Genetic and Molecular Biomarkers in Aggressive Pheochromocytomas and Paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are rare neoplasms producing catecholamines that occur as hereditary syndromes in 25-40% of cases. To date, PPGLs are no longer classified as benign and malignant tumors since any lesion could theoretically metastasize, even if it occurs only in a minority of cases (approximately 10-30%). Over the last decades, several attempts were made to develop a scoring system able to predict the risk of aggressive behavior at diagnosis, including the risk of metastases and disease recurrence; unfortunately, none of the available scores is able to accurately predict the risk of aggressive behavior, even including clinical, biochemical, and histopathological features. Thus, life-long follow-up is required in PPGL patients. Some recent studies focusing on genetic and molecular markers (involved in hypoxia regulation, gene transcription, cellular growth, differentiation, signaling pathways, and apoptosis) seem to indicate they are promising prognostic factors, even though their clinical significance needs to be further evaluated. The most involved pathways in PPGLs with aggressive behavior are represented by Krebs cycle alterations caused by succinate dehydrogenase subunits (SDHx), especially when caused by SDHB mutations, and by fumarate hydratase mutations that lead to the activation of hypoxia pathways and DNA hypermethylation, suggesting a common pathway in tumorigenesis. Conversely, PPGLs showing mutations in the kinase cascade (cluster 2) tend to display less aggressive behavior. Finally, establishing pathways of tumorigenesis is also fundamental to developing new drugs targeted to specific pathways and improving the survival of patients with metastatic disease. Unfortunately, the rarity of these tumors and the scarce number of cases enrolled in the available studies represents an obstacle to validating the role of molecular markers as reliable predictors of aggressiveness.

Case report: A challenging case of severe Cushing's syndrome in the course of metastatic thymic neuroendocrine carcinoma with a synchronous adrenal tumor.

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 follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy.

Robotic Left Pancreatectomy with Perirenal Tissue Excision and Left Adrenalectomy (Posterior Ramps) for Pancreatic Ductal Adenocarcinoma Abutting the Adrenal Gland.

BACKGROUND: Radical antegrade modular pancreato-splenectomy (RAMPS) has been largely described in left-sided pancreatic cancers.1.J Hepato-Biliary-Pancreat Sci 29:1156-1165 Its prognostic advantage is not clear, although a theoretical improvement in R0 resection rate has been shown.2.J Am Coll Surg 204:244-249 Furthermore, RAMPS is usually carried out without adrenal gland removal, the so-called anterior RAMPS, while extending the resection to the adrenal plane could impair perioperative outcomes.3.HPB 25:311-319 METHODS: A 40 mm pancreatic ductal adenocarcinoma (PDAC) was found in a 70-year-old patient. Tumor infiltrates the adrenal gland and a robotic posterior RAMPS was indicated. RESULTS: After sectioning the splenic vessels and the pancreatic neck, the dissection was directed vertically in a sagittal plane along the left border of the superior mesenteric artery to identify the left renal vein. Our dissection plane was then directed on a caudo-cranial axis, after identification of the left renal artery and below the adrenal gland. The resection was also delimitated medially by the left borders of the superior mesenteric artery and the aorta, and posteriorly by the renal parenchyma. Postoperative course was marked by a biochemical leak. The patient was discharged on postoperative day (POD) 5 and the drain removed at POD 18. Pathological examination confirmed a pT2N2 PDAC with negative margins, with 4/18 positive nodes. CONCLUSIONS: The robotic platform is routinely employed in pancreatic surgery. Thanks to its increased degree of movement, its dexterity, and the magnification, this approach can help surgeons with vascular identification and control, in performing extended lymphadenectomies, and finding the correct planes of dissection. All these elements are crucial in a well-performed posterior RAMPS.

Management of metastatic pheochromocytomas and paragangliomas: when and what.

Recently, the treatment landscape for metastatic pheochromocytomas and paragangliomas (MPPGL) has seen both progress and setbacks. We provide an up-to-date review of the multimodality management of MPPGL and discuss novel opportunities and current challenges in the treatment landscape. Given the unique clinical presentation of MPPGL, we discuss the management of hormone-related clinical sequelae and traditional modalities of therapy. Advances in the understanding of the molecular biology of these diverse tumors have enabled novel strategies such as augmenting DNA damage by targeted delivery of radionuclides such as 131I and 177Lu, abrogating tumor angiogenesis, hypoxia resistance, and DNA damage repair. Despite progress, we address the significant challenges still faced by patients and researchers engaged in efforts to improve outcomes in these rare cancers.

Safety and efficacy of thermal ablation of adrenal metastases secondary to lung cancer.

