Extra-adrenal Chromaffin Tissue Research Articles

PSAT027 An Incidentally-Discovered Retro-Cardiac Paraganglioma Presenting as NSTEMI

Abstract Introduction/Background Paragangliomas are rare tumors arising from extra-adrenal chromaffin tissue (1,2). The majority of paragangliomas occur in the head and neck, with the heart representing an uncommon site (3). We present a rare case of a patient who was incidentally found to have a hypersecretory retro-cardiac paraganglioma. Clinical Case A 72-year-old woman with a history of hypertension, hyperlipidemia, migraines, and prior cerebrovascular accident presented to the Emergency Department with sudden, substernal, pleuritic chest pain. She described weeks of a "fluttering sensation" in the chest with one episode of syncope. She denied shortness of breath or diaphoresis. Vitals were normal and EKG did not demonstrate ischemia. Troponin uptrended and the patient was admitted due to concern for non-ST-elevation myocardial infarction (NSTEMI). She promptly underwent cardiac catheterization which revealed non-obstructive coronaries and a left atrial mass with blood supply from the right coronary artery and the left circumflex artery. Cardiac MRI demonstrated an extracardiac, interpericardial 42×24×37 mm mass below the left atrium without aggressive features, and delayed homogenous enhancement with dynamic perfusion, suggestive of a paraganglioma. Biochemical evaluation demonstrated elevated free plasma normetanephrines of 5.5 nmol/L (normal: < 0.90 nmol/L) and normal free plasma metanephrines. Chromogranin-A was elevated at 454 ng/ml (normal: <93 ng/ml). 24-hour urine total urine metanephrines were markedly elevated at 1438 mcg/24h (normal: 180-646 mcg/24h) with mainly urine normetanephrines of 1390 mcg/24h (normal: 148-560 mcg/24h). The patient's TSH, free T4, and total T3 were normal. PET/CT scan was negative for metastatic disease. The patient denied a family history of paraganglioma or pheochromocytoma. She was seen in follow-up with Cardiac Surgery, who felt the resection would be technically difficult, but that there were no other alternatives. The patient's procedure was postponed due to a COVID-19 surge and patient was begun on alpha- and beta-blockade, instead of pure alpha-blockade with phenoxybenzamine, in view of her recent history of NSTEMI. Conclusion We present a rare case of an incidentally-found cardiac mass, discovered during cardiac catheterization, with biochemical and radiographic evaluations concerning for a retro-atrial paraganglioma. Cardiac paragangliomas can present with a range of symptoms, from hypertension to different obstructive symptoms, including ischemia, depending on the tumor's location. The secretory activity of cardiac paragangliomas can also vary; the literature reports that about 31% are biochemically active (2). Though rare, our case highlights the importance of understanding the atypical presentation and evaluation of cardiac paragangliomas.

Metabolism and secretion mechanism of catecholamine syndrome and related treatment strategies

: Catecholamine syndrome, also known as pheochromocytoma, is a kind of tumor that originate from adrenal or extra-adrenal chromaffin tissue, secreting a large amount of catecholamines. Some typical gene mutations such as VHL, RET and NF1 play roles in the development of pheochromocytoma. Besides, headache, sweating, and palpitations are the usual manifestations of pheochromocytoma. Most clinical symptoms such as hypertension, headache, sweating and palpitation are related to excessive catecholamine secretion. Though preoperative pretreatment with α-blockers was routine before pheochromocytoma surgery, it showed a lot of limitations because the blockage took effect after catecholamine releasing. Thus, blocking catecholamine production before its releasing shows great significance. For this purpose, in this review, we described the synthesis and metabolic process of catecholamines, the ion channels associated with catecholamine secretion and the influencing factors of the section of catecholamine. We then discussed the related treatment strategies which based on the metabolism and secretion of catecholamine to lay a foundation for the clinical medication of pheochromocytoma.

