Symptoms Of Catecholamine Excess Research Articles

Silent pheochromocytoma in adrenal incidentaloma: unveiling clinical and radiological characteristics.

Silent pheochromocytoma refers to tumors without signs and symptoms of catecholamine excess. This study aimed to clarify the clinical, radiological characteristics, and perioperative features of silent pheochromocytomas diagnosed after adrenalectomy for adrenal incidentaloma. Medical records of patients who underwent adrenalectomy for adrenal incidentaloma and were subsequently diagnosed with silent pheochromocytoma between January 2000 and December 2020 were retrospectively reviewed for demographic, diagnostic, surgical, and pathological findings. Of the 130 patients who underwent adrenalectomy for incidentaloma, 8 (6.1%) were diagnosed with silent pheochromocytoma. Almost all patients had no hypertensive symptoms and their baseline hormonal levels remained within normal ranges. All patients exhibited tumor size >4 cm, precontrast Hounsfield unit >10, and absolute washout <60%. Intraoperative hypertensive events were noted in 2 patients (25.0%) in whom antiadrenergic medications were not administered. All patients in the intraoperative hypertensive event group exhibited atypical features on CT, whereas 83.3% of patients in the non-intraoperative hypertensive event group showed atypical features on CT imaging. Silent pheochromocytomas share radiological traits with malignant adrenal tumors. Suspicious features on CT scans warrant surgical consideration for appropriate treatment. Administering alpha-blockers can enhance hemodynamic stability during adrenalectomy in suspected silent pheochromocytoma cases.

SAT307 Intraoperative Radiofrequency Ablation Of An Unresectable Abdominal Paraganglioma Promoted Objective Tumor Response And Complete Biochemical Remission

Abstract Disclosure: I.P. de Magalhães: None. B.S. Boger: None. N.L. Gomes: None. G.L. Martins: None. L.A. Bomfim Jr: None. G.F. Fagundes: None. A.F. Afonso: None. J. Petenuci: None. F.M. Coelho: None. V. Srougi: None. F.Y. Tanno: None. J.L. Chambo: None. A. Latronico: None. M.B. Fragoso: None. A.O. Hoff: None. B.B. Mendonca: None. M.R. Menezes: None. M.Q. Almeida: None. Background: Metastatic pheochromocytoma and paraganglioma (PPGL) are incurable neuroendocrine tumors. Few reports demonstrated the efficacy of radiofrequency ablation (RFA) in achieving tumor control of metastatic lesions (usually &amp;lt;3 cm). However, intraoperative RFA of large and unresectable primary PPGLs was not previously demonstrated. Case Report: A 31-year-old male patient was diagnosed with symptoms of catecholamine excess, high levels of plasma metanephrines and a 9 cm retroperitoneal tumor. The patient underwent an open laparotomy, which revealed unresectable disease. Anatomopathological and immunohistochemical analysis was compatible with the diagnosis of paraganglioma. The patient was treated with 13 cycles of cytotoxic chemotherapy (cyclophosphamide, vincristine and dacarbazine) without objective tumor response by RECIST. Then, he was referred to our Institution for evaluation of additional therapies. Blood pressured was well controlled with doxazosin 16 mg/d, propranolol 40 mg/d and losartan 100 mg/d. A magnetic resonance imaging (MRI) revealed an extensive retroperitoneal mass with 9.0 x 8.6 x 6.0 cm (208 ml) that involved the inferior portion of the vein inferior vena cava, inferior mesenteric artery and infrarenal aorta. Biochemical evaluation demonstrated very high levels of plasma normetanephrine (20.2 nmol/L; normal range &amp;lt;0.9 nmol/L) and normal metanephrine level (0.2 nmol/L; &amp;lt;0.5 nmol/L). The genetic investigation showed the germline pathogenic variant c.1591delC (p.Ser198Alafs*22) in SDHB gene. I131-metaiodobenzylguanidine scintigraphy was negative and Ga68-dotatate PET-CT scan displayed a high uptake in the abdominal mass without metastatic disease. Unfortunately, lutetium177 treatment is not available in our Institution. Due to the lack of alternative therapies, we proposed a debulking open laparotomy with intraoperative RFA in the remaining tumoral lesion. Nevertheless, the tumor did not present a clear cleavage plane with the large vessels and had a large caliber intratumoral vasculature. Intraoperative RFA was performed by a very experienced team (interventional radiologist and anesthesiologist to control blood pressure during the procedure). After 2 months, the dose of doxazosin decreased from 16 mg to 8 mg (50% reduction), plasma normetanephrines dropped to 4.6 nmol/L (79%), and the largest tumor diameter at MRI reduced to 6.8 cm (88.8 ml, 57% reduction). After 7 months of the RFA procedure, the tumor continues shrinking (4.8 cm, 45 ml, 78% reduction) and plasma normetanephrine completely normalized. Conclusion: This is the first report of intraoperative RFA of a large primary unresectable paraganglioma. The patient presented a striking clinical success, complete biochemical remission and an objective tumor response. Support: Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6 (to M.Q. Almeida). Presentation: Saturday, June 17, 2023

