Search

Background: Neuroblastoma (NB) primarily arises in children who are <10 years of age, and originates from developing sympathetic nervous system, which results in tumors in adrenal glands and/or sympathetic ganglia. The diagnosis of NB involves a combination of laboratory and imaging tests, and biopsies. Small extracellular vesicles (sEVs) have gained attention as potential biomarkers for various types of tumors. Here, we performed proteomic analysis of serum sEVs and identified potential biomarkers for NB. Methods: Label-free proteomics of serum sEVs were performed in the discovery phase. A bulk RNA-seq dataset of NB tissues was used to analyze the association between genes encoding sEVs proteins and prognosis. Potential biomarkers were validated via multiple reaction monitoring (MRM) or western blot analysis in the validation phase. A public single-cell RNA-seq (scRNA-seq) dataset was integrated to analyze the tissue origin of sEVs harboring biomarkers. Results: A total of 104 differentially expressed proteins were identified in NB patients with label-free proteomics, and 26 potential biomarkers were validated with MRM analysis. Seven proteins BSG, HSP90AB1, SLC44A1, CHGA, ATP6V0A1, ITGAL and SELL showed the strong ability to distinguish NB patients from healthy controls and non-NB patients as well. Integrated analysis of scRNA-seq and sEVs proteomics revealed that these sEVs-derived biomarkers originated from different cell populations in tumor tissues. Conclusion: sEVs-based biomarkers may aid the molecular diagnosis of NB, representing an innovative strategy to improve NB detection and management. [ABSTRACT FROM AUTHOR]

The diagnosis of primary aldosteronism (PA) is critical for determining treatment strategies. The aim of the present study was to investigate the clinical value of preoperative adrenal venous sampling (AVS) for determining the benefit of PA surgery. Patients diagnosed with PA at Liaocheng People's Hospital (Liaocheng, China) between January 2015 and December 2020 were selected and divided into two groups: Group A underwent adrenal computed tomography (CT) only, whereas Group B underwent adrenal CT and successful AVS. Subsequently, the improvement rate of adrenal CT and adrenal CT + AVS in the treatment of PA was compared. A total of 164 patients were included, with an average age of 46.69±13.64 years. There were 62 patients in Group A and 102 in Group B. Among the patients diagnosed with unilateral lesions on adrenal CT scan, 82.61% of patients in group A and 87.72% in group B showed improvement; however, the difference was not significant (X² =0.534, P=0.465). Among the patients diagnosed with bilateral lesions on adrenal CT images, 62.50% of patients in Group A and 91.11% of patients in Group B showed improvement (P=0.019). In conclusion, unilateral adrenal lesions detected by CT did not benefit significantly from surgical decision-making after AVS. AVS should be advised for all patients with bilateral adrenal PA who are willing to undergo adrenal surgery, which is conducive to correct lateral segmentation and improve treatment choices. [ABSTRACT FROM AUTHOR]

Pheochromocytoma (PCC) and abdominal paraganglioma (aPGL) (together abbreviated PPGL) frequently present with an underlying genetic event in a PPGL driver gene, and additional susceptibility genes are anticipated. Here, we re-analyzed whole-exome sequencing data for PCC patients and identified two patients with rare missense variants in the calcium voltage-gated channel subunit 1H gene (CACNA1H). CACNA1H variants were also found in the clinical setting in PCC patients using targeted sequencing and from analysis of The Cancer Genome Atlas database. In total, CACNA1H variants were found in six PCC cases. Three of these were constitutional, and two are known to have functional consequences on hormone production and gene expression in primary aldosteronism and aldosteroneproducing adrenocortical adenoma. In general, PPGL exhibited reduced CACNA1H mRNA expression as compared to normal adrenal. Immunohistochemistry showed strong CACNA1H (CaV3.2) staining in adrenal medulla while PPGL typically had weak or negative staining. Reduced CACNA1H gene expression was especially pronounced in PCC compared to aPGL and in PPGL with cluster 2 kinase signaling phenotype. Furthermore, CACNA1H levels correlated with HIF1A and HIF2A. Moreover, TCGA data revealed a correlation between CACNA1H methylation density and gene expression. Expression of rCacna1h in PC12 cells induced differential protein expression profiles, determined by mass spectrometry, as well as a shift in the membrane potential where maximum calcium currents were observed, as determined by electrophysiology. The findings suggest the involvement of CACNA1H/CaV3.2 in pheochromocytoma development and establish a potential link between the etiology of adrenomedullary and adrenocortical tumor development. [ABSTRACT FROM AUTHOR]

Gender medicine is also becoming increasingly more important in the field of surgery of endocrine and neuroendocrine diseases. Gender differences in the incidence, symptoms and disease progression are common to all (neuro)endocrine diseases. Understanding these special features, which include socioeconomic aspects as well as different anatomical and biological factors, is essential for the selection of optimal diagnostics and treatment but in some cases further scientific research is required. To date, there is a paucity of gender-specific recommendations in established guideline recommendations. There is an enormous potential in all areas of endocrine surgery to take advantage of differences between men and women in the diagnostics, surgical treatment and perioperative management. Individualized approaches could lead to improved surgical outcomes, reduced perioperative complications and improved follow-up. [ABSTRACT FROM AUTHOR]

Background: Supine hypotension syndrome (SHS) has been reported to occur due to compression by a giant tumor such as ovarian tumor. We herein report a case of retroperitoneal ganglioneuroma with SHS treated with laparoscopic resection. Case presentation: The patient was an 11-year-old male with right-sided abdominal pain. He had a pale complexion and tachycardia while falling asleep. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a giant mass lesion (60 × 35 mm) with compression of the inferior vena cava (IVC) and duodenum ventrally and the right kidney caudally. The IVC was flattened by mass compression. Abdominal ultrasonography (US) revealed narrowing of the IVC due to the mass and accelerated blood flow after IVC stenosis in the supine and left lateral recumbent position. His pale complexion and tachycardia while falling asleep was thought to be due to decreased venous return caused by the tumor compressing the IVC, resulting hypotension. 123I-MIBG scintigraphy revealed no abnormal findings. Tumor markers were normal. He was diagnosed with SHS due to a right adrenal gland tumor. The tumor compressed the IVC from the dorsal side, and hemostasis was expected to be difficult during bleeding. Therefore, a guidewire was inserted from the right femoral vein into the IVC for emergency balloon insertion during bleeding. A laparoscopic tumor resection was performed. A histopathological examination confirmed the diagnosis of primary retroperitoneal ganglioneuroma. Conclusions: The treatment of symptomatic retroperitoneal tumors requires a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Adrenal tumors, such as adrenocortical carcinoma (ACC), adrenocortical adenoma (ACA), and pheochromocytoma (PCC) are complex diseases with unclear causes and treatments. Mitochondria and mitochondrial-derived peptides (MDPs) are crucial for cancer cell survival. The primary aim of this study was to analyze samples from different adrenal diseases, adrenocortical carcinoma, adrenocortical adenoma, and pheochromocytoma, and compare them with normal adrenal tissue to determine whether the expression levels of the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) gene and protein vary between different types of adrenal tumors compared to healthy controls using qPCR, ELISA, and IHC methods. Results showed decreased MOTS-c mRNA expression in all adrenal tumors compared to controls, while serum MOTS-c protein levels increased in ACA and PCC but not in ACC. The local distribution of MOTS-c protein in adrenal tissue was reduced in all tumors. Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex. Tumor size and testosterone levels positively correlated with MOTS-c mRNA but negatively with serum MOTS-c protein. Additionally, serum MOTS-c protein correlated positively with glucose, total cholesterol, HDL, LDL, and SHGB levels. These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue associated with disease progression. This study provides a detailed examination of MOTS-c mRNA and protein in adrenal tumors, indicating the potential role of MDPs in tumor biology and progression. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. In a single-center study, 96 patients (19 with adrenal cortical carcinoma and 77 with benign tumors) underwent an adrenalectomy. A total of 14 unaffected adrenal gland tissues from kidney donors were used as controls. Fasting blood samples were collected for laboratory tests, and mRNA expressions of leptin receptor isoforms were assessed by RT-qPCR. The study analyzed correlations between mRNA expressions and clinical data and measured NCI-H295R cell proliferation via a real-time cell analyzer. All adrenal lesions expressed leptin receptor isoforms. Significantly lower LepR1 expression was observed in carcinoma tissues than in adenomas and controls (p = 0.016). Expressions of LepR3&LepR6 were correlated with overall survival (p = 0.036), while LepR2&LepR4 and LepR5 expressions were inversely related to morning serum cortisol levels (p = 0.041). Leptin reduced NCI-H295R cell proliferation (p < 0.0001). The study highlights the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. Specifically, LepR1 may serve as a diagnostic marker for carcinomas, while LepR3&LepR6 have potential use as prognostic markers. [ABSTRACT FROM AUTHOR]

