Giant Cystic Pheochromocytoma Associated With Neurofibromatosis Type 1: A Case Report.

Pheochromocytomas are tumors that develop from the chromaffin cells of the adrenal medulla. More than 40% of cases of pheochromocytomas are associated with genetic conditions such as neurofibromatosis type 1 (NF1) or von Hippel-Lindau syndrome. Cystic pheochromocytomas are rare, generally asymptomatic, and thus of bigger size at the time of diagnosis. Surgical treatment is necessary to prevent cardiovascular morbidity and malignancy risk. We report the case of a 27-year-old patient admitted for further examination of a left adrenal mass that was discovered by an abdominal CT scan in the context of abdominal pain associated with hypertension evolving for three years. The clinical examination showed the presence of multiple café au lait spots, axillary and inguinal freckling with two dermal neurofibromas diagnosed clinically, as well as Lisch nodules on bilateral ophthalmic examination, thus meeting the clinical criteria for the diagnosis of NF1. The clinical laboratory investigation showed elevated urinary metanephrine and normetanephrine levels. CT scan examination showed a 10 cm left adrenal cystic mass on abdominal CT. This mass uptake of the radioligand in metaiodobenzylguanidine (MIBG) scintigraphy without secondary extra-adrenal localization allowed the diagnosis of a seemingly benign cystic pheochromocytoma to be made. The patient was put on presurgical drug preparation with volume expansion and then underwent left unilateral adrenalectomy. The histopathological study was in favor of a rather aggressive cystic pheochromocytoma with a pheochromocytoma of the adrenal gland scaled (PASS) score of 9. Blood pressure and urine catecholamines at seven days, three months, six months, and one year after surgery were normalized. Cystic pheochromocytoma is a rare tumor with a potentially poor prognosis. It is characterized by a more insidious evolution and a larger volume at diagnosis. It should be considered a diagnosis in patients with a cystic adrenal mass or an extra-adrenal mass with fluctuating blood pressure during surgery. This case illustrates the importance of both presurgical preparation and screening for pheochromocytoma in neurofibromatosis type 1.

Clinical Significance of Pheochromocytoma Size on the Timing and Extent of Surgery.

INTRODUCTION: Elevated metanephrine and catecholamine levels 3-fold upper limit of normal (ULN) are diagnostic for pheochromocytoma. We sought to determine whether size correlates with biochemical activity or symptoms which could guide timing of surgery. METHODS: Data from consecutive patients undergoing adrenalectomy for pheochromocytoma at our institution over a 10-year period were retrospectively collected. These included maximal lesion diameter on preoperative imaging, plasma/urine metanephrine and/or catecholamine levels, demographic variables and presence of typical paroxysmal symptoms. Receiver operating characteristic curves were used to assess predictive accuracy. RESULTS: Sixty-three patients were included in the analysis (41 females and 22 males). Median age was 56 (43, 69) years. Due to various referring practices, 31 patients had documented 24-h urine metanephrine, 26 had 24-h urine catecholamine, and 52 had fractionated plasma metanephrine levels available for review. Values were converted to fold change compared to ULN and the maximum of all measured values was used for logistic regression. Median tumor size was 3.40 (2.25, 4.55) cm in greatest dimension. Tumor size at which pheochromocytoma produced > 3-fold ULN was ≥2.3 cm (AUC of 0.84). Biochemical activity increased with doubling tumor size (odds ratio = 8, P = 0.0004) or ≥ 1 cm increase in tumor size (odds ratio = 3.03, P = 0.001). 40 patients had paroxysmal symptoms, but there was no significant correlation between tumor size/biochemical activity and symptoms. CONCLUSIONS: In our study, tumor size directly correlated with the degree of biochemical activity and pheochromocytomas ≥2.3 cm produced levels 3 times ULN. These findings may allow clinicians to adjust timing of operative intervention.

[Personalized treatment of pheochromocytoma]. / Personalisierte Therapie des Phäochromozytoms.

