Plasma Metanephrines Research Articles

FRI264 A Case Of Composite Pheochromocytoma And Ganglioneuroma

Abstract Disclosure: D. He: None. J. Pullman: None. S. Stefan: None. B.Y. Wong: None. Background: Pheochromocytomas are catecholamine-secreting tumors that arise from chromaffin cells in the adrenal medulla or paraganglia. Representing 1-9% of pheochromocytomas, composite pheochromocytomas are rare tumors composed of pheochromocytoma and neural tumor components such as neuroblastoma, ganglioneuroblastoma, ganglioneuroma or peripheral nerve sheath tumor1. We present a case of composite pheochromocytoma and ganglioneuroma. Clinical Case: A 69-year-old man presented with recurrent dyspnea at rest, diaphoresis and tachycardia. He was diagnosed with heart failure with reduced ejection fraction and management included metoprolol 50 mg daily. On work-up, he was incidentally found to have a 1.2 cm left upper lobe lung lesion and an indeterminate 2.4 cm right adrenal mass on CTA chest. PET/CT scan showed an intensely avid left upper lobe lung nodule and a right adrenal mass with mild FDG uptake (SUV max 3.8). MRI abdomen demonstrated a 3.1 cm right adrenal lesion with a mildly thickened enhancing rim and a central enhancing nodular component suspicious for pheochromocytoma, metastases, schwannoma or ganglioneuroma. He then had a stroke with mild residual right-sided weakness. Oncological work-up of his lung and adrenal lesions eventually directed tissue sampling to biopsy of the adrenal lesion and pathology was consistent with pheochromocytoma. Subsequent biochemical evaluation revealed elevated plasma metanephrines of 194 pg/mL (<= 57 pg/mL), plasma normetanephrines of 474 pg/mL (<= 148 pg/mL), 24-hour urine metanephrines of 389 mcg (90-315 mcg) and 24-hour urine normetanephrines of 428 mcg (122-676 mcg). Pre-operatively, he was placed on phenoxybenazmine 10 mg twice daily and metoprolol 62.5 mg every 8 hours. The patient then underwent right adrenalectomy. The tumor nodule was adherent to and dissected off the inferior vena cava. Pathology showed composite pheochromocytoma with a small component of ganglioneuroma. Conclusion: This rare case of a composite pheochromocytoma with ganglioneuroma was diagnosed through histopathology as composite pheochromocytomas are clinically and radiographically indistinguishable from pheochromocytomas1. Management of composite pheochromocytomas with ganglioneuroma is similar to the management of pheochromocytomas, and surgical resection remains the first line treatment. Combined alpha and beta-adrenergic blockade is recommended to prevent intraoperative hypertensive crisis. However, more studies are needed to further understand these rare composite pheochromocytomas.

SAT314 Bilateral Sporadic Carotid Paraganglioma As A Rare Cause Of Syncope

Abstract Disclosure: A.G. Olafimihan: None. U.A. Ogar: None. I. Asemota: None. E. Krishnaraju: None. A. Okafor: None. Introduction: Carotid body tumors (CBT) are rare, mostly non-secretory skull-based neuroendocrine tumors originating from the parasympathetic ganglia. They are the most common (60%) paragangliomas of the head and neck. Bilaterality is seen in 5% of patients with sporadic CBT. CBT mainly presents as an asymptomatic neck mass. Seldomly, it compresses the carotid sinus, inducing bradycardia and hypotension, and presenting with recurrent syncope. Case presentation: A 70-year-old Eritrean woman visiting the US with a history of myasthenia gravis status post thymectomy on pyridostigmine presented following an episode of presyncope with five similar episodes in the past year. She described it as sudden onset lightheadedness that resolves with sitting and sometimes results in syncope. She had no palpitations, headaches, or sweating.Her admitting vital signs were significant for bradycardia (48bpm) with hypotension (112/54mmhg). A physical exam revealed mobile, mildly tender, palpable neck masses bilaterally, with reproducible worsening bradycardia on palpation of the masses. ECG was unremarkable except for sinus bradycardia. A CT angiogram head and neck with contrast showed multiple hyper-enhancing lesions (two on the right, one on the left; largest = 1.6 x 1.0 cm) at the junction of bilateral carotid bulbs suggestive of multiple paragangliomas. An MRI of the neck re-demonstrated these lesions with the classical ‘salt and pepper’ appearance. CT of the brain, chest, abdomen and pelvis were negative for metastatic lesions. Biochemical testing including plasma metanephrines, catecholamines and dopamine levels was normal, suggesting nonfunctional tumors. Genetic testing was negative for mutations associated with paragangliomas. She did not have more episodes during her three-day admission but remained bradycardic with uneventful telemetry. She was counseled to avoid sudden neck movement and neck pressure. She was discharged with multidisciplinary (endocrinology, neurology, vascular surgery, and ENT surgery) outpatient follow-up. Over the five months post-discharge, she had only two mild symptomatic episodes. Following multi-specialist deliberations at the tumor board, including a risk-benefit assessment of a surgical excision, and extensive discussions with our patient and her family, the decision to hold off surgery was made. Surgical intervention was associated with possible vagal nerve injury, and high aspiration risk given her comorbid myasthenia gravis. Her conservative management plan included a cardiology work-up for symptom-directed therapy with a pacemaker placement. Conclusion: Recurrent syncope is an uncommon presentation of carotid body tumors requiring workup to rule out functionality, genetic mutations, and metastases. Management involves a multi-disciplinary approach and individual risk-benefit assessment of treatment options. Presentation: Saturday, June 17, 2023