Cushing's syndrome is characterized by chronic glucocorticoid oversecretion and diverse clinical manifestations. Distinguishing between adrenocorticotropic hormone (ACTH)‐independent and ACTH‐dependent forms is crucial for determining treatment options. Plasma ACTH levels aid in the differential diagnosis, with undetectable or low levels suggesting ACTH‐independent hypercortisolemia. ACTH is derived from pro‐opiomelanocortin, and its processing involves prohormone convertase 1/3. High‐molecular‐weight ACTH is generally found in ACTH‐producing pituitary tumors and ectopic ACTH syndrome. The mechanism of negative feedback and the process of high‐molecular‐weight ACTH alternation during ACTH‐independent Cushing's syndrome remain unclear. A 40‐year‐old woman with hypertension and multiple fractures developed symptoms suggestive of Cushing's syndrome. Computed tomography revealed a left adrenocortical tumor along with atrophy of the right adrenal gland. ACTH levels were undetectable at the previous clinic, indicating ACTH‐independent Cushing's syndrome. However, subsequent measurements at our hospital revealed non‐suppressed ACTH (18.1 pg/mL), prompting further investigation. Gel exclusion chromatography confirmed the presence of high‐molecular‐weight ACTH. Metyrapone treatment decreased the cortisol levels. In this situation, in which ACTH levels should be elevated, a decrease in high‐molecular‐weight ACTH levels was observed. Histological findings revealed cortisol‐producing adenoma without ACTH expression. This case highlights the importance of assay differences in evaluating ACTH concentrations and introduces a novel finding of circulating high‐molecular‐weight ACTH. The observed decline in high‐molecular‐weight ACTH levels suggests a potential time lag in the negative feedback within the hypothalamic–pituitary–adrenal axis exhibited by glucocorticoids. This temporal aspect of the regulation of ACTH‐related molecules warrants further exploration to enhance our understanding of the hypothalamic–pituitary–adrenal axis feedback mechanism. [ABSTRACT FROM AUTHOR]

The transformation of an adrenocortical adenoma (ACA) to an adrenocortical carcinoma (ACC) is extremely rare. Current guidelines suggest against further imaging studies and follow-up in patients with nonfunctional adrenal incidentalomas (NFAIs) with benign imaging characteristics. Herein, we present a 64-year-old male patient diagnosed initially with a NFAI of 3 cm in size with imaging characteristics consistent with an ACA. However, 13 years after initial diagnosis, this apparent ACA developed into a high-grade cortisol and androgen-secreting ACC with synchronous metastases. The literature review revealed a further 9 case reports of adrenal incidentalomas initially characterized as ACA that subsequently developed into ACC within a period ranging from 1 to 10 years. The pathogenesis of transformation of an initially denoted ACA to ACC is not fully delineated, although the existing literature focuses on the preexisting or changing genetic background of these lesions, highlighting the need to develop robust prognostic markers to identify patients at risk and individualize the follow-up of these unique cases. [ABSTRACT FROM AUTHOR]

Non‐immune hydrops fetalis represents the end‐stage status of a variety of diseases, including metastatic tumors. We report a case of non‐immune hydrops fetalis associated with multiple disseminated echogenic nodular lesions detected by ultrasound and confirmed by magnetic resonance. Cordocentesis demonstrated anemia and thrombopenia. Differential diagnosis included histiocytosis X, acute leukemia or metastatic disease. A stillbirth was diagnosed at week 25 + 6. The autopsy revealed hydrops fetalis, a right adrenal gland mass, multiple disseminated nodules histologically composed of small round blue cells positive for synaptophysin, and placental involvement, concordant findings with congenital undifferentiated neuroblastoma Stage M. No chromosomal abnormalities were associated, nor amplification abnormalities in MYCN and ALK genes. Metastatic neuroblastoma should be considered in the differential diagnosis of non‐immune hydrops fetalis associated with multiple nodular lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: The adrenal glands represent a frequent localization area for metastases of various primary tumors. The standard of care for treating adrenal metastases is currently surgical resection, but radiotherapy is becoming a feasible and well-tolerated treatment alternative. However, the literature shows contradictory results regarding the optimal local treatment for adrenal metastases. This study analyzed oncological outcomes (local control, progression free survival, and overall survival) and complication rates after stereotactic body radiotherapy or surgical resection of adrenal metastases to further asses the benefits of stereotactic body radiotherapy. To our knowledge, this analysis is the first direct comparison of stereotactic body radiotherapy and adrenalectomy for adrenal metastases. Background: This single-center retrospective study aimed to evaluate the efficacy and toxicity profiles of stereotactic body radiotherapy (SBRT) and surgical resection in patients with adrenal metastases originating from solid tumors. Methods/Materials: Patients with advanced tumor conditions or comorbidities typically received SBRT, whereas those considered physically fit underwent standard surgical treatment. Endpoints included local control (LC), progression free survival (PFS), overall survival (OS), and complication rates (CR). Results: 41 patients with 48 adrenal metastases were included, with 27 (65.9%) patients receiving SBRT and 14 (34.1%) patients undergoing adrenalectomy. One- and two-year LC values were 100% for both periods after adrenalectomy, and 70.0% and 52.5% after SBRT (p = 0.001). PFS showed values of 40.2% and 32.1% at one and two years after adrenalectomy and of 10.6% for both periods after SBRT (p = 0.223). OS was 83.3% both one and two years after surgery and 67.0% and 40.2% after SBRT (p = 0.031). There was no statistically significant difference between the two groups regarding acute complications (p = 0.123). Conclusion: Despite potential confounders, adrenalectomy exhibited statistically significant superior LC and OS compared to SBRT in managing adrenal metastases, while both treatment methods displayed acceptable toxicity profiles. However, patient selection bias must be taken into account when directly comparing the two therapy modalities. Nevertheless, the study provides new and important results for the scientific and medical communities regarding oncological outcomes after SBRT or surgical resection of adrenal metastases. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) is a rare form of cancer that primarily affects individuals in their fifth or sixth decade of life, with a slightly higher incidence in females. While most cases are sporadic, ACC can also be associated with certain hereditary syndromes. The prognosis for ACC is variable, with a median overall survival of 3 years. Surgery is currently the only curative treatment option for ACC. Diagnosing ACC can be challenging, especially when it presents as an adrenal incidentaloma. A multidisciplinary approach involving surgeons, endocrinologists, pathologists, nuclear medicine physicians, and radiologists is necessary for managing ACC. The article provides information on when to suspect and how to diagnose ACC, including the clinical presentation, biological assessment, and imaging techniques. The recommended surgical approach for ACC depends on various factors, such as tumor size and invasion of adjacent organs. Adjuvant mitotane treatment is standard after ACC resection, and long-term follow-up is crucial for monitoring recurrence. [Extracted from the article]