Actualización sobre el manejo diagnóstico y terapéutico del feocromocitoma y el paraganglioma

Pheochromocytomas and paragangliomas are catecholamine-producing tumours originating from chromaffin cells of the sympathetic nervous system of the adrenal medulla or extra-adrenal chromaffin tissue, respectively. They can be sporadic or be associated with genetic diseases in up to 30% of cases. Biochemical confirmation of the elevation of plasma and/or urinary metanephrines will establish the diagnosis of pheochromocytoma, whereas computed tomography or magnetic resonance imaging is used for the initial location diagnosis. In metastatic pheochromocytoma, 123I-metaiodobenzylguanidine (MIBG) scintigraphy and 18F-FDG or 68Ga-DOTATATE positron emission tomography may be helpful. Surgical resection, the only curative option in these patients, is the treatment of choice for pheochromocytomas and paragangliomas being correct preoperative preparation essential to reduce morbidity and mortality. Malignant pheochromocytoma is a rare entity that can only be diagnosed when metastases are present. There is no effective curative treatment; genetic predisposition, tumor development, disease progression and location of metastases will determine its prognosis.

MON-394 Spontaneous Hemorrhage of Undiagnosed Adrenal Pheochromocytome Following Anticoagulation for Unstable Angina

Introduction: Pheochromocytomas are rare catecholamine producing neuroendocrine tumors of the adrenal medulla or extra-adrenal chromaffin tissue with a prevalence of less than 1%. Pheochromocytoma presenting with acute hemorrhage is extremely rare and can be the cause of massive and lethal retroperitoneal hemorrhage. Symptoms are due to periodic catecholamine discharge into the vasculature, mass effect of the lesion or adrenal insufficiency. This report highlights a case of retroperitoneal hemorrhage in a patient with undiagnosed pheochromocytoma who was anticoagulated for unstable angina. Case Report: We present a 41 year old female who was admitted to our hospital due to concern of recurrent episodes of headaches associated with nausea, vomiting and left sided abdominal pain radiating to her chest along with diaphoresis. Her medical history was notable for hypertension, diabetes type 2, CVA and obstructive sleep apnea. In the ER she was noted to have elevated blood pressure and tachycardia with some episodes of bradycardia. Her examination was unremarkable except left sided flank pain. Her labs were unremarkable except acute kidney injury. She had an EKG done which did show some T wave inversions in inferior leads. She was evaluated by CVICU who recommended to start the patient on anticoagulation. She was admitted to the floor for unstable angina and did receive a therapeutic dose of lovenox. After receiving lovenox she developed severe left sided flank pain and elevated blood pressure in the 240/140,s range. In view of severe abdominal pain CT abdomen was done which revealed hemorrhage of left retroperitoneal mass. She was transferred to ICU and started on nicardipine drip for blood pressure control and retroperitoneal bleed was monitored. Given her history of episodic spells of hypertension, diaphoresis and headache combined with retroperitoneal mass, work up for pheochromocytoma was initiated. Patient was noted to have elevated serum metanephrines and normetanephrines with values more than 4 times normal. Patient was started on prazosin for blood pressure control and was discharged home when blood pressure improved with recommendations for blood pressure optimization with medications for 2 weeks prior to surgical intervention. Conclusion: Spontaneous hemorrhage within a pheochromocytoma is rare and it bears medical and surgical challenges because of massive release of catecholamines and hemodynamic instability associated with it. Thus an accurate diagnosis and adequately prepared surgical removal are important for a good postoperative prognosis. This case reinforces the need for maintaining a high index of suspicion for pheochromocytoma in similar cases.

Paraganglioma of the Urinary Bladder: A Rare Cause of Hypertension and Urinary Tract Infections

Pheochromocytoma is a neoplasm, which develops from cells of the chromaffin tissues that are derived from the ectodermic neural system and mostly situated within the adrenal medulla. Approximately 15% of pheochromocytoma cases arise from extra-adrenal chromaffin tissue. Pheochromocytoma of the bladder is rare and accounts for less than 0.06% of all bladder neoplasms and less than 1% of all pheochromocytomas. We report a case of a young woman who presented with uncontrolled hypertension, recurrent urinary tract infections and micturition attacks and was found to have a metastatic bladder paraganglioma. In addition, we provide a summary table of the clinical manifestations of paragangliomas based on anatomic locations.