Mediastinal Paraganglioma: A retrospective analysis of 51 cases

BackgroundParagangliomas are rarely found in the mediastinum, where they account for a small proportion of mediastinal masses. This study aimed to better characterize the presenting features and relevant aspects in optimizing the diagnosis and treatment of mediastinal paragangliomas. MethodsA computer-assisted search of electronic health records was performed to identify adult patients (≥18 years) who underwent evaluation for a primary mediastinal paraganglioma at Mayo Clinic between January 2000 and April 2022. Medical charts, laboratory tests and radiology images were reviewed to collect data. ResultsThe study included 51 patients, each with a single mediastinal paraganglioma. The median age was 47 years (IQR: 39–67), 67% females. Symptoms of catecholamine excess were manifest in 39% of patients, and 14% presented with mass effect, while the remaining 47% had no paraganglioma-related symptoms. Genetic testing was performed in 35 patients; 66% harbored a pathogenic variant in the succinate dehydrogenase enzyme complex. Most paragangliomas (71%) were in the middle mediastinum and showed uptake of intravenous contrast on chest imaging. Biopsies were performed in 30 (59%) patients; 27% were inconclusive and 10% resulted in major complications. Surgical resection occurred in 75%, primarily for relief of symptoms (50%) followed by proximity to critical structures (45%). Perioperative complications were common (66%), but there were no cases of local tumor recurrence during the follow-up period (median 8 years; IQR: 4–13). ConclusionMediastinal paragangliomas are most located in the middle mediastinum and can often be diagnosed noninvasively using a combination of clinical, biochemical, and radiological features.

Biochemical Assessment of Pheochromocytoma and Paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) require prompt consideration and efficient diagnosis and treatment to minimize associated morbidity and mortality. Once considered, appropriate biochemical testing is key to diagnosis. Advances in understanding catecholamine metabolism have clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves are important for effective diagnosis. These metabolites, normetanephrine and metanephrine, produced respectively from norepinephrine and epinephrine, can be measured in plasma or urine, with choice according to available methods or presentation of patients. For patients with signs and symptoms of catecholamine excess, either test will invariably establish the diagnosis, whereas the plasma test provides higher sensitivity than urinary metanephrines for patients screened due to an incidentaloma or genetic predisposition, particularly for small tumors or in patients with an asymptomatic presentation. Additional measurements of plasma methoxytyramine can be important for some tumors, such as paragangliomas, and for surveillance of patients at risk of metastatic disease. Avoidance of false-positive test results is best achieved by plasma measurements with appropriate reference intervals and preanalytical precautions, including sampling blood in the fully supine position. Follow-up of positive results, including optimization of preanalytics for repeat tests or whether to proceed directly to anatomic imaging or confirmatory clonidine tests, depends on the test results, which can also suggest likely size, adrenal vs extra-adrenal location, underlying biology, or even metastatic involvement of a suspected tumor. Modern biochemical testing now makes diagnosis of PPGL relatively simple. Integration of artificial intelligence into the process should make it possible to fine-tune these advances.

