Malignant Pheochromocytoma Research Articles

Diagnostic Performance of 124I-Metaiodobenzylguanidine PET/CT in Patients with Pheochromocytoma.

123/131I-metaiodobenzylguanidine (MIBG) scintigraphy has shown a high specificity for imaging pheochromocytoma and paraganglioma, but with low sensitivity because of low spatial resolution. 124I-MIBG PET may be able to overcome this limitation and improve the staging of patients with (suspected) pheochromocytoma. Methods: We analyzed the sensitivity, specificity, and positive and negative predictive values of 124I-MIBG PET in 43 consecutive patients with suspected (recurrence of) pheochromocytoma using histopathologic (n = 25) and clinical validation (n = 18) as the standard of truth. Furthermore, we compared the detection rate of 124I-MIBG PET versus contrast-enhanced (CE) CT on a per-patient and per-lesion basis in 13 additional patients with known metastatic malignant pheochromocytoma. Results:124I-MIBG PET/CT was positive in 19 (44%) of 43 patients with suspected pheochromocytoma. The presence of pheochromocytoma was confirmed in 22 (51%) of 43. 124I-MIBG PET/CT sensitivity, specificity, and positive and negative predictive values were 86%, 100%, 100%, and 88%, respectively. 124I-MIBG PET was positive in 11 (85%) of 13 patients with malignant pheochromocytoma. Combined 124I-MIBG PET and CE CT detected 173 lesions, of which 166 (96%) and 118 (68%) were visible on 124I-MIBG PET and CE CT, respectively. Conclusion:124I-MIBG PET detects pheochromocytoma with high accuracy at initial staging and a high detection rate at restaging. Future assessment of 124I-MIBG PET for treatment guidance, including personalized 131I-MIBG therapy, is warranted.

567O First International Randomized Study in Malignant Progressive Pheochromocytoma and Paragangliomas (FIRSTMAPPP): An academic double-blind trial investigating sunitinib

Malignant pheochromocytoma and paraganglioma (MPP) is a very rare cancer (annual incidence < 1 per million). Here, we report the first academic randomized double-blind phase II study results assessing Sunitinib efficacy compared to placebo.

Supportive Management of Patients with Advanced Pheochromocytomas and Paragangliomas Receiving PRRT.

Peptide receptor radionuclide therapy (PRRT) is used to treat patients with advanced malignant pheochromocytomas (PCCs) and paragangliomas (PGLs). Patients are at risk of a PRRT-induced catecholamine crisis, and standard guidelines regarding the prevention and management of infusion reactions are lacking. In this case series, the institutional experience of five sequential patients with metastatic PCCs and PGLs receiving PRRT on an outpatient basis is described, of which four had symptomatic tumors and three had a high burden of disease. All patients with symptomatic tumors were treated with preventive management prior to the initiation of PRRT, and no infusion reactions or catecholamine crises were documented. PRRT may be delivered safely on an outpatient basis for patients with metastatic PCCs and PGLs with the involvement of an interdisciplinary team.

Malignant pheochromocytoma: A diagnostic and therapeutic dilemma.

IntroductionMalignant pheochromocytomas are rare endocrine tumors that develop within chromaffin tissue. The diagnosis of malignancy is based on neoplastic recurrence or the presence of metastasis in organs that lack chromaffin tissue. We report a series of four cases because of their diagnostic and therapeutic particularities.Presentation of casewe describe four clinical cases of patients with malignant pheochromocytoma whose Menard triad “headache-palpitations-sweating” was present in three out of four patients, the methoxylated derivatives were measured in 4 patients, 3 of which had high values, all of our patients carried out a CT scan which objectified signs of malignancy, MRI was performed on a single patient; presenting with a neoplastic recurrence; looking for a locoregional invasion.DiscussionPheochromocytoma (PC) is a rare neuroendocrine tumor derived from the chromaffin cells of the adrenal medulla. Its annual incidence is 2 to 8 per million adults. A peak frequency is observed between 30 and 40 years of age. Approximately 10% of pheochromocytomas are malignant and in 10% of cases, bilateral localization is observed. Criteria for malignancy include the invasion of neighboring organs, a large tumor, the presence of lymphadenopathy on imaging, or fixation on scintigraphy. Surgery for MAP is not always curative. In the case of multiple liver metastases, treatment is based on adrenalectomy, which can be effectively combined with chemoembolization, cryoablation, or radiofrequency techniques.ConclusionThe main prognostic factors of the malignant pheochromocytomas are a large tumor volume, the existence or number of visceral metastases, and the presence of a mutation in the SDHB (Succinate dehydrogenase B) gene.