Excision of a Sub-Coronary Artery Primary Cardiac Paraganglioma of the Right Atrioventricular Groove

Paragangliomas are neoplasms of neural crest origin arising from extra-adrenal chromaffin tissue. Less than 2% of all paragangliomas are located in the thoracic cavity with primary cardiac paragangliomas especially rare, typically originating from the left atrium. They are usually benign although malignancy can occur, commonly in association with hereditary pheochromocytoma-paraganglioma syndrome. Patients may present with symptoms related to either catecholamine excess or local compression however most are asymptomatic. Given their rarity, surgical experience with cardiac paragangliomas is limited, with simple excision, excision with reconstruction, autotransplantation and even orthotopic heart transplantation described. We present the case of a primary cardiac paraganglioma in an asymptomatic 38-year-old male with hereditary pheochromocytoma-paraganglioma syndrome and a family history of fatal malignant paraganglioma. The mass was located in the right atrioventricular groove beneath the right coronary artery (RCA) in juxtaposition with the right atrial appendage. Only three primary cardiac paragangliomas of the right atrioventricular groove have been reported previously. Given his family history, a decision for intervention was made after both the size of the mass on serial imaging and his serum catecholamines were noted to be increasing on follow-up. After median sternotomy, the neoplasm was enucleated with the use of cardiopulmonary bypass and cardioplegic arrest to allow for a still operative field. Multiple feeding vessels between the mass and the RCA were ligated with clips and diathermy. The postoperative course was uneventful with normalisation of his serum catecholamines and discharge day 5 postoperatively.

Glomus Tumor of the Larynx: A Rare Synchronous Paraganglioma in a Patient with Bilateral Carotid Body Tumor Detected on 68Ga-DOTANOC PET/CT.

Paragangliomas are neoplasms arising from extra-adrenal chromaffin tissue. They frequently cause symptoms by overproduction of catecholamines with known predilection to multicentricity. We describe the case of a patient with bilateral carotid body tumor who underwent a baseline 68 Gallium labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide

Laparoscopic adrenalectomy in a pediatric patient

A pheochromocytoma is a highly vascular neuroendocrine tumor of the medulla of the adrenal glands, originating from the chromaffin cells or extra-adrenal chromaffin tissue and secreting an excessive amount of catecholamines. Medical management of this tumor includes correction of hypertension and arrhythmias, and assessment of end organ damage. This can be achieved by alpha-receptor blockade and beta-receptor blockade, calcium channel blockers (CCBs), alpha-methyl-tyrosine, etc. Surgical excision of the tumor, either open laparotomy or laparoscopy, is the definitive management. A laparoscopic approach offers several advantages compared with an open laparotomy such as decreasing fluid shifts that may accompany an open procedure, potentially decreasing the surgical stress imposed on the patient, decreasing the need for postoperative analgesia, shortening postoperative convalescence including an intensive care unit stay, and decreasing the overall hospital stay. A 11-year-old male patient with left adrenal mass measuring 2.9 cm × 3.9 cm × 4.7 cm on alpha-blocker and beta-blocker for laparoscopic adrenalectomy was successfully managed perioperatively.

Phäochromozytom: Diagnostik und Therapie

Pheochromocytomas (P) are rare catecholamine producing neuroendocrine tumors originating from the chromaffin cells of the adrenal medulla or in 15 % of cases from extra adrenal chromaffin tissue and termed paragangliomas (PGL). Because of secretion of the catecholamines - adrenaline, noradrenaline and dopamine - the tumors are dangerous with a risk of life threating hypertensive crises. Measurements of plasma metanephrine, normetanephrine and methoxytyramine by liquid chromatography with tandem mass spectrometry provides the most accurate and precise method for biochemical diagnosis. Approximately 30-40 % of the tumors have a hereditary background due to mutations of 11 known susceptibility genes, with identification facilitated by targeted genetic testing according to clinical presentation. Apart from syndrome-dependent clinical stigmata, other hints to an underlying mutation can be provided by biochemical profiles of the catecholamine metabolites, tumor location, patient age and presence of metastatic disease. Surgery with minimal invasive procedures is the recommended therapeutic way after pretreatment with an alpha receptor blocking medication.

