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 The patient's ECMO was withdrawn after 6 days without any complications.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

Metastatic pheochromocytomas and paragangliomas (PPGLs) are frequently associated with skeletal complications. Primary objective: to describe the frequency of adverse skeletal related events (SREs) in PPGL patients with bone metastases (BMs). Secondary objectives: to 1) identify predictive and prognostic factors for SREs and 2) obtain information on the effectiveness of bone resorption inhibitors in reducing SRE risk and improving outcomes in term of survival and SREs time onset. In this retrospective multicenter, multinational study, 294 PPGL patients were enrolled. SREs occurred in 90 patients (31 %). Fifty-five patients (19 %) had bone fractures, 47 (16 %) had spinal cord compression, and 11 (4 %) had hypercalcemia. Twenty-two patients (7 %) had more than one SRE. Sixty-four patients (22 %) underwent surgery, and 136 (46 %) underwent radiotherapy. SREs occurred a median of 4.4 months after diagnosis of BM (range, 0-246.6 months). Independent factors associated with reduced risk of SREs in multivariable analysis were I-131-MIBG radionuclide therapy (hazard ratio [HR], 0.536 [95 % CI, 0.309-0.932]; P = .027) and absence of liver metastases (HR, 0.638 [95 % CI, 0.410-0.992]; P = .046). The median overall survival duration was 5.3 year. In multivariable analysis, age younger than 48 years at PPGL diagnosis (HR, 0.558 [95 % CI, 0.3877-0.806]; P = .002), absence of liver metastases (HR, 0.618 [95 % CI, 0.396-0.965]; P = .034), treatment with bisphosphonates or denosumab (HR, 0.598 [95 % CI, 0.405-0.884]; P = .010), and MIBG radionuclide therapy (HR, 0.444 [95 % CI, 0.274-0.718]; P = .001) were associated with a reduced risk of death. SREs occur frequently and early in bone-metastatic PPGL patients but do not negatively impact survival. MIBG radionuclide therapy and treatment with bone resorption inhibitors are associated with favorable outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hypertensive crises in pediatric patients are rare conditions. However, determining their precise prevalence is more challenging than in adults due to the heterogeneity in the definition itself. These crises frequently occur without a prior diagnosis of hypertension and may indicate an underlying cause of secondary hypertension, including pheochromocytoma/paraganglioma (PPGL). The mechanisms of hypertensive crises in the pediatric population with PPGL are directly related to different types of catecholamine excess. Noradrenergic tumors typically present with sustained hypertension due to their predominant action on α1-adrenoceptors in the vasculature. Conversely, adrenergic tumors, through epinephrine binding to β2-adrenoceptors in addition to stimulation of α1- and α2-adrenoceptors, more frequently cause paroxysmal hypertension. Furthermore, the biochemical phenotype also reflects the tumor localization and the presence of a genetic mutation. Recent evidence suggests that more than 80% of PPGL in pediatric cases have a hereditary background. PPGL susceptibility mutations are categorized into three clusters; mutations in cluster 1 are more frequently associated with a noradrenergic phenotype, whereas those in cluster 2 are associated with an adrenergic phenotype. Consequently, the treatment of hypertensive crises in pediatric patients with PPGL, reflecting the underlying pathophysiology, requires first-line therapy with alpha-blockers, potentially in combination with beta-blockers only in the case of tachyarrhythmia after adequate alpha-blockade. The route of administration for treatment depends on the context, such as intraoperative or pre-surgical settings, and whether it presents as a hypertensive emergency (elevated blood pressure with acute target organ damage), where intravenous administration of antihypertensive drugs is mandatory. Conversely, in cases of hypertensive urgency, if children can tolerate oral therapy, intravenous administration may initially be avoided. However, managing these cases is complex and requires careful consideration of the selection and timing of therapy administration, particularly in pediatric patients. Therefore, facing these conditions in tertiary care centers through interdisciplinary collaboration is advisable to optimize therapeutic outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bima, Lopez, Tuli, Munarin, Arata, Procopio, Bollati, Maccario, De Sanctis and Parasiliti-Caprino.)

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

Background: Hypertension (HT) is one of the most common manifestations in patients with catecholamine-secreting neuroendocrine tumors. Although the cardiovascular manifestations of these tumors have been described, there have been no large-scale investigations of the profile of HT and changes in cardiac structure and function that occur in patients with pheochromocytomas and paragangliomas (PPGL)., Materials and Methods: In this study, we investigated the prevalence of HT and left ventricular remodeling (LVR) in a cohort of 598 patients who underwent surgery for PPGL at our center between January 2001 and April 2022. Information on demographics, reason for hospitalization, medical history, biochemical parameters, findings on echocardiography, and tumor characteristics were recorded. The LVR index was compared according to whether or not there was a history of HT., Results: The average age was 47.07 ± 15.07 years, and 277 (46.32%) of the patients were male. A history of HT was found in 423 (70.74%) of the 598 patients. Paraganglioma was significantly more common in the group with HT (26.00% vs. 17.71%, P = 0.030) and significantly less likely to be found incidentally during a health check-up in this group (22.93% vs. 59.43%, P < 0.001). Among 365 patients with complete echocardiography data, left ventricular mass index (86.58 ± 26.70 vs. 75.80 ± 17.26, P < 0.001) and relative wall thickness (0.43 ± 0. 08 vs. 0.41 ± 0.06, P = 0.012) were significantly higher in patients with PPGL and a history of HT. The proportions with left ventricular hypertrophy (LVH) (19.40% vs. 8.25%, P = 0.011) and LVR (53.73% vs. 39.18%, P = 0.014) were also higher when there was a history of HT. After adjusting for age, gender, body mass index, alcohol consumption, smoking status, diabetes, stroke, creatinine level, tumor location, and tumor size, a history of HT was significantly correlated with LVH (odds ratio 2.71, 95% confidence interval 1.18-6.19; P = 0.018) and LVR (odds ratio 1.83, 95% confidence interval 1.11-3.03; P = 0.018)., Conclusion: HT is common in patients with PPGL (70.74% in this cohort). PPGL without a history of HT is more likely to be found incidentally (59.43% in our cohort). HT is associated with LVR in PPGL patients with complete echocardiography data. These patients should be observed carefully for cardiac damage, especially those with a history of HT., (© 2024. The Author(s).)