131I-MIBG treatment in malignant pheochromocytoma: A case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Malignant pheochromocytomas and paragangliomas: clinical and pathological characteristics of a tertiary hospital’ cohort

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Outcomes of malignant pheochromocytoma based on operative approach: A National Cancer Database analysis

BackgroundMalignant pheochromocytoma is often managed with adrenalectomy. Most literature focusing on postoperative outcomes are from single institutions. This study aimed to describe outcomes of adrenalectomy for malignant pheochromocytoma using a national database. We hypothesized that minimally invasive approaches might be associated with improved short-term outcomes but potentially inferior oncologic efficacy. MethodsPatients who underwent adrenalectomy for malignant pheochromocytoma were identified in the National Cancer Database (2010–2016). Patients were categorized as minimally invasive adrenalectomy or open adrenalectomy. Short- and long-term outcomes were compared. ResultsA total of 276 patients underwent adrenalectomy for malignant pheochromocytoma: 50.7% open adrenalectomy and 49.3% minimally invasive adrenalectomy. Demographics were similar, except those who underwent open adrenalectomy had larger tumors compared to minimally invasive adrenalectomy (8.2 cm vs 4.7 cm; P < .001). Tumor size ≥6 cm was associated with a reduced likelihood of minimally invasive adrenalectomy (relative to open adrenalectomy) on multivariable regression (odds ratio = 0.23; P < .001). Open adrenalectomy was associated with longer duration of stay relative to minimally invasive adrenalectomy (6 vs 3 days; P < .001). Rates of positive margins, unplanned readmissions, or 30-/90-day mortalities were similar based on operative approach. Five-year survival rates were similar (open adrenalectomy 74.3%, minimally invasive adrenalectomy 79.1%). There was no association between overall survival and operative approach on multivariable Cox analysis when controlling for tumor size, laterality, and clinicodemographic variables. ConclusionPatients with larger malignant pheochromocytomas were more likely to undergo an open adrenalectomy. With the exception of an increased duration of stay, there was no difference in short- or long-term postoperative outcomes. These data suggest that minimally invasive adrenalectomy appears safe among tumors <6 cm.

Synchronous Malignant Pheochromocytoma With Renal Cell Carcinoma: A Case Report

Introduction: In the US, Pheochromocytoma/paraganglioma incidence is estimated to be 2–8 per 1 million people each year with around 100–200 of these cases being malignant. Malignant pheochromocytoma is defined by documented presence of metastases or evidence of extensive local invasion. There are certain genetic syndromes which are also associated with renal cell carcinoma, including SDHB mutations type 4, VHL disease and familial pheochromocytoma. These syndromes are important to recognize as they may signify a worse prognosis. Here, we describe a case of co-occurrence of malignant PC with renal cell carcinoma.Case Report: A 53-year-old Hispanic male with history of HTN and recently diagnosed metastatic pheochromocytoma was admitted for surgical debulking of the left retroperitoneal/adrenal and renal masses. Symptoms began five months prior after he presented with an ischemic stroke in the setting of labile hypertension. He was diagnosed with a 6.3 x 4.6 x 6.8 cm incidental left retroperitoneal mass and suspicious left renal mass on CT imaging but also noted several lytic bony lesions concerning for bone metastasis. A spinal biopsy was obtained which was consistent with a well-differentiated metastatic neuroendocrine tumor. Laboratory evaluation was notable for Chromogranin A level of 6959ng/mL (25–140). He was started on Lanreotide. Given persistently difficult to control HTN he underwent work up for secondary hypertension. Hormonal evaluation was notable for plasma free metanephrine of 534pg/mL (<57pg/mL), normetanephrine 6155pg/mL(<148pg/mL), and total metanephrine of 6689pg/mL (205pg/mL) consistent with metastatic Pheochromocytoma. After appropriate alpha blockade he underwent left adrenalectomy, nephrectomy and liver tumor microwave ablation. Pathology was consistent with an 8.7cm pheochromocytoma with extensive retroperitoneal soft tissue invasion and PASS score of 9 as well as a 3.6 cm renal cell (clear cell-papillary type) carcinoma. On follow up, Plasma metanephrine decreased significantly postoperatively to a free metanephrine of 28pg/ml, normetanephrine 1153pg/ml, and total metanephrine of 1181pg/mL. He was referred for genetic testing but unfortunately, he was readmitted one month later with cerebral hemorrhage and expired.Conclusion: Advancements in genetics have led to improved understanding of the molecular etiologies of pheochromocytomas. A number of genetic defects are associated with PC and RCC, including SDHB mutations type 4, VHL and familial pheochromocytoma. Our case underscores the high morbidity and mortality in patients with metastatic PC with RCC and perhaps the catastrophic outcomes in such patients. Assessing patient’s genetics in these cases is now the standard of care, however further research studies are warranted to better understand the significance of tumor genetics on prognosis and management.