BACKGROUND: Pheochromocytoma is a rare but severe disease of the adrenal glands. The aim of this study is to present and discuss recent developments in the diagnosis and treatment of pheochromocytoma. MATERIAL AND METHODS: A narrative review article based on the most recent literature is presented. RESULTS AND DISCUSSION: The proportion of pheochromocytomas as tumors of adrenal origin is about 5% of incidentally discovered adrenal tumors. The classical symptomatic triad of headaches, sweating, and palpitations occurs in only about 20% of patients, while almost all patients show at least 1 of these symptoms. To diagnose pheochromocytoma, levels of free plasma metanephrines or alternatively, fractionated metanephrines in a 24­h urine collection is required in a first step. In the second step an imaging procedure, computed tomography (CT) or magnetic resonance imaging (MRI), is performed to localize the adrenal tumor. Functional imaging is also recommended to preoperatively detect potential metastases. Genetic testing should always be offered during the course of treatment as 30-40% of pheochromocytomas are associated with genetic mutations. The dogma of preoperative alpha blockade is increasingly being questioned and has been controversially discussed in recent years. Minimally invasive removal of the adrenal tumor is the standard surgical procedure to cure patients with pheochromocytoma. The transabdominal and retroperitoneal laparoscopic approaches are considered equivalent. The choice of the minimally invasive procedure depends on the expertise and experience of the surgeon and should be tailored accordingly. Individualized and regular follow-up care is important after surgery.

False-positive results for pheochromocytoma associated with norepinephrine reuptake blockade.

Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a problem, particularly in patients taking norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and methoxytyramine in 61 patients taking norepinephrine reuptake blockers (tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors) and 17 others taking selective serotonin reuptake inhibitors, all without pheochromocytoma/paraganglioma. We highlight a singular case with strongly elevated plasma normetanephrine and methoxytyramine concentrations associated with norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without tumors. Plasma normetanephrine was 40% higher (P < 0.0001) in patients on norepinephrine reuptake blockers and methoxytyramine was 127% higher (P = 0.0062) in patients taking tricyclic antidepressants compared to patients not taking uptake blockers and without tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for normetanephrine and from 0.9% to 28.6% for methoxytyramine. Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma normetanephrine and methoxytyramine were elevated more than six times above upper reference limits. A pheochromocytoma/paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of norepinephrine reuptake blockers. These findings clarify that norepinephrine reuptake blockers usually result in mild elevations of normetanephrine and methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in normetanephrine and methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the norepinephrine reuptake blockade.

Malignant Pheochromocytoma With Intravascular Extension to the Heart.

Background: Malignant pheochromocytomas are rare and aggressive tumors that arise from the adrenal medulla and secrete catecholamines. Patients exhibit episodic symptoms of hypertension, headaches, sweating, and palpitations. The diagnosis is supported by elevated levels of urinary metanephrines, and imaging is used to determine the stage. Treatment involves surgical resection when possible. Case Report: A 57-year-old male presented with hematemesis and melena, and endoscopy revealed upper gastrointestinal bleeding. Imaging showed a malignant pheochromocytoma that had infiltrated the upper lobe of the right kidney and the right lobe of the liver, with a tumor thrombus extending into the hepatic inferior vena cava, the right atrium, and the right ventricle. The patient denied surgery and was treated with palliative medical therapy until he died 3 months later. Conclusion: Although rare, malignant pheochromocytomas may present with upper gastrointestinal bleeding. While metastasis to the liver is a typical manifestation of malignant pheochromocytomas, invasion of the inferior vena cava with infiltration to the right ventricle resulting in tricuspid valve malfunction is a rare finding.

Comparison of Perioperative Outcomes Between Laparoscopic and Robot-Assisted Adrenalectomy for Large Pheochromocytoma (≥ 5cm): A Retrospective Study.

Purpose: The objective of this study was to compare perioperative outcomes in patients with large (≥5cm) pheochromocytomas who underwent adrenalectomy. Patients and Methods: We retrospectively reviewed patients who underwent laparoscopic adrenalectomy (LA) and robot-assisted adrenalectomy (RA) for large pheochromocytoma (≥ 5cm) at our center between January 2015 to February 2023. We compared the perioperative outcomes between the two groups and investigated impact of high Nor-Metanephrine (NMN) levels on perioperative outcomes by analyzing this subgroup. Results: A total of 115 patients were included in the study, with 48 patients in the robotic group and 67 patients in the laparoscopic group. The following significant difference were identified in favor of RA: shorter operative (excluding docking time) time (190.0 vs 220.0 min, p=0.002), lower estimated blood loss (50.0 vs 120.0 mL, p=0.013), however, RA group has higher surgical expenses (37933.0 vs 7936.0 CNY, p< 0.001). This finding remained consistent when analyzing patients with high NMN levels. Conclusion: Patients with large pheochromocytoma may experience reduced blood loss and shorter operative time when undergoing robot-assisted adrenalectomy. However, it is important to note that the RA approach is associated with significantly higher costs.