Pheochromocytoma is a tumor derived from neural crest cells able to produce sympathomimetic substances and, hence, a particular clinical picture. It is responsible for less than 1% of high blood pressure cases, with an estimated incidence between 0.4 and 0.6 cases per 100,000 people each year, and an average survival of seven years. Pheochromocytoma is a solid tumor with a high genetic component, as heritability can reach 40%. Once diagnosed, its treatment and prognosis are partly conditioned by the associated pathogenic variants that can be documented, especially those related to RET, SDHx, VHL, and NF1 genes. We present the case of a young woman with abdominal pain and high blood pressure, who was found to have a pheochromocytoma. Genetic testing detected a rare and recently discovered pathogenic variant: the SDHA:c.1A>C (p.Met1Leu). The patient responded adequately to the surgical treatment and continued the follow-up without documented recurrences. The diagnostic approach for pheochromocytoma patients must start with a clinical suspicion, followed by metabolite measurement in blood and urine, and finally, imaging. Currently, technology development allows precision medicine applicability. In this case of pheochromocytoma, recent developments in precision medicine resulted in the detection of associated genetic components involving the patient and her family. Adequate screening of the index patient is required for documenting pathogenic variants and better characterizing the disease.

Bladder paragangliomas (bPGLs) account for only 0.06% of all bladder tumours, most commonly presenting with post-micturition syncope and hypertensive crisis. Silent paragangliomas are very rare, and failure to recognise them in the perioperative setting can precipitate a hypertensive crisis in the absence of sufficient alpha-blockade. Here, we describe a case of unrecognised bPGL in a woman with pre-existing hypertension and a single prior episode of haematuria thought to be related to urothelial carcinoma. She was found to have a low-grade non-invasive papillary urothelial carcinoma (potentially the cause of her haematuria) and an unrelated vascular-appearing tumour causing hypertensive crisis and broad complex tachycardia on resection. This was confirmed to be a bPGL on histology for which she underwent definitive management with a partial cystectomy following blood pressure management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Pheochromocytomas and paragangliomas are neuroendocrine tumors producing catecholamines. Pheochromocytomas occur in the adrenal medulla, while paragangliomas are those that occur outside the adrenal gland. Here we describe a case series of children with a pathological diagnosis of pheochromocytoma or paraganglioma who consulted at a tertiary care children's hospital in Argentina. A total of 21 patients (14 males) were included; their median age was 11.4 years; 8 children had pheochromocytoma and 13, paraganglioma. Arterial hypertension was observed in 14/21. Most paragangliomas were para-aortic (9/13). Since they are a potentially curable cause of hypertension, clinical suspicion is very important. An early diagnosis and the initiation of an adequate antihypertensive treatment, which allows the patient to undergo surgery with normal blood pressure, ensure a cure in most cases if tumor resection is complete., (Sociedad Argentina de Pediatría.)

This study aimed to elucidate the clinical diagnostic value of plasma catecholamines and their metabolites for pheochromocytoma and paraganglioma (PPGL)-induced secondary hypertension using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). The study population included 155 patients with PPGL that were divided into the PPGL with hypertension (n = 79) and a PPGL without hypertension (n = 76) groups, and 90 healthy volunteers and 90 patients with primary hypertension as the control groups. UPLC-MS/MS was performed to detect plasma levels of catecholamines and their metabolites, including dopamine, vanillylmandelic acid (VMA), norepinephrine, metanephrine, and normetanephrine. Receiver operating characteristic curves were generated to analyze the diagnostic value of the plasma levels of catecholamines and their metabolites in PPGL-induced secondary hypertension. Patients in the primary hypertension and PPGL without hypertension groups had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal group (all p < .05). On the other hand, patients in the PPGL with hypertension group had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal, primary hypertension, and PPGL without hypertension groups (all p < .05). Collectively, our findings showed that dopamine, VMA, norepinephrine, metanephrine, and normetanephrine are all effective biomarkers for the diagnosis of PPGL and PPGL-induced secondary hypertension., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Here, we report a case of a woman in her 50s who was referred for an incidentally discovered lesion anterior to the origin of inferior vena cava suspicious for a paraganglioma following a CT scan for vaginal bleeding. A follow-up 68 Ga-DOTATATE PET-CT and MRI of the abdomen reinforced the radiological impression of an extra-adrenal paraganglioma (EAP). The EAP was deemed non-functional given normal urine biogenic amine, supine plasma fractionated metanephrines and chromogranin A levels. The mass was resected laparoscopically without perioperative blockade. Histological examination revealed a venous malformation. Extrahepatic abdominal venous malformations are rare and can be indistinguishable from an EAP on imaging preoperatively. Although benign, the lesion nevertheless warrants excision as it is associated with a risk of haemorrhage., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing's syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT., Methods: Retrospective European multicenter study of 263 patients (mean age 49 years, 50% females; 58 PHT, 69 PPGL, 37 CS, 99 PA) in whom targeted metabolomic and adrenal steroid profiling was available. The association of 13 adrenal steroids with differences in 79 metabolites between PPGL, CS, PA and PHT was examined after correction for age, sex, BMI, and presence of diabetes mellitus., Results: After adjustment for BMI and diabetes mellitus significant association between adrenal steroids and metabolites - 18 in PPGL, 15 in CS, and 23 in PA - were revealed. In PPGL, the majority of metabolite associations were linked to catecholamine excess, whereas in PA, only one metabolite was associated with aldosterone. In contrast, cortisone (16 metabolites), cortisol (6 metabolites), and DHEA (8 metabolites) had the highest number of associated metabolites in PA. In CS, 18-hydroxycortisol significantly influenced 5 metabolites, cortisol affected 4, and cortisone, 11-deoxycortisol, and DHEA each were linked to 3 metabolites., Discussions: Our study indicates cortisol, cortisone, and catecholamine excess are significantly associated with metabolomic variances in EHT versus PHT patients. Notably, catecholamine excess is key to PPGL's metabolomic changes, whereas in PA, other non-defining adrenal steroids mainly account for metabolomic differences. In CS, cortisol, alongside other non-defining adrenal hormones, contributes to these differences, suggesting that metabolic disorders and cardiovascular morbidity in these conditions could also be affected by various adrenal steroids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Knuchel, Erlic, Gruber, Amar, Larsen, Gimenez-Roqueplo, Mulatero, Tetti, Pecori, Pamporaki, Langton, Peitzsch, Ceccato, Prejbisz, Januszewicz, Adolf, Remde, Lenzini, Dennedy, Deinum, Jefferson, Blanchard, Zennaro, Eisenhofer and Beuschlein.)