Bilateral Familial Pheochromocytoma: Difficulty of Diagnosis and Management

Introduction: Bilateral pheochromocytoma is a rare tumor, often seen in the context of a family illness. The majority of pheochromocytomas are sporadic, but they can also occur within the framework of genetic diseases (10%): MEN2, VPL, NF1, familial paraganglioma (mutation of SDHB)⋯ In the context of a familial genetic disease, the pheochromocytoma can be either unilateral or bilateral, benign in 95% of cases and malignant in 5%. It still poses several problems related to its diagnosis, genetic aspects, especially in the absence of a family history. And the criteria of malignancy, given the non-existence to date of a certain & universal criterion that judges the malignancy of the tumor. We present through this article the exceptional case of “bilateral familial pheochromocytomas with strong suspicion of malignancy”.Clinical Case: A 29-year-old lady, hypertensive since 4 years, admitted for exploration of severe secondary hypertension. She reports a triad of menard and severe lumbar pain, the somatic examination shows hypersensitivity of the flanks, a BP of 240/120 mmhg. the abdominal CT scan confirmed by an MRI show a right adrenal mass of 5 cm & another left of 1 cm, of suspicious appearance (irregular contours, areas of necrosis, heterogeneity, spontaneous density at 35 HU, a wash out at 33% with presence of L4 spinal angioma and peri-aortic lymph nodes. urinary methoxylated derivatives (UMD) returned high. The genetic study was positive VPL (on various radiological tests, there was just a spinal angioma) We retained the diagnosis of familal bilateral pheochromocytoma. In front of the clinical & radiological signs of malignancy, we decided to do: a right total adrenalectomy & a left partial adrenalectomy. Unfortunately, the blood pressure didn’t drop, and UMD were still positive; the anatomopathological study shows a pheochromocytoma with a PASS score estimated at 3 (benign!) Faced with conflicting clinical-radiological and histological data, we decided to total adrenalectomy without lymph node dissection and to closely monitor the progress. the post Op blood pressure was normalized and the UMD returned negative.Conclusion: Malignant familial bilateral pheochromocytoma is a very rare & very difficult entity to diagnose, manage & monitor. A good management requires serious collaboration between: endocrinologist, radiologist, urologist, pathologist