PS-BPR01-5: DOPAMINE-SECRETING PHEOCHROMOCYTOMA: AN OVERLOOKED CAUSE OF INCIDENTALLY DISCOVERED ADRENAL TUMOR AND NORMAL BLOOD PRESSURE

A 64-year-old woman with a history of chronic thyroiditis and no family history of endocrine disease was incidentally determined to have a left retroperitoneal mass on abdominal ultrasonography. A subsequent abdominal computed tomography (CT) scan revealed a 5.6 × 5.1 × 10.6 cm left adrenal tumor (10–50 Hounsfield Units of CT attenuation value), which showed marginal irregularity and an internal cystic structure [Figure 1A]. She was admitted to our hospital for further investigation of a suspected adrenocortical carcinoma. On admission, she was normotensive and had no symptoms of catecholamine excess. The 24-hour urine catecholamine level showed normal norepinephrine (122.9 ug/day), epinephrine (24.3 ug/day), whereas markedly elevated dopamine (148,212.4 ug/day). 123I-MIBG scintigraphy revealed tumor uptake. After alpha-blockade as preoperative management, she successfully underwent laparoscopic left adrenalectomy and was finally diagnosed with an exclusively dopamine-secreting pheochromocytoma. The tumor was histologically comprised of small polygonal cells with high cellularity and was immunohistochemically positive for all three catecholamine synthesizing enzymes: tyrosine hydroxylase (very weak), dopamine beta-hydroxylase (heterogeneous), and phenylethanolamine N-methyltransferase (very weak). Electron microscopy revealed very few catecholamine-containing small vesicles with a few organelles, which reflected immature cells. No biochemical or imaging evidence of recurrence or metastasis was evident 1 year after the surgery. To our knowledge, this is the first case of an exclusively dopamine-secreting pheochromocytoma in which immunostaining of catecholamine synthetic enzymes and electron microscopy of tumor tissues were performed together to identify the mechanism underlying a dopamine-secreting PPGL. The purpose of this report was to identify the mechanism underlying a dopamine-secreting pheochromocytoma from the histopathological findings. We also discuss the reasons for the lack of catecholamine excess symptoms, whether preoperative management of alpha-blockade is needed, and the association between the prognosis and genetic mutation with an extensive literature review. JOURNAL/jhype/04.03/00004872-202301001-00862/figure1/v/2023-10-24T163949Z/r/image-jpeg

Abstract #1322752: A Rare Case of Cardiac Paraganglioma

Cardiac paragangliomas are rare, there is a paucity of cohort data, and they raise dilemmas about management when encountered. Some of them are metabolically active and may present with symptoms of catecholamine excess, whereas some may be incidentally diagnosed. We report a case of an exceptionally rare cardiac paraganglioma in a young lady who underwent a curative surgical excision.

PSAT032 Metoclopramide Induced Pheochromocytoma Multisystem Crisis: An Unusual Initial Presentation of Pheochromocytoma

Abstract Introduction Pheochromocytoma is a rare catecholamine secreting tumor arising from the adrenal medulla. It presents with hypertension and symptoms of catecholamine excess (episodic headache, sweating, palpitations). Pheochromocytoma crisis (PC) can encompass multiple organ failure, lactic acidosis, elevated temperature, encephalopathy, and hypertension and/or hypotension. Metoclopramide is a D2 receptor blocker and is known to precipitate pheochromocytoma crisis. It is commonly used in the emergency department (ED) for nausea and is often used as part of the "migraine cocktail". Case presentation 41-year-old female with primary hypothyroidism and hypertension diagnosed 5 months prior on two anti-hypertensive agents, presented to the ED with a severe headache. She recently had been placed on a Holter monitor for evaluation of episodes of palpitation/tachycardia. She was hemodynamically stable. Intravenous metoclopramide was administered as part of a "migraine cocktail". Shortly thereafter, she developed tachycardia with heart rate (HR) in the 130s, hypertension with blood pressure (BP) in the 180s/120s and proceeded to have generalized tonic-colonic seizures that lasted for 3 minutes. She was treated with lorazepam and was intubated for airway protection. Initial labs were only significant for mild leukocytosis. The urine drug screen was unrevealing. Due to the unexpected rapid clinical deterioration, computed tomography (CT) of the head, chest, abdomen, and pelvis were obtained. CT abdomen revealed a large 6.4×5.7×5.2 cm right adrenal mass. HR and BP remained elevated in the 170s and 200s/100s respectively. Given CT findings, a PC was suspected. She was started on doxazosin and labetalol. Phenoxybenzamine was later started. Biochemical testing was consistent with pheochromocytoma with elevated normetanephrine (NE) &amp;gt;20,000 pg/mL (&amp;lt;=148 pg/mL), metanephrine (M)&amp;gt;20,000 pg/mL (&amp;lt;=60 pg/mL), and total urinary metanephrines (TM) &amp;gt;40,000 pg/mL (&amp;lt;=205 pg/mL). HR and BP stabilized with treatment and the patient was subsequently extubated. She was noted to have new dysarthria and visual field deficits. Magnetic resonance imaging and CT angiography revealed findings consistent with posterior reversible encephalopathy syndrome (PRES) and acute cerebellar infarct. Dotatate scan was negative for metastasis. She later underwent right adrenalectomy; pathology report confirmed the diagnosis of nonmalignant pheochromocytoma. Repeat NE, M, and TM 10 days post-op were unremarkable. The patient follows with endocrinology clinic outpatient and has been doing well. Conclusion Multiple cases of metoclopramide-induced pheochromocytoma crisis have been reported in the literature. These accounts indicate that the empiric use of metoclopramide for individuals presenting with headaches/nausea is not without risk especially for those with a history of hypertension and other symptoms of catecholamine excess. This case also highlights the importance of suspecting pheochromocytoma crisis in patients who develop rapid onset hypertensive crisis and other symptoms of catecholamine excess immediately after administering metoclopramide. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

