Incidence Of Pheochromocytoma Research Articles

A Narrative Review of Pheochromocytoma in VHL.

This systematic review aims to investigate the clinical presentation, diagnostic methods, and management strategies for pheochromocytoma in patients with von Hippel-Lindau (VHL) disease, an autosomal dominant disorder that predisposes individuals to the development of various tumors, including pheochromocytomas. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla that occurs sporadically or as part of an inherited syndrome. The incidence of pheochromocytoma in VHL patients is estimated to be between 10-20%, making it the second most common tumor associated with VHL. Early detection and management of pheochromocytoma in VHL patients are critical for patient outcomes, as these tumors can cause severe hypertension, cardiovascular complications, and death. This review highlights the importance of screening for pheochromocytoma in VHL patients and discusses the current diagnostic and management strategies to optimize patient care.

SAT344 Takotsubo Cardiomyopathy Complicating Cholecystectomy In A Patient With Clinically Silent Pheochromocytoma

Abstract Disclosure: K.B. Huynh: None. T.A. Nguyen: None. J.P. Perdomo Rodriguez: None. Introduction: Pheochromocytomas (PCC) are responsible for 85 to 90 % of all catecholamine-secreting tumors, which originate from chromaffin cells of the adrenal medulla. Normotensive Incidental Pheochromocytoma (NIP) may be a distinct entity and has been reported in up to 55% in case series. Case description: A 48-year-old woman with a history of gestational hypertension presented to the hospital with acute cholecystitis. Shortly after cholecystectomy, she developed severe hypertension and flash pulmonary edema. The hospital course was complicated by an acute ischemic stroke secondary to cardiogenic emboli. She was diagnosed with Takotsubo cardiomyopathy, and a transthoracic echocardiology (TTE) revealed an ejection fraction (EF) between 20% and 45 %. CT scan of the abdomen/pelvis revealed a complex 8.3 x 6.2 x 0.6 centimeter left adrenal tumor. PET DOTATE has been declined. She was discharged on carvedilol 25 mg twice daily but not on ACE inhibitors due to soft blood pressure. She was referred to outpatient endocrinology for pheochromocytoma. Metanephrine level was elevated to 1023 pg/mL, normetanephrine was 2209 pg/mL and the total level was 3232 pg/mL. Adrenal steroids including aldosterone, cortisol, and DHEA sulfate were within normal limits. Chromogranin A was normal. Germline genetic analysis was negative. Hypertension was treated with prazosin titrated slowly to 8 mg three times daily, and carvedilol was continued. Home blood pressure readings ranged between 85/55 and 113/72 without orthostatic hypotension. Pulse ranged between 55 and 73 beats per minute. Weeks later, left adrenalectomy was aborted due to hypertension urgency and bradycardia. However, a TTE revealed normal EF. Carvedilol was discontinued, and treatment was changed to nifedipine and phenoxybenzamine, which was titrated to 40 mg three times daily until she became orthostatic over 4 weeks. She underwent successful left adrenalectomy. Discussion: Normotensive pheochromocytomas have been described in 13.5 % to 55% of incidental pheochromocytoma series. Moreover, hypertensive crises have been reported following surgery in patients with unsuspected pheochromocytoma. Hence, plasma metanephrines should be checked in all adrenal incidentalomas. While normotension is thought to mostly occur when the tumor is too small, a study by Haissaguerre et al found no correlation between size and biochemical parameters in NIP, and the NIP group was characterized by a global reduction in catecholamine and metanephrine secretion and a mean size of 52 +/- 6.7 millimeters. Our case was a much larger pheochromocytoma with 18- and 15-fold elevation in metanephrine and normetanephrine respectively. It has been described that normotensive pheochromocytoma exhibit down-regulation of different proteins involved in key processes of catecholamine metabolism that may lead to reductions in the storage and release of catecholamines. Presentation: Saturday, June 17, 2023

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

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

The most common indications for measuring metanephrine and normetanephrine in plasma - a rational approach.