Composite Pheochromocytoma With Ganglioneuroblastoma: A Case Report

Introduction: A composite pheochromocytoma (PC) is an adrenal tumor that is often diagnosed post-operatively on histopathology. PCs are unique in that it is a combination of typicalpheochromocytoma and neural crest derived tumors. The incidence is reported to be less than 3%of adrenal neoplasms. The most common co-existing tumor within a PC is a ganglioneuroma. Wepresent a rare case of PC containing ganglioneuroblastoma (PC-GNBL) in a woman withoutsignificant biochemical manifestation of excess catecholamine production. Case Report: A 63-year-old woman with a prolonged history of uncontrolled hypertension on 4 oral anti-hypertensive medications (Amilodipine 10mg daily, Valsartan/HCTZ 320/25mg daily andClonidine 0.1mg/24h patch) and uncontrolled type 2 diabetes on insulin was diagnosed with a1.5x1.8x1.5cm right adrenal incidentaloma 2 years prior on CT imaging for abdominal pain. Hormonal evaluation was notable for plasma free metanephrine of 66 (<57pg/ml),normetanephrine 229 (<148pg/ml), and total metanephrines of 295 (205 pg/ml). However, 24-hour urine metanephrine evaluation was normal on two occasions: metanephrine 121 and 168mcg/24h (90-315), norepinephrine 237 and 336 mcg/24h (122-676) and total metanephrines 358and 504mcg/24 h (224-832). Hyperaldosteronism and hypercortisolism were ruled out. Follow-up CT scan 14 months later demonstrated growth of the right adrenal nodule to 1.7x2x2cm with49% washout. She underwent laparoscopic right adrenalectomy without perioperativecomplications. Pathology was consistent with a PC-GNBL. The PASS score was 7, consistentwith malignant pheochromocytoma. Within weeks of surgery, she had marked clinicalimprovement. Blood pressure was controlled on one anti-hypertensive and Hgb A1c decreased to7.1% from 11% without requiring insulin. CT abdomen/pelvis 6 months post-operatively did notshow evidence of metastasis. She was referred for genetic testing. Conclusion: This case highlights an unusual presentations of pheochmocytoma. It’s important to recognizethat resistant hypertension can present without episodic headaches, diaphoresis, palpitations, andwithout biochemical evidence of catecholamine excess. Composite PCs are indistinguishableclinically or radiologically from ordinary pheochmocytomas. These exceedingly rare mixedtumors are only diagnosed via surgical pathology. To date, there are only a few cases reported inthe medical literature of co-existing PC-GNBL tumors. Due to the scarcity of composite PCscases, important information regarding its presentation and prognosis are unknown. It remains tobe seen whether the GNBL part of the tumor changes the prognosis of the tumor. However, inour case, the clinical status of our patient improved.

Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World.

Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both “cold”, particularly octreotide and lanreotide, and “hot” analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with 68Ga-DOTATATE and 177Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in succinate dehydrogenase subunit B gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of 68Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.

The use of immunotherapy treatment in malignant pheochromocytomas/paragangliomas: a case report

BackgroundPheochromocytomas are a subset of paragangliomas, which are a rare group of neural crest cell-derived tumors. Malignant cases of both pheochromocytomas and paragangliomas are even rarer, and currently there is no standard of care. This case report details the use of off-label immunotherapy and its efficacy in the management of the aforementioned tumor.Case presentationHerein is presented a case of a 60-year-old Caucasian female with a rare malignant pheochromocytoma. The tumor was determined to be unresectable because of involvement of surrounding organs. Radiation therapy was also not a viable option because of concerns over appreciable toxicity in relation to mass size. As there is no standard of care for malignant cases, the patient was started on chemotherapeutic agents but was soon shown to be intolerant to this treatment. As she was ineligible for several clinical trials, the patient was started on the off-label immunotherapeutic agents nivolumab and ipilimumab. Immunotherapy use resulted in decreased tumor size, improved quality of life, and reconsideration for radiation therapy.ConclusionsThe use of immunotherapy in pheochromocytoma in this patient clearly demonstrated substantial benefit, as she was able to be reconsidered for radiation therapy. Not only has the patient been tolerant of this treatment, but she has exhibited progression-free survival of over 20 months. As there is no current standard treatment for malignant pheochromocytomas, the success of its use in this patient lends support to the ongoing clinical trials regarding the use of immunotherapy in rare tumors, including pheochromocytomas.