A Carotid Body Tumor Mimicking a Thyroid Nodule

Paragangliomas (PGLs) are neuroendocrine tumors arising from the extra-adrenal chromaffin tissue of the autonomic nervous system. They are most frequently found in the head and neck, mainly associated with the carotid body, vagus nerve, jugulotympanic paraganglia, and occasionaly, the superior-inferior paraganglia. Paragangliomas are rarely encountered in thyroid as well, and thyroid paragangliomas can be misinterpreted as medullary thyroid carcinomas. However, cases of paragangliomas mimicking thyroid nodules were also reported in literature rarely. In this article, we reported a case first giving an impression of a thyroid nodule, then suggesting the likelihood of a medullary thyroid carcinoma or intrathyroidal paraganglioma via core needle biopsy, but finally was diagnosed as a carotid body tumor. J Med Cases. 2014;5(3):125-128 doi: http://dx.doi.org/10.14740/jmc1966e

Cell Loss and Autophagy in the Extra‐Adrenal Chromaffin Organ of Zuckerkandl are Regulated by Glucocorticoid Signalling

Neuroendocrine chromaffin cells exist in both intra- and extra-adrenal locations; the organ of Zuckerkandl (OZ) constitutes the largest accumulation of extra-adrenal chromaffin tissue in mammals. The OZ disappears postnatally by modes that are still enigmatic but can be maintained by treatment with glucocorticoids (GC). Whether the response to GC reflects a pharmacological or a physiological role of GC has not been clarified. Using mice with a conditional deletion of the GC-receptor (GR) gene restricted to cells expressing the dopamine β-hydroxylase (DBH) gene [GRfl/fl; DBHCre abbreviated (GRDBHCre)], we now present the first evidence for a physiological role of GC signalling in the postnatal maintenance of the OZ: postnatal losses of OZ chromaffin cells in GRDBHCre mice are doubled compared to wild-type littermates. We find that postnatal cell loss in the OZ starts at birth and is accompanied by autophagy. Electron microscopy reveals autophagic vacuoles and autophagolysosomes in chromaffin cells. Autophagy in OZ extra-adrenal chromaffin cells is confirmed by showing accumulation of p62 protein, which occurs, when autophagy is blocked by deleting the Atg5 gene (Atg5DBHCre mice). Cathepsin-D, a lysosomal marker, is expressed in cells that surround chromaffin cells and are positive for the macrophage marker BM8. Macrophages are relatively more abundant in mice lacking the GR, indicating more robust elimination of degenerating chromaffin cells in GRDBHCre mice than in wild-type littermates. In summary, our results indicate that extra-adrenal chromaffin cells in the OZ show signs of autophagy, which accompany their postnatal numerical decline, a process that is controlled by GR signalling.

Metastatic paraganglioma: management of orthostatic hypotension – a case report

Paragangliomas, also referred to as extra-adrenal phaeochromocytomas, are neoplasms of extra-adrenal chromaffin tissue which synthesise cathecholamines.1 The increased production and release of catecholamines causes symptoms as a result of excess alpha- and beta-adrenoceptor stimulation. These may include headaches, palpitations and profuse sweating. On examination hypertension and tachycardia may be present, although these can be paroxysmal.2 Chromaffin cell tumours are extremely rare, and about 5–10% of these comprise paragangliomas located in the para-aortic sympathetic chains or the urinary bladder; least commonly, paragangliomas are found in the thoracic or head and neck regions.3 Although most commonly benign, they can occasionally (approximately 3% of paragangliomas) be malignant, with either local invasion (gross or microscopic), seen at the time of primary resection, or distant metastatic spread, which is usually only recognised at tumour recurrence.4 Malignant disease can often be successfully managed with high-dose radiolabelled metaiodobenzylguanidine (MIBG)5 with or without combination chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD).6 The rarity of the disease means the evidence base of management is currently relatively poor. Orthostatic hypotension can also be present with cathecholamine-secreting tumours. 7 It can be defined as more than 20mmHg fall in systolic blood pressure (BP) and/or more than 10mmHg fall in diastolic BP, over a 2 minute period after standing.8 The aetiological basis of orthostatic hypotension in this context remains unclear. For some time it has been postulated that the increase in circulating catecholamines leads to depression of sympathetic vascular response, due to alpha-adrenoceptor down-regulation; reduced blood volume is also thought to be involved, as a consequence of pressure-induced natriuresis especially when hypertension is severe and paroxysmal.9,10 It has also been proposed that sympathetic vascular modulation is involved in the aetiology.11 The existing literature contains reports of orthostatic hypotension in benign disease, where measures such as increased fluid and salt intake have been used with some success. However, in the rare cases of malignant disease, with or without distant metastases, very little has been described as regards how best to manage this debilitating and poorly understood symptom. Here we describe a case of in- and out-patient management of orthostatic hypotension in a patient with metastatic paraganglioma.