Competing Interests: The authors report no conflicts of interest.

Background: Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype., Methods: We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines., Results: According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P =0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P =0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis., Conclusions: We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy., Competing Interests: Disclosures None.

Purpose: To identify presurgical and surgical risk factors for intraoperative hypertensive crisis in patients with pheochromocytomas and sympathetic paragangliomas (PGLs) (PPGLs)., Methods: Retrospective multicenter cohort study of patients with PPGLs from 18 tertiary hospitals. Intraoperative hypertensive crisis was defined as systolic blood pressure (SBP) greater than 200 mmHg lasting more than 1 min and postoperative hypertensive crisis as SBP greater than 180 mmHg or diastolic blood pressure (DBP) greater than 110 mmHg., Results: A total of 296 surgeries were included. Alpha presurgical blockade was employed in 93.2% of the cases and beta-adrenergic in 53.4%. Hypertensive crisis occurred in 20.3% ( n  = 60) of the surgeries: intraoperative crisis in 56 and postoperative crisis in 6 cases (2 cases had both types of crises). We identified as risk factors of intraoperative hypertensive crisis, absence of presurgical glucocorticoid therapy (odds ratio [OR] 3.48; 95% confidence interval [CI] 1.19-10.12) higher presurgical SBP (OR 1.22 per each 10 mmHg, 95% CI 1.03-1.45), a larger tumor size (OR 1.09 per each 10 mm, 95% CI 1.00-1.19) and absence of oral sodium repletion (OR 2.59, 95% CI 1.25-5.35). Patients with hypertensive crisis had a higher rate of intraoperative bleeding ( P  < 0.001), of intraoperative hemodynamic instability ( P  < 0.001) and of intraoperative hypotensive episodes ( P  < 0.001) than those without hypertensive crisis., Conclusion: Intraoperative hypertensive crisis occurs in up to 20% of the PPGL resections. Patients not pretreated with glucocorticoid therapy before surgery, with larger tumors and higher presurgical SBP and who do not receive oral sodium repletion have a higher risk for developing hypertensive crisis during and after PPGL surgery., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Clinical Case: The 59-year-old patient complained of hearing loss on the left, ear murmur for a long time, periodic pain and discomfort in the left ear, dizziness for 6 months. She was found to have concurrent vestibular schwannoma in the internal auditory canal and temporal bone paraganglioma. Both tumors were removed in one operation. The schwannoma was removed by translabirinth access due to preoperative deafness, while the glomus tumor was removed during this access. Postoperative biopsy showed the presence of two unrelated diseases: paraganglioma (ICD-0 code 8690/3) and schwannoma (ICD-0 code 9560/0).

Vagal paragangliomas (VPs) are rare tumors arising from paraganglionic tissue within the vagal nerve's perineurium. Usually, benign vascular tumors, VPs tend to invade the surrounding structures. Herein, we report the case of a VP presenting as a neck mass, which was evaluated as a glomus caroticum tumor preoperatively. A 65-year-old female complaining of a left-sided neck mass and intermittent hoarseness was assessed and operated on for possible glomus caroticum tumor. During the tumor excision, the vagal nerve was also involved, and hence, sacrificed. Histopathological examination revealed an encapsulated tumor associated with a nerve and ganglion and immunohistochemical staining tested positive for succinate dehydrogenase, confirming the diagnosis of VP. Postoperative residual hoarseness was corrected by vocal rehabilitation. While evaluating a retropharyngeal prestyloid neck mass, a VP should always be considered. Surgical excision involving vagal scarification, followed by vocal rehabilitation may be the appropriate treatment strategy.

Phaeochromocytomas and paragangliomas (PPGLs) release catecholamines leading to catecholamine-induced hypertensive (CIH) crises, with blood pressure greater than or equal to 180/120 mm Hg. CIH crises can be complicated by tachyarrhythmias, hypotension, or life-threatening target organ damage while treatment remains undefined, often requiring co-management between endocrinologists and cardiologists. Furthermore, biochemical diagnosis of a PPGL as a cause of a CIH crisis can be difficult to identify or confounded by comorbid conditions, potentially resulting in misdiagnosis. Here, we combine relevant evidence, 60 years of collective clinical experience, insights derived from assessing over 2600 patients with PPGL, and supplementary outcomes from 100 patients (treated at the National Institutes of Health) with a CIH crisis to inform diagnosis and treatment of CIH crises. Recognising that disparities exist between availability, cost, and familiarity of various agents, flexible approaches are delineated allowing for customisation, given institutional availability and provider preference. A CIH crisis and its complications are readily treatable with available drugs, with effective intervention defining an avenue for mitigating consequent morbidity and mortality in patients with PPGL., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Pheochromocytomas and paragangliomas (PPGLs) are a group of rare neuroendocrine tumors. Dysglycemia has been observed in patients with PPGLs in some small case series. However, there is limited information available on the factors associated with development and resolution of dysglycemia in these patients., Patients and Methods: The clinical data of consecutive patients admitted to our hospital with PPGLs between January 2018 and June 2020 were retrospectively analyzed. Clinical characteristics were compared between patients with and without dysglycemia. Logistic regression analysis was used to identify risk factors and receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the variables., Results: Among 163 patients, 58.9% had preoperative dysglycemia. Patients with dysglycemia were significantly older at diagnosis ( p  = 0.01) and were significantly more likely to have hypertension ( p  = 0.007). White blood cell counts ( p  = 0.016), 24-hour urinary epinephrine (24hU-E) levels ( p  < 0.001) and 24-hour urinary norepinethrine levels ( p  = 0.008) were significantly higher in patients with dysglycemia. Regression analysis showed that age (odds ratio [OR] 1.028, 95% confidence interval [CI] 1.001-1.055; p  = 0.041), hypertension (OR 2.164, 95% CI 1.014-4.619; p  = 0.046) and the 24hU-E concentration (OR 1.010, 95% CI, 1.001-1.019; p  = 0.025) were positively associated with preoperative dysglycemia. Taking age, hypertension, and 24hU-E into account in the same model, the area under the ROC curve for prediction of preoperative dysglycemia was 0.703. The proportion of patients with dysglycemia decreased significantly after surgery ( p  < 0.001) and patients with preoperative dyssglycemia that resolved after surgery tended to have a larger preoperative tumor diameter ( p  = 0.018)., Conclusion: Age, hypertension, and the 24hU-E concentration are risk factors for preoperative dysglycemia. Removal of PPGLs can improve dysglycemia in most patients, and postoperative remission of dysglycemia is associated with the preoperative tumor diameter. These results are important for risk assessment and for selecting optimal therapies in patients with dysglycemia in PPGLs.KEY MESSAGESThere have been insufficient data to identify factors associated with development and resolution of dysglycemia in patients with PPGLs.Our results show that approximately half of the patients with PPGLs develop dysglycemia; age, hypertension, and the 24hU-E concentration are risk factors for preoperative dysglycemia.Removal of the PPGLs improves dysglycemia in a majority of patients, and a large preoperative tumor diameter is associated with remission of dysglycemia after surgery.