RF33 | PSUN04 Luteinizing Hormone-Chorionic Gonadotrophin Receptor in Pheochromocytomas

Abstract Background Pheochromocytomas and paragangliomas (PPGL) are catecholamine-producing neuroendocrine tumors that arise from the adrenal medulla or ganglia and display the highest heritability rate among all human tumours. Genomic analyses allowed identification of molecular subgroups of PPGL which are organized into 2 main clusters. Cluster 1 contains SDHx- and VHL-mutated tumors which do not produce epinephrine while cluster 2 includes the epinephrine-secreting PPGL related to RET, NF1, TMEM127 and MAX mutations. PPGL must be early diagnosed and treated to prevent adrenergic crises which can be life-threatening. Detection of PPGL is particularly important during pregnancy since PPGL are associated with a high risk of either maternal or fetal complications in this context. Reciprocally, pregnancy can favor adrenergic crises in patients with previously undiagnosed or silent pheochromocytoma (PCC). These dangerous events can be triggered by tumor compression resulting from fetus growth, or labor and delivery. However, it is known that surges in plasma catecholamines may also occur during early gestation suggesting that pregnancy may also activate the secretory activity of PPGL through the involvement of non-mechanical factors, such as gestational hormones. Methods In the present study, we report a case of silent PCC revealed in a pregnant woman by life-threatening adrenergic myocarditis occurring at 31 weeks of gestation. Analysis of PPGL susceptibility genes showed the presence of a heterozygous germline RET variant of uncertain significance. The fact that the first symptoms of catecholamine excess had appeared during the first trimester of pregnancy led us to conduct in vitro studies to investigate the effects of estradiol and the pregnancy hormone chorionic gonadotropin (hCG) on epinephrine secretion by cultured cells derived from the resected patient's tumor. Expression of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) was searched for in the tumor and an additional series of 12 PCC by RT-qPCR and immunohistochemistry. LHCGR expression was also analyzed in silico in the PPGL cohorts of the COMETE and The Cancer Genome Atlas (TCGA) databases. Results hCG stimulated epinephrine secretion by primary cultured PCC cells. The tumor expressed the LHCG receptor, which was colocalized with catecholamine-producing enzymes. A similar expression pattern of the LHCG receptor was also observed in 5 out of a series of 12 PCCs. Moreover, in silico studies revealed that PPGL display the highest expression levels of LHCGR mRNA among the 32 solid tumor types of TCGA cohort. Interestingly, expression of LHCGR was higher in cluster 2 than in cluster 1 PPGL. Conclusion We show that PCC can express functional LHCG receptor. Consequently, pregnancy may activate catecholamine production by previously silent pheochromocytoma as early as the first trimester of gestation especially in women with gene mutations that predispose to cluster 2 epinephrine-secreting PCC. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:18 p.m. - 1:23 p.m.