Aim To determine the most common indications for measuring metanephrine and normetanephrine in plasma by gender and age and to compare the concentrations of metanephrine and normetanephrine by indication, gender and age. Methods The study was conducted on 224 patients whose plasma metanephrine and normetanephrine concentrations were measured at the Clinical Institute for Laboratory Diagnostics at the University Hospital Centre Osijek for one year, until 1st January 2020. Results The most frequent indications for biochemical testing were adrenal incidentaloma, 138 (6.6 %), and symptoms of pheochromocytoma, 41 (18.3%). Metanephrine concentration was lower in females (p=0.009). No significant correlation was found between age and metanephrine concentration, while age and normetanephrine concentration were positively correlated (p=0.01). Of the 224 patients, only one patient was diagnosed with pheochromocytoma, whose indication for measurement of metanephrine and normetanephrine was adrenal incidentaloma. Conclusion Adrenal incidentalomas and symptoms suggestive of pheochromocytoma are very common in the general population, while the incidence of pheochromocytoma is extremely low. Clear guidelines for the referral of patients for biochemical testing are needed to avoid unnecessary costs and to identify the correct diagnosis promptly.

Genetic Characteristics of Incidental Pheochromocytoma and Paraganglioma.

Pheochromocytomas and paragangliomas (PPGLs) are being increasingly discovered by imaging performed for unrelated conditions. The genetic landscape of incidental PPGLs remains to be elucidated. We aimed to describe the genetic characteristics of PPGLs discovered incidentally in a large PPGL cohort. This retrospective cross-sectional study included 697 patients with pathology confirmed PPGLs, including 283 incidentalomas and 414 nonincidentalomas, at 2 tertiary care centers in China in 2009-2019. Tumor DNA samples were sequenced by next-generation sequencing. Identified genetic mutations were confirmed by Sanger sequencing and tested in 277 available matched blood DNA samples. There was a lower proportion of patients with mutations identified (53% vs 63.3%; P = 0.0067) in incidental than nonincidental PPGLs. In incidental PPGLs, HRAS (11.7%), FGFR1 (11%), and RET (9.2%) were the top 3 mutated genes, whereas HRAS (17.9%), VHL (9.2%), and NF-1 (8.7%) exhibited the highest rate of mutations in nonincidental PPGLs. In incidental pheochromocytomas, the most frequently mutated genes were RET (10.9%), HRAS (10.4%), and VHL (8.6%), while in incidental paragangliomas, FGFR1 (32.8%), HRAS (16.4%), and EPAS1 (9.8%) topped the list. The frequency of NF-1 mutations was significantly lower in incidental than nonincidental pheochromocytomas (4.1% vs 11%; P = 0.0042), while FGFR1 mutations were far more common in incidental than nonincidental paragangliomas (32.8% vs 15.3%; P = 0.0076). More than half of patients with incidental PPGLs had mutations in common susceptibility genes. The search for susceptibility genes should take both the mode of discovery (incidental vs nonincidental) and tumor location (pheochromocytoma vs paraganglioma) into consideration.

Prikaz prve laparoskopske adrenalektomije zbog feohromocitoma u pedijatrijskoj populaciji u Republici Srbiji

Pheochromocytoma is a tumor that arises from adrenal medulla and it is characterized by increased secretion of catecholamines. The incidence of pheochromocytoma is 3 to 8 cases per million inhabitants, of which about 10 to 20% of diagnosed pheochromocytomas occurs in the pediatric population, with a higher frequency in boys. In 1.7% of the pediatric population with hypertension, the cause of hypertension is pheochromocytoma. Due to headaches and verified hypertension on twenty-four-hour holter blood pressure monitoring, the 13-year-old female patient underwent ultrasound, followed by scintigraphy and magnetic resonance imaging of the abdomen, which described an oval change above the right kidney about 4.5 cm in diameter suspected of pheochromocytoma. Twenty-four-hour urine cateholamines showed elevated noradrenaline values as much as 45 times higher than the reference range, as well as elevated Dopamine values. After adequate preparation with phenoxybenzamine and bisoprolol for two weeks, a right laparoscopic adrenalectomy was performed at the University Children's Clinic in Tirsova, which is also the first operation of this type in the pediatric population. Intraoperatively, the maximum value of tension was 180/120 mmHg. Pathohistological findings confirmed pheochromocytoma. Although a rare cause of hypertension in the pediatric population, young patients with newly diagnosed hypertension should be examined for possible pheochromocytoma. Laparoscopic adrenalectomy through both the lateral transabdominal and posterior retroperitoneoscopic approach is the gold standard for the treatment of pheochromocytomas in both the adult and pediatric populations.