Objectives: Machine learning methods can be applied successfully to various medical imaging tasks. Our aim with this study was to build a robust classifier using radiomics and clinical data for preoperative diagnosis of Wilms tumor (WT) or neuroblastoma (NB) in pediatric abdominal CT. Material and methods: This is a single-center retrospective study approved by the Institutional Ethical Board. CT scans of consecutive patients diagnosed with WT or NB admitted to our hospital from January 2005 to December 2021 were evaluated. Three distinct datasets based on clinical centers and CT machines were curated. Robust, non-redundant, high variance, and relevant radiomics features were selected using data science methods. Clinically relevant variables were integrated into the final model. Dice score for similarity of tumor ROI, Cohen's kappa for interobserver agreement among observers, and AUC for model selection were used. Results: A total of 147 patients, including 90 WT (mean age 34.78 SD: 22.06 months; 43 male) and 57 NB (mean age 23.77 SD:22.56 months; 31 male), were analyzed. After binarization at 24 months cut-off, there was no statistically significant difference between the two groups for age (p =.07) and gender (p =.54). CT clinic radiomics combined model achieved an F1 score of 0.94, 0.93 accuracy, and an AUC 0.96. Conclusion: In conclusion, the CT-based clinic-radiologic-radiomics combined model could noninvasively predict WT or NB preoperatively. Notably, that model correctly predicted two patients, which none of the radiologists could correctly predict. This model may serve as a noninvasive preoperative predictor of NB/WT differentiation in CT, which should be further validated in large prospective models. Clinical relevance statement: CT-based clinic-radiologic-radiomics combined model could noninvasively predict Wilms tumor or neuroblastoma preoperatively. Key Points: • CT radiomics features can predict Wilms tumor or neuroblastoma from abdominal CT preoperatively. • Integrating clinic variables may further improve the performance of the model. • The performance of the combined model is equal to or greater than human readers, depending on the lesion size. [ABSTRACT FROM AUTHOR]

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. Mild autonomous cortisol secretion from benign adrenocortical adenomas (usually diagnosed incidentally) is associated with cardiometabolic risk and other comorbidities, but without the signs of overt Cushing syndrome. This Review outlines the mechanisms, complications and comorbidities, diagnosis and management of mild autonomous cortisol secretion. Key points: Mild autonomous cortisol secretion (MACS) is diagnosed based on the 1 mg overnight dexamethasone test and is found in 20–50% of patients with adrenal adenomas lacking signs and symptoms of Cushing syndrome. Patients with adrenal adenomas show distinct changes in the steroid and global metabolome, which correlate with the degree of cortisol excess across MACS and Cushing syndrome. MACS is associated with an increased likelihood of having cardiovascular risk factors and an increased risk of mortality. Management of MACS must be individualized based on patient characteristics; the options range from adrenalectomy to long-term follow-up and conservative management of comorbidities. Post-operative adrenal insufficiency is seen in around 50% of patients with MACS who undergo unilateral adrenalectomy. [ABSTRACT FROM AUTHOR]

The human adrenal gland is a complex endocrine tissue. Studies on adrenal renewal have been limited to animal models or human foetuses. Enhancing our understanding of adult human adrenal homeostasis is crucial for gaining insights into the pathogenesis of adrenal diseases, such as adrenocortical tumours. Here, we present a comprehensive cellular genomics analysis of the adult human normal adrenal gland, combining single‐nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland homeostasis. As expected, we identified primary cells of the various zones of the adrenal cortex and medulla, but we also uncovered additional cell types. They constitute the adrenal microenvironment, including immune cells, mostly composed of a large population of M2 macrophages, and new cell populations, including different subpopulations of vascular‐endothelial cells and cortical‐neuroendocrine cells. Utilizing spatial transcriptome and pseudotime trajectory analysis, we support evidence of the centripetal dynamics of adrenocortical cell maintenance and the essential role played by Wnt/β‐catenin, sonic hedgehog, and fibroblast growth factor pathways in the adult adrenocortical homeostasis. Furthermore, we compared single‐nuclei transcriptional profiles obtained from six healthy adrenal glands and twelve adrenocortical adenomas. This analysis unveiled a notable heterogeneity in cell populations within the adenoma samples. In addition, we identified six distinct adenoma‐specific clusters, each with varying distributions based on steroid profiles and tumour mutational status. Overall, our results provide novel insights into adrenal homeostasis and molecular mechanisms potentially underlying early adrenocortical tumorigenesis and/or autonomous steroid secretion. Our cell atlas represents a powerful resource to investigate other adrenal‐related pathologies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of adrenalectomy on hypertension in patients with nonfunctional adrenal tumors. Subjects and methods: Between January 2020 and October 2022, patients with adrenal lesions were retrospectively screened for nonfunctional adrenal tumors at the Zhongnan Hospital of Wuhan University. All patients underwent detailed endocrinological examination and computed tomography to characterize the lesions. One year after discharge, follow-up blood pressure (BP) was assessed and compared to the blood pressure on admission. Univariate analysis and multivariate regression analysis were performed to determine factors predicting favorable hypertension outcomes after adrenalectomy. Results: A total of 309 patients were found to be eligible, including 123 who underwent adrenalectomy. Patients who underwent adrenalectomy were stratified into two groups: (Bancos I (2022) Adrenal Incidentalomas: Insights Into Prevalence. Ann Intern Med 175:1481–1482. https://doi.org/10.7326/M22-2600) those with improved hypertension (n = 71), and (Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J et al. (2023) European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 189:G1–42. https://doi.org/10.1093/ejendo/lvad066) those without improved hypertension (n = 52). In contrast, the blood pressure levels of conservatively treated patients remained relatively stable 1 year after discharge. Univariate analysis and multivariate regression analysis showed that body mass index (BMI) and duration of hypertension were significantly different between the hypertension improvement group and the non-improvement group (p < 0.05). Conclusion: Adrenalectomy has been shown to be effective in improving hypertension in certain patients with nonfunctional adrenal tumors. BMI and duration of hypertension were independent factors associated with favorable hypertension outcomes after adrenalectomy. [ABSTRACT FROM AUTHOR]