Relapse of Pheochromocytoma with Hipertensive Heart Disease Mildly Reduced Left Ventricle Ejection Fraction

Pheochromocytoma is a tumor originating from the medulla of the adrenal gland. This tumor is rare and is caused by excessive production of catecholamines. There are three classic triads of pheochromocytoma: diaphoresis, palpitations and headaches. Elevated metanephrines and normetanephrine in plasma or urine confirm the diagnosis. At the same time, radiological examination helps in the tumor's location and the presence of local invasion or metastasis. Hypertension is a health problem that is quite dangerous worldwide because it is a significant risk factor for cardiovascular diseases such as heart attack, heart failure, stroke, and kidney disease. Hypertension can cause Hypertensive Heart Disease, which is a significant cause of morbidity and mortality due to cardiovascular disease. This scientific report presents a case study of a 19-year-old woman diagnosed with relapsed pheochromocytoma and hypertensive heart disease with mildly reduced left ventricular ejection fraction. This patient was previously diagnosed at the age of 13 with pheochromocytoma, where the patient experienced symptoms of headache, sweating, especially in the forehead area, trembling hands, and hypertension. Hence, the patient had to be treated. The patient underwent further examination and found a right adrenal tumor, so an adrenalectomy was performed on the patient. Similar complaints appeared again in the patient, and further examination was carried out. Moreover, an increase in plasma metanephrine and normetanephrine levels was found. A CT scan of the abdomen revealed a right adrenal tumor, so this patient underwent another adrenalectomy.

Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL). To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients. Patients undergoing polysomnography for suspected OSA were recruited. Plasma free and 24-hour urinary metanephrines were measured by HPLC-MS/MS. Patients with elevated levels had repeat measurements, abdominal imaging, and follow-up to diagnose or exclude a PPGL. Seventy-six patients completed polysomnography and biochemical testing; 68 (89.5%) patients had OSA, of whom 19 (27.9%) had elevated plasma and/or urinary metanephrines. On follow-up, one patient had a bladder paraganglioma, while PPGL was excluded in the remaining patients. OSA patients had more false-positive urinary metanephrines (17 of 67, 25.4%) than plasma metanephrines (2 of 67, 3.0%), P < .01, and this was more common in severe OSA (13 of 34, 38.2%), compared to moderate/mild OSA (4 of 33, 12.1%), P < .01. Both plasma and urinary metanephrines decreased after treatment with continuous positive airway pressure. On multivariable analysis, severe OSA, obesity, and family history of hypertension were positive predictors for false-positive urinary metanephrines in patients with suspected OSA. In OSA patients, plasma metanephrines are less likely to yield false-positive results for the diagnosis of PPGL than 24-hour urinary metanephrines. In patients with suspected OSA, obesity, or a family history of hypertension, plasma metanephrines may be the preferred first-line test to avoid unnecessary anxiety or follow-up.

The Role of Chromogranin A Assay in the Diagnosis of Pheochromocytomas

Background: Pheochromocytomas (Pheo) are rare neuroendocrine tumors with a suggestive clinical picture, characterized by hypersecretion of catecholamines and other neuroendocrine biomarkers. Methods: The purpose of the study was to analyze the diagnostic features of Pheo and investigate the role played by different neuroendocrine and hormonal markers in diagnosing Pheo.The retrospective study involved a group of 69 patients diagnosed and treated with Pheo, who had both urinary and plasma catecholamines and neuroendocrine markers measured pre- and postoperatively. Results: After comparing pre- and postoperative hormonal parameters and neuroendocrine biomarker changes, numerous statistically significant findings were found. The analysis of the relationships between chromogranin A (CgA) levels, plasma and urine metanephrines, and normetanephrine and Pheo tumor size was included in the study. Additionally, we evaluated Cg A's diagnostic efficacy in comparison to plasma metanephrines, normetanephrine, and neuron-specific enolase (NSE) for Pheo. Conclusions: We obtained statistically significant data on pre- and postoperative differences for plasma and urinary catecholamines, CgA and NSE. Pheo tumor size is interdependent with serum levels of Cg A, plasma and urinary metanephrines, and normetanephrine. The best diagnostic power for Pheo was plasma normetanephrine, followed by plasma metanephrines and CgA.

