masses require evaluation for malignancy, whether primary or metastatic, and all masses require evaluation for inappropriate hormonal secretion. In the event of adrenal insufficiency, the etiology of cortisol inadequacy must be identified and appropriately treated to prevent life-threatening complications., Competing Interests: Disclosure No commercial/financial conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Multiple endocrine neoplasia type 1 is a rare genetic neuroendocrine syndrome caused by over 1500 different germline mutations. It can cause 20 different endocrine tumors affecting primarily the parathyroid glands, gastroenteropancreatic tract, and the anterior pituitary gland. Multiple endocrine neoplasia type 2A (MEN2A) and Multiple endocrine neoplasia type 2B (MEN2B) are autosomal dominant genetic syndromes because of a germline variant in the 'rearranged during transfection' (RET) proto-oncogene. There are common RET mutations causing receptor hyperactivation and induction of downstream signals that cause oncogenesis. Common conditions with MEN2A are medullary thyroid cancer (MTC), pheochromocytoma, and primary hyperparathyroidism. Common conditions with MEN2B include MTC, pheochromocytomas, and benign ganglioneuromas., Competing Interests: Disclosure L.A. Greenberg has no commercial or financial conflicts of interest and no funding sources., (Published by Elsevier Inc.)

Neuroendocrine neoplasms (NENs), also known as neuroendocrine tumors (NETs), are rare tumors derived from cells with characteristics of both nerve and endocrine cells. The clinical presentation, diagnosis, and treatment of NENs vary significantly depending on the type, location, whether the neoplasm is hormonally functional, how aggressive it is, and whether it has metastasized to other parts of the body. This article provides an overview of specific types of NETs, clinical presentations and related syndromes, diagnosis, and approach to management of common NENs., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Adrenal hemangiomas are extremely rare benign tumors that often need to be distinguished from malignancies. Adrenal tumors >4 cm in size are treated surgically because the possibility of malignancy cannot be ruled out. Traditionally, open surgery has been the mainstay of treatment; however, in recent years, robot-assisted surgery has been increasingly used for tumors of larger size and suspected malignancy. Here, we report a case of robot-assisted adrenalectomy for an 11 cm adrenal hemangioma., Case Report: A 62-year-old male with lateral abdominal pain was referred to our hospital for further examination and treatment. His medical history was significant for hypertension, diabetes, and dyslipidemia. Computed tomography revealed an 11 cm left adrenal tumor, and all endocrinological screening tests were negative. Because the possibility of malignancy could not be ruled out, a robot-assisted adrenalectomy was performed. The operation time was 129 min, and the estimated blood loss was 7 ml. Pathological findings revealed an adrenal hemangioma. The postoperative course was uneventful, and patient's condition subsequently improved postoperatively., Conclusion: Robot-assisted adrenalectomy was performed for a giant adrenal hemangioma without any complications. Robotic surgery is useful for resecting adrenal hemangiomas even exceeding 11 cm in diameter., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To evaluate the function of serum dehydroepiandrosterone sulfate (DHEAS) in adult adrenal space-occupying lesions. Methods: In this cross-sectional study, 395 patients with adrenal space-occupying lesions who had their DHEAS levels measured were collected from the First Medical Center of Chinese PLA General Hospital from January 2010 to June 2021. They were divided into the adrenal Cushing syndrome (ACS) group ( n =100) and non-ACS group ( n =295). The former was divided into the cortisol-producing adrenal adenoma (CPA) group ( n =67) and primary bilateral macronodular adrenal hyperplasia (PBMAH) group ( n =33). Clinical data of each group were collected and compared among groups by independent samples t -test, chi-square test, and Mann-Whitney U test. Serum DHEAS ratio corrected for age and sex was further constructed to identify the receiver operating characteristic curve and the optimal tangent point value for different adrenal occupation. Results: Patients in the ACS group were younger (44.9±13.7 vs. 49.9±12.5, P =0.001); had a larger proportion of women (79/100 vs.139/295, P =0.001); and had higher cortisol levels [8∶00Am, 497.31 (343.52, 606.50) vs. 353.11 (267.50, 487.91) nmol/L, P <0.001] than those in the non-ACS group. The serum DHEAS level and ratio in the ACS group were significantly lower than those in the non-ACS group [0.50 (0.40, 1.21) vs. 2.68 (1.56, 4.32) μmol/L, 1.00 (0.43, 1.68) vs. 3.17 (2.21, 4.54), both P <0.001]. When the serum DHEAS ratio cut-off point was 1.29, the sensitivity and specificity for differential diagnosis of ACS and non-ACS were 72.0% and 91.5% respectively. The ratio of DHEAS in the CPA group was lower [0.58 (0.27, 1.05) vs. 1.14 (1.04, 2.40), P< 0.001] than that in the PBMAH group. When the serum DHEAS ratio cut-off point was 0.99, the sensitivity and specificity for differential diagnosis of CPA and PBMAH were 64.2% and 81.2% respectively. Conclusion: Corrected age-sex DHEAS ratio can assist in the functional assessment of adrenal space-occupying lesions.