OBJECTIVES: Assess safety and efficacy of thermal ablation for adrenal metastases (AM) secondary to non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This retrospective study included patients with NSCLC AM treated with thermal ablation between 2/2010-11/2021. Local tumor progression free survival (LTPFS) and overall survival (OS) were calculated using Kaplan-Meier method. Adverse events were graded using Common Terminology Criteria for Adverse Events v5. RESULTS: Seven patients (mean age ± SD, 63.9 ± 12.5 years; 6 males) with seven AM were treated in eight sessions. Retreatment was performed in one patient with residual disease. Five sessions were with microwave ablation and 3 with radiofrequency ablation. Mean tumor size was 20.1 ± 7.0 mm. Median number of ablation probes used was 1 (range, 1-5), with a median of 3 activations (range, 1-3), and average ablation time of 14.4 ± 15.0 minutes. Response based on RECIST v 1.1 or PERCIST criteria revealed stable disease in 1 tumor, progression of disease in 3 tumors (one was re-ablated), and partial response in 3 tumors. Median LTPFS was not reached (NR) [95 % CI: 1- NR]. Median OS was 47.97 months (95 % CI: 18.63- NR). Intraprocedural hypertension (blood pressure ≥180 mmHg) occurred during 5/8 (62.5 %) sessions and intraoperative tachycardia occurred during 2/8 (25 %) sessions. Complications within one month of ablation occurred in 3/8 (37.5 %) sessions: grade 2 pneumothorax, grade 1 hematuria, and grade 2 adrenal insufficiency. CONCLUSIONS: In this small series, thermal ablation for NSCLC AM resulted in prolonged local control and OS with no major complications.

Characterisation of an Adult Zebrafish Model for SDHB-Associated Phaeochromocytomas and Paragangliomas.

Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours arising from chromaffin cells. Pathogenic variants in the gene succinate dehydrogenase subunit B (SDHB) are associated with malignancy and poor prognosis. When metastases arise, limited treatment options are available. The pathomechanism of SDHB-associated PPGL remains largely unknown, and the lack of suitable models hinders therapy development. Germline heterozygous SDHB pathogenic variants predispose to developing PPGLs with a life-long penetrance of around 50%. To mimic the human disease phenotype, we characterised adult heterozygous sdhb mutant zebrafish as a potential model to study SDHB-related PPGLs. Adult sdhb mutant zebrafish did not develop an obvious tumour phenotype and were anatomically and histologically like their wild-type siblings. However, sdhb mutants showed significantly increased succinate levels, a major hallmark of SDHB-related PPGLs. While basal activity was increased during day periods in mutants, mitochondrial complex activity and catecholamine metabolite levels were not significantly different. In conclusion, we characterised an adult in vivo zebrafish model, genetically resembling human carriers. Adult heterozygous sdhb mutants mimicked their human counterparts, showing systemic elevation of succinate levels despite the absence of a tumour phenotype. This model forms a promising basis for developing a full tumour phenotype and gaining knowledge of the pathomechanism behind SDHB-related PPGLs.

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

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

Metastatic diseases to the adrenal gland: A comprehensive study from an academic institution with emphasis on clinical occult cases.

The adrenal gland is one of the common sites of metastasis and distinguishing metastatic diseases from adrenal primary neoplasms is essential for accurate clinical management of patients. Our study aimed to elucidate the spectrum and clinicopathologic features of metastatic solid tumors to the adrenal gland at an academic institution, with special focus patients presented with solitary adrenal masses without previously known malignancies. Our departmental database (2013-2022) was retrospectively searched and 129 patients with metastatic solid tumors involving the adrenal gland were identified. The median age at the initial diagnosis of metastatic diseases was 64 years old (range, 54-70 years). The majority of the diseases were presented as unilateral (n=118) or unifocal (n=119) involvement. Most patients had known prior or concurrent malignancies (n=125), whereas adrenal gland involvement was the initial clinical presentation in 4 patients. The most common primary carcinomas included renal cell carcinoma (n=84), lung adenocarcinoma (n=21), urothelial carcinoma (n=3) and hepatocellular carcinoma (n=3). In 104 (80 %) patients with available follow up (median of 39 months, ranging 0-81 months), 43 patients died of disease. Metastatic diseases are usually exercised in the differential diagnosis when there is clinically known malignant primary. In patients without clinical known malignancies, close clinical and radiologic correlation and thorough relevant clinical work up are critical, because clinical occult malignancy may metastasize to the adrenal gland as a solitary mass at the initial presentation, although it is rare.

[The relationship between clinical characteristics and pathological features in patients with pheochromocytomas/paragangliomas].