Pheochromocytomas Most Commonly Present As Adrenal Incidentalomas: A Large Tertiary Center Experience.

Pheochromocytomas are increasingly diagnosed in incidentally detected adrenal masses. However, the characteristics of incidental pheochromocytomas are unclear. We aimed to assess the proportion and clinical, biochemical, radiological, genetic, histopathological, and follow-up characteristics of incidental pheochromocytomas. A retrospective review was conducted of patients with pheochromocytoma seen between January 2010 and October 2022 at a large UK tertiary care center. The diagnosis was confirmed histologically or by the combined presence of increased plasma and/or urinary metanephrines (MN), indeterminate adrenal mass on cross-sectional imaging, and metaiodobenzylguanidine avidity. We identified 167 patients with pheochromocytoma; 144 (86.2%) underwent adrenalectomy, for 23 (13.8%) surgery was either awaited, deemed unsuitable due to frailty or other metastatic malignancy, or declined by the patients. Excluding pheochromocytomas diagnosed via screening genetically predisposed individuals (N = 20), 37 of 132 (28.0%) presented with adrenergic symptoms and/or uncontrolled hypertension, while 91 of 132 (69.0%) patients presented with an incidentally detected adrenal mass. Incidentally detected patients were older (median age 62 years) than those detected due to clinical suspicion (aged 42 years) or after genetic screening (aged 33 years) (all P < .05). Incidentally detected pheochromocytomas were smaller (median 42 mm) than tumors detected due to adrenergic symptoms/uncontrolled hypertension (60 mm), but larger than tumors identified by genetic screening (30 mm) (all P < .05). Increased MN excretion showed a similar pattern (symptomatic/uncontrolled hypertension > incidental > genetic screening) (all P < .05). Hereditary predisposition was detected in 20.4% of patients (incidental, 15.3%; symptomatic/uncontrolled hypertension, 42.9%). The majority of pheochromocytomas are diagnosed incidentally and have distinct clinical, radiological, biochemical, and genetic features. Their detection at older age but smaller size may point to a different underlying tumor biology.

A clinical case of drug-induced arterial hypertension caused by glycyrrhizic acid

Background: In clinical practice, drug-induced arterial hypertension (AH) often remains undiagnosed, since the identification of an ethical disease in this form of AH avoids the initiation of antihypertensive therapy. A critical part in the differential diagnosis of hypertension and planning of long-term strategies for managing a patient requires a thorough study of the properties of the drugs taken and the pathophysiological mechanisms that depend on the increase in high blood pressure against the background of taking one or another substance. Clinical case description: Assumption of pregnancy in a random 57-year-old Caucasian female patient with AH syndrome and history of AD crisis during the year. Against the background of two-component antihypertensive therapy, indapamide 2.5 mg + telmisartan 80 mg, increased blood pressure. From the anamnesis of life, it is noteworthy that the patient should keep records with a hepatologist; with a diagnosis of chronic viral hepatitis C with moderate activity, she takes Phosphogliv. Physical examination confirmed the presence of grade 2 hypertension; no signs of target organ detection were found. Laboratory and instrumental research showed cytolytic syndrome of minimal activity (AST, 74.8 U/l; ALT, 60.5 U/l), hypokalemia (K+ 2.1 mmol/l), unknown etiology, aldosterone within the normal range, metanephrine (80.4 pg/ml at a rate of 64 pg/ml), and normetanephrine (276 pg/ml at a rate of 176 pg/ml) in blood plasma are increased. MSCT of the kidneys and adrenal glands revealed no enlarged formations. Drug-induced arterial hypertension was clinically diagnosed. Concomitant diseases: Chronic viral hepatitis C, moderate activity. Varicose veins, venous infection of the extremities. Dynamics and outcome. After the abolition of glycyrrhizic acid, blood pressure and potassium levels in the blood plasma returned to normal, which is not recommended to take antihypertensive drugs. Conclusion: An exceptional clinical situation is a pronounced manifestation of a rare side effect of glycyrrhizic acid in the form of drug-induced hypertension.

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors.

Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are non-functioning adrenocortical adenomas, but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and updated systematic reviews on four predefined clinical questions crucial for the management of incidentalomas: A) How to assess risk of malignancy? ; B) How to define and manage mild autonomous cortisol secretion? ; C) Who should have surgical treatment and how should it be performed? ; D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: 1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with HU ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. 2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/l (≤1.8 µg/dl)). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/l (>1.8 µg/dl) harbor increased risk of morbidity and mortality. For this condition, we propose the term 'mild autonomous cortisol secretion' (MACS). 3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (e.g. hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. 4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. 5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. 6) Surgery is not usually indicated in patients with an asymptomatic, non-functioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of non-operated patients, management of patients with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest ten important research questions for the future.