UNSUSPECTED CAUSES OF HYPERTENSION

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pheochromocytomas (PC) are catecholamine-secreting tumors that arise from the chromaffin cells of the adrenal medulla and other extra-adrenal sources. The annual incidence of PC is approximately 0.8 per 100,000 person-years, however this is thought to be an underestimation as a substantial portion of PC's were diagnosed at autopsy (Beard et al). With the relative rarity of this disease coupled with its often-complicated presentation, it is not uncommon to see this disease misdiagnosed. CASE PRESENTATION: We present a 68-year-old Caucasian female with a past medical history significant for chronic tobacco use, hypertension, hypothyroidism secondary to partial thyroidectomy, coronary artery disease, paroxysmal atrial fibrillation, periodic headaches, backpain and dizziness who presented after a fall at home. An elevated troponin with normal EKG led to treatment for NSTEMI. CT head returned within normal limits and a cardiac catheterization revealed LVEF of 35-40% with 60% mid-LAD stenosis and Coreg and Ramipril were started. A few weeks later, she presented to the ED again with chest pain radiating between her shoulder blades. A CTA chest was significant for a 1.7cm soft tissue density in the right lower lung lobe and a 1.6cm right adrenal nodule. A follow-up PET/CT showed a peak SUV (standardized uptake value) of 1.6 in the lung nodule and a peak SUV of 2 in the adrenal gland nodule. Biopsy of the lung nodule via bronchoscopy was unattainable due to its small size and anatomic location. The decision to proceed to a CT-guided needle biopsy of the right adrenal mass was made with pathology returning consistent with a PC. Further evaluation included measurement of urine metanephrines, which returned elevated. Due to continued suspicion of the right lower lobe nodule likely representing an unrelated, early-stage bronchogenic carcinoma, cardiothoracic surgery consultation was obtained. Pathology of the right lower lobectomy with lymph node biopsies returned consistent with adenocarcinoma of likely lung primary origin. DISCUSSION: It is estimated that approximately 0.2-0.6% of patients with hypertension have a concurrent PC (Omura et al). In fact, approximately 15-30% of the population of hypertensive patients have secondary hypertension and resistant hypertension was noted in approximately 34% of hypertensive patients in the ALLHAT trial (Koch et al). This patient's presentation attests to the semi-cryptic nature of PC. CONCLUSIONS: This case also demonstrates that, despite a suspected cardiac etiology and incidental pulmonary malignant process, searching for the overall causation of the patients presenting symptoms may be more difficult than it first appears. After completing a secondary hypertension workup (as well as dietary and lifestyle changes) with unremarkable results it is important to consider endocrinopathies as an underlying cause, despite their rarity. REFERENCE #1: Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc. 1983 Dec;58(12):802-4. PMID: 6645626. REFERENCE #2: Omura M, Saito J, Yamaguchi K, et al. Prospective Study on the Prevalence of Secondary Hypertension among Hypertensive Patients Visiting a General Outpatient Clinic in Japan. Hypertens Res. 2004;27(3):193–202. REFERENCE #3: Koch C, Papadopoulou-Marketou N, Chrousos GP. Overview of Endocrine Hypertension. 2020 Feb 4. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, Grossman A, Hershman JM, Hofland J, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Purnell J, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. PMID: 25905214. DISCLOSURES: No relevant relationships by David Heintze, source=Web Response no disclosure on file for Billy Rosson

Феохромоцитома без артериальной гипертензии: редкий клинический случай с кратким обзором литературы