Pediatric Metastatic Pheochromocytoma and Paraganglioma: Clinical Presentation and Diagnosis, Genetics, and Therapeutic Approaches

Although pediatric pheochromocytomas and paragangliomas (PPGLs) are rare, they have important differences compared to those in adults. Unfortunately, without timely diagnosis and management, these tumors have a potentially devastating impact on pediatric patients. Pediatric PPGLs are more often extra-adrenal, multifocal/metastatic, and recurrent, likely due to these tumors being more commonly due to a genetic predisposition than in adults. This genetic risk results in disease manifestations at an earlier age giving these tumors time to advance before detection. In spite of these problematic features, advances in the molecular and biochemical characterization of PPGLs have heralded an age of increasingly personalized medicine. An understanding of the genetic basis for an individual patient’s tumor provides insight into its natural history and can guide clinicians in management of this challenging disease. In pediatric PPGLs, mutations in genes related to pseudohypoxia are most commonly seen, including the von Hippel-Lindau gene (VHL) and succinate dehydrogenase subunit (SDHx) genes, with the highest risk for metastatic disease associated with variants in SDHB and SDHA. Such pathogenic variants are associated with a noradrenergic biochemical phenotype with resultant sustained catecholamine release and therefore persistent symptoms. This is in contrast to paroxysmal symptoms (e.g., episodic hypertension, palpitations, and diaphoresis/flushing) as seen in the adrenergic, or epinephrine-predominant, biochemical phenotype (due to episodic catecholamine release) that is commonly observed in adults. Additionally, PPGLs in children more often present with signs and symptoms of catecholamine excess. Therefore, children, adolescents, and young adults present differently from older adults (e.g., the prototypical presentation of palpitations, perspiration, and pounding headaches in the setting of an isolated adrenal mass). These presentations are a direct result of genetic determinants and highlight the need for pediatricians to recognize these differences in order to expedite appropriate evaluations, including genetic testing. Identification and familiarity with causative genes inform surveillance and treatment strategies to improve outcomes in pediatric patients with PPGL.

Adrenocortical Tumors and Pheochromocytoma/Paraganglioma Initially Mistaken as Neuroblastoma-Experiences From the GPOH-MET Registry.

In children and adolescents, neuroblastoma (NBL), pheochromocytoma (PCC), and adrenocortical tumors (ACT) can arise from the adrenal gland. It may be difficult to distinguish between these three entities including associated extra-adrenal tumors (paraganglioma, PGL). Precise discrimination, however, is of crucial importance for management. Biopsy in ACT or PCC is potentially harmful and should be avoided whenever possible. We herein report data on 10 children and adolescents with ACT and five with PCC/PGL, previously mistaken as NBL. Two patients with adrenocortical carcinoma died due to disease progression. Two (2/9, missing data in one patient) patients with a final diagnosis of ACT clearly presented with obvious clinical signs and symptoms of steroid hormone excess, while seven patients did not. Blood analyses indicated increased levels of steroid hormones in one additional patient; however, urinary steroid metabolome analysis was not performed in any patient. Two (2/10) patients underwent tumor biopsy, and in two others tumor rupture occurred intraoperatively. In 6/10 patients, ACT diagnosis was only established by a reference pediatric pathology laboratory. Four (4/5) patients with a final diagnosis of PCC/PGL presented with clinical signs and symptoms of catecholamine excess. Urine tests indicated possible catecholamine excess in two patients, while no testing was carried out in three patients. Measurements of plasma metanephrines were not performed in any patient. None of the five patients with PCC/PGL received adrenergic blockers before surgery. In four patients, PCC/PGL diagnosis was established by a local pathologist, and in one patient diagnosis was revised to PGL by a pediatric reference pathologist. Genetic testing, performed in three out of five patients with PCC/PGL, indicated pathogenic variants of PCC/PGL susceptibility genes. The differential diagnosis of adrenal neoplasias and associated extra-adrenal tumors in children and adolescents may be challenging, necessitating interdisciplinary and multidisciplinary efforts. In ambiguous and/or hormonally inactive cases through comprehensive biochemical testing, microscopical complete tumor resection by an experienced surgeon is vital to preventing poor outcome in children and adolescents with ACT and/or PCC/PGL. Finally, specimens need to be assessed by an experienced pediatric pathologist to establish diagnosis.

Pheochromocytomas and Abdominal Paragangliomas: A Practical Guidance.