Treatment of recurrent hunting-associated respiratory distress episodes in 2 dogs.

Noncardiogenic pulmonary edema (NCPE) in hunting dogs is an uncommon and poorly described condition for which no preventive treatment is available. Two dogs were presented for recurrent respiratory distress strictly associated with hunting activities. Diagnosis was based on bilateral, symmetrical, interstitial-to-alveolar pattern in the caudodorsal lung fields on thoracic radiographs, exclusion of other causes, and spontaneous clinical and radiographic improvement. Considering that the pathogenesis of exercise-induced NCPE likely involves α- and ß-adrenergic overstimulation, treatment with sympathetic blockers was used in both dogs. The first dog no longer showed respiratory signs during hunting activities. However, treatment failed to prevent respiratory distress in the other dog. Based on the large number of red blood cells in the bronchoalveolar lavage fluid of the second dog, exercise-induced pulmonary hemorrhage was suspected, as described in racing horses. The loop diuretic furosemide successfully prevented further hunting-associated respiratory distress episodes in this dog.

A Sizeable Adrenal Ganglioneuroma: A Case Report.

Adrenal ganglioneuromas are mostly asymptomatic, although they may manifest with compressive local effects. We present a 27-year-old man with no medical history who was referred to the surgical oncology clinic due to the incidental finding of a left adrenal mass. The initial computed tomography (CT) abdomen revealed a large mass causing displacement of adjacent organs. A CT-guided biopsy was inconclusive, and further evaluation with an NM endo-adrenal (MIBG) medullary scan pointed to a possible diagnosis of pheochromocytoma. Laboratory tests showed normal levels of urinary metanephrine and normetanephrine. The patient's history revealed chronic abdominal pain, with no symptoms of hypertension, headache, palpitations, or sweating. Subsequently, the patient underwent a left adrenalectomy without complications. This case underscores the importance of a comprehensive approach in managing adrenal masses, particularly when dealing with non-specific symptoms, emphasizing the importance of timely diagnosis and appropriate treatment.

Adrenal adenoma associated with raised metanephrine level: A case report.

INTRODUCTION AND IMPORTANCE: Adrenal adenomas are benign neoplasms of the adrenal cortex which can be functional or non-functional. The functional tumors manifest as Cushing syndrome. Rarely, they are associated with high levels of metanephrine due to pheochromocytoma. Here, we report an extremely rare case of adrenal adenoma associated with raised metanephrine, but no histopathological evidence of medullary changes. CASE PRESENTATION: A 30-year female with diabetes, hypothyroidism, and hypertension was admitted for resistant hypertension, severe refractory hypokalemia, decreased sleep, fearfulness, anxiety, and palpitation. Facial puffiness, ecchymoses on upper and lower limbs, and bilateral pedal edema were present. Laboratory investigation revealed raised 24-hour-urine cortisol (52.5 µmol/dL) and metanephrine (56.00 µmol/24 h), very low ACTH (<5.0 pg/mL), and negative dexamethasone suppression test. MRI brain findings were normal. CT scan of the abdomen revealed a well-defined soft tissue lesion in the right adrenal gland and diffuse osteopenia vertebrae. Hence, diagnosis of Cushing Syndrome secondary to adrenal adenoma, and pheochromocytoma was made, and laparoscopic adrenalectomy was done under pheochromocytoma protocol. The patient improved dramatically, thereafter. Histopathological findings showed adrenocortical adenoma only; no evidence of pheochromocytoma was found. CLINICAL DISCUSSION: We came across many articles reporting adrenal adenoma associated with high levels of metanephrine due to co-existing pheochromocytomas either in the ipsilateral or contralateral adrenal gland. But, in our case, the adrenal adenoma was associated with high metanephrine levels with no histopathologic features of pheochromocytoma. CONCLUSION: Cushing syndrome due to Cortisol secreting Adrenal adenoma can be associated with biochemical and clinical features suggestive of Pheochromocytoma which could resolve after adrenalectomy.