Objective: Carney complex is a rare autosomal dominant syndrome that has been shown to be associated with inactivation due to PRKAR1A mutations. We revealed a novel PRKAR1A gene mutation in Chinese patient with Carney complex and review the literature to enhance understanding of Carney complex. Case presentation: A 23-year-old Chinese male patient with a family history cardiac myxoma was admitted to our Department of Endocrinology because of central obesity and hyperpigmentation. Physical examination revealed a maximum blood pressure of 150/93mmHg, awaist circumference of 102cm, aweight of 70kg, a height of 170cm, and a BMI of 24.22kg/m2. Additionally, there was spotty skin pigmentation on the lip mucosa, purple striae on the abdomen, thin skin on both legs, and visible veins. Blood examination revealed hypercortisolemia, decreased adrenocorticotropic hormone (ACTH) levels and failure to suppress cortisol with lowand high-dose dexamethasone suppression tests.Magnetic resonance imaging (MRI) scan revealedmultiple small adrenal nodules and Retroperitoneal neurogenic tumor. Genetic testing showed a novel heterozygous mutation in exon 5 of PRKAR1A (c.500_;502 + 8delAAGGTAAGGGC). The patient underwent resection of the right adrenal gland and retroperitoneal neoplasms in 2020. Postoperative pathology following the right adrenal gland resection showed nodular hyperplasia of the adrenal cortex. The pathology from the retroperitoneal tumor resection revealed spindle cell tumors rich in pigment and cells. The patient was diagnosed as Carney complex according to Stratakis CA in 2001 guidelines. After long-term follow-up, the patient's condition was stable, with weight loss, waist circumference reduction, significantly lower cortisol levels, and normal blood lipids. Conclusion: This case reported a Carney complex in a Chinese patient, characterized clinically by non-ACTH-dependent Cushing's syndrome, familial recurrent cardiac myxomas, psammomatous melanotic schwannoma (PMS) and skin and mucosal pigmentation. A novel subtype of PRKAR1A mutation was discovered, which may affect the characteristics of the PRKAR1A protein and contribute to the development of Carney complex. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Surgical resection for pheochromocytoma (PCC) is still challenging. This study assessed the perioperative outcomes of adrenalectomy for PCC and investigated the risk factors for intraoperative hemodynamic instability (HI).This retrospective study included 571 patients with adrenal tumors who underwent adrenalectomy at Kobe University Hospital and other related hospitals between April 2008 and October 2023. The perioperative outcomes of laparoscopic adrenalectomy were compared between PCC (n = 92) and non‐PCC (n = 464) groups. In addition, we investigated several potential risk factors for intraoperative HI in patients with PCC (n = 107; open, n = 11; laparoscopic, n = 92; robot‐assisted, n = 4).While patients with PCC had a significantly larger amount of blood loss in comparison to those with non‐PCC (mean, 70 and 30 mL, respectively; p = 0.004), no significant difference was observed in the rate of perioperative grade ≥III complications (1.1% vs. 0.6%; p = 0.516), and no perioperative mortality was observed in either group. A tumor size of ≥40 mm, with preoperative hypertension and urinary metanephrines at a level ≥3 times the upper limit of the normal value, were found to be significant predictors of HI, with odds ratios of 2.74 (p = 0.025), 3.91 (p = 0.005), and 3.83 (p = 0.004), respectively.Our data suggest that laparoscopic adrenalectomy for PCC may be as safe as that for other types of adrenal tumors and that large tumors and hormonally active disease may be risk factors for intraoperative HI. The optimal perioperative management for PCC with these risk factors should be established. [ABSTRACT FROM AUTHOR]

Background: Adrenocortical carcinoma is a very rare endocrinopathy that has a poor prognosis and is frequently associated with ACTH-independent Cushing's syndrome. Despite having an adrenocortical carcinoma, our patient surprisingly had an ACTH-dependent Cushing's syndrome. Case report. A 26-year-old female presented with Cushing's syndrome and an abdominal mass. Imaging studies revealed an adrenal mass consistent with a high-grade malignancy. Laboratory workup showed hypercortisolism, hyperandrogenism, and hypokalemia with normal levels of metanephrines. Unexpectedly, her ACTH levels were remarkably elevated. The pathological analysis of a tumor sample was conclusive for adrenocortical carcinoma with immunopositivity for ACTH. Conclusions: Our patient suffered from an adrenocortical carcinoma that was ectopically producing ACTH. This case emphasizes that physicians should have a broad-minded approach when evaluating cases of rare endocrine malignancies. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the effect of adrenal mass functionality and different hormone subtypes synthesized by the adrenal masses on laparoscopic adrenalectomy (LA) outcomes. Materials and methods: The study included 298 patients, 154 of whom were diagnosed with nonfunctional masses. In the functional group, 33, 62, and 59 patients had Conn syndrome, Cushing's syndrome, and pheochromocytoma, respectively. The variables were analyzed between the functional and nonfunctional groups and then compared among functional masses through subgroup analysis. Results: The incidence of diabetes mellitus, hypertension, and obesity, blood loss, and length of hospital stay (LOH) were significantly higher in the functional group than in the nonfunctional group. In the subgroup analysis, patients with pheochromocytoma had significantly lower body mass index but significantly higher mass size, blood loss, and LOH than the other two groups. A positive correlation was found between mass size and blood loss in patients with pheochromocytoma (p ≤ 0.001, r = 0.761). However, no significant difference in complications was found among the groups. Conclusions: In this study, patients with functional adrenal masses had higher comorbidity rates and American Society of Anesthesiologists scores. Moreover, blood loss and LOH were longer on patients with functional adrenal masses who underwent LA. Mass size, blood loss, and LOH in patients with pheochromocytoma were significantly longer than those in patients with other functional adrenal masses. Thus, mass functionality did not increase the complications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Rare disease 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 FROM AUTHOR]

Primary aldosteronism (PA) is a subtype of secondary hypertension categorized as either unilateral PA (eg, aldosterone-producing adenoma [APA]) or bilateral PA. CYP11B2, an aldosterone synthase, is highly expressed in APA. Recent studies have revealed a high prevalence of pathogenic variants in KCNJ5 and the role of DNA methylation on CYP11B2 in APA. We present a case of unilateral PA with pathogenic variants in KCNJ5 and suppressed CYP11B2 expression. A 55-year-old woman with hypertension was referred to our hospital. A high aldosterone-renin ratio was observed; PA was confirmed using the captopril challenge test and the furosemide upright test. Although computed tomography showed no evident tumors in either adrenal gland, adrenal vein sampling revealed left gland dominance. Postoperatively, the aldosterone-renin ratio decreased and captopril challenge test showed negative findings. Pathogenic variants in the KCNJ5 were detected in the adenoma. Although immunohistochemistry for CYP11B2 was negative in adenoma, an aldosterone-producing cell cluster was confirmed in the adjacent left adrenal gland. Furthermore, DNA methylation analysis of the adenoma indicated hypermethylation in the CYP11B2 promoter region. The pathogenic variant in KCNJ5, specific to APA, induces CYP11B2 overexpression, resulting in excess aldosterone. However, these effects can be suppressed by DNA methylation. [ABSTRACT FROM AUTHOR]