Simple SummaryPheochromocytomas and abdominal paragangliomas (PPGLs) are rare. They can be discovered incidentally by imaging with computed tomography or magnetic resonance imaging and during hormonal surveillance in patients with known genetic variants that are associated with PPGLs. As most PPGLs are functioning, a hormonal work-up evaluating for catecholamine excess is recommended. Classical symptoms, such as tachycardia, hypertension and headache, can be present, but when the PPGL is discovered as an incidentaloma, symptoms may be lacking or be more discrete. PPGLs carry malignant potential, and patients should undergo close surveillance, as recurrence of disease or metastasis may develop. Genetic susceptibility for multifocal disease has gained more attention, and germline variants are commonly detected, thus facilitating detection of hereditary cases and afflicted family members. Any patient with a PPGL should be managed by an expert multidisciplinary team consisting of endocrinologists, radiologists, surgeons, pathologists and clinical geneticists.Pheochromocytomas and abdominal paragangliomas (PPGLs) are rare tumors arising from the adrenal medulla or the sympathetic nervous system. This review presents a practical guidance for clinicians dealing with PPGLs. The incidence of PPGLs has risen. Most cases are detected via imaging and less present with symptoms of catecholamine excess. Most PPGLs secrete catecholamines, with diffuse symptoms. Diagnosis is made by imaging and tests of catecholamines. Localized disease can be cured by surgery. PPGLs are the most heritable of all human tumors, and germline variants are found in approximately 30–50% of cases. Such variants can give information regarding the risk of developing recurrence or metastases as well as the risk of developing other tumors and may identify relatives at risk for disease. All PPGLs harbor malignant potential, and current histological and immunohistochemical algorithms can aid in the identification of indolent vs. aggressive tumors. While most patients with metastatic PPGL have slowly progressive disease, a proportion of patients present with an aggressive course, highlighting the need for more effective therapies in these cases. We conclude that PPGLs are rare but increasing in incidence and management should be guided by a multidisciplinary team.

Non-functional urinary bladder paraganglioma with negative Ga-DOTA-NOC PET/CT uptake

BackgroundParaganglioma of the urinary bladder is a very rare benign tumor that constitutes less than 0.5% of all bladder tumors. It can be functional and non-functional. Functional tumors present with symptoms of catecholamine excess, and non-functional tumors usually remain asymptomatic.Case presentationHere, we present a case of non-functional urinary bladder paraganglioma in a 36-year-old female who presented to us with a history of intermittent hematuria. The routine hematological and biochemical parameters were within normal limits. Diagnostic computed tomography (CT) revealed a hypervascular lesion in the urinary bladder dome with no significant uptake in gallium-68-labelled-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid peptides-NaI3-octreotide positron emission tomography (DOTA-NOC PET/CT). Histopathology and immunohistochemistry confirmed the diagnosis of paraganglioma.ConclusionWe present this case because of the rare location of paraganglioma in the urinary bladder and being non-functional with low/absent somatostatin receptor expression.

Dopamine-Secreting Pheochromocytoma and Paraganglioma.

Predominantly or exclusively dopamine-secreting pheochromocytoma and paraganglioma are very rare. We report a 64-year-old woman with an adrenal incidentaloma. She was normotensive and had no symptoms of catecholamine excess. The 24-hour urine catecholamine level showed normal norepinephrine (122.9 μg/day), normal epinephrine (24.3 μg/day), and markedly elevated dopamine (148 212.4 μg/day). 123I-metaiodobenzylguanidine (MIBG) scintigraphy revealed tumor uptake. After α-blockade as preoperative management, she successfully underwent laparoscopic left adrenalectomy and was finally diagnosed with an exclusively dopamine-secreting pheochromocytoma. The tumor was histologically comprised of small polygonal cells with high cellularity and was immunohistochemically positive for all 3 catecholamine-synthesizing enzymes: tyrosine hydroxylase (very weak), dopamine β-hydroxylase (heterogeneous), and phenylethanolamine N-methyltransferase (very weak). Electron microscopy revealed very few catecholamine-containing small vesicles with a few organelles, which reflected immature cells. No biochemical or imaging evidence of recurrence or metastasis were evident 1 year after the surgery. We conducted a literature search in the PubMed database. A total of 33 cases were collected. Our case had the second-highest 24-hour urinary dopamine excretion and was the first in which immunostaining for catecholamine synthase and electron microscopy were performed together. Histological findings in our case give a possible hypothesis that the mechanism underlying a dopamine-secreting pheochromocytoma is associated with immature catecholamine vesicles in which dopamine β-hydroxylase is localized, thus resulting in inhibited conversion from dopamine to norepinephrine. We also discuss the reasons for the lack of catecholamine excess symptoms, whether preoperative management of α-blockade is needed, and the association between the prognosis and genetic mutation, with an extensive literature review.