The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management

ABSTRACT Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.

Resection of a hormonally active carotid body tumor.

Treatment of carotid body tumors (CBTs) can be complicated by the presence of hormonal activity. This case describes the treatment of a 65-year-old woman that presented with an abnormally high blood pressure and was found to have a neck mass. Diagnostic imaging along with urine metanephrines revealed this mass to be a hormonally active CBT. Careful resection along with preoperative treatment with an alpha blockade allowed for a successful complete removal of the tumor without any complications. Although CBTs tend to be benign, and hormonally active tumors are rare, one must always maintain a level of suspicion of hormonal activity to prevent catastrophic operative events.

The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management.

Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.

[Resistant hypertension - pheochromocytoma].

We report a case of a man with a 30-year history of treatment-resistant hypertension, hydropoiesis, tachycardic spells and dysgeusia. Despite repeated visits to the emergency department and work-up in an out-patient clinic, the diagnosis was unknown. Three years prior to remittance to an endocrinologist, the hypertension worsened, and he developed diabetes type-II. Further work-up revealed a 3 cm extra-adrenal pheochromocytoma, a paraganglioma. After surgical removal of the tumor, he is without medication and symptom free. Pheochromocytoma and paraganglioma are rare causes of hypertension, estimated to explain 0.1-0.6% of all cases, but nonetheless an important diagnosis to make, due to serious side effects.

Erratum: Low number of neurosecretory vesicles in neuroblastoma impairs massive catecholamine release and prevents hypertension.

[This corrects the article DOI: 10.3389/fendo.2022.1027856.].

Prevalence of Cortisol Cosecretion in Patients With Primary Aldosteronism: Role of Metanephrine in Adrenal Vein Sampling.

CONTEXT: Adrenal venous sampling (AVS) is the gold standard procedure for subtype diagnosis in patients with primary aldosteronism (PA). Cortisol is usually adopted for the normalization of aldosterone levels in peripheral and adrenal samples. However, asymmetrical cortisol secretion can potentially affect the lateralization index, leading to subtype misdiagnosis. OBJECTIVE: We aimed to assess the prevalence of asymmetrical cortisol secretion in patients undergoing AVS and whether variations in adrenal vein cortisol might influence AVS interpretations. We then evaluated the use of metanephrines for the normalization of aldosterone levels for lateralization index. METHODS: We retrospectively included 101 patients with PA who underwent AVS: 49 patients underwent unstimulated AVS, while 52 patients underwent both unstimulated and cosyntropin-stimulated AVS. Eighty-eight patients had bilateral successful AVS according to metanephrine ratio. We assessed the prevalence of asymmetrical cortisol secretion through the cortisol to metanephrine (C/M) lateralization index (LI). We then evaluated whether the use of aldosterone to metanephrine (A/M) LI can improve the diagnostic accuracy of AVS compared with aldosterone to cortisol (A/C) LI. RESULTS: Asymmetrical cortisol secretion is present in 18% of patients with PA. Diagnosis with A/M LI and A/C LI is discordant in 14% of patients: 9% had a diagnosis of unilateral PA with A/M LI instead of bilateral PA with A/C LI and 5% had a diagnosis of bilateral PA with A/M LI instead of unilateral PA. CONCLUSION: The assessment of metanephrine levels in AVS is useful for the determination of selectivity and lateralization, allowing an accurate diagnosis, especially in patients with asymmetrical cortisol secretion.

DESI-MSI-based technique to unravel spatial distribution of COMT inhibitor Tolcapone.