A previously healthy 49-year-old male presented with abdominal pain, constitutional syndrome, paroxysmal palpitations and diaphoresis. Full-body CT scan showed a large malignant adrenal mass with abdominal lymph node and pulmonary metastasis. Biochemical studies revealed hypersecretion of catecholamines, cortisol, sexual steroids and steroid precursors; ACTH was not suppressed, and chromogranin A was negative. 18F-fluorodeoxyglucose PET/CT showed intense tracer uptake in the adrenal mass and abdominal lymph nodes. He was placed under adrenergic blockade and offered cytoreductive surgery, but his evolution was unfavorable with rapid clinical deterioration due to compressive abdominal symptoms, uncontrolled pain, peripheral oedema, cachexia and severe dilated cardiomyopathy. 123I-metaiodobenzylguanidine scintigraphy was negative. Poor clinical status precluded any surgical or systemic treatments. A biopsy of the adrenal mass suggested adrenocortical carcinoma. Two weeks later he developed recurrent level 3 non-insulin mediated hypoglycemias, with suppressed levels of insulin, C-peptide, IGF-1 and IGF-BP3. He responded poorly to palliative measures and died within a week, four months after the initial diagnosis. We present a puzzling case of an aggressive stage IV adrenal malignancy with bizarre secretory profile. Although we could not obtain a surgical specimen, combined available data suggested adrenocortical carcinoma. The pathophysiology is uncertain, and we explored exceedingly rare scenarios, including adrenocortical carcinoma masquerading as pseudo-pheochromocytoma; synchronous adrenocortical carcinoma and pheochromocytoma; adrenal mixed corticomedullary tumor; and ACTH-producing pheochromocytoma. The presence of ectopic ACTH-dependent hypercortisolism, discordant plasma and urinary metanephrine levels and IGF-2 mediated hypoglycemias were also quite perplexing. To our knowledge, this is the first report of a malignant adrenal tumor co-secreting steroid hormones with ACTH-dependent hypercortisolism, catecholamines and IGF-2. We faced obvious diagnostic and therapeutic challenges and encourage future studies to explore the complex interactions between cortical and chromaffin cells of the adrenal gland, that may have bidirectionally contributed to this patient's condition., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork. Teams should ideally include adult and paediatric endocrinologists, oncologists, cardiologists, surgeons, geneticists, pathologists, radiologists, clinical psychologists and nuclear medicine physicians. Provision of an international Consensus Statement should improve care and outcomes for children and adolescents with these tumours., Competing Interests: Competing interests R.T.C. has received a Novartis speaker honorarium and is in an editorial position in Clinical Endocrinology. C.J. has received funding to his institution from Lantheus, Progenics, Exelixis, Merck Sharpe and Dohme and is a clinical adviser for Lantheus and Merck Sharpe and Dohme. S.D.M. is the Director of the NIHR Clinical Research Facility at Great Ormond Street Hospital, London. D.T. has received speaker and attendance honoraria from AAA/NOVARTIS. M.F. is an unpaid member of the ExCo of the European Society of Endocrinology. J.W.M.L. is an unpaid member of the advisory board of the Phaeochromocytoma and Paraganglioma Alliance., (© 2024. Crown.)