PARAGANGLIOMA AS CAUSE OF RESISTANT ARTERIAL HYPERTENSION: A CASE REPORT

Objective: Approximately 3%of patients with resistant arterial hypertension are diagnosed with pheochromocytoma. On other hand, paragangliomas of the head and neck are rare, representing &lt;0,5% of all head and neck tumors. They arise in a number of locations along the carotid sheath. Design and method: Herein, we present the case of a 66-year-old Caucasian woman (BMI 29,3 kg/m2) with resistant arterial hypertension (BP 160-170/100-110 mmHg while taking antihypertensive drugs: valsartan 320 mg/day, hydrochlorothiazide 25 mg/day, amlodipin 10 mg/day) and episodic headaches. Over the last 5 years prior to presentation, she had resistant hypertension and each year normal urinary metanephrine level and CT scan of the abdomen. Results: At the presentation a tumor (4,6x3,6x2,9 cm) was detected by ultrasound in the left submandibular region and laboratory tests detected a normal plasma metanephrine level - 0,16 nmol/l (reference values &lt;0,36 nmol/l) and normal plasma 3-methoxytyramine level -&lt;0,06 nmol/l (reference values&lt;0,15 nmol/l) and increased plasma normetanephrine level - 3,25 nmol/l (reference values&lt;1,05 nmol/l. The tumor was surgically removed and a carotid paraganglioma was confirmed histologically. After surgery, patient's blood pressure is controlled (130/80 mmHg) by taking a fixed combination valsartan 80/hydrochlorothiazide 6,25 mg /day). Conclusions: Patients with resistant arterial hypertension should be screened for secondary hypertension, even if such screening has already been done in previous years.

ASSOCIATION OF PLASMA METANEPHRINES LEVELS WITH CARDIOMETABOLIC RISK IN ESSENTIAL HYPERTENSIVE INDIVIDUALS

Objective: The aim of the study was to evaluate a possible relationship between plasma metanephrine concentrations and some surrogate parameters of cardio-metabolic damage such as carotid intima media thickness (IMT), cardiac left ventricular mass (LVM) and left ventricular hypertrophy (LVH) in patients with essential hypertension (EH). Design and method: From January 2021 to September 2022, we consecutively enrolled 719 essential hypertensive patients (367 men and 352 women, mean age 52.2 ± 15 years) without cardiovascular complications, distinguishing patients in quartiles according to plasma metanephrine concentration (PMC). Results: compared with the first quartile, the highest PMC quartile was associated with the highest levels of of 24-h μalbuminuria (20.1 ± 8.9 mg/24 h and 11.4 ± 6.2 mg/24 h, p = 0.04), serum creatinine (0.96 ± 0.2 mg/dl vs 0.90 ± 0.22 mg/dl; p = 0.002), plasma calcium (9.5 ± 0.4 mg/dl vs 9.38 ± 0.4 mg/dl; p = 0.004) and a lower prevalence of metabolic syndrome (18% vs 32%; p = 0.001). More male hypertensives belonged to the fourth quartile than to the first quartile (64% vs 43%, p&lt;0.001). Moreover, we found that the fourth PMC quartile was associated with higher values of 24h-ABPM diastolic blood pressure (78.8 ± 9.0 mmHg vs 76.3 ± 9.1 mmHg; p = 0.007), higher values of left ventricular myocardial mass indexed for body surface area (LVMi) (89.0 ± 27.0 g/m2 vs 81.8 ± 21.9 g/m2; p = 0.01) and left ventricular hypertrophy (LVH) (18% vs 11%, p = 0.031) prevalence than the first PMC quartile. PMC was also found to be an independent predictor of the presence of LVH and μalbuminuria. Conclusions: Our results revealed that higher PMC values are strongly associated with increased LVMi and μalbuminuria that, together with elevated blood pressure values, are strictly correlated with higher risk of atherosclerosis and cardiovascular complications.

POST HOC ERGO PROPTER HOC? NOT EVERYTHING THAT HAPPENS AFTER COVID-19 IS LONG COVID. OR, THE MANY MASQUERADES OF PHEOCHROMOCYTOMA