Case report on a very rare tumour of the urinary bladder: paraganglioma

Urinary bladder tumours are usually of three types; urothelial carcinoma, squamous cell carcinoma and adenocarcinoma. Urothelial carcinoma is the most common type of bladder carcinoma and accounts for almost 90% of all bladder carcinoma. It is also known as transitional cell carcinoma. Squamous cell carcinoma accounts for 4% and adenocarcinomas 2% of all bladder carcinomas. Urinary bladder paragangliomas are a very rare variety of bladder tumours which account for less than 0.06% of all bladder tumours. They are clusters of neuroendocrine cells associated with sympathetic and parasympathetic nervous system. Paragangliomas are tumours arising from these chromaffin cells. They are most commonly seen in the head and neck and account for about 70% of all paragangliomas. The same type of tumour when found in the adrenal glands is referred to as a pheochromocytoma. Paraganglioma is usually seen in the age group of 30 and 50 years. The tumour is often slow growing and benign. These tumours may be functional or non-functional. Functional ones present with symptoms of catecholamine excess, which include hypertension, palpitations, diaphoresis, headache, and post-micturition syncope.

SAT-229 Bilateral Pheochromocytoma as Incidental Finding in a Patient with Neurofibromatosis Type 1

Background.In contrast to other genetic syndromes associated with Pheochromocytoma and Paraganglioma (PPGL) in which yearly biochemical screening is recommended, in neurofibromatosis due to the low penetrance of these tumors, screening is only recommended when there is clinical suspicion1. Given that signs and symptoms of catecholamine excess are vague and non-specific, clinicians should keep a low threshold for biochemical testing in these patients.Clinical Case.70 year old female with Neurofibromatosis type 1 (NF-1) diagnosed at age 24, hypertension and atrial fibrillation, was referred to our institution after being found incidentally with bilateral adrenal nodules. She had a 2 year history of poorly controlled, labile hypertension. Treatment at the time of presentation included doxazosin, metoprolol, valsartan and hydralazine. She denied other symptoms of catecholamine excess.Further workup revealed elevated 24 hour urine normetanephrine at 2,530 mcg (ULN 500 mcg) and metanephrine at 1,325 mcg (ULN 290 mcg). Serum metanephrines were also elevated with free metanephrine of 1.6 nmol/L (ULN 0.5 nmol/L) and free normetanephrine of 4.1 nmol/L (ULN 0.9 nmol/L). Her biochemical metanephrine profile was consistent with pheochromocytomas in NF-1. MIBG uptake confirmed the presence of bilateral pheochromocytomas. She underwent a complete right adrenalectomy and a left cortical sparing adrenalectomy. Her adrenocortical function remains adequate. Post operatively while her blood pressures were no longer labile, she continued to require anti-hypertensive therapy.Conclusion.Patients who are at risk of developing pheochromocytomas and paragangliomas due to genetic syndromes or known germline mutations need ongoing clinical follow and biochemical testing for timely case detection. While in NF-1 pheochromocytomas are usually unilateral and present during early adulthood, they can present with bilateral disease and later in life2. During surgical treatment, even with unilateral disease, adrenocortical function should be preserved when possible3. Hypertension may persist despite complete surgical resection.

Efficacy and Safety of Ablative Therapy in the Treatment of Patients with Metastatic Pheochromocytoma and Paraganglioma.