Феохромоцитома — довольно редкая нейроэндокринная опухоль, которая секретирует в кровоток высокоактивные адренергические нейромедиаторы — катехоламины. При этом не все случаи феохромоцитом демонстрируют яркую симптоматику. В клинической практике иногда случаются скрытые и атипичные формы, нормотензивная (с нормальным артериальным давлением) варианты феохромоцитом. Важнейший этап диагностики феохромоцитомы заключается в своевременном распознавании признаков, симптомов и других проявлений заболевания, которые могут указывать на необходимость дальнейшего обследования. Авторы представили редкий случай нормотензивной случайно выявленной большой феохромоцитомы левого надпочечника. 41-летний мужчина, родом из отдаленного села, без артериальной гипертензии и сахарного диабета, поступил в клинику с предварительным диагнозом инциденталомы надпочечника. По данным ультразвукового обследования брюшной полости, у пациента заподозрили образование левого надпочечника размером 47 × 36 мм. За исключением жалоб на неопределенную боль в верхней части живота, пациент не указывал на головную боль, приступы сердцебиения, чрезмерное потоотделение или изменение массы тела. Семейный анамнез в отношении нейрофиброматоза или любых опухолей щитовидной железы, паращитовидных желез, почек и других органов брюшной полости не отягощен. Пациент правильного телосложения, в удовлетворительном состоянии, без кушингоидных симптомов и поражений кожных покровов. В лежачем и в стоячем положениях в течение двух минут его частота сердечных сокращений и артериальное давление (АД) составили 76 уд/мин и 132/80 мм рт.ст., 90 уд/мин и 126/76 мм рт.ст. соответственно. Не отмечалось никаких офтальмологических нарушений или изменений со стороны органов грудной клетки и органов брюшной полости. Интенсивный мониторинг АД не обнаружил пиков пароксизмальной гипертензии. При отсутствии артериальной гипертензии и других классических клинических особенностей феохромоцитомы в сочетании с нормальным уровнем метанефрина в плазме для авторов было неожиданностью, что образование при гистологическом исследовании оказалось феохромоцитомой. Только временное повышение АД во время операции удаления опухоли указывало на возможность феохромоцитомы.

Incidental Pheochromocytoma: Silent but Violent

Background: Pheochromocytoma is a rare catecholamine secreting neuroendocrine tumor. It arises from the chromaffin cells of adrenal medulla. It is diagnosed in 5–6.5% of adrenal incidentalomas which is not common. The usual clinical presentation includes the classic triad of sweating, headache and tachycardia. However, asymptomatic cases are seen in 8% of the patients with pheochromocytoma. We present a clinically asymptomatic patient diagnosed during work up of adrenal incidentaloma. The possible etiology for silent presentation includes one of the following:(i) Presence of a smaller functional tissue (ii)Accelerated turnover of the tumor causing release of the unmetabolized catecholamines in small amounts (iii) Pulsatile tumor secretion (iv)Tumors triggered by stress (v) Laboratory errors due to inappropriate handling of specimen at high-temperature (vi) False negative test results secondary to caffeine ingestion in the prior 24 hours.Clinical Case: 59 years old Caucasian female with past medical history of type 2 diabetes mellitus, obesity, essential hypertension, nonischemic cardiomyopathy, and asthma presented to the emergency room with complaints of worsening shortness of breath and pedal edema for 1 month. Physical exam: Blood pressure 146/78 mm of Hg and heart rate 82 beats/min, mild pedal edema, no pulmonary crackles. On imaging, CT angio chest showed irregularly enhancing right adrenal mass measuring 3.4 cm. This adrenal incidentaloma was not visualized on imaging done 5 years ago. Further, MRI abdomen revealed 4.1 cm right adrenal mass. Laboratory testing showed high total plasmametanephrines: 890 pg/ml (< or = 205), 24-hour urine metanephrines: 2337 (140–785), A1C: 10%. This confirmed the diagnosis of adrenal pheochromocytoma. Preoperatively, she was started on phenoxybenzamine 10 mg BID and encouraged on liberal salt intake. During the course, her blood pressure and heart rate were monitored daily. She underwent right adrenalectomy. Surgical pathology revealed 4.1 cm pheochromocytoma, negative margins with extension to the adipose tissues and vascular invasion, PASS score = 4. Post operatively, patient declined to get labs done. Due to high risk behavior of the tumor, patient needs to be monitored annually for lifelong.Conclusion: Pheochromocytoma is an uncommon tumor with varied clinical presentation. It can manifest itself widely from being silent to aggressive disease. This warrants high suspicion, early detection and management, thereby reducing the morbidity and mortality. Lately, there has been increased incidence of adrenal incidentalomas owing to widespread use of radiological investigations. We report a case of incidental pheochromocytoma which is biochemically active but clinically asymptomatic. This emphasizes the importance of being more vigilant during the evaluation of adrenal incidentalomas.