Objective: A seemingly endless list of symptoms and conditions are being labeled as long COVID or post-COVID syndrome, but not everything that happens after a COVID-19 episode can be attributed to it. We hereby present a clinical case in which pheochromocytoma was masquerading as long COVID. Design and method: Review of the patient's clinical record and the relevant literature. Results: A previously healthy, non-smoker, 57-year-old woman was admitted in October 2020 with fever, dyspnea and asthenia. She was diagnosed with SARS-CoV-2 bilateral bronchopneumonia and required oxygen therapy but not assisted ventilation or intensive care. Three months after discharge the patient was asymptomatic but in the two following years she progressively developed symptoms of confusion, dizziness, inability to concentrate, gait instability, tachycardia, palpitations, anxiety and insomnia. The syndrome was labeled as post-COVID and in March 2022 began treatment with alprazolam and propranolol. Subsequently she complained of severe non-pulsatile holocranial headache accompanied by vertigo, nausea and skin pallor. In October 2022 she was admitted in Emergency Care with a BP reading of 226/118 mmHg, HR 132 bpm, ECG: sinus rhythm without repolarization anomalies. She was referred to our Outpatient Hypertension Clinic for workup of suspected secondary hypertension. Physical exam: BMI 27.3 kg/m2, BP 156/94 mmHg, FC 112 lpm, normal cardiopulmonary auscultation, no murmurs or oedema. Lab: Plasma glucose, ionogram, lipid profile, blood count, free T4, TSH, aldosterone, renin, ARR, NT-pro-BNP: normal, metanephrines 876/1238 pg/mL, albuminuria 56 mg/g Cr. Echocardiography: slight LVH (13 mm septum and posterior wall) with preserved function. Abdominal CT: Left adrenal mass, 54 mm, hyperdense, heterogeneous. MIBG scintigraphy: hyperintense left adrenal uptake without additional anomalies. After standard presurgical conditioning the patient underwent laparoscopic adrenalectomy, uneventfully. Pheochromocytoma was pathologically confirmed, without suggestion of malignancy (Ki-67 &lt;2%). Three months afterwards the patient is normotensive and asymptomatic without medication, with normal plasma metanephrines. Conclusions: The clinical presentation of pheochromocytoma may be atypical and sometimes bizarre. Sustained hypertension may be absent, but the paradoxical hypertensive response to beta-adrenergic blockade is highly suggestive. Anyhow, a ‘post-COVID syndrome’ label may be masking unrelated and solvable serious diseases.

CHANGES IN BLOOD COUNT INDUCED BY DOXAZOSIN TREATMENT IN SUBJECTS WITH PHEOCHROMOCYTOMA

Objective: Not only pre-treatment with with alfa-receptor antagonists and high-sodium diet, but also intravenous fluid administration immediately before surgery are recommended to minimalize per- and postoperative complications in subjects with pheochromocytoma or paraganglioma (PPGL). Aim of this study was to search for changes in blood count induced by doxazosin. Design and method: We studied PPGL subjects treated with doxazosin before operation and approximately one year after tumor removal. We measured count of blood elements – leukocytes, erythrocytes, thrombocytes, and hemoglobin level before initiation of treatment with doxazosin, during the treatment, and after tumor removal. Diagnosis of PPGL was based on elevated levels of plasma metanephrines preoperatively and was confirmed by histopathology. Results: In this retrospective study, we included 40 subjects with PPGL (15 males and 25 females, 51.8±14 years). Average doxazosin dose was 3.4±1.6 mg and median of duration of doxazosin treatment was 41 (25; 55) days. Leukocyte count decreased from 8.5±2.8 G/L to 7±2 G/L (P&lt;0.001) after doxazosin treatment and to 6.5±1.6 G/L/l (P&lt;0.001 vs. preoperatively) after surgery. Erythrocyte count decreased from 4.7±0.5 T/L to 4.3±0.5 T/L after doxazosin treatment (P = 0.01) and returned back after surgery: 4.6±0.3 T/L (P = 0.04 vs. after doxazosin). Similar results were found for hemoglobin levels: decrease from 140±15 g/L to 130±16 g/L (P&lt;0.001) after doxazosin and increase after surgery to 140±14 g/L (P&lt;0.001 vs. after doxazosin), and for hematocrit values: decrease from 0.42±0.04 to 0.39±0.04 (P&lt;0.001) after doxazosin and increase after surgery to 0.41±0.05 (P&lt;0.001). Platelets decreased significantly from 296±75 G/L to 263±78 G/L (P&lt;0.001) after doxazosin and to 239±63 G/L after tumor removal (P = 0.02 vs. after doxazosin). Conclusions: These data show that doxazosin pretreatment before surgery was accompanied with a significant decrease in red blood cell count, and hemoglobin level and hematocrit compared to values before initiation of doxazosin treatment and after surgery (the highest decrease of hemoglobin value after doxazosin was almost 30 g/l). We conclude that routine fluid administration before PPGL surgery is not supported by presented data.

Plasma-Metanephrines in Patients with Autoimmune Addison's Disease with and without Residual Adrenocortical Function.

Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison's disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin. We included 50 patients with verified RAF and 20 patients without RAF who served as controls upon cosyntropin stimulation testing. The patients had abstained from glucocorticoid and fludrocortisone replacement > 18 and 24 h, respectively, prior to morning blood sampling. The samples were obtained before and 30 and 60 min after cosyntropin stimulation and analyzed for serum cortisol, plasma metanephrine (MN), and normetanephrine (NMN) by liquid-chromatography tandem-mass pectrometry (LC-MS/MS). Among the 70 patients with AAD, MN was detectable in 33%, 25%, and 26% at baseline, 30 min, and 60 min after cosyntropin stimulation, respectively. Patients with RAF were more likely to have detectable MN at baseline (p = 0.035) and at the time of 60 min (p = 0.048) compared to patients without RAF. There was a positive correlation between detectable MN and the level of cortisol at all time points (p = 0.02, p = 0.04, p < 0.001). No difference was noted for NMN levels, which remained within the normal reference ranges. Even very small amounts of endogenous cortisol production affect MN levels in patients with AAD.