Background: Pheochromocytoma and extra-adrenal paragangliomas increasingly coming into light nowadays because of improved imaging techniques and biochemical investigations. There is sparse literature available regarding cytological findings of adrenal and extra-adrenal paragangliomas., Material and Methods: We studied 16 cytological specimens retrospectively over a period of 3 years, where subsequent histological diagnosis of phaeochromocytoma or paraganglioma was available., Results: A total of 16 cytology specimens were studied. Nine patients had adrenal SOLs and seven patients had extra-adrenal lesions. Age range was 12 to 60 years Majority of the cytology smears were cellular (87.5%). The smears were composed of small clusters as well as dispersed plasmacytoid cells with eccentric nuclei containing salt and pepper chromatin and moderate to abundant granular cytoplasm. Large cellular clusters mimicking the Zellballen pattern was present in one case. Anisonucleosis was mild to moderate, except in three cases where marked anisonucleosis posed diagnostic challenges. The background was hemorrhagic in all cases, however, two cases in addition had necroinflammatory background. All cases lacked mitotic activity and cytoplasm was delicate with indistinct cell borders. Bare oval nuclei were a frequent finding. Nuclear grooves or cytoplasmic vacuoles were absent. In 12 out of 16 cases, the initial cytological diagnosis correlated with final histological diagnosis, with an overall diagnostic accuracy of 75%. Four misdiagnosed cases had some atypical cytological features like marked anisonucleosis, necroinflammatory background, and presence of prominent nucleoli., Conclusion: Here we have highlighted some of the distinguishing cytological features that can help in cytological diagnosis of paragangliomas. Hemorrhagic background with plasmacytoid morphology, granular cytoplasm, naked nuclei, and absence of mitosis are useful clues., (© 2024 Wiley Periodicals LLC.)

The prevalence of adrenal incidentaloma (AI) in imaging studies, including those of the adrenal glands, is estimated to be 1-5%. Essential factors for the proper management of AI include a correct diagnosis, adequate surgical skills, appropriate perioperative management, and sound dialogue with the patient. Aside from the possibility of overdiagnosis, patients with apparent signs or symptoms attributable to adrenal hormone excess have reasonable indications for surgery. At the same time, milder patients may be candidates for active surveillance without intervention. Even individuals with nonfunctioning AI may benefit from surgery if imaging studies depict the tumor as suggestive of malignancy. However, a differential diagnosis of AI may not be easy for surgeons with little experience in seeing such patients.Furthermore, a patient without a correct diagnosis may miss the window of opportunity for a cure or incur a greater risk of developing complications, such as adrenal insufficiency or cardiovascular events during or after surgery, due to inadequate management. The clinical practice guidelines for AI from around the world may be helpful for shared decision-making; however, Japan lacks established guidelines. In this review article, we propose practical guidelines relevant to management by summarizing the evidence for five key questions that are often asked in dialog with patients with AI., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest in association with the present study. Ethical approval: As the present study used information from published articles only and did not obtain data at the individual patient level, ethical approval was not required., (© 2023. The Author(s).)