Purpose of Review: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that commonly produce excess catecholamines causing significant morbidity and mortality. Patients with cyanotic congenital heart disease (CCHD) develop PPGLs at a higher frequency than the general population. This review will summarize recent research in the association of PPGL and CCHD., Recent Findings: Advances in molecular genetics have provided new insights into a variety of germline mutations and somatic mutations related to PPGLs. In the CCHD population, mutations can occur in the hypoxia signaling pathway with gain-of-function somatic mutations in EPAS1, which prevent degradation of hypoxia-inducible factor-2 alpha. These mutations are implicated in oncogenesis. PPGLs associated with CCHD develop as early as age 15 years and have predominantly noradrenergic secretion. Surgical removal is considered the first line of therapy, although belzutifan, a HIF-2α inhibitor, is currently being tested as a potential therapy. Early screening with plasma metanephrines may assist in identifying PPGLs in patients with CCHD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Paragangliomas are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, i.e., small organs consisting mainly of neuroendocrine cells that are derived from the embryonic neural crest and have the ability to secrete catecholamines. Paragangliomas can derive from either parasympathetic or sympathetic paraganglia. Most of the parasympathetic ganglia-derived paragangliomas are nonfunctional, and symptoms result from mass effect. Conversely, the sympathetic paragangliomas are functional and produce catecholamine. Although such patients could have symptoms similar to pheochromocytoma, mass effect symptoms, or non-specific symptoms, being benign tumors, they can also present with anemia, specifically iron-deficiency anemia. Considering that neoplastic pathology is chronically accompanied by moderate, normochromic, normocytic anemia, association between paragangliomas that are mostly benign but with a potential degree of malignancy and anemia is not as frequent as expected, with only 12 cases reported in the literature. We report a case of a 54-year-old female patient diagnosed with a paraganglioma of the carotid glomus accompanied by severe normochromic, normocytic anemia, which reached normal limits after excision of the paraganglioma.

BACKGROUND Paragangliomas are neuroendocrine neoplasms derived from paraganglia of the sympathetic and parasympathetic nervous systems. Parasympathetic ganglia-derived tumors, also called non-chromaffin, are located almost exclusively in the neck and skull base and are usually non-secretory and inactive. A case of malignant glomus jugulare with a metastatic cervical lymph node is described here. CASE REPORT A 24-year-old woman was referred to an otolaryngology clinic for concern of voice change for 1 month, which was associated with right progressive hearing loss, pulsating tinnitus, and right facial weakness. A clinical examination revealed a reddish mass in the right ear behind an intact tympanic membrane with right facial weakness of House-Brackmann grade VI. A bedside flexible nasopharyngoscopy revealed an immobile right vocal fold. A computed tomography scan of the brain revealed a destructive lesion within the right jugular foramen. The patient underwent embolization followed by glomus tumor resection via infra-temporal fossa with Fisch type A approach. Pathology revealed that the tumor was an infiltrative epithelioid tumor with a spindle and nesting pattern separated by fibrovascular stroma. The submitted lateral neck lymph node revealed a metastatic tumor. CONCLUSIONS Glomus jugulare tumors are uncommon paragangliomas, and malignant behavior with metastasis is extremely rare. Metastatic tumors are often associated with facial and vagal nerves palsy. There are no histological features that distinguish malignant glomus jugulare tumors. Malignant neoplasms are characterized by the presence of metastases. Tumors of the glomus jugulare that are malignant are treated with surgery, radiotherapy, or both. However, our search of the literature revealed no clear guidelines, given the scarcity of cases. Moreover, the presence of metastasis increases the risk of death.

The major adrenal tumors with endocrine activity are primary aldosteronism, Cushing's syndrome/mild autonomous cortisol secretion, and pheochromocytoma/paraganglioma. Excessive aldosterone secretion in primary aldosteronism causes cardiovascular, renal, and other organ damage in addition to hypertension and hypokalemia. Cortisol hypersecretion in Cushing's syndrome/mild autonomous cortisol secretion causes obesity, hypertension, impaired glucose tolerance, and cardiometabolic syndrome. Massive secretion of catecholamines in pheochromocytoma/paraganglioma causes hypertension and cerebrocardiovascular disease due to rapid blood pressure fluctuation. Moreover, pheochromocytoma multi-system crisis is a feared and possibly fatal presentation of pheochromocytoma/paraganglioma. Thus, adrenal tumors with endocrine activity are considered an indication for adrenalectomy, and perioperative management is very important. They have a risk of perioperative complications, either due to direct hemodynamic effects of the hormone hypersecretion or due to hormone-related comorbidities. In the last decades, deliberate preoperative evaluation and advanced perioperative management have significantly reduced complications and improved outcomes. Furthermore, improvements in anesthesia and surgical techniques with the feasibility of laparoscopic adrenalectomy have contributed to reduced morbidity and mortality. However, there are still several challenges to be considered in the perioperative care of these patients. There are very few data available prospectively to guide clinical management, due to the rarity of adrenal tumors with endocrine activity. Therefore, most guidelines are based on retrospective data analyses or small case series. In this review, the latest knowledge is summarized, and practical pathways to reduce perioperative complications and improve outcomes in adrenal tumors with endocrine activity are presented., (© 2023 The Japanese Urological Association.)