Ascertaining compound exposure and its spatial distribution are essential steps in the drug development process. Desorption electrospray ionization mass spectrometry (DESI-MSI) is a label-free imaging technique capable of simultaneously identify and visualize the distribution of a diverse range of biomolecules. In this study, DESI-MSI was employed to investigate spatial distribution of tolcapone in rat liver and brain coronal - frontal and striatal -sections after a single oral administration of 100 mg/Kg of tolcapone, brain-penetrant compound. Tolcapone was evenly distributed in liver tissue sections whereas in the brain it showed differential distribution across brain regions analyzed, being mainly located in the olfactory bulb, basal forebrain region, striatum, and pre-frontal cortex (PFC; cingulate, prelimbic and infralimbic area). Tolcapone concentration in tissues was compared using DESI-MSI and liquid-chromatography mass spectrometry (LC-MS/MS). DESI-MSI technique showed a higher specificity on detecting tolcapone in liver sections while in the brain samples DESI-MSI did not allow a feasible quantification. Indeed, DESI-MSI is a qualitative technique that allows to observe heterogeneity on distribution but more challenging regarding accurate measurements. Overall, tolcapone was successfully localized in liver and brain tissue sections using DESI-MSI, highlighting the added value that this technique could provide in assisting tissue-specific drug distribution studies.

Clinical, imaging and biochemical presentation of cystic pheochromocytomas.

OBJECTIVE: Cystic adrenal mass is a rare imaging presentation of pheochromocytoma. We aimed to describe the clinical, biochemical and imaging characteristics of patients with cystic pheochromocytoma. DESIGN: Single-centre, retrospective study, 2000-2020. PATIENTS: Consecutive patients with cystic pheochromocytoma were identified from our institutional pathology and adrenal tumour database. RESULTS: Of the 638 patients with pheochromocytomas, 21 (3.2%) had cystic pheochromocytomas (median age: 57 years, 57% women). Most pheochromocytomas were discovered incidentally (57%) or due to symptoms of catecholamine excess (24%). The median tumour size was 6.4 cm. On imaging, cystic pheochromocytomas were round or oval (90%), heterogeneous lesions (86%) with a thick solid rim (median rim thickness 13.9 mm, unenhanced computed tomography (CT) attenuation 40 Hounsfield units (HU), venous-phase CT attenuation 83 HU), and a median cystic component of 40% (unenhanced CT attenuation 17.6 HU, venous-phase CT attenuation 20.4 HU), and rarely with calcifications (15%). All 20 patients with biochemical testing had functioning tumours (adrenergic in 80%, noradrenergic in 20%). Total urinary metanephrine excretion correlated with the volume of the solid component (R2 = .75, p < .0001) but not the cystic component (R2 = .04, p = .4386). All patients underwent adrenalectomy (48% laparoscopic, 52% open), and the median duration of hospital stay was 4 days. CONCLUSIONS: Cystic pheochromocytomas are rare, large tumours with a phenotypic appearance that can masquerade as other adrenal cystic lesions. The degree of biochemical abnormality in cystic pheochromocytomas is associated with the volume of the solid component. All patients with adrenal cysts that have a solid component or an unenhanced attenuation >10 HU should undergo biochemical testing for pheochromocytoma.

Low number of neurosecretory vesicles in neuroblastoma impairs massive catecholamine release and prevents hypertension.

Introduction: Neuroblastoma (NB) is a pediatric cancer of the developing sympathetic nervous system. It produces and releases metanephrines, which are used as biomarkers for diagnosis in plasma and urine. However, plasma catecholamine concentrations remain generally normal in children with NB. Thus, unlike pheochromocytoma and paraganglioma (PHEO/PGL), two other non-epithelial neuroendocrine tumors, hypertension is not part of the usual clinical picture of patients with NB. This suggests that the mode of production and secretion of catecholamines and metanephrines in NB is different from that in PHEO/PGL, but little is known about these discrepancies. Here we aim to provide a detailed comparison of the biosynthesis, metabolism and storage of catecholamines and metanephrines between patients with NB and PHEO. Method: Catecholamines and metanephrines were quantified in NB and PHEO/PGL patients from plasma and tumor tissues by ultra-high pressure liquid chromatography tandem mass spectrometry. Electron microscopy was used to quantify neurosecretory vesicles within cells derived from PHEO tumor biopsies, NB-PDX and NB cell lines. Chromaffin markers were detected by qPCR, IHC and/or immunoblotting. Results: Plasma levels of metanephrines were comparable between NB and PHEO patients, while catecholamines were 3.5-fold lower in NB vs PHEO affected individuals. However, we observed that intratumoral concentrations of metanephrines and catecholamines measured in NB were several orders of magnitude lower than in PHEO. Cellular and molecular analyses revealed that NB cell lines, primary cells dissociated from human tumor biopsies as well as cells from patient-derived xenograft tumors (NB-PDX) stored a very low amount of intracellular catecholamines, and contained only rare neurosecretory vesicles relative to PHEO cells. In addition, primary NB expressed reduced levels of numerous chromaffin markers, as compared to PHEO/PGL, except catechol O-methyltransferase and monoamine oxidase A. Furthermore, functional assays through induction of chromaffin differentiation of the IMR32 NB cell line with Bt2cAMP led to an increase of neurosecretory vesicles able to secrete catecholamines after KCl or nicotine stimulation. Conclusion: The low amount of neurosecretory vesicles in NB cytoplasm prevents catecholamine storage and lead to their rapid transformation by catechol O-methyltransferase into metanephrines that diffuse in blood. Hence, in contrast to PHEO/PGL, catecholamines are not secreted massively in the blood, which explains why systemic hypertension is not observed in most patients with NB.