Introduction: Adrenal hemorrhage (AH) is a very rare and potentially life-threatening disease which may be secondary to trauma or of non-traumatic etiology. Aim: The aim of the study was to present the characteristics and management of adrenal hemorrhage and show that adrenal hemorrhage is more common than expected and that the clinical symptoms are not specific. Materials and methods: This retrospective study involved 199 patients with postoperative diagnosis of adrenal hemorrhage. Discussion: The factors identified as potential causes of adrenal hemorrhage are adrenocortical carcinoma, pheochromocytoma, and adrenal adenoma. The study group included 199 patients with postoperative diagnosis of AH. It showed that all patients with postoperative diagnosis had pheochromocytoma (n = 54), adrenal adenoma (n = 68), or adenocarcinoma (n = 17). If we look more careful at the results, we can find only 30% of patients (n = 39) with preoperative diagnosis of AH. This group of 39 patients was prepared for expedited surgery. In this group of patients, the preoperative diagnosis of AH was pheochromocytoma 28% (n = 11), adenocarcinoma (n = 4), and adrenal adenoma (n = 9). Conclusions: Bleeding into adrenal tumors is still an insufficiently understood topic due to its unpredictability and, as can be seen in our material, of varying severity. Out of 199 patients, only 30% (n = 39) were prepared for surgery with a preoperative diagnosis of AH; most of them had pheochromocytoma. We suggest that is very important to prepare patients for surgery with a preoperative diagnosis of AH using α-adrenoreceptor antagonists. Prolongation of the diagnostic process (time between the imaging examination and the surgery) may result in the disease progressing and adrenal bleeding. [ABSTRACT FROM AUTHOR]

Importance: This case report presents the successful surgical removal of a pheochromocytoma in a dog using indocyanine green (ICG) fluorescence imaging. Case Presentation: A 10-year-old, 6.87 kg, spayed female poodle was referred for an abdominal mass and eight episodes of vomiting. Computed tomography revealed masses in the spleen and left adrenal gland. Based on the plasma normetanephrine levels, the patient was diagnosed with pheochromocytoma. Subsequently, a total splenectomy and left adrenalectomy were performed. A dose of 5 mg/kg ICG was administered intravenously 24 h prior to surgery. Using ICG allowed visualization of tumor margins, aiding in complete resection and minimizing anesthesia-related risks. Conclusions and Relevance: No evidence of recurrence or metastasis has been observed for 12 months. To our knowledge, this is the first report of the surgical removal of a pheochromocytoma using intraoperative ICG imaging in veterinary medicine. This case highlights the efficacy of ICG fluorescence imaging as a valuable tool for the surgical management of adrenal tumors in veterinary medicine. [ABSTRACT FROM AUTHOR]

Context Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5% to 35% of PGLs, and there are no reliable predictors of metastatic disease. Objective This work aimed to develop a prognostic score of metastatic potential in PGLs. Methods A retrospective analysis was conducted of clinical data from a cohort with PGLs and tumor histological assessment. Patients were divided into metastatic PGL (presence of metastasis) and nonmetastatic PGL (absence of metastasis ≥96 months of follow-up) groups. Univariate and multivariable analysis were performed to identify predictors of metastatic potential. A prognostic score was developed based on coefficients of multivariable analysis. Kaplan-Meier curves were generated to estimate disease-specific survival (DSS). Results Out of 263 patients, 35 patients had metastatic PGL and 110 patients had nonmetastatic PGL. In multivariable analysis, 4 features were independently related to metastatic disease and composed the Prognostic Score of Paragangliomas (PSPGL): presence of central or confluent necrosis (33 points), more than 3 mitosis/10 high-power field (HPF) (28 points), extension into adipose tissue (20 points), and extra-adrenal location (19 points). A PSPGL of 24 or greater showed similar sensitivity with higher specificity than the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). PSPGL less than or equal to 20 was associated with a risk of metastasis of approximately 10%, whereas a PSPGL of 40 or greater was associated with approximately 80%. The presence of metastasis and Ki-67 of 3% or greater were related to lower DSS. Conclusion The PSPGL, composed of 4 easy-to-assess parameters, demonstrated good performance in predicting metastatic potential and good ability in estimating metastasis risk. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC. Patients and Methods We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022. Results VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade ≤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival. Conclusion Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC. [ABSTRACT FROM AUTHOR]

Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on followup imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radioand chemotherapy. [ABSTRACT FROM AUTHOR]

In the setting of metastatic adrenocortical cancer, there are limited therapy options such as mitotane and platinum-based chemotherapy with only low response rates. Ipilimumab and nivolumab are approved for several solid cancer types. Tumor mutational burden is one established marker to predict treatment success of immunotherapy and has been associated with improved response rates to immune checkpoint inhibitors. We here present the case of a 68-year-old woman with metastatic adrenocortical cancer and high tumor mutational burden treated with ipilimumab and nivolumab in a fourth-line setting. She showed a stable disease for at least 48 weeks, which is significantly longer than the treatment response to mitotane or platinum-based chemotherapy. To the best of our knowledge, this is the first successful use of a long-term two-drug immunotherapy (48 weeks) in a patient with metastatic adrenocortical cancer and high mutational burden. Ipilimumab and nivolumab should be considered as a new therapy option in this patient group. [ABSTRACT FROM AUTHOR]

Background: Leiomyosarcoma (LMS) originating from the adrenal gland is exceedingly rare, constituting a minute fraction of soft tissue sarcomas. Due to its rarity, with less than 50 documented cases in English medical literature, the diagnosis and management of adrenal LMS remain challenging. The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers and report our specific case. Methods: A systematic review of the literature was conducted using PubMed, Web of Science, Google Scholar, and Scopus databases, up to December 2020. The search utilized MeSH terms such as "Adrenal Gland Neoplasms," "Leiomyosarcoma," "Adrenalectomy," and "Smooth Muscle Tumor." The inclusion criteria focused on studies reporting patients with a histopathological diagnosis of adrenal leiomyosarcoma. The PRISMA guidelines were followed to ensure a comprehensive analysis. Results: Out of 63 identified studies, 43 met the inclusion criteria and were reviewed. These studies highlighted the rarity and aggressive behavior of adrenal leiomyosarcoma. Surgical excision remains the cornerstone of treatment, often complemented by adjuvant therapies. The reviewed case involved a 52-year-old woman who underwent a right laparoscopic adrenalectomy for a 9 × 7 × 6 cm grade 3 leiomyosarcoma. Despite subsequent adjuvant chemotherapy, hepatic metastases were detected, illustrating the aggressive nature of the disease. The literature underscores the importance of histopathological analysis and long-term surveillance for managing disease progression. Conclusions: Optimal management of adrenal leiomyosarcoma requires a multidisciplinary approach and meticulous follow-up. The rarity of the disease poses challenges for standardizing treatment, but surgical excision and tailored adjuvant therapies show promise. Further research is essential to refine treatment strategies and improve prognosis for this rare malignancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Adrenal metastases are frequent in solid malignancies such as lung cancer and melanoma. Recent studies support the use of ablative local therapies in oligometastatic or oligoprogressive patients. Online adaptive MR-guided radiotherapy improves tumor coverage and organ-at-risk sparing compared to non-adaptive radiotherapy. However, clinical data, especially the long-term results of this promising technique, are still limited. We here report the long-term outcomes of a large single-center cohort. (1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED10) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED10 of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT. [ABSTRACT FROM AUTHOR]