Metastatic pheochromocytoma and paraganglioma (PPGL) are incurable neuroendocrine tumors. The goals of treatment include palliating symptoms and reducing tumor burden. Little is known about the use of radiofrequency ablation (RFA), cryoablation (CRYO), and percutaneous ethanol injection (PEI) to treat metastatic PPGL. We performed a retrospective study of patients age 17 years and older with metastatic PPGL who were treated with ablative therapy at Mayo Clinic, USA, between June 14, 1999 and November 14, 2017. Our outcomes measures were radiographic response, procedure-related complications, and symptomatic improvement. Thirty-one patients with metastatic PPGL had 123 lesions treated during 42 RFA, 23 CRYO, and 4 PEI procedures. The median duration of follow-up was 60 months (range, 0–163 months) for non-deceased patients. Radiographic local control was achieved in 69/80 (86%) lesions. Improvement in metastasis-related pain or symptoms of catecholamine excess was achieved in 12/13 (92%) procedures. Thirty-three (67%) procedures had no known complications. Clavien-Dindo Grade I, II, IV, and V complications occurred after 7 (14%), 7 (14%), 1 (2%), and 1 (2%) of the procedures, respectively. In patients with metastatic PPGL, ablative therapy can effectively achieve local control and palliate symptoms.

Pheochromocytoma and paraganglioma-an update on diagnosis, evaluation, and management.

Pheochromocytomas and paragangliomas (PPGLs) generally grouped together are rare catecholamine-secreting endocrine tumors. Symptoms of catecholamine excess are non-specific and therefore a high index of suspicion in children with sustained hypertension, family history of endocrine tumors, or features of syndromes associated with PPGLs leads to a timely diagnosis and treatment. Freemetanephrines in theplasma or 24-h urine are the preferred tests to establish catecholamine excess. Considerations for false-positive conditions improve diagnostic yield and accuracy. Functional imaging, targeting either specific cell membrane transporters or vesicular catecholamine transport systems, is indicated for incidental lesions suspicious for PPGLs with inconclusive biochemical testing, assessment of regional extension or multifocality, and exclusion of metastases. Surgery is the mainstay of treatment for PPGLs. Preoperatively, sequential use of alpha adrenergic receptor blockade and volume expansion followed by beta blockade is mandatory to reduce intraoperative intravascular instability and blood pressure fluctuation due to tumor manipulation. Since genetic mutations have been reported in tumor susceptibility genes in nearly 50% of patients with PPGLs, genetic counselling and testing should be considered in all patients with a confirmed tumor.

Non-functional retroperitoneal paraganglioma: A case report

Paragangliomas are extra-adrenal tumors of the autonomic nervous system and may be found within the skull base, neck, chest, and abdomen. When presenting within the abdominal cavity, they may arise as a primary retroperitoneal neoplasm and can mimic vascular malformations or other conditions related to specific retroperitoneal organs such as the pancreas, kidneys.[1] They synthesize, store, and secrete catecholamines because of which they may present with headache, sweating, palpitation, and symptoms of hypertension (functional).[2] In the absence of histological diagnosis and symptoms of catecholamine excess (non-functional), these may be mistaken for GISTs.[3] We are reporting a case of a 36-year-old female who was clinically diagnosed as GIST, underwent excision, and postoperative histopathological examination was found to be paraganglioma.

Malignant Pheochromocytoma with Widespread Bony and Pulmonary Metastases

Pheochromocytoma is a rare benign tumor of the adrenal gland. A select few cases may be malignant, and metastatic cases are exceedingly rare. It often presents with symptoms of catecholamine excess, such as sweating, palpitations, headaches, and characteristic paroxysmal hypertension. Due to its diffuse symptoms, it is difficult to diagnose and is often diagnosed late. We describe the unique case of a 44-year-old female patient who presented with uncontrolled hypertension and vomiting, accompanied by lower back pain. She was diagnosed with malignant pheochromocytoma with multiple metastases to the lungs, vertebrae, scapulae, and skull. Because of the advanced state of her disease, the patient was started on treatment with the chemotherapeutic combination of cyclophosphamide, vincristine, and dacarbazine. However, she had a complicated hospital course and died because of aspiration pneumonia and sepsis.

Case Report: Mediastinal Ganglioneuroma Presented as Chronic Diarrhea in a Young Saudi Girl

Ganglioneuromas (GN) are rare, benign neurogenic tumors that arise from sympathetic ganglia. They are often asymptomatic. However, in rare cases, they may secrete catecholamines, vasoactive intestinal polypeptides (VIP), or androgenic hormones and manifest with flushing, symptoms of catecholamine excess or chronic diarrhea. We report a young Saudi girl with chronic secretory diarrhea, severe hypokalemia and abdominal distension. After an extensive work up, a well-defined hypodense heterogeneous mediastinal mass was noted in radio imaging. A complete recovery was seen after surgical removal of that mediastinal mass which turned to be a ganglioneuroma.