Retrospective Evaluation of The Cases with Malignant Pheochromocytoma: A Single Center Experience

IIntroduction&#x0D; &#x0D; The aim of this study was to evaluate the clinicodemographic factors and features of tumors in patients with malignant pheochromocytoma.&#x0D; &#x0D; Methods:&#x0D; &#x0D; We retrospectively evaluated the data of 5 cases admitted to our department between 2013 and 2020 and diagnosed with malignant pheochromocytoma.&#x0D; &#x0D; Results:&#x0D; &#x0D; The patients included three females with mean age of 45 years at presentation. Three cases were diagnosed with pheochromocytoma after hypertensive attack and two cases were diagnosed after detection of adrenal mass. The average diameter of the adrenal mass of the cases was 58 mm. Extesion to periadrenal adipose tissue was detected in two patients, vascular invasion in one patient, and capsule invasion in 1 patient in the surgery-resected specimen. Intraabdominal lymph node metastasis was found in 1 patient and metastatic focus was seen in the liver in 1 patient at the time of the diagnosis. During follow-up, perirenal region metastasis was detected in 1 patient. Bone metastasis was seen in 3 patients, lymph node metastasis in 2 patients and lung metastasis in 1 patient. Transperitoneal surrenalectomy was performed in all cases. Lutetium-177, radiotherapy and surgery were the preferred adjuvant therapies. Three patients died because of progression of the disease or acute complications and the other 2 patients are still under follow-up in our clinic.&#x0D; &#x0D; Conclusion:&#x0D; &#x0D; Malignant pheochromocytoma is rare and definitive criteria for malignancy is not established. Prognosis is poor and there is no curative treatment. Resection of malignant pheochromocytoma with intent to cure, which may improve symptoms and possibly survival is important.

MITOCHONDRIA: Succinate dehydrogenase subunit B-associated phaeochromocytoma and paraganglioma.

Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours. So far, over 20 causative genes have been identified, of which the most frequent and strongest indicator for malignancies are mutations in succinate dehydrogenase subunit B. No curative therapy is available for patients with metastases resulting in poor prognosis. Therapy development has been hindered by lack of suitable model systems. The succinate dehydrogenase complex is located in the inner membrane of the mitochondria and plays a crucial role in the oxidative phosphorylation chain and the tricarboxylic acid-cycle. Succinate dehydrogenase deficiency results in accumulation of the oncometabolite succinate inducing hypoxia inducible factor stabilization, deoxyribonucleic acid and histone methylation inhibition, and impaired production of adenosine triphosphate. It remains unknown which combination of pathways and/or triggers are decisive for metastases development. In this review, the role of mitochondria in malignant succinate dehydrogenase subunit B-associated phaeochromocytomas and paragangliomas and implications for mitochondria as therapeutic target are discussed.

Клініко-морфологічний аналіз патології надниркових залоз у Харківському регіоні (за даними архівного матеріалу у період 2015-2019 рр.)

The adrenal glands play an important role in the functioning of the human body. There are more opportunities for early tumors detection of these endocrine glands thanks to modern diagnostic procedures, but the problem is very relevant. Morphological investigation is the basis for differentiating adrenocortical adenoma from carcinoma. Material and methods. The article presents the clinical and morphological features of the adrenal glands pathology in Kharkiv region in the period 2015-2019 by analyzing the archival histological material of 77 patients who were operated in hospitals of the State Institution "Institute of General and Emergency Surgery named after V. T. Zaitsev of National Academy of Medical Sciences of Ukraine" and "V. Danilevsky Institute for Endocrine Pathology Problems of the National Academy of Medical Sciences of Ukraine". Results and discussion. The study established that in 2015 there were 18 cases (including 8 malignant tumors), in 2016 – 16 cases (2 cases with bilateral damage, 1 malignant tumor), in 2017 – 12 cases, in 2018 – 20 cases, in 2019 – 11 cases. All tumors were benign in the last 3 years of the study. We calculated that 48.6 years was the average age of patients with this localization tumor processes (20-75 years). Women suffered more often than men (61.03% and 38.97%, respectively). Both adrenal glands had pathological changes in 2 people. The left gland is most often affected. The vast majority of the formations in 2015-2019 were benign (88.61%). Adrenocortical adenomas (45 cases, mostly clear cell variant, leftward, in women) and mature pheochromocytomas (13 cases, uncomplexed variant, leftward, in men), adrenal cysts (6 cases, more often on the right, in men, with a dense fibrous capsule), hyperplasia of the cortical, cerebral or both layers (4 cases), ganglioneuroma of the adrenal medulla (1 case) and a combination of pheochromocytoma with two adrenocorticosteromas (1 case) were among them. Conclusion. Malignant tumors were represented by malignant corticosteromas (5 cases out of 9, leftward, various sizes, with secondary changes in tumor tissue), malignant pheochromocytomas (3 cases out of 9, right, different size) and malignant paraganglioma (1 case). The larger size of the tumor did not always correlate with the nature of the process