Plasma and urinary metanephrine and normetanephrine concentrations using liquid chromatography with tandem mass spectrometry in healthy cats and in a cat with pheochromocytoma

Pheochromocytoma (PCC) is rare in cats and plasma (PL) and urinary (U) metanephrines (metanephrine [MN]; normetanephrine [NMN]) measurement is rarely described in cats. We evaluated the utility of PL and U MNs measurement in 10 healthy cats and a cat with a confirmed diagnosis of pheochromocytoma (PheoCat), using liquid chromatography with tandem mass spectrometry (LC-MS-MS). Urine and EDTA PL samples collected from each of the 10 cats and the PheoCat were promptly stored at -80°C and remained frozen until analysis. To evaluate U MNs stability, an additional urine sample collected from the healthy cats was refrigerated for 24 hours before freezing. Urinary creatinine concentration (Creat) was assessed using the same spot urine samples to calculate U MNs-to-creatinine ratios. The PL-MN and PL-NMN median concentrations of the healthy cats were 2.73 and 7.02 nmol/L, respectively. The median U-MN/Creat and U-NMN/Creat ratios were 70 and 139 μg/g, respectively. The PheoCat had a PL-MN of 3.68 nmol/L, PL-NMN of 66.27 nmol/L, U-MN/Creat of 179 μg/g, and U-NMN/Creat of 1262 μg/g. The PheoCat had markedly increased concentrations of both PL and U MNs when compared to the healthy cats. No significant difference was found between U MNs measured in urine samples that underwent 24 hours of refrigeration in comparison to those that were frozen immediately. We report preliminary reference intervals for PL and U MNs in cats using LC-MS-MS and the potential clinical applicability of these biomarkers for the diagnosis of PCC in cats.

PD03-05 PHEOCHROMOCYTOMA: IS THERE A ROLE FOR ULTRASONOGRAPHY IN THE SCREENING OF ADRENAL MASS IN HYPERTENSIVE PATIENTS?

You have accessJournal of UrologyCME1 Apr 2023PD03-05 PHEOCHROMOCYTOMA: IS THERE A ROLE FOR ULTRASONOGRAPHY IN THE SCREENING OF ADRENAL MASS IN HYPERTENSIVE PATIENTS? Bruno Di Domenico, Gabriel Simoes, Caio de Oliveira, Luiz Gustavo Brandao, Helena Lima, and Marcelo Lima Bruno Di DomenicoBruno Di Domenico More articles by this author , Gabriel SimoesGabriel Simoes More articles by this author , Caio de OliveiraCaio de Oliveira More articles by this author , Luiz Gustavo BrandaoLuiz Gustavo Brandao More articles by this author , Helena LimaHelena Lima More articles by this author , and Marcelo LimaMarcelo Lima More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003220.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Pheochromocytomas are catecholamine-producing tumors derivate from chromaffin cells. Their clinical presentation is variable, with arterial hypertension being the most frequent finding and paroxysms (headache, palpitations, and sweating) the most characteristic. Diagnosis is clinical, through the measurement of serum and/or urinary metanephrines and imaging methods. The great challenge is how to identify these patients. It is estimated that 0.1% of hypertensive patients have pheochromocytomas. The hypertension of these patients can be treated surgically by laparoscopic adrenalectomies. The objective of the study was to evaluate the use of ultrasonography as a screening test for pheochromocytoma in hypertensive patients. METHODS: The medical records of all patients who underwent adrenalectomy between 1999 and 2020 were reviewed. Only the patients with a pathologic diagnosis of pheochromocytoma were selected. RESULTS: A total of 29 laparoscopic adrenalectomies were performed in 25 patients, including four bilateral adrenalectomies. The average patient age was 40.2 years old (range 18-66). Ultrasonography was the first exam performed on twenty-nine hypertensive patients in the imaging investigation that showed adrenal masses with a mean diameter of 2.8 cm. After that, all patients underwent computed tomography scanning or magnetic resonance imaging, and meta-[131I]iodobenzylguanidine (131I-MIBG) whole-body scintigraphy before adrenalectomy. Measurements of plasma metanephrines and/or urinary catecholamines were high in all patients. Although abdominal ultrasonography usually has low sensitivity and specificity, it was fundamental to identifying patients with adrenal mass and proceeding with the investigation. CONCLUSIONS: Ultrasonography was an efficient method for screening investigation of pheochromocytoma in the hypertensive population and is considered a safe, low-cost and fast imaging exam. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e76 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bruno Di Domenico More articles by this author Gabriel Simoes More articles by this author Caio de Oliveira More articles by this author Luiz Gustavo Brandao More articles by this author Helena Lima More articles by this author Marcelo Lima More articles by this author Expand All Advertisement PDF downloadLoading ...