We report a rare case of a functional bladder paraganglioma diagnosed in a young man who presented with acute compressive thoracic myelopathy secondary to vertebral metastasis. A histological diagnosis of a metastatic paraganglioma was made following biopsy of a rib lesion. CT revealed a lesion in the inferior wall of the bladder, which demonstrated avid uptake on 68Ga-DOTATATE PET/CT. Serum metanephrine levels were more than 40 times the upper limit of normal. The patient was hypertensive and treatment with doxazosin was initiated. In view of neurological deterioration, he required urgent spinal decompression to preserve neurological function and prevent permanent paraplegia. Despite inadequate alpha-blockade, surgery was successful, and the perioperative course was uneventful. Alpha-blockade was subsequently optimised. Treatment with cyclophosphamide, vincristine and dacarbazine was started but, in view of disease progression, treatment was subsequently changed to sunitinib., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that frequently produce and release catecholamines. Catecholamine excess can manifest in several cardiovascular syndromes, including cardiomyopathy. PPGL-induced cardiomyopathies occur in up to 11% of cases and are most often associated with an adrenal pheochromocytoma (90%) and rarely with a paraganglioma derived from the sympathetic ganglia (10%). PPGL-associated cardiomyopathies can be chronic or acute, with takotsubo cardiomyopathy being the most often reported. These two types of PPGL-induced cardiomyopathy seem to have different pathophysiological backgrounds. Acute catecholaminergic stress inundates myocardial β-adrenoceptors and leads to left ventricle stunning and slight histological apoptosis. In chronic cardiomyopathy, prolonged catecholamine exposure leads to extended myocardial fibrosis, inflammation, and necrosis, and ultimately it causes dilated cardiomyopathy with a low ejection fraction. Sometimes, especially in cases associated with hypertension, hypertrophic cardiomyopathy can develop. The prognosis appears to be worse in chronic cases with a higher hospital mortality rate, higher cardiogenic shock rate at initial presentation, and lower left ventricular recovery rate after surgery. Therefore, establishing the correct diagnosis at an early stage of a PPGL is essential. This mini-review summarizes current data on pathophysiological pathways of cardiac damage caused by catecholamines, the clinical presentation of PPGL-induced cardiomyopathies, and discusses treatment options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Szatko, Glinicki and Gietka-Czernel.)

Purpose: We present a prospective case series that aimed to report the functional (voice and swallowing) outcomes of delayed laryngeal reinnervation following vagal interruption by resection of vagal paraganglioma and schwannoma., Materials and Methods: A dedicated, anonymized database was established in 2012 with a minimum eighteen-month follow up set for this report. Internationally validated self- and observer-reported measures were recorded preoperatively and at six, 12 and, 18 months together with demographics, diagnoses, and operative details., Results: A total of eight patients with a median age of 46 (37-54) underwent excision of vagal paraganglioma (five) and schwannoma (three) with few mild complications. Three underwent selective and five non selective reinnervation. Seven out of eight patients underwent synchronous injection medialization. The voice handicap index (VHI-30) improved from a baseline median 83 (range 52-102) to 7.5 (5-58) at 18 months; maximum phonation time improved from median 8 (range 5-15) to 10.5 (8.5-11); voice grade ("G" in grade, roughness, breathiness, asthenia, and strain [GRBAS] scoring) improved from median three (severe impairment, range 0-3) to one (mild impairment, 0-2); Eating Assessment Tool (EAT-10) score improved from median 12 (range 3.5-27) preoperatively to one (0-16); and reflux symptom index (RSI) improved from median 25 (range 17-36) to 7 (0-36). One patient exhibited no discernible reinnervation, while the remainder exhibited good cord bulk and tone, though without purposive abduction., Conclusion: Delayed laryngeal reinnervation for high vagal paralysis is a safe technique associated with good voice and swallowing outcomes by 12-18 months. Potential confounders in this small series and the absence of a control arm both limit conclusions, but this study suggests that further prospective, controlled studies, and/or case registration are merited., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Gain-of-function mutations in the EPAS1/HIF2A gene have been identified in patients with hereditary erythrocytosis that can be associated with the development of paraganglioma, pheochromocytoma and somatostatinoma. In the present study, we describe a unique European collection of 41 patients and 28 relatives diagnosed with an erythrocytosis associated with a germline genetic variant in EPAS1. In addition we identified two infants with severe erythrocytosis associated with a mosaic mutation present in less than 2% of the blood, one of whom later developed a paraganglioma. The aim of this study was to determine the causal role of these genetic variants, to establish pathogenicity, and to identify potential candidates eligible for the new hypoxia-inducible factor-2 α (HIF-2α) inhibitor treatment. Pathogenicity was predicted with in silico tools and the impact of 13 HIF-2b variants has been studied by using canonical and real-time reporter luciferase assays. These functional assays consisted of a novel edited vector containing an expanded region of the erythropoietin promoter combined with distal regulatory elements which substantially enhanced the HIF-2α-dependent induction. Altogether, our studies allowed the classification of 11 mutations as pathogenic in 17 patients and 23 relatives. We described four new mutations (D525G, L526F, G527K, A530S) close to the key proline P531, which broadens the spectrum of mutations involved in erythrocytosis. Notably, we identified patients with only erythrocytosis associated with germline mutations A530S and Y532C previously identified at somatic state in tumors, thereby raising the complexity of the genotype/phenotype correlations. Altogether, this study allows accurate clinical follow-up of patients and opens the possibility of benefiting from HIF-2α inhibitor treatment, so far the only targeted treatment in hypoxia-related erythrocytosis disease.