Preoperative Factors Associated with Intraoperative Maximum Arterial Pressures in Patients with Pheochromocytoma and Paraganglioma.

Background: Surgery for pheochromocytoma and paraganglioma (PPGL) can lead to life-threatening complications, such as intraoperative hypertensive crises, even when adequate doses of preoperative α-receptor blockades are administered. Objectives: The aim of this study was to identify preoperative factors associated with intraoperative maximum arterial pressure (AP) in patients with PPGL. Methods: We retrospectively reviewed the cases of 61 PPGL patients who underwent surgical resection in our hospital between 2006 and 2020. The primary outcome was intraoperative maximum AP as a single index for continuous variables. Simple and multiple linear regression model were used for statistical analysis. Results: The median maximum systolic AP during surgery was 165 mmHg (interquartile range: 150 - 180 mmHg). Log24-h urinary-fractionated metanephrine (MN) and normetanephrine (NMN) was correlated with intraoperative maximum AP (R-squared = 0.218, P < 0.001). Multiple regression analyses showed that diabetes mellitus, one or more of the classic triad, and log24-h urinary-fractionated MN and NMN were independent factors associated with intraoperative maximum AP. Conclusions: Patients with PPGL accompanied by diabetes mellitus, one or more of the classic triad, and high log 24-h urinary-fractionated MN and NMN values may be at risk for hypertensive crises during surgery regardless of whether preoperative α-receptor blockades are used. Clinicians should manage these patients more carefully and effectively.

Metanephrine and normetanephrine associated with subclinical myocardial injuries in pheochromocytoma and paraganglioma.

Objective: To analyze the correlation between metanephrine and normetanephrines (MNs) and subclinical myocardial injuries (SMI) diagnosed by low left ventricular global longitudinal strain (LV GLS) in patients with pheochromocytoma and paraganglioma (PPGL). Methods: Seventy-six patients who underwent surgery for pheochromocytoma or paraganglioma from September 2017 to April 2022 were examined. All the patients enrolled had normal left ventricular ejection fraction (LVEF) and myocardial injury biomarkers including cardiac troponin I and B-natriuretic peptide. Univariate analysis and multivariate analysis were performed to evaluate the association of MNs and subclinical myocardial injury (SMI)(defined as LV GLS<18). Results: LV GLS of 13(17.11%) PPGL patients was less than 18. The percentage of patients with elevation of single hormone (metanephrine, normetanephrine, 3-methoxytyramine) or any one of MNs was not significantly correlated with SMI (P=0.987, 0.666, 0.128 and 0.918, respectively). All MNs elevation was associated with SMI (OR: 11.27; 95% CI, 0.94-135.24; P= 0.056). After adjusting for age, All MNs elevation was significantly correlated with SMI (OR: 16.54; 95% CI, 1.22-223.62; P= 0.035). Conclusion: MNs might be an important factor influencing myocardial function. All MNs elevation might indicate SMI. If all MNs elevated, LV GLS measurement was recommended for PPGL patients to detect SMI in the absence of decrease LVEF or other heart disease in clinical practice.