The Stability Evaluation of Plasma and Urine Metanephrines for Diagnosing Pheochromocytoma and Paraganglioma by LC-MS/MS

The Stability Evaluation of Plasma and Urine Metanephrines for Diagnosing Pheochromocytoma and Paraganglioma by LC-MS/MS

Establishment of reference intervals for plasma metanephrines in seated position measured by LC-MS/MS and assessment of diagnostic performance in pheochromocytoma/paraganglioma.

The use of supine reference intervals instead of the corresponding seated reference intervals for seated plasma-free metanephrines (MNs) in pheochromocytoma /paraganglioma (PPGL) screening has been controversial in recent years. Each clinical laboratory should choose the optimal sampling posture and diagnostic strategy according to local conditions. The reference population consisted of 736 cases aged 14 to 92 years old and the validation population consisted of 1068 patients aged 8 to 87 years old. Seated MNs were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the reference intervals and diagnostic cut-off values were established and the diagnostic performance compared with reference intervals established in a supine position. There was no correlation between seated plasma MNs and age (P>0.05) and there were differences in MNs among the various disease groups (P<0.05). MNs were different in gender (P<0.0001). The upper reference limit (URL) established in this study had the same sensitivity (100%) and better specificity (94.6% vs 83.5%) compared with the published age-adjusted supine reference intervals. The proportion of suspected patients with MNs within the URL-2×URL range was lower using seated reference intervals compared to supine intervals (5.3% vs 15.7%). Using the corresponding seated reference intervals for seated plasma MNs can reduce the unnecessary re-examinations of suspected patients with slightly elevated MNs. The cut-off value established by seated plasma MNs has good diagnostic performance in PPGL. Use of seated sampling is an acceptable practice and is more convenient and economical than supine sampling.

Validation of Vanillylmandelic Acid (VMA) with Plasma Metanephrine and Normetanephrine for Screening Adrenal Medullary Disorders

Objective: To validate urinary Vanillylmandelic acid (VMA) for screening adrenal medullary disorders, taking plasma-free Metanephrine as the gold standard.&#x0D; Study Design: Cross-sectional validation study.&#x0D; Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology,Rawalpindi, in collaboration with Armed Forces Institute of Urology, Rawalpindi from Pakistan, Jan 2020 to Mar 2021.&#x0D; Methodology: One hundred and thirty (130) symptomatic hypertensive patients with adrenal masses on ultrasound were selected Urine and blood samples were collected under specified conditions after taking necessary precautions and subsequently analyzed. Taking plasma Metanephrine as a reference, sensitivity, specificity and predictive values were calculated at predefined cut-off values. &#x0D; Results: In a young population with a mean age of 28.55±5.54 years, headache, palpitations and sweating were the predominant symptoms having a frequency of 130(100%), 116(89.2%) and 111(85.4%), respectively. Twenty-four hours urinary Vanillylmandelic acid had lower sensitivity (66.3%) than a random urinary VMA/cr ratio (72.1%) but similar specificity(97.7%). On the other hand, plasma-free Normetanephrine had 100% sensitivity but lower specificity (93.2%). ROC curve was plotted, and AUC for 24 hours urinary VMA, urinary VMA/cr ratio and plasma-free Normetanephrine were 0.820, 0.849 and0.966, respectively.&#x0D; Conclusion: Plasma-free Metanephrine could be used for screening pheochromocytoma and other adrenal medullary disorders like paraganglionoma. In addition, VMA/cr ratio can be used for biochemical confirmation of the disease owing to the high specificity found in our study.

Could primary hyperparathyroidism develop in cases with neurofibromatosis type-1-associated pheochromocytoma: Two cases with pheochromocytoma gene panel analysis