Rationale: 3P association (3PA) is a rare condition with co-occurrence of pituitary adenoma and pheochromocytoma/paraganglioma. There have been less than a hundred documented cases of 3PA, which can be sporadic or related to genetic mutations. The present case report describes the first Iranian patient with 3PA and a 90th case of 3PA in the available literature., Patient Concerns and Interventions: A 36-year-old Caucasian male was admitted with headache and sudden increase in blood pressure. An abdominal CT scan revealed a retroperitoneal mass posterior to the inferior vena cava, later removed and diagnosed as a pheochromocytoma. Four years later, he noticed occasional mild headaches and a painless mass on the right side of his neck. The ultrasonography evaluations suggested a carotid body tumor, which was surgically removed. About a month after his second surgery, the severity of the patient's headaches worsened, and he developed right homonymous hemianopia. A brain MRI showed a mass in favor of macroadenoma, craniopharyngioma, or meningioma, and elevated prolactin level led to the diagnosis of macroprolactinoma., Diagnoses: Based on the provided history, this patient was diagnosed with 3PA, and a genetic study identified a positive succinate-dehydrogenase-complex subunit b mutation, possibly linked to his family history of carotid body tumor., Outcomes: He has remained symptom-free during his visits every 3 months., Lessons: The number of cases diagnosed with 3PA worldwide is increasing. Using clinical and genetic assessments, we can timely diagnose and adequately monitor individuals with or at risk of 3PA., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This case report presents a 10-year-old patient diagnosed with pheochromocytoma/paraganglioma syndrome type 1 (PPGL1), underlined by a novel heterozygous pathogenic variant (c.154&#95;161del, p.ser52Profster14) in the SDHD gene. Initially, the patient manifested symptoms unusual for pheochromocytoma, including polyuria and polydipsia; however, further diagnostic investigations revealed a pheochromocytoma (PCC) tumor in the adrenal gland. Subsequently, whole exome sequencing (WES) test identified a pathogenic frameshift variant in the SDHD gene, strongly suggestive of PPGL1. This study highlights the importance of considering atypical symptoms in diagnosing rare pediatric pheochromocytoma/paraganglioma tumors and underscores the value of genetic testing in identifying underlying genetic causes, thereby facilitating personalized management of the condition., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Pheochromocytomas and paragangliomas are distinctive neuroendocrine tumors which frequently produce excess catecholamines with resultant cardiovascular morbidity. These tumors have a strong genetic component, with up to 40% linked to hereditary pathogenic variants; therefore, germline genetic testing is recommended for all patients. Surgical resection offers the only potential cure in the case of localized disease. Given the potential for catecholaminergic crises, appropriate perioperative management is crucial, and all patients should undergo alpha-adrenergic blockade before resection. Therapeutic options for metastatic disease are limited and include surgical debulking, radiopharmaceutical therapies, and conventional chemotherapy., Competing Interests: Disclosure H. Wachtel received support from the National Institutes of Health, United States National Cancer Institute, United States Grant #K08 CA270385., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The majority of incidentally discovered adrenal tumours are benign adrenocortical adenomas and the prevalence of adrenocortical adenomas is around 1-7% on cross-sectional abdominal imaging. These can be non-functioning adrenal tumours or they can be associated with autonomous cortisol secretion on a spectrum that ranges from rare clinically overt adrenal Cushing syndrome to the much more prevalent mild autonomous cortisol secretion (MACS) without signs of Cushing syndrome. MACS is diagnosed (based on an abnormal overnight dexamethasone suppression test) in 20-50% of patients with adrenal adenomas. MACS is associated with cardiovascular morbidity, frailty, fragility fractures, decreased quality of life and increased mortality. Management of MACS should be individualized based on patient characteristics and includes adrenalectomy or conservative follow-up with treatment of associated comorbidities. Identifying patients with MACS who are most likely to benefit from adrenalectomy is challenging, as adrenalectomy results in improvement of cardiovascular morbidity in some, but not all, patients with MACS. Of note, diagnosis and management of patients with bilateral MACS is especially challenging. Current gaps in MACS clinical practice include a lack of specific biomarkers diagnostic of MACS-related health outcomes and a paucity of clinical trials demonstrating the efficacy of adrenalectomy on comorbidities associated with MACS. In addition, little evidence exists to demonstrate the efficacy and safety of long-term medical therapy in patients with MACS., (© 2024. Springer Nature Limited.)