Extra-adrenal Pheochromocytoma in the Organ of Zuckerkandl: Diagnosis and Treatment Strategies

Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare catecholamine-secreting neuroendocrine tumors arising from chromaffin tissue and can occur within the adrenal medulla (PHEO) or extra-adrenal sites (PGL). The most common site for PGL is the organ of Zuckerkandl, extra-adrenal chromaffin tissue near the origin of the inferior mesenteric artery.We here present 2 patients with extra-adrenal PGL in the organ of Zuckerkandl, located by iodine-123-metaiodobenzylguanadine ( (123)I-MIBG) scintigraphy and thereafter treated surgically or with iodine-131-metaiodobenzylguanadine ( (131)I-MIBG). First, in a 15-year-old boy with clinical suspicion of PHEO, the diagnosis was established by biochemical evaluation and confirmed by further imaging studies, including CT and (123)I-MIBG, as PGL in the Zuckerkandl organ. The tumor was completely resected by laparotomy. Second, in a 70-year-old woman presenting with progressive hypertension and palpitations, MR and (123)I-MIBG revealed a singular tumor lesion with abnormal (123)I-MIBG uptake in the Zuckerkandl organ. Due to severe general vascular disease, surgery was not performed and instead the patient underwent (131)I-MIBG therapy. The patient showed a good symptomatic response with improvement of symptoms and no relevant side-effects of therapy.

Paraganglioma funcional extraadrenal, una causa infrecuente de eclampsia

Functional paragangliomas are rare tumors which originate in the extra-adrenal chromaffin tissue which produces catecolaminas; and, their appearance during pregnancy is even rarer; very few cases have been reported upon in the literature. Nevertheless, the suspicion of paraganglioma should be considered as a differential diagnosis in pregnant patients with hypertension, especially when occuring paroxistically before the 20th month of gestation, and when associated with facial flushing unaccompanied by proteinuria or edemas. Confirmation is made with biochemical or imaging tests, and treatment is primarily surgical. Special attention is paid to patient's blood pressure stats and hemodynamic state at pre-, trans- and postoperative stages, due to the nature of the tumor. This article presents the case of an adult female diagnosed with functional extradrenal paraganglioma whose first clinical manifestation was eclampsia. A brief review of the related literature is also included.

Surgical Anatomy of the Retroperitoneal Spaces, Part V: Surgical Applications and Complications

Knowledge of the surgical anatomy of the retroperitoneum is crucial for surgery of the retroperitoneal organs. Surgery is essential for treatment of retroperitoneal pathologies. The list of these diseases is extensive and comprises acute and chronic inflammatory processes (abscess, injury, hematoma, idiopathic fibrosis), metastatic neoplasms, and primary neoplasms from fibroadipose tissue, connective tissue, smooth and striated muscle, vascular tissue, somatic and sympathetic nervous tissue, extraadrenal chromaffin tissue, and lymphatic tissue. The retroperitoneum can be approached and explored by several routes, including the transperitoneal route and the extraperitoneal route. The retroperitoneal approach to the iliac fossa is used for ectopic renal transplantation. Safe and reliable primary retroperitoneal access can be performed for laparoscopic exploration. The anatomic complications of retroperitoneal surgery are the complications of the organs located in several compartments of the retroperitoneal space. Complications may arise from incisions to the somatic wall, somatic nerves, blood and lymphatic vessels, lymph nodes, visceral autonomous plexuses, and neighboring splanchna.

High frequency of SNAIL-expressing cells confirms and predicts metastatic potential of phaeochromocytoma

Phaeochromocytomas are uncommon tumours of adrenal or extra-adrenal chromaffin tissue. About 2-26% of these have been reported to metastasize, but, on histological criteria, it is virtually impossible to predict malignant behaviour of the tumour. Using immunohistochemistry, we analysed the protein expression of SNAIL, a zinc-finger transcription factor, in a series of 50 phaeochromocytoma specimens from 42 patients. We found that SNAIL-expressing cells are frequent in metastatic primary tumours and their metastases, whereas in tumours without metastases, SNAIL expression is commonly absent. We conclude that the expression of SNAIL may be of use in predicting the metastatic potential of phaeochromocytoma.