Abstract Introduction Neurofibromatosis type-1 (NF-1) is an autosomal dominant genetic disorder. It is associated with the development of café-au-lait macules, axillary and/or inguinal frecklings, Lisch nodules, hypertension, osteoporosis, skeletal abnormalities, as well as benign and malignant tumors, such as optic gliomas, peripheral nerve sheet tumors, and rarely, pheochromocytomas. However, primary hyperparathyroidism is rarely documented in patients with bilateral pheochromocytomas associated with NF-1 and is typically linked to MEN-2 A syndrome. Here we present two cases of NF-1-associated bilateral pheochromocytomas who developed primary hyperparathyroidism during follow-up. Clinical case In 2010, diagnostic ultrasonography performed for abdominal pain in a 60-year-old female patient revealed an adrenal mass. Multiple neurofibromas, axillary freckling, café-au-lait macules, and lisch nodules were found on physical examination (Figure 1A, B, C, and D). A diagnosis of pheochromocytoma was confirmed by high urine metanephrines and a hyperintense, 35 x40 mm mass on T2 weighted MRI sequences. The patient underwent right adrenalectomy. One year later, a diagnosis of primary hyperparathyroidism was made based on the high serum levels of calcium and intact PTH, and low serum phosphorus levels (Table-1). Radiotracer uptake was seen on a parathyroid MIBI scan in the thyroid's right inferior area. During follow-up, a 50×51 mm mass, hyperintense on T2 weighted MRI sequences was discovered on the left adrenal gland (figure 1-E). A diagnosis of pheochromocytoma was confirmed by detecting high plasma metanephrine and normetanephrine levels. The patient underwent left adrenalectomy 5 years following the initial diagnosis. Clinical case A 64-year-old female patient was admitted due to recently developed hypercalcemia. She had previously undergone two successive adrenalectomies, 4 years apart in 1999 and 2003, and was confirmed to have bilateral pheochromocytomas by histopathological analysis. Multiple neurofibromas, axillary freckling, café-au-lait macules, and Lisch nodules were found on physical examination. A diagnosis of primary hyperparathyroidism was made by detecting high serum calcium, intact parathormone, and low serum phosphorus levels. The patient underwent a right parathyroidectomy in 2012. In both cases, a panel analysis of pheochromocytoma gene mutations was carried out. In cases 1 and 2, a heterozygous nonsense mutation (17q11.2, C.2023G&amp;gt;T (P.G675*) and a non-frameshift deletion (17q11.2 c.5036) in the NF-1 gene were respectively found. Both instances tested negative for genetic alterations for RET, FH, MAX, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM-127, and VHL. Conclusion The development of primary hyperparathyroidism in these two cases of pheochromocytomas associated with genetically confirmed NF-1 raises the possibility that primary hyperparathyroidism may develop in patients with NF-1-associated pheochromocytoma.

Difficult situation in treatment of medullary thyroid carcinoma in patient with multiple endocrine neoplasia type 2 B(MEN2B)

Abstract Introduction Multiple endocrine neoplasia type 2B (also known as ‘MEN2B’,‘Multiple endocrine neoplasia type 3′ or ‘Wagenmann–Froboese syndrome’) is a genetic disease characterized by the presence of medullary carcinoma of the thyroid, pheochromocytoma, mucosal neuromas, marfanoid features and multiple skeletal abnormalities such as kyphoscoliosis and pes cavus. Clinical Case A 16 years male presented with neck swelling and dysmorphic feature in the form of marfanoid habitus, including multiple tongue and oral mucosal swelling with mucosal neuromas on the anterior third of the tongue, the lips and the inner eyelid. Lips are thickened and bumpy. Visible neck swelling, palpable solid neck mass, high arm span to height ratio at &amp;gt;1.05, elongated fingers, pes cavus and positive wrist sign which is defined as when the distal phalanges of the thumb and fifth finger overlap on encircling the opposite wrist, were present. Ultrasound of the neck revealed a left solid irregular mass (57mmx33mm), that is hypoechoic, has coarse calcification, hypervascularity, that is mostly central, Multiple cervical lymph node(abnormal nodes include shape (round), absent hilum, intranodal necrosis, reticulation, calcification, peripheral vascularity),Investigation at beginning, Normal thyroid function test and biochemical and electrolyte were observed, Chest x ray was normal, FNAC done for thyroid nodule that showed multiple clumps of large hyperchromatic oval cells picture suggesting high suspicion of thyroid malignancy, thyroid biopsy advised, The patient was referred the FDEMC center for further evaluation and investigation prior to the surgery. During investigation at FDEMC center, thyroid function test normal, biochemistry normal, including PTH and electrolytes, Calcitonin was very high 465 pg/mL (0.2–27.7 pg/mL),GH under GTT was normal, IGF 1 182µg/L (150–350),Plasma metanephrine 40 pg/ml(&amp;lt;90pg/ml),and Plasma normetanephrine 27pg/ml(&amp;lt;196pg/ml) were normal. The patient referred to surgery, total thyroidectomy with radical neck dissection with multiple lymph node resection was performed. The biopsy revealed medullary thyroid carcinoma with cervical lymph node secondaries (bilateral multiple foci in both lobes). The patient kept on levothyroxine tab 100mcg.The follow up of the patient after one month by ultrasound and calcitonin level revealed residual thyroid tissue and two large cervical LN in the the ultrasound and a calcitonin level of 322 pg/mL Another surgical neck dissection to the metastatic LN &amp;lt;multiple LN 7×5cm, multiple suprasternal mass dissection 3×2.5cm,remnant of thyroid tissue 0.8cm,Follow up the patient after one month by ultrasound and calcitonin level still showed that there is residual pathological cervical LN, while the calcitonin level still high 412 pg/mL. PET scan done for him showed there is uptake in the head, neck and chest. The calcitonin was repeatedly was high.