Background: Currently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and localization diagnostic techniques. We report a typical case of ectopic adrenocortical adenomas and the data of treatment follow-up, and review the literature of 31 available cases of ectopic adrenocortical adenomas. Case presentation: A 27-year-old Chinese female patient was admitted to our hospital for hypertension, hyperglycaemia and primary amenorrhea. The patient was functionally diagnosed with ACTH-independent CS and hypogonadotropic hypogonadism. Radiological evaluations, including Computed Tomography (CT) and functional imaging, identified a mass at the left renal hilum. Histological assessments post-surgical excision confirmed the mass to be an ectopic adrenocortical adenoma. A subsequent 3-month follow-up showed no signs of disease recurrence, a swift recovery of the cortisol axis was observed, with a partial recuperation of the gonadal axis. Review: Our literature review shows that the most common ectopic areas of cortisol adenomas are renal hilum and hepatic region. The most positive biomarker is Melan A, and only a few cases have been diagnosed with functional localization. Conclusion: Ectopic adrenocortical adenomas may be asymptomatic in the early stage and can impact gonadal function. Physicians who treat hypogonadism must be aware of the need to test cortisol levels and perform functional localization in patients with lumps present. [ABSTRACT FROM AUTHOR]

A mutation in the steroidogenic acute regulatory protein (STAR) gene, which encodes a protein that plays a crucial role in steroid hormone synthesis, causes a severe form of congenital adrenal hyperplasia (CAH) known as lipoid CAH (LCAH). LCAH presents with primary adrenal insufficiency (PAI) as well as atypical genitalia. Individuals with LCAH require adrenal steroid hormone supplements for survival. Masculinization in males with STAR deficiency varies from incomplete to normal virilization. Radiological examinations reveal enlarged and lipid-laden adrenals. A 10-year-old boy born of second-degree consanguinity presented with weight gain and hyperpigmentation for 1 year. He was diagnosed with PAI at age 7 months and treated with hydrocortisone and fludrocortisone. Dynamic adrenal gland testing revealed undetectable hormone reserves. Imaging detected hypoplastic adrenals and a small testis with testicular adrenal rests (TART). Genetic analysis indicated a novel homozygous pathogenic variant of STAR in exon 7, c.814C > G(pArg272Gly) associated with LCAH (OMIM No. 201710). Testing revealed that asymptomatic family members and relatives were heterozygotes for the variant. The patient was diagnosed with nonclassic LCAH with hypoplastic adrenals and TART. Adequate hormone supplementation resulted in TART regression. This genetic variation is reported for the first time. [ABSTRACT FROM AUTHOR]

Adrenalectomy generally has favorable outcomes. It is unknown if patients with functional adrenal tumors experience different clinical outcomes than those with benign adrenal tumors, due to the presence of comorbid conditions secondary to the functional tumor. We investigated outcomes following open and laparoscopic adrenalectomy for benign nonfunctional (BNF) versus functional adrenal masses. Patients undergoing adrenalectomy were identified in the 2015-2020 National Surgical Quality Improvement Program database, then categorized as BNF, hyperaldosteronism, hypercortisolism, and pheochromocytoma. The primary outcome of interest was 30-d morbidity and secondary outcomes included 30-d mortality, 30-d readmission, and postoperative length of stay (LOS). Subgroup analysis was performed based upon surgical approach. Univariate analysis was performed, followed by multivariable logistic regression for individual outcomes that differed significantly between patients with BNF and functional neoplasm, factoring in patient demographics and operative approach with statistical significance on univariate analysis. Descriptive statistics and outcomes were analyzed using Pearson's χ2 test and Mann–Whitney U -test as appropriate. There were 3291 patients with BNF while 484 had hyperaldosteronism, 263 hypercortisolism, and 46 pheochromocytomas. Within the laparoscopic group of 3615 (88.5%) of adrenalectomy patients, compared to BNF patients, patients with hyperaldosteronism had lower rates of postoperative morbidity (1.9% versus 5.2%, P < 0.001) and shorter LOS (1 d, interquartile range (IQR) [1-1] versus 1d IQR [1-2], P = 0.003); these persisted on multivariate analysis (OR 0.32, 95% confidence interval [CI] 0.14-0.74 and odds ratio 0.47, 95% CI 0.36-0.60, P < 0.001). Patients with hypercortisolism had higher morbidity (7.3% versus 5.2%, P < 0.001), 30-d readmission rates (5.3% versus 2.9%, P = 0.042) and longer LOS (2d, IQR [1-3] versus 1d, IQR [1-2, P < 0.001). On multivariate analysis, presence of hypercortisolism was independently associated with increased likelihood of readmission within 30 d (OR 2.20, 95% CI 1.11-2.99, P = 0.012) and longer LOS (>1 d) (OR 1.79, 95% CI 1.33-2.40, P < 0.001). Compared to BNF patients, patients with pheochromocytoma had higher rates of postoperative morbidity (6.2% versus 5.2%, P < 0.001). Within the open group of 469 (11.5% of adrenalectomy patients), there were no statistically significant differences in outcomes between patients with BNF and functional adrenal masses. Outcomes after adrenalectomy performed for functional neoplasms differ based on surgical indication. [ABSTRACT FROM AUTHOR]

Aim: The Hounsfield unit (HU) used in non-contrast computed tomography (CT) imaging can predict adrenal masses. In the literature, a HU measurement of >10 on non-contrast CT has been reported to have a wide range of sensitivity (33-72%) in detecting malignancy in patients with adrenal masses, and the size of malignant masses is >4 cm in approximately 90% of cases. The current study investigated the role of the HU value and tumor diameter measured on preoperative CT imaging in the differentiation of benign and malignant masses. Methods: Data analysis was conducted on patients undergoing adrenalectomy for adrenal masses at two different tertiary care centers between January 1, 2019 and January 1, 2023. Patients who underwent an adrenalectomy non-contrast CT scans were assessed for HU and tumor size. The patients were divided into two groups according to histopathologically confirmed benign or malignant masses. Statistical analysis, including receiver operating characteristic curve assessment, was performed to evaluate the diagnostic accuracy. Results: The study included 108 patients, of whom 66.7% (n=72) were female and 33.3% (n=36) were male. The mean age was 51.01±14.01 years. The laparoscopic technique was used in 72 patients, the robotic technique in 17, and the open technique in 19. The mean length of hospital stay was 4 (2-37) days. The mean tumor size was 55 (10-230) mm. The mean operative time was 80 (50-180) minutes. The mean amount of intraoperative blood loss was 40 (20-300) milliliters. The surgical method, tumor diameter, operative time, amount of intraoperative blood loss, and HU value of the mass statistically significantly differed between the groups (p<0.001). We found that the cut-off values of HU and tumor diameter for distinguishing malignant masses from benign masses were 30.5 and 72.5 mm, respectively. At a cut-off value of 30.5 or above, HU had a sensitivity of 100% and a specificity of 81.6% in identifying malignant masses, whereas a sensitivity of 100% and a specificity of 88.7% were determined for malignant masses with a tumor size of 72.5 mm or above. Conclusion: The HU value and tumor diameter were crucial for distinguishing between benign and malignant adrenal masses, enhancing diagnostic accuracy, and informing treatment decisions. [ABSTRACT FROM AUTHOR]