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., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Adult- and adolescent-onset neuroblastomas are rare, with no established therapy. In addition, rare pheochromocytomas may harbor neuroblastic components. This study was designed to collect epidemiological, diagnostic and therapeutic data in order to better define the characteristics of malignant peripheral neuroblastic tumors (MPNT) and composite pheochromocytomas (CP) with MPNT., Procedure: Fifty-nine adults and adolescents (aged over 15 years) diagnosed with a peripheral or composite neuroblastic tumor, who were treated in one of 17 institutions between 2000 and 2020, were retrospectively studied., Results: Eighteen patients with neuroblastoma (NB) or ganglioneuroblastoma (GNB) had locoregional disease, and 28 patients had metastatic stage 4 NB. Among the 13 patients with CP, 12 had locoregional disease. Fifty-eight percent of the population were adolescents and young adults under 24 years of age. The probability of 5-year event-free survival (EFS) was 40% (confidence interval: 27%-53%)., Conclusions: Outcomes were better for patients with localized tumor than for patients with metastases. For patients with localized tumor, in terms of survival, surgical treatment was the best therapeutic option. Multimodal treatment with chemotherapy, surgery, radiotherapy, and immunotherapy-based maintenance allowed long-term survival for some patients. Adolescent- and adult-onset neuroblastoma appeared to have specific characteristics associated with poorer outcomes compared to pediatric neuroblastoma. Nevertheless, complete disease control improved survival. The presence of a neuroblastic component in pheochromocytoma should be considered when making therapeutic management decisions. The development of specific tools/resources (Tumor Referral Board, Registry, biology, and trials with new agents or strategies) may help to improve outcomes for patients., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Adrenal incidentalomas have increased due to advanced and more sensitive imaging modalities, their increased utilization, and the aging population. Most adrenal incidentalomas are nonfunctional and benign, but a subset of patients has functional and/or malignant tumors. The evaluation of patients with an adrenal incidentaloma involves addressing 2 clinical questions: (1) Is the tumor functional? (2) Is the tumor malignant? A careful history and physical examination focused on signs and symptoms of adrenal functional tumors, biochemical testing, and imaging features are the cornerstone in the evaluation of patients with an adrenal incidentaloma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered MAX germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of MAX germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (72.3%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The MAX germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with MAX germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the MAX gene.

A 16-year-old castrated male shih tzu dog was brought to the emergency service because of an acute (24 h) history of gagging, coughing, and lethargy. Physical examination revealed dyspnea concurrent with diffuse, bilateral, pulmonary crackles and wheezes. Oxygen saturation, measured with a pulse oximeter, was < 95%. Thoracic radiographs revealed a multifocal alveolar pattern superimposed over a diffuse interstitial pattern with normal heart size. The dog continued to be dyspneic despite oxygen therapy. In accordance with the radiographic findings, further supportive care was recommended. Due to the unknown prognosis and financial constraints, the owner elected humane euthanasia. Necropsy confirmed a pheochromocytoma and lung changes without evidence of congestive heart failure. Findings were consistent with diffuse alveolar damage. These findings correlated with the dog's clinical diagnosis of acute respiratory distress syndrome (ARDS). No other disease processes associated with ARDS were identified. The purpose of this case report is to describe an unusual presentation of ARDS likely associated with a pheochromocytoma and confirmed by necropsy. Acute respiratory distress syndrome associated with a pheochromocytoma has been described in medical literature but has never been reported in veterinary medicine. Key clinical message: Pheochromocytomas should be added to the list of risk factors associated with ARDS in dogs. Dogs with a suspected diagnosis of pheochromocytoma whose owners elect against surgical removal should be closely monitored for an acute onset of respiratory distress, which could suggest the development of ARDS., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