Context: Pheochromocytomas and paragangliomas (PPGL) are rare causes of secondary hypertension, but when unrecognized, they can lead to serious complications. Data regarding PPGL screening are lacking., Objective: This study aimed to assess the rates and patterns of PPGL screening among eligible patients., Methods: We conducted a retrospective review of adults with hypertension seen in outpatient clinics of a large academic center between January 1, 2017, and June 30, 2020. We included patients with treatment-resistant hypertension, hypertension at age < 35 years, and/or adrenal mass(es)., Results: Of 203 535 patients with hypertension identified, 71 088 (35%) met ≥ 1 inclusion criteria, and 2013 (2.83%) were screened for PPGL. Patients screened were younger (56.2 ± 17.4 vs 64.0 ± 17.1 years), more often women (54.1% vs 44.2%), and never-smokers (54.6% vs 47.5%, P < 0.001 for all). The rate of screening was highest in patients with hypertension and adrenal mass(es) (51.7%, vs 3.9% in patients with early-onset hypertension, and 2.4% in those with treatment-resistant hypertension). Multivariable logistic regression showed higher odds ratio (OR) of PPGL screening in women (OR [95% CI]: 1.48 [1.34-1.63]); Black vs White patients (1.35 [1.19-1.53]); patients with adrenal mass(es) (55.1 [44.53-68.15]), stroke (1.34 [1.16-1.54]), dyslipidemia (1.41 [1.26-1.58]), chronic kidney disease (1.40 [1.26-1.56]), and obstructive sleep apnea (1.96 [1.76-2.19])., Conclusion: PPGL screening is pursued in roughly half of patients with adrenal nodules and hypertension, but rarely in patients with treatment-resistant or early-onset hypertension. Similar to screening for other forms of secondary hypertension, PPGL screening occurs more often after serious complications develop., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Functioning pituitary adenomas and pheochromocytomas/paragangliomas are rare in the general population. Pituitary adenomas occur in the familial setting in approximately 5% of cases, whereas pheochromocytomas/paragangliomas can be hereditary in 30-40% of cases. Hereditary syndromes associated with pituitary adenomas include multiple endocrine neoplasia types 1 and 4, familial isolated pituitary adenomas, and Carney complex. Hereditary syndromes associated with pheochromocytomas/paragangliomas and genes, mutations in which predispose to their development, are more numerous. The first clinical descriptions of the co-occurrence of pituitary adenoma and pheochromocytoma/paraganglioma in one patient date back to the mid 20th century, however delineating such a co-occurrence into a particular syndrome («3PAs» (pituitary adenoma, pheochromocytoma, paraganglioma)) was suggested only in 2015. To date, approximately 100 cases of such a co-occurrence have been described in the literature. Mutations in genes encoding subunits of succinate dehydrogenase complex II (SDHx) are revealed in the majority of cases, much less common are mutations in MAX, MEN1 and some other genes. This review summarizes the current information on the «3PAs» syndrome.

Background: The new presentation of pheochromocytoma or paraganglioma in pregnancy is very rare and can be life-threatening for mother and child., Case Presentation: We present the case of a 26-year-old gravida 3 para 2 otherwise healthy Caucasian woman at 34 weeks gestation who presented with new onset hypertension associated with headaches, dry heaves, diaphoresis, and palpitations. She was initially diagnosed with preeclampsia and treated with labetalol and an urgent cesarean section, delivering a healthy baby girl. The diagnosis of preeclampsia came into question when, 6 weeks postpartum, she continued to have hypertension with atypical features. Testing revealed metastatic paraganglioma associated with a succinate dehydrogenase B gene mutation. The patient was then started on alpha-adrenergic blockade and has had close blood pressure monitoring while discussion of advances therapies is ongoing., Conclusion: This case demonstrates how paraganglioma/pheochromocytoma can be misdiagnosed as preeclampsia due to the overlapping features of new-onset hypertension late in pregnancy accompanied by headache and proteinuria. It is impractical to routinely screen for paraganglioma/pheochromocytoma in all pregnant patients diagnosed with preeclampsia due to the rarity of these tumors and the harm from high false-positive rates. Therefore, it is incumbent on the provider to have a high degree of suspicion for paraganglioma/pheochromocytoma when clinical features are unusual for preeclampsia, such as intermittent palpitations, diaphoresis, orthostatic hypotension, or hyperglycemia. Early detection of paraganglioma/pheochromocytoma with interventions to mitigate the risk of hypertensive crisis greatly reduce maternal and fetal mortality. Fortunately, our patient delivered a healthy baby and did not have any additional pregnancy complications despite the delay in her diagnosis., (© 2023. The Author(s).)

Pheochromocytomas (PHEOs) and paragangliomas are generally grouped as rare chromaffin cell tumors. The co-occurrence of PHEOs and paragangliomas of the organ of Zuckerkandl (POZ) is extremely rare. The most common symptom of pheochromocytoma-paraganglioma (PPGL) is hypertension, and open surgery is still recommended for the treatment of large PPGLs. Herein, we report a case of a successful simultaneous laparoscopic resection of a large PHEO accompanied by POZ in a 40-year-old man with normal blood pressure. DNA analysis revealed a mutation in the succinate dehydrogenase subunit B in both the PHEO and the POZ. To the best of our knowledge, this is the first report of tumors occurring simultaneously in these two locations. We believe that the co-occurrence of PHEO and POZ is extremely rare, and the possibility of PPGL cannot be ruled out in patients with normal blood pressure. The decision to perform laparoscopic surgery remains questionable for patients with a large PHEO and POZ. In addition, a genetic examination should be performed to identify the existence of PPGL-related inherited syndromes.

Purpose: In this article, we aimed to elaborate on perioperative and complication management in treatment of pheochromocytoma crisis with extracorporeal membrane oxygenation (ECMO)., Material and Methods: We report a case of relatively rare grant paraganglioma-induced pheochromocytoma crisis leading to severe circulatory failure, treated with venoarterial extracorporeal membrane oxygenation (V-A ECMO) as a bridge to curative adrenalectomy. Weaning of ECMO was followed by successful surgical removal of the tumor, and patient survival. However, distal ischemia of the cannulated leg occurred during ECMO operation, which eventually led to amputation. In addition, the patient developed new cerebral infarction and left hemiplegia, half a month after paraganglioma resection., Conclusions: We believe that patients with pheochromocytoma crisis, who cannot maintain blood circulation, are eligible for V-A ECMO treatment. Moreover, care should be taken to prevent thrombosis and individualized and precise blood pressure management targets. Early detection and treatment of thrombosis is imperative to long-term prognosis of patients with ECMO.

Background: Paraganglioma of genitourinary tract is uncommon, and origin from ureter is even rarer. We aim to present a case of paraganglioma from ureter in a 48-year-old female patient, who presented with gross hematuria., Case Presentation: We present a 48-year-old female who complained of gross hematuria for one week. A left ureteral tumor was found by image study. However, hypertension was unexpectedly recorded during diagnostic ureteroscopy survey. Due to persisted gross hematuria and bladder tamponade, she underwent left nephroureterectomy with bladder cuff resection. Blood pressure surged again when the tumor was surgically approached. Ureteral paraganglioma was confirmed according to pathological report. After the surgery, the patient recovered well, and no more gross hematuria was noted. She is now under regular follow-up at our outpatient clinic., Conclusion: Ureteral paraganglioma should be kept in mind not only when blood pressure fluctuates during operation, but also before we manipulate the ureteral tumor when gross hematuria is the only sign. Whenever the presumption of paraganglioma is raised, laboratory evaluation and anatomical or even functional imaging should be considered. The concomitant anesthesia consultation before the surgery should not be deferred, either., (© 2023. The Author(s).)