Benign tumor incidence increased as a result of bad lifestyle and dietary habits. Finding natural dietary antioxidants may help control tumor incidence and spread. Pheochromocytoma is a rare neoplastic chromaffin cell-based benign tumor in the adrenal glands medulla. Pheochromocytoma incidence may increase as a result of the aging process or due to dietary consumption of sugar alcohols. Ellagic acid is a naturally occurring polyphenolic molecule that possesses multiple health benefits and can potentially compete with the development of pheochromocytoma. 50 male Wistar rats were used to investigate the efficacy of ellagic acid in protecting against aging and dietary-induced pheochromocytoma. Biochemical parameters in all experimental rats were determined. Results revealed that both aged and dietary-induced pheochromocytoma caused significant (p≤0.05) boost in systolic blood pressure, catecholamines (dopamine and norepinephrine),metabolites, blood glucose, and serum calcium levels. It also impaired significantly (p≤0.05) renal and hepatic functions, induced oxidative inflammatory status as well as apoptotic gene expression. Ellagic acid consumption protects from pheochromocytoma biochemical alterations and maintains normal body function and hemostasis. Pheochromocytoma is associated with many adverse biochemical changes that may be lethal if it is not diagnosed and treated quickly. Ellagic acid is a promising antioxidant and its consumption can protect from benign tumors. The study is expected to encourage people to change their bad dietary habits and consume natural antioxidants from nature. [ABSTRACT FROM AUTHOR]

Background: Pheochromocytoma is one of the most hereditary human tumors with at least 20 susceptible genes undergoing germline and somatic mutations, and other mutations less than 1% -2%. In recent years, other rare mutations have gradually been discovered to be possibly related to the pathogenesis and metastasis of pheochromocytoma. Most patients with pheochromocytoma experience common symptoms like headaches, palpitations, and sweating, while some may have less common symptoms. The diversity of symptoms, genetic mutations, and limited treatment options make management challenging. Case presentation: A 53-year-old woman was hospitalized after experiencing episodic epigastric pain for one month. A mass was found in her right adrenal gland and she underwent robot-assisted laparoscopic surgery, revealing a pheochromocytoma. At the 16-month follow-up, multiple metastatic lesions consistent with metastatic pheochromocytoma were found. A germline mutation in the dihydrolipoamide succinyltransferase (DLST) gene (c.330 + 14A>G) was detected, and despite trying chemotherapy and adjuvant therapy, the patient had a limited response with an overall survival of 27 months. Conclusions: DLST mutation is one of the rare pheochromocytoma-related mutated genes, and genetic sequencing is crucial for effective clinical management. [ABSTRACT FROM AUTHOR]

Pheochromocytoma is a tumor that usually originating from adrenal medullary chromaffin cells and producing one or more catecholamines, can manifest as hereditary or sporadic. While the majority pheochromocytomas are sporadic, hereditary forms are often associated with genetic syndromes such as von Hippel–Lindau, multiple endocrine neoplasia type 2, and neurofibromatosis type 1. This study aims to analyze data from our series of surgically excited pheochromocytoma patients and compare the characteristics between hereditary and sporadic cases. We retrospectively evaluated 33 diagnosed pheochromocytoma patients, documenting clinical features, surgical complications, and tumor characteristics in both hereditary and sporadic cases. Among the patients, 21% (7 individuals) had hereditary pheochromocytoma, while 79% (26 individuals) had sporadic cases. During diagnosis, hereditary pheochromocytoma patients exhibited a significantly lower mean age compared to the sporadic group (26.4 ± 9.9 years vs. 50.4 ± 14.0 years; p < 0.001). The maximum tumor size was also lower in hereditary cases compared to sporadic cases (p = 0.004). Adrenal tumor localization analysis showed that 63.6% were right‐sided, 24.2% were left‐sided, and 12.1% were bilateral. Laboratory analysis revealed significantly higher urinary norepinephrine levels in hereditary pheochromocytoma patients (p = 0.021). Our findings suggest that hereditary pheochromocytoma cases are characterized by a younger age at diagnosis, smaller tumor size, and a higher prevalence of multiple bilateral adrenal adenomas. We recommend genetic testing for all pheochromocytoma patients, particularly those with early‐onset disease and bilateral adrenal tumors. [ABSTRACT FROM AUTHOR]

Background: Cystic lesions in the adrenal glands are infrequent and unusual occurrences, with only a handful of cases documented thus far. These lesions come in various types, exhibiting diverse origins and sharing similar clinical presentations, ranging from benign to potentially malignant cystic growths. Typically, they do not cause symptoms, but in some rare instances, they may lead to abdominal discomfort or a sense of fullness. Due to their rarity, there is ongoing debate surrounding the most effective approach for managing adrenal cysts. Case Presentation: This case report presents a case of a 36-year-old female who presented with a history of abdominal pain and was incidentally found to have a right adrenal cyst during a CT scan. She exhibited no additional symptoms, such as hypertension, headache, or palpitations. Laparoscopic right adrenalectomy was performed, successfully removing the cystic mass without complications. Preoperative laboratory tests, including endocrine function tests, were unremarkable. Imaging studies, including ultrasound and contrast-enhanced CT, characterized the cyst as a large, wellcircumscribed, low-attenuated structure with peripheral calcifications, distinct from the right suprarenal gland. Gross examination revealed a collapsed cyst measuring 7 x 3 cm with a smooth inner wall, and the right adrenal gland measured 4 x 2.5 cm. The histological analysis identified the lesion as an adrenal pseudocyst with a fibrous wall containing focal dystrophic microcalcifications and embedded adrenocortical cells. No endothelial lining, eosinophils, or parasites were present. The patient's postoperative course was uneventful, and she was discharged in stable condition the following day. Conclusion: This case demonstrates the effective management of a large adrenal pseudocyst through laparoscopic adrenalectomy, resulting in a successful outcome without complications. Comprehensive imaging and histopathological evaluation were crucial in confirming the diagnosis and guiding treatment. [ABSTRACT FROM AUTHOR]

Background: A recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal studies evaluated the development of arterial hypertension, hyperglycemia, dyslipidemia and bone impairment in patients with AI. The aim of this study is to analyze the impact of sex in the development of these comorbidities during long-term follow-up. Methods: We retrospectively evaluated 189 patients (120 females, 69 males) with AI, from four referral centers in Italy and Croatia. Clinical characteristics, comorbidities and cortisol after 1-mg dexamethasone suppression test (1-mg DST) were assessed at baseline and at last follow-up visit (LFUV). Median followup was 52 (Interquartile Range 25-86) months. Results: The rates of arterial hypertension and hyperglycemia increased over time both in females (65.8% at baseline versus 77.8% at LFUV, p=0.002; 23.7% at baseline versus 39.6% at LFUV, p<0.001; respectively) and males (58.0% at baseline versus 69.1% at LFUV, p=0.035; 33.8% at baseline versus 54.0% at LFUV, p<0.001; respectively). Patients were stratified in two groups using 1.8 µg/dl as cut-off of cortisol following 1-mg DST: non-functional adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS). In the NFAT group (99 patients, females 62.6%), at baseline, we did not observe any difference in clinical characteristics and comorbidities between males and females. At LFUV, males showed a higher frequency of hyperglycemia than females (57.6% versus 33.9%, p=0.03). In the MACS group (89 patients, females 64.0%), at baseline, the prevalence of hypertension, hyperglycemia and dyslipidemia was similar between sexes, despite females were younger (60, IQR 55-69 versus 67.5, IQR 61-73, years; p=0.01). Moreover, females presented higher rates of bone impairment (89.3% versus 54.5%, p=0.02) than males. At LFUV, a similar sexrelated pattern was observed. Conclusion: Patients with AI frequently develop arterial hypertension and hyperglycemia and should be periodically checked for these comorbidities, regardless of sex. In patients with MACS, the lack of difference between sexes in the frequency of cardiometabolic comorbidities despite that females are younger, and the higher frequency of bone impairment in females, suggest a sex-specific effect of cortisol. [ABSTRACT FROM AUTHOR]