The understanding of the nature of catecholamine-secreting tumors has changed significantly in recent years, affecting terminology and classification. Phaeochromocytoma/paraganglioma (PCC/PG) is a rare neuroendocrine tumor from chromaffin tissue that produces and secretes catecholamines. The incidence of PCC/PG is relatively low, with 2-8 cases per 1 million population per year; among patients with arterial hypertension, their prevalence is 0.2-0.6%. However, delayed diagnosis of PCC/PG is associated with a high risk of cardiovascular complications and a high mortality rate. The consensus presents the clinical manifestations of the disease with an emphasis on the course of arterial hypertension as the most common symptom in PCC/PG; modern ideas about the features of diagnosis, aspects of preoperative preparation, treatment, and follow-up of patients with PCC/PG are considered.

Competing Interests: Declaration of interests We declare no competing interests.

Phaeochromocytomas and paragangliomas are rare catecholamine-producing neuroendocrine tumours which can potentially cause catastrophic crises with high morbidity and mortality. This best practice article considers the causes and presentation of such tumours, screening and diagnostic tests, management of these patients and consideration of family members at risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Bilateral adrenal masses, increasingly encountered in clinical practice, manifest across diverse contexts, including incidental discovery, malignancy staging, and targeted imaging after hormonal diagnosis of adrenal disorders. The spectrum encompasses various pathologies, such as cortical adenomas, macronodular adrenal disease, pheochromocytomas, myelolipomas, infiltrative disorders, and primary and secondary malignancies. Notably, not all masses in both adrenal glands necessarily share the same etiology, often exhibiting diverse causes. Recently, the European Society of Endocrinology and the European Network for the Study of Adrenal Tumors updated guidelines, introduced a 4-option schema based on imaging, aiding in targeted hormonal testing and management. This "Approach to the Patient" review delves into the latest advancements in imaging, biochemical, and genetic approaches for the diagnostic and management nuances of bilateral adrenal masses. It provides insights and a contemporary framework for navigating the complexities associated with this clinical entity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Congenital adrenal hyperplasia (CAH) encompassed a bunch of autosomal recessive disorders characterized by impaired cortisol levels due to an enzymatic deficiency in steroid synthesis. In adult male patients with CAH, a frequent complication related to poor disease control is the development of ectopic adrenocortical tissue in the testes, named testicular adrenal rest tumors (TART). Conversely, ovarian adrenal rest tumors (OART) in females are extremely rare and adrenal rests in sites other than gonads are so uncommon to have been described only few times in literature., Case Presentation: We report a case of a male patient with untreated CAH and oncologic history of pleomorphic sarcoma who presented with massive bilateral adrenal enlargement and adrenal rest tumors in peri-lumbar and peri-cecal sites, which mimicked metastasis from sarcoma., Conclusions: The development of massive adrenal enlargement and ectopic adrenal rest tumors in sites other than gonads, even if very uncommon, should be suspected in patients with CAH and prolonged periods of undertreatment., (© 2024. The Author(s).)