Background: Pheochromocytoma and paraganglioma (PPGL) are catecholamine producing tumors of chromaffin cell origin, known to cause varied cardiovascular manifestations from hypertension to myocardial infarction. This study sought to objectively evaluate the cardiac changes in PPGL patients and their reversal following curative surgery., Methods: The PheoCard study was registered in ClinicalTrials.gov (NCT05082311) and involved 35 consecutive PPGL patients managed as per standard protocol involving alpha blockade followed by curative surgery. They underwent detailed cardiac evaluation using 2D-echocardiography and speckle tracking echocardiography at the time of diagnosis, 7-10 days after alpha blockade, and at 7 days, 3 months, and 6 months after surgical removal. Age- and gender-matched essential hypertensives and healthy individuals (10 in each group) served as two control groups., Results: Patients with PPGLs had significantly higher mean blood pressure, left ventricle end-diastolic dimension and volume (LVEDD, LVEDV), left ventricle end-systolic volume (LVESV), septal wall thickness, LV hypertrophy, lower mean LV ejection fraction (LVEF), early diastolic mitral annular velocity (E/A), decreased amplitude of LV longitudinal strain, and increased circumferential strain (p < 0.001) when compared with the control groups at baseline. After alpha blockade, there was marked reduction in the mean LVEDD, LVEDV, LVESV, and normalization of E/A ratio (p < 0.001) in the PPGL patients. Following curative surgery (normalization of fractionated urinary metanephrines at 7-10 days post-operatively), there was early improvement in all echocardiographic parameters and it continued to improve even at 6 months after surgery. There was marked improvement in the global longitudinal strain as seen on serial speckle tracking echocardiography with recovery of most of the segments of LV depicting the reversal of subclinical endocardial dysfunction (p < 0.001)., Conclusion: PPGL patients despite normal systolic function have subclinical LV diastolic dysfunction which is reversed after curative surgery., Trial Registration: ClinicalTrials.gov NCT05082311., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: Cardiac paragangliomas (PGLs) are clinically rare, with hypertension and metabolic changes as the main symptoms. The tumor is highly related to gene mutation, and surgery is presently the effective treatment. Medical history and clinical manifestations of the patient, routine laboratory examinations and imaging examinations, and pathological examination can help the final diagnosis., Case Presentation: The present study presents a 31-year-old male patient with a left atrial mass. The initial symptom was cough. Cardiac enlargement was found during the chest X-ray. The follow-up imaging examination revealed a left atrial occupying lesion, and the possibility of malignant occupying lesions was not ruled out. The patient underwent surgical resection of the mass. The final pathological result revealed paraganglioma. The thoracic computed tomography review two months after the operation revealed that the original occupying lesion disappeared, and no new lesion was found., Conclusions: Pheochromocytomas and paragangliomas (PPGLs) are a kind of neuroendocrine tumors. PPGLs can cause secondary hypertension, and lead to a series of clinical syndromes, including myocardial injury, metabolic changes, and so on. The occurrence of PPGIs is related to gene mutation. Biochemical detection, imaging examination, and genetic testing can help diagnose. The tumor should be surgically removed as soon as possible after the diagnosis. As a functional tumor, PPGLs should be fully prepared before surgery to avoid anesthesia and huge fluctuations in blood pressure during and after surgery, or the occurrence of fatal hypertensive crisis and intractable hypotension after tumor resection. Adequate preoperative preparation directly affects the prognosis of patients after surgery. Therefore, multidisciplinary cooperation before, during, and after the operation is extremely important., (© 2023. The Author(s).)

Pheochromocytoma is a rare form of secondary hypertension characterized by excessive production of catecholamines typically due to a benign tumor in the adrenal medulla. Among the potential cardiac repercussions of pheochromocytoma and paraganglioma, previous studies described echocardiographic abnormalities such as dynamic left ventricular outflow tract obstruction (i), cardiomyopathy (ii, iii, iv), reversible dilatation of the left ventricle (v) and left ventricular functional changes (vi) in patients with pheochromocytoma., (© 2023 Wiley Periodicals LLC.)