Laparoscopic Excision of a Familial Paraganglioma

Pheochromocytomas are rare neuroendocrine tumors that secrete catecholamines and usually arise from the adrenal medulla. Catecholamine-producing tumors that arise from extra-adrenal chromaffin tissue are referred to as paragangliomas, or extra-adrenal pheochromocytomas. Contrary to the traditional "Rule of Tens," as many as 25% of pheochromocytomas occur in hereditary tumor syndromes, such as multiple endocrine neoplasia-2, von Hippel-Lindau disease, neurofibromatosis-1, or hereditary or familial paraganglioma syndrome. Surgical resection remains the only curative therapy for pheochromocytomas, and advances in minimally invasive techniques have shown laparoscopic adrenalectomy to be safe and effective. Paragangliomas are extremely rare tumors, especially in children, and the role of laparoscopy in their treatment is evolving. This case report and the accompanying video demonstrate that the laparoscopic approach to retroperitoneal paraganglioma resection provides excellent exposure of the tumor and surrounding structures. Given proper patient preparation and perioperative monitoring, laparoscopic exploration and resection of paragangliomas can be safely and successfully accomplished in children. In addition, genetic analysis should be considered for all patients presenting with these tumors.

Paraganglioma of a Bladder with a Bladder Stone

Paragangliomas of the urinary bladder are very rare tumors of the paraganglion system that arise from chromaffin cells in or near the sympathetic ganglia. Only approximately 15% of them develop from extra-adrenal chromaffin tissue. Most of these tumors are hormonally active and secrete mainly noradrenaline (rarely adrenaline), calcitonin, and adrenocorticotropic hormone. Paragangliomas are generally benign tumors, with less than 10% being malignant. Here we report a case of a paraganglioma arising in a urinary bladder with a bladder stone.

Small Clusters of Granule-Containing Cells at the Lateral Side of the Posterior Cricoarytenoid Muscle of the Young Adult Rat

Small clusters consisting of granule-containing cells, sustentacular cells and capillaries around them, similar in structure to the carotid body-like paraganglia, sometimes existed at the lateral side of the posterior cricoarytenoid (PCA) muscle of young adult (3 months) rats. Differing from the paraganglia, however, these cell clusters were discontinuously invested by slender cytoplasmic processes of fibroblasts. In individual granule-containing cells, granules varied in size and had a concentrically or eccentrically arranged, electron-dense material, resembling those of chromaffin cells of the adrenal medulla. A series of desmosome-like structures were frequently observed between adjacent granule-containing cells, but synapses between them were not necessarily clear. Nerve endings containing clear synaptic vesicles and occasional granulated vesicles, being possibly cholinergic in nature, sometimes formed synapses with the granule-containing cells, probably indicating that the granule-containing cells receive the efferent nerve innervation. On the other hand, the sustentacular cells lacked cytoplasmic granules and sent their cytoplasmic processes around the granule-containing cells. Capillaries in and around clustered cells were of the fenestrated type. From these findings, it is suggested that unlike the carotid body-like paraganglia, the noncapsulated cell clusters at the lateral side of the PCA muscle of the young adult rat may be identical to groups of extra-adrenal chromaffin tissues.

Familial pheochromocytomas and paragangliomas associated with mutations of the succinate dehydrogenase genes

Pheochromocytomas and other sympathetic paragangliomas are rare tumors of the adrenal gland or extra-adrenal chromaffin tissue. Mutations of the genes encoding three subunits of the mitochondrial enzyme succinate dehydrogenase give rise to hereditary paraganglioma. We will review the distinct clinical phenotypes of familial paraganglioma syndromes associated with mutations in genes encoding for three different subunits of succinate dehydrogenase. The current insights in optimal strategies for biochemical testing, tumor localization and therapy of paraganglioma will be discussed. Furthermore, we provide recommendations regarding genetic testing and tumor screening among relatives of patients with succinate dehydrogenase-related paraganglioma.