Objective: To explore the correlation between clinical characteristics and pathological features in patients with pheochromocytoma/paraganglioma (PPGLs). Methods: A case series study. A retrospective analysis was conducted on patients with single and primary PPGLs after postoperative pathological diagnosis who were admitted to Peking Union Medical College Hospital between January 2019 and December 2022. The patients were divided into the Ki-67<3% group and the Ki-67≥3% group with Ki-67 proliferation index of 3% as the threshold. The relationship between clinical and pathological characteristics of PPGLs was analyzed. Results: A total of 399 PPGLs patients were included, with 177 males and 222 females, aged [M(Q1, Q3)] 45.0(35.5, 53.0) years. Among them, 226 (56.6%) cases originated from the adrenal gland, while 104 cases (26.1%) from the retroperitoneum. 20.9% (27/129) of the patients were found to harbor germline mutations of susceptibility genes, with SDHB mutations being the most common (10.1%, 13/129). The Ki-67 staining was performed on 302 cases, with a Ki-67 proliferation index [M(Q1, Q3)] of 2.0% (1.0%, 3.0%). There were 194 cases in Ki-67<3% group and 108 cases in Ki-67≥3% group. Compared with the patients in Ki-67<3% group, the age of onset in Ki-67≥3% group was younger (P=0.029). Compared with the patients with paragangliomas without SDHB or Cluster 1A-related gene mutations, positive 131I-meta-iodobenzylguanidine (131I-MIBG) imaging or negative O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry staining, those with SDHB or Cluster 1A-related gene mutations, negative 131I-MIBG imaging or positive MGMT immunohistochemistry staining had a higher Ki-67 index (all P<0.05). Compared with adrenal pheochromocytoma, retroperitoneal paragangliomas had a higher proportion of SDHB mutations and a higher proportion of normetanephrine (NMN) secretory types (all P<0.05). Compared with adrenal pheochromocytoma, the maximum diameter of head and neck paraganglioma tumors was smaller [3.0 (1.9, 3.8) cm vs 4.7 (3.4, 6.4) cm, P<0.001] and the proportion of Ki-67≥3% was higher (61.3% vs 33.8%, P=0.007). Conclusions: PPGLs patients with earlier onset age, SDHB or Cluster 1A-related gene mutations, negative 131I-MIBG imaging, or positive MGMT immunohistochemistry staining tend to have a higher Ki-67 index. Head and neck tumors, though smaller, exhibit a higher proliferation potential.

Uncommon adrenal rest tumors and massive adrenal enlargement in adult with congenital adrenal hyperplasia mimicking metastasis from pleomorphic sarcoma.

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.

Management of a giant adrenal schwannoma.

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.

Multimodal integration of radiology and pathology signatures for distinguishing between aldosterone-producing adenomas and nonfunctional adrenal adenomas.

OBJECTIVE: To develop and validate a nomogram combining radiomics and pathology features to distinguish between aldosterone-producing adenomas (APAs) and nonfunctional adrenal adenomas (NF-AAs). METHODS: Consecutive patients diagnosed with adrenal adenomas via computed tomography (CT) or pathologic analysis between January 2011 and November 2022 were eligible for inclusion in this retrospective study. CT images and hematoxylin & eosin-stained slides were used for annotation and feature extraction. The selected radiomics and pathology features were used to develop a risk model using various machine learning models, and the area under the receiver operating characteristic curve (AUC) was determined to evaluate diagnostic performance. The predicted results from radiomics and pathology features were combined and visualized using a nomogram. RESULTS: A total of 211 patients (APAs, n = 59; NF-AAs, n = 152) were included in this study, with patients randomly divided into either the training set or the testing set at a ratio of 8:2. The ExtraTrees model yielded a sensitivity of 0.818, a specificity of 0.733, and an accuracy of 0.756 (AUC = 0.817; 95% confidence interval [CI]: 0.675-0.958) in the radiomics testing set and a sensitivity of 0.999, a specificity of 0.842, and an accuracy of 0.867 (AUC = 0.905, 95% CI: 0.792-1.000) in the pathology testing set. A nomogram combining radiomics and pathology features demonstrated a strong performance (AUC = 0.912; 95% CI: 0.807-1.000). CONCLUSION: A nomogram combining radiomics and pathology features demonstrated strong predictive accuracy and discrimination capability. This model may help clinicians to distinguish between APAs and NF-AAs.

Sibutramine-induced pheochromocytoma crisis: A rare and lethal occurrence.