Pheochromocytoma: A three-decade clinical experience in a multicenter study

ObjectiveTo analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). Design and MethodsA multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. ResultsA total of 106 patients (61 [57.5%] women, mean age 52.3 ± 14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ± 14.2 years vs 54.5 ± 13.9 years, p < .001). Familial PCCs were more frequently associated with MEN2A (n = 8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3 cm (3–6 cm); 27.7% of the patients had tumors ≥6 cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4 cm [2.4–5.0 cm] vs 5.6 cm [4.0–7.0 cm], p < .001). Scintigraphy by ¹²³I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). ConclusionsPCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.

Current trend in the diagnosis and management of malignant pheochromocytoma: Clinical and prognostic factors

Current trend in the diagnosis and management of malignant pheochromocytoma: Clinical and prognostic factors

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.

1166MO Clinical evaluation of serum succinate levels as a new biomarker in SDH-related paragangliomas and pheochromocytomas

MPP (malignant paragangliomas and pheochromocytomas) are rare neuroendocrine tumors that can be associated with succinate dehydrogenase subunits (SDHx) germline mutations. SDH encodes for a TCA enzyme that catalyzes the oxidation of succinate to fumarate. When mutated SDH losses its function, leading to succinate accumulation. We have evaluated serum succinate levels as a new biomarker in SDHx-mutated MPP patients. Retrospective monocentric study of 88 MPP patients (43 sporadic: SDHxWT; 45 mutated SDHx, among which 35 where SDHB) and 17 tumor-free familial asymptomatic carriers (SDH-B: 13, SDH-C: 2, SDH-D: 2). Clinical and biological data were available in all. 18F-FDG-PET was available in 32 metastatic MPP (15 sporadic, 17 SDH-B). 18F-FDG-PET analyses were performed on an Advantage Workstation (GE Healthcare). A healthy control group (n=10) is included. Serum succinate levels (n=290) were quantified by LC-MS/MS (Waters). Statistical analyses were performed with GraphpadPrism®. Serum succinate levels were increased in the disease-free SDHx group (median: 7.3 μM) compared to the control group (median: 4.8 μM). Succinate levels >6.9 μM allowed to identify disease-free SDHx mutated cases compared to the healthy control group (100% specificity; 85% sensitivity). When tumor is detected, mutated SDH-B patients had a significantly increased median succinate level (13.5 μM) compared to sporadic patients (7.9 μM) (p<0.01). Metastatic SDH-B patients showed a higher median succinate level (14.9 μM). Extension of the metastatic disease evaluated by the total lesion glycolysis (TLG) activity (18F-FDG-PET) was correlated to the succinate levels (r=0.76). In the SDHB group, patients with the highest tumor burden (3rd and 4th TLG quartiles) showed significant increased succinate levels compared to the sporadic group (p<0.001). Serum succinate is a metabolic biomarker that might be useful to identify SDHx mutated carriers (tumor-free familial asymptomatic carriers and metastatic MPP patients) and as a marker of metabolic tumor burden in patients with metastatic MPP.

Feocromocitoma: experiencia clínica de tres décadas en un estudio multicéntrico

ObjectiveTo analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). Design and methodsA multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. ResultsA total of 106 patients (61 [57.5%] women, mean age 52.3 ± 14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ± 14.2 years vs. 54.5 ± 13.9 years, p<.001). Familial PCCs were more frequently associated with MEN2A (n=8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3cm (3-6cm); 27.7% of the patients had tumors ≥6cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4cm [2.4-5.0cm] vs. 5.6cm [4.0-7.0cm], p<.001). Scintigraphy by 123I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). ConclusionsPCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.