In this case report, we present a man in his 60s who presented with an incidentally discovered right adrenal mass, which turned out to be an adrenal schwannoma. This is a very rare tumour that originates from Schwann cells and involves the peripheral nerves. The tumour was removed by open adrenalectomy, and this 15-cm adrenal schwannoma is one of the largest reported in the literature, with none >16 cm having ever been reported. This case highlights the importance of keeping an open mind about the cause of an incidentally discovered adrenal mass, which is an increasingly common way for adrenal tumours to present given the increased access to cross-sectional imaging. As well as presenting the case and the pathological basis behind adrenal schwannomas, we include a review of the literature and a general discussion about incidentally discovered adrenal masses., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND Hemangiomas of the adrenal gland are rare benign non-functional tumors arising from the gland's vascular endothelium. Adrenal hemangiomas are rare in clinical settings, often discovered incidentally during an unrelated diagnostic investigation. CASE REPORT A 39-year-old man presented with a heterogeneous, enhancing 4.56×4.24×3.9-cm mass originating from the right adrenal gland's lateral limb, discovered incidentally on computed tomography (CT) to investigate renal colic. He was routinely followed up for 2 years with serial CT scans; the mass exhibited considerable growth compared with baseline, with a relatively stable appearance with hyperdense soft tissue component, fat, and foci of calcification. Dexamethasone suppression test demonstrated suppressed cortisol response, indicating a non-functional mass. Therefore, laparoscopic right adrenalectomy was performed, owing to the benign nature of the preoperative diagnosis of myelolipoma and mass size. The patient experienced an uneventful recovery, with no perioperative complications. The resected mass was 5×4×4 cm in size and weighed 30 g. Histopathology confirmed adrenal hemangioma. Serial sectioning revealed an encapsulated lesion with heterogeneous solid and cystic surfaces. Light microscopy examination showed dilated and congested vascular channels lined by flattened endothelium. Focal mature adipose tissue was seen. CONCLUSIONS The infrequent occurrence of adrenal hemangiomas and their nonspecific clinical and radiological presentation results in a considerable diagnostic challenge and, often, misdiagnosis. Surgical resection is usually necessary to exclude malignant disease, alleviate pressure-related symptoms, and decrease risk of retroperitoneum hemorrhage. These lesions are associated with a good prognosis. One limitation of this report is the lack of preoperative adrenal magnetic resonance imaging of the incidental adrenal mass.

Abstract: Ganglioneuroma (GN) is the most differentiated and benign variant of neuroblastic tumors, most commonly located in the posterior mediastinum, followed by the retroperitoneum and adrenal gland. Children of <10 years of age are more commonly affected than adults. Though benign, GNs can very rarely metastasize to regional lymph nodes or distant sites like liver, bone, spleen, and soft tissues. Metastatic lesions are assumed to represent neuroblastomas in which the metastasis and the primary tumor, both have matured. This differentiation can occur spontaneously or after treatment. We present a primary ganglioneuroma of adrenal gland in a 4-year-old child with nodal metastasis, without any blastemal component at any site., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

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, 11β-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., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Selective venous sampling (SVS), an invasive radiographic procedure that depends on contrast media, holds a unique role in diagnosing and guiding the treatment of certain types of secondary hypertension, particularly in patients who may be candidates for curative surgery. The adrenal venous sampling (AVS), in particular, is established as the gold standard for localizing and subtyping primary aldosteronism (PA). Throughout decades of clinical practice, AVS could be applied not only to PA but also to other endocrine diseases, such as adrenal Cushing syndrome (ACS) and Pheochromocytomas (PCCs). Notably, the application of AVS in ACS and PCCs remains less recognized compared to PA, with the low success rate of catheterization, the controversy of results interpretation, and the absence of a standardized protocol. Additionally, the AVS procedure necessitates enhancements to boost its success rate, with several helpful but imperfect methods emerging, yet continued exploration remains essential. We also observed renal venous sampling (RVS), an operation akin to AVS in principle, serves as an effective means of diagnosing renin-dependent hypertension, aiding in the identification of precise sources of renin excess and helping the selection of surgical candidates with renin angiotensin aldosterone system (RAAS) abnormal activation. Nonetheless, further basic and clinical research is needed. Selective venous sampling (SVS) can be used in identifying cases of secondary hypertension that are curable by surgical intervention. Adrenal venous sampling (AVS) and aldosterone measurement for classificatory diagnosis of primary aldosteronism (PA) are established worldwide. While its primary application is for PA, AVS also holds the potential for diagnosing other endocrine disorders, including adrenal Cushing's syndrome (ACS) and pheochromocytomas (PCCs) through the measurements of cortisol and catecholamine respectively. In addition, renal venous sampling and renin measurement can help to diagnose renovascular hypertension and reninoma., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)