Pheochromocytoma is a neuroendocrine tumor that secretes catecholamines; excessive catecholamine secretion can lead to pheochromocytoma crisis (PCC), a rare and life-threatening condition. Sibutramine, a serotonin and norepinephrine reuptake inhibitor, was previously used for obesity treatment but is now banned due to its cardiovascular side effects. Although fatalities related to PCC and adverse events associated with sibutramine have been frequently reported individually, there is no documented literature addressing PCC-induced by sibutramine. Here we report a rare case of fatal sibutramine-induced PCC in a previously asymptomatic young female with undiagnosed pheochromocytoma. The 25-year-old patient took a weight-loss pill containing sibutramine for the first time and subsequently experienced nausea, vomiting, chest tightness, and other symptoms. She went to hospital about 6 hours after taking the pill but died approximately 4 hours later despite the resuscitation efforts. An autopsy revealed a pheochromocytoma in the right adrenal gland. The cause of death was attributed to sibutramine-induced PCC. To our knowledge, this is the first report to document the occurrence of sibutramine-induced PCC.

Evaluating the diagnostic efficacy of whole-body MRI versus 123I-mIBG/131I-mIBG imaging in metastatic pheochromocytoma and paraganglioma.

This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled meta-iodo-benzylguanidine (mIBG) imaging techniques in patients with metastatic pheochromocytoma and paraganglioma (PPGL). This retrospective study included 13 patients had pheochromocytoma and 5 had paraganglioma, who were all suspected of having metastatic tumors. Each patient underwent WB-MRI and 123I-mIBG as a pretreatment screening for 131I-mIBG therapy. Two expert reviewers evaluated WB-MRI, 123I-mIBG images, and post-therapy 131I-mIBG images for the presence of metastatic lesions in the lungs, bones, liver, lymph nodes, and other organs. Diagnostic measures for detecting metastatic lesions, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristics (ROC)-area under the curve (AUC), were calculated for each imaging technique. We analyzed WB-MRI images for detecting metastatic lesions, which demonstrated sensitivity, specificity, accuracy, PPV, NPV, and AUC of 82%, 97%, 90%, 96%, 86%, and 0.92, respectively. These values were 83%, 95%, 89%, 94%, 86%, and 0.90 in 123I-mIBG images and 85%, 92%, 89%, 91%, 87%, and 0.91 in post-therapy 131I-mIBG images, respectively. Our results reveal the comparable diagnostic accuracy of WB-MRI to one of the mIBG images.

Inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1: a case report.

BACKGROUND: Inflammatory rhabdomyoblastic tumors are relatively recently recognized soft tissue tumors with a low malignant potential. Here, we present a case of concurrent inflammatory rhabdomyoblastic tumor (IRMT), adrenal pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1 (NF1). To our knowledge, this is the first time that this constellation of tumors has been described in the literature. CASE PRESENTATION: A female patient in her late 20s with known NF1 was diagnosed with an inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a short succession. IRMT was found to harbor a near-haploid genome and displayed a typical immunohistochemical profile as well as a focal aberrant p53 expression pattern. CONCLUSIONS: This case report strengthens the theory that defects in the tumor suppressor NF1 play a central role in the pathogenesis of inflammatory rhabdomyoblastic tumors and that IRMT may be part of the spectrum of neurofibromatosis type 1 related tumors.

Primary diffuse large B-cell lymphoma of adrenal gland: A case report.

INTRODUCTION: Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor with unknown etiology, atypical clinical symptoms, nonspecific imaging manifestations, difficult disease diagnosis and poor prognosis. CASE REPORT: This case report details a 42-year-old woman who was admitted to the hospital with a 1-year-old bilateral adrenal mass and 1-month-old left upper abdominal pain. Enhanced CT of the abdomen showed a right adrenal nodule and a large occupying lesion in the left adrenal region, with a high probability of pheochromocytoma. Intraoperatively, a huge tumor measuring about 12*12*10 cm was found in the left adrenal region, infiltrating the left kidney, spleen and pancreatic tail. Postoperative pathology: lymphocytes were found in the renal capsule and subcapsule, lymphocytes were found in the pancreas; lymphocytes were found in the spleen. Consider a tumor of the lymphohematopoietic system, possibly lymphoma. CONCLUSION: This case demonstrates that primary adrenal diffuse large B-cell lymphoma (PADLBCL) is highly aggressive, has a poor prognosis, is prone to recurrence, has poor therapeutic outcomes, and is difficult to diagnose. Clinicians should consider the possibility of PADLBCL when encountering huge adrenal-occupying lesions and consider chemotherapy before surgery. Reducing the tumor size before surgery is a more favorable therapeutic approach, thus prolonging the patient life and improving the quality of survival.