Background: Angiosarcoma of the adrenal gland is a very rare malignant vascular neoplasm. The clinical symptoms are atypical or completely absent. Angiosarcomas of the adrenal gland are therefore often discovered incidentally, and the diagnosis is made histologically after resection. Case presentation: A 46-year-old white Spanish male who was a previous smoker and nondrinker and was slightly overweight (92 kg, 176 cm, body mass index 29.7 kg/m2) with no relevant medical history presented to the internal medicine emergency department of our hospital with an unclear 12 cm tumor of the right adrenal gland. Prior to the computed tomography scan, he had had persistent evening fevers for 4 months and unintentional weight loss of 5 kg. The laboratory results showed anemia and an elevated C-reactive protein, but no hormone production. We performed an open adrenalectomy of the right adrenal gland. Finally, the histologic findings revealed an angiosarcoma of the adrenal gland. Conclusion: Even though angiosarcomas of the adrenal gland are rare, the differential diagnosis of an angiosarcoma should be considered if a malignant tumor of the adrenal gland is suspected. Treatment decisions should be made on an interdisciplinary basis and preferably in a specialized center. Owing to the rarity of angiosarcomas of the adrenal gland, it is necessary to continue to share clinical experience to gain a better understanding of this particular tumor entity. [ABSTRACT FROM AUTHOR]

EpCAM is expressed in many epithelial tumors and is used for the distinction of malignant mesotheliomas from adenocarcinomas and as a surrogate pan-epithelial marker. A tissue microarray containing 14,832 samples from 120 different tumor categories was analyzed by immunohistochemistry. EpCAM staining was compared with TROP2 and CKpan. EpCAM staining was detectable in 99 tumor categories. Among 78 epithelial tumor types, the EpCAM positivity rate was ≥90% in 60 categories—including adenocarcinomas, neuroendocrine neoplasms, and germ cell tumors. EpCAM staining was the lowest in hepatocellular carcinomas, adrenocortical tumors, renal cell neoplasms, and in poorly differentiated carcinomas. A comparison of EpCAM and CKpan staining identified a high concordance but EpCAM was higher in testicular seminomas and neuroendocrine neoplasms and CKpan in hepatocellular carcinomas, mesotheliomas, and poorly differentiated non-neuroendocrine tumors. A comparison of EpCAM and TROP2 revealed a higher rate of TROP2 positivity in squamous cell carcinomas and lower rates in many gastrointestinal adenocarcinomas, testicular germ cell tumors, neuroendocrine neoplasms, and renal cell tumors. These data confirm EpCAM as a surrogate epithelial marker for adenocarcinomas and its diagnostic utility for the distinction of malignant mesotheliomas. In comparison to CKpan and TROP2 antibodies, EpCAM staining is particularly common in seminomas and in neuroendocrine neoplasms. [ABSTRACT FROM AUTHOR]

Myelolipoma is a kind of benign lipoma containing myeloid cells. It is a rare type of tumor that typically presents as an occasional adrenal tumor, generally manifesting as a nonfunctional adrenal mass. Although it can occur in extra-adrenal tissues, its occurrence in bone tissue is extremely rare. Most cases are discovered accidentally during physical examinations of adults, and there are currently no reports of cases with pathological fractures as the main symptoms. We present a case of a 15-year-old teenager who developed a pathological fracture caused by femoral myelolipoma. The diagnosis of the specific type of bone tumor of the patient was determined through pathology and imaging. To treat the condition, we utilized a technique known as the "soft drill" to fully access the tumor space, remove the bone septum, and scrape away the diseased tissue. The fracture was then stabilized using a hybrid external fixation. After a 2-year follow-up period, there was no recurrence of the bone tumor. This case is the first case of intraosseous myelolipoma that occurred in a minor with the initial symptom of pathological fracture, filling the gap in our existing body of knowledge and providing a reference for the treatment of this type of intraosseous myelolipoma. [ABSTRACT FROM AUTHOR]

A boy aged 55 months was diagnosed with stage IV Neuroblastoma (NB) of the right adrenal gland 2 years ago. Preoperative chemotherapy was given and he was then treated with retroperitoneal tumor resection and lymph node dissection. After surgery, the children were transferred to the Hemato-Oncology Department for chemotherapy according to the high-risk group NB, with outpatient follow-up every 6 months. In the second postoperative year, abdominal computed tomography (CT) scan revealed a rounded hypodense area in the upper part of the right posterior lobe of the liver, with marked inhomogeneous enhancement in the venous phase after enhancement, which was surgically resected, and postoperative pathology confirmed inflammatory myofibroblastic tumor (IMT) of liver. The patient was not given any special treatment after surgery. In this study, whole transcriptome sequencing was performed on the postoperative specimen of adrenal NB and the specimen of IMT of liver. This unusual case emphasizes the need for close monitoring of second tumor development in NB survivors even in the absence of known predisposing factors. [ABSTRACT FROM AUTHOR]

Human T-cell leukemia virus type I (HTLV-I) is an oncogenic virus whose infection can cause diverse diseases, most notably adult T-cell leukemia/lymphoma (ATL or ATLL), an aggressive and fatal malignancy of CD4 T cells. The oncogenic ability of HTLV-I is mostly attributed to the viral transcriptional transactivator Tax. Tax alone is sufficient to induce specific tumors in mice depending on the promotor used to drive Tax expression, thereby being used to understand HTLV-I tumorigenesis and model the tumor types developed in Tax transgenic mice. Tax exerts its oncogenic role predominantly by activating the cellular transcription factor NF-κB. Here, we report that genetic deletion of NF-κB1, the prototypic member of the NF-κB family, promotes adrenal medullary tumors but suppresses neurofibromas in mice with transgenic Tax driven by the HTLV-I Long Terminal Repeat (LTR) promoter. The adrenal tumors are derived from macrophages. Neoplastic macrophages also infiltrate the spleen and lymph nodes, causing splenomegaly and lymphadenopathy in mice. Nevertheless, the findings could be human relevant, because macrophages are important target cells of HTLV-I infection and serve as a virus reservoir in vivo. Moreover, the spleen, lymph nodes and adrenal glands are the most common sites of tumor cell infiltration in HTLV-I-infected patients. These data provide new mechanistic insights into the complex interaction between Tax and NF-κB, therefore improving our understanding of HTLV-I oncogenic pathogenesis. They also expand our knowledge and establish a new animal model of macrophage neoplasms and adrenal tumors. [ABSTRACT FROM AUTHOR]