Background: Maintaining intraoperative haemodynamic stability can reduce cardiovascular complications during surgery for pheochromocytoma and paraganglioma (PPGL). Risk factors such as tumour size and catecholamine levels are reported to predict haemodynamic responses during surgery for PPGL. We hypothesized that additional factors including body composition and genetic information could further improve prediction., Methods: Consecutive patients with PPGL confirmed by surgical pathology between June 2010 and June 2019 were retrospectively included. Cross-sectional computed tomography images at the L3 level were used to assess body composition parameters including skeletal muscle area and visceral fat area. Next-generation sequencing was performed using a panel containing susceptibility genes of PPGL. Differences in clinical-genetic characteristics and body composition parameters were analysed and compared in patients with and without intraoperative haemodynamic instability (HDI)., Results: We included 221 patients with PPGL (median age 47 [38-56] years, and 52% male). Among them, 49.8% had Cluster 2 mutations (related to kinase signalling pathways), 44.8% had sarcopenia, and 52.9% experienced intraoperative HDI. Compared with patients without HDI, more patients with HDI had Cluster 2 mutations (59.8% vs. 38.5%, P = 0.002) and less had sarcopenia (35.9% vs. 54.8%, P = 0.005). Multivariate analysis showed that urine vanillylmandelic acid ≥ 58 μmol/day (adjusted odds ratio [OR] = 1.840, 95% confidence interval [CI] = 1.012-3.347, P = 0.046), tumour size ≥ 4 cm (adjusted OR = 2.278, 95% CI = 1.242-4.180, P = 0.008), and Cluster 2 mutations (adjusted OR = 2.199, 95% CI = 1.128-4.285, P = 0.021) were independent risk factors for intraoperative HDI, while sarcopenia (adjusted OR = 0.475, 95% CI = 0.266-0.846, P = 0.012) decreased the risk., Conclusions: Body composition and genotype were associated with intraoperative haemodynamics in patients with PPGL. Our results indicated that inclusion of body composition and genotype in the overall assessment of patients with PPGL helped to predict HDI during surgery, which could assist in implementing preoperative and intraoperative measures to reduce perioperative complications., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose: The co-occurrence of cyanotic congenital heart disease (CCHD) and PHEO/PGL has been reported, but the role of the hypoxic environment in the pathogenesis of PHEO/PGL remains unclear. Our aim was to compare plasma metanephrine and normetanephrine levels between patients with CCHD and patients with acyanotic congenital heart disease (ACCHD)., Methods: We performed a cross-sectional study in a prospective cohort of 44 patients with congenital heart disease (CHD) (31 (70.5%) females) with a median age of 37.5 (31.0-55.6) years at the time of evaluation. Thirty-two (73%) patients had CCHD and 12 (27%) patients had ACCHD. Morning blood samples for plasma determination of metanephrine and normetanephrine were collected., Results: Plasma normetanephrine levels were significantly higher in patients with CCHD compared to ACCHD (p = 0.002). Ten (31.3%) patients with CCHD had plasma normetanephrine levels elevated above the reference range, while all ACCHD patients had normal levels. Patients with lower oxygen saturation and higher proBNP had significantly higher normetanephrine levels (ρ = -0.444, p = 0.003 and ρ = 0.449, p = 0.002, respectively). No chromaffin cell tumors were detected., Conclusion: Increased plasma normetanephrine levels in patients with CCHD can be explained by the effect of hypoxia. Future research is needed to better understand the impact of chronic hypoxia in CCHD on increased sympathetic outflow, hyperplastic response of chromaffin tissue, and the role of somatic mutations in CCHD-PHEO/PGL pathogenesis related to hypoxia., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Coexistence of a catecholamine-secreting tumor and an adrenal cortical tumor is quite rare which makes both diagnosis and management challenging. The purpose of this article is to describe the presence of this condition, share a stepwise approach for preoperative evaluation, and review the related literature., Case Presentation: A 44-year-old male patient had a history of hypertension and aggravating hypokalemia for years. Abdominal computed tomography incidentally found concomitant bilateral adrenal and left para-aortic tumors. Comprehensive adrenal hormone tests revealed a high aldosterone renin ratio and mildly elevated 24-h urine vanillylmandelic acid and norepinephrine levels. Subsequently, a metaiodobenzylguanidine scan showed uptake over the left para-aortic tumor, and NP-59 adrenal scintigraphy showed uptake over the left adrenal tumor. Further confirmatory tests, including captopril suppression, irbesartan suppression, and saline infusion, all confirmed the diagnosis of hyperaldosteronism. Adrenal venous sampling following 2 months of preparation with an alpha blocker demonstrated a left aldosterone-producing adrenal adenoma. Combining hormonal analysis, imaging studies, and adrenal venous sampling, the patient was diagnosed with left adrenal aldosteronoma, right adrenal nonfunctional tumor, and left para-aortic paraganglioma (PGL). Accordingly, laparoscopic left adrenalectomy and left PGL excision were performed smoothly under alpha blocker maintenance. The pathology report confirmed left adrenal cortical adenoma and left para-aortic PGL. Postoperatively, the blood pressure, biochemical tests, and adrenal hormone assays returned to normal, and related symptoms disappeared and were relatively stable during the follow-up period of two years., Conclusions: This is the first case of left para-aortic PGL coexisting with an ipsilateral aldosterone-producing adenoma presenting as a left para-aortic tumor associated with bilateral adrenal tumors. Awareness of the rarity of this coexistence can avoid unexpected disasters during the process of evaluation and management., (© 2022. The Author(s).)

Rationale: Paragangliomas are extremely rare neuroendocrine tumors arising from ganglia. These tumors are barely found in the middle mediastinum., Patient Concerns: A 31-year-old male patient was admitted to our hospital for treatment of an middle mediastinal tumor which was found incidentally on echocardiography during a medical checkup. Contrast-enhanced chest computed tomography (CT) demonstrated a well-defined hypervascularized heterogeneous mass located in the middle mediastinum. The tumor showed strong 18F-fluorodeoxyglucose (FDG) activity on positron emission tomography-computed tomography (PET-CT)., Diagnosis: Before the surgery, we presumed the mass was an angiogenic or neurogenic tumor. As a result, the histological features favored a diagnosis of paraganglioma., Interventions: The tumor was completely removed by anterior thoracotomy, along with the proximal segment of the left anterior descending artery (LAD), and coronary artery bypass grafting (CABG) was performed immediately after the tumor excision., Outcomes: The patient had an uneventful recovery. The patient did well in the postoperative follow-up without any complications and signs of recurrence at 3 months, 1 year, 2 year and 4 year., Lessons: This report can increase the confidence in surgeries of mediastinal paragangliomas adhering tightly the adjacent structures., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pheochromocytomas and paragangliomas can induce severe cardiovascular manifestations such as Takotsubo-like cardiomyopathy. What the perioperative outcomes are of patients presenting with pheochromocytomas/paragangliomas preceded by Takotsubo-like cardiomyopathy remains an unresolved question., Methods: From 2006 to 2019, all patients who underwent surgery for pheochromocytomas/paragangliomas preceded by Takotsubo-like cardiomyopathy were included from 3 high-volume centers, with specific attention to perioperative hemodynamic instability and postoperative outcomes., Results: Overall, 37 patients were included, with a median age of 45 years. Patients were operated on 2 months (1-4) after a Takotsubo-like cardiomyopathy episode; 33 (89%) had a laparoscopic approach. All those who underwent surgery presented in a hemodynamically stable situation. All except 1 of the pheochromocytomas/paragangliomas patients had at least 1 antihypertensive treatment at the time of surgery. The median preoperative systolic blood pressure in the Takotsubo-like cardiomyopathy group was 120 mm Hg (95-132). Overall, 27/34 (79%) of patients required vasoactive drugs during surgery with nicardipine (n = 22), esmolol (n = 12), and/or norepinephrine (n = 8). No patient presented a catecholamine-induced life-threatening complication such as hypertensive crisis, cardiac arrhythmias, pulmonary edema, cardiac ischemia, or Takotsubo-like cardiomyopathy in the perioperative period. Severe morbi-mortality was nil. The systematic review identified 5 studies including 38 pheochromocytomas/paragangliomas patients with at least 1 episode of acute heart failure considered as Takotsubo-like cardiomyopathy before surgery, of which 28 patients had delayed surgery with 1 postoperative death., Conclusion: Hemodynamically stabilized patients with pheochromocytomas/paragangliomas preceded by Takotsubo-like cardiomyopathy can be safely scheduled for an elective pheochromocytomas/paragangliomas surgery, with similar intra and postoperative outcomes as those without Takotsubo-like cardiomyopathy., (Copyright © 2022 Elsevier Inc. All rights reserved.)