[Endocrine oncology : An update on surgical treatments]. / Endokrine Onkologie : Neues zu chirurgischen Therapien.

BACKGROUND: In the management of solid tumours, routine concepts are increasingly being transformed into individualized patient treatment. Endocrine surgery is traditionally characterized by resection strategies that are adapted to phenotype and genotype of the underlying disease. As complication rates in surgery correlate with the extent of resection, continuous efforts are made to identify selection criteria in order to limit the extent of surgery without compromising the oncological outcome. The aim is to design risk-stratified precision endocrine surgery. MATERIALS AND METHODS: A search was carried out in PubMed for new and modern strategies and approaches for oncological endocrine surgery. RESULTS: Several developments in surgical technique and technology, molecular pathology, medical therapy, and study data identify the potential to adapt the surgical strategy in all areas of endocrine surgery. CONCLUSION: According to prevalent data, limited extent of resection in thyroid cancer surgery shows a reduction in complication rates while preserving oncological outcome when adequate selection criteria are implemented. New insights and innovative technologies also influence additional areas in oncological endocrine surgery for parathyroid, adrenal, and neuroendocrine neoplasia. However, the broad practice of these new concepts needs to be evaluated with regard to long-term oncological outcome.

Beyond symptomatology: A comparative analysis of unilateral and bilateral macronodular mild autonomous cortisol secretion.

OBJECTIVE: To investigate the clinical, laboratory findings and signal intensity index (SII) on magnetic resonance imaging (MRI) of patients with bilateral and unilateral macronodular mild autonomous cortisol secretion (MACS). PATIENTS AND MEASUREMENTS: Clinical and laboratory findings of 81 patients with MACS were examined from retrospective records. SII of adenomas and internodular areas were evaluated by MRI. The unilateral group included patients with an adrenal macronodule (≥1 cm) in a single adrenal gland, while the bilateral group included patients with at least one macronodule in both adrenal glands. RESULTS: In total, 46 patients were in the unilateral (57%), while 35 (43%) patients were in the bilateral groups. The dehydroepiandrosterone sulphate (DHEA-S) level was lower in the unilateral than in the bilateral group (p < .001). The presence of type 2 diabetes mellitus (T2DM), glycosylated haemoglobin (HbA1c) and low-density lipoprotein (LDL) concentrations were higher in the bilateral group (p < .05). However, no significant difference was detected in terms of adrenocorticotropic hormone (ACTH) and overnight 1 mg dexamethasone suppression test (DST) between the two groups (p > .05). There was no difference in SII between adenomas within the same patient, as well as between the unilateral and bilateral groups (p > .05). Logistic regression analysis based on the differentiation between unilateral and bilateral macronodular MACS demonstrated that DHEA-S, HbA1c and LDL concentrations were associated factors. CONCLUSION: DHEA-S levels may not be as suppressed in patients with bilateral macronodular MACS as compared to those with unilateral adenoma. T2DM and hypercholesterolaemia have a higher frequency in bilateral patients. However, ACTH, overnight 1 mg DST and SII may not provide additional information for differentiation of bilaterality and unilaterality.

Seventy years of pheochromocytomas and paragangliomas in Argentina. The FRENAR database.

Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors characterized by the excessive production of catecholamines. This study aims to describe the clinical characteristics of PPGL cases in Argentina over recent decades. A multicenter retrospective cross-sectional analysis was carried out using a database comprising both pediatric and adult patients with confirmed PPGL diagnoses based on pathological reports. A cohort of 486 patients with PPGL was recruited. Women represent 58.4% of the patients, with a mean age of 38.3 years old at the time of diagnosis and 15.2% of the patients were under the age of 18. Hypertension, as well as classic signs and symptoms, were present in 80.9% of the patients. The adrenal incidentaloma, as a mode of presentation, increased in the last two decades rising from 3.9% (1953-2000) to 21.8% (2001-2022), p<0.001. Most tumors were located within the adrenal glands, accounting 83.0% of the cases, with bilateral occurrences noted in 20.0%. The median tumor size was 4.8cm. Local recurrence and metastases were observed in 10.9% and 12.2%. Out of 412 patients, 87.0% exhibited urinary excretion elevation of catecholamines and/or their metabolites. Furthermore, 148 patients, representing 30.4% of the study population, displayed a distinct genetic profile indicative of hereditary syndromes. The distribution of hereditary syndromes revealed that MEN2, VHL, and PGL4 constituted the most prevalent syndromes. This population-based study, spanning seven decades, offers valuable insights into the demographic and clinical characteristics of PPGL patients in Argentina.