Atypical Presentation of an Adrenal Mass

Catecholamine-secreting tumours arise from chromaffin cells of the adrenal medulla, and the sympathetic ganglia referred to as pheochromocytomas and catecholamine secreting paragangliomas, respectively. The incidence of pheochromocytoma is less. This was about a 38-years-old male patient that complained of burning sensation while micturition and right loin pain. On evaluation he was found to have a right adrenal mass of size of 6 cm. The patient was found to have right ureteric caliculi and right Double J Stent (DJ) was done. He was advised for further evaluation but he was not willing at that point of time. Thus, pheochromocytoma has to be one of the differentials in a young person presenting with hypertension or with atypical presentation. Because pheochromocytoma is one of the correctable causes of hypertension and a person can have a near normal or average life span after surgery. This patient presented with urinary symptoms followed by typical features of cholelithiasis rather than symptoms of pheochromocytoma.

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.

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.

Abstract A108: Differences in incidence by sex and race/ethnicity of adrenocortical carcinomas and malignant pheochromocytomas and paragangliomas in California

Abstract Background: Malignant pheochromocytomas (PHEO), paragangliomas (PGL), and adrenocortical carcinomas (ACC) are rare endocrine malignancies with limited data regarding risk factors. To further elucidate their epidemiology, we sought to characterize the burden of malignant PHEO, PGL, and ACC in California. Methods: Using the population-based California Cancer Registry, we identified all new diagnoses of malignant PHEO, PGL, and ACC in California from 1992-2016 (ICD-O-3 codes 8700/3, 8680/3, and 8393/3). We calculated age-adjusted incidence rates (AIR) standardized to the 2000 United States census. We compared AIRs by sex, race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and Asian/Pacific Islander), and county of residence (categorized as urban versus suburban/rural) using SEER*Stat and generated IR ratios (IRR). Results: Between 1992-2016, there were 261 incident cases of malignant PHEO, 271 of malignant PGL, and 866 of ACC in California. Overall AIR per 100,000 person-years were 0.03 for PHEO, 0.03 for PGL, and 0.10 for ACC. Incidence differed by both sex and race/ethnicity. Men had a higher incidence of PGL than women (IRR 1.49, 95% confidence interval [CI] 1.13-1.98; p&amp;lt;0.05) and tended towards higher incidence of PHEO (IRR 1.24, 95% CI 0.97-1.60; p=0.09), while men had a lower incidence of ACC than women (IRR 0.80, 95% CI 0.69-0.92; p&amp;lt;0.05). Compared with non-Hispanic White Californians, non-Hispanic Black Californians had higher PHEO incidence (IRR 1.65, 95% CI 1.05-2.51; p&amp;lt;0.05), whereas PGL incidence was lower for Hispanic (IRR 0.60, 95% CI 0.41-0.87; p&amp;lt;0.05) and Asian/Pacific Islander Californians (IRR 0.60, 95% CI 0.35-0.97; p&amp;lt;0.05). Compared with non-Hispanic White Californians, ACC incidence was lower in non-Hispanic Black (IRR 0.58, 95% CI 0.40-0.82; p&amp;lt;0.05), Hispanic (IRR 0.65, 95% CI 0.54-0.78; p&amp;lt;0.05), and Asian/Pacific Islander Californians (IRR 0.60, 95% CI 0.46-0.76; p&amp;lt;0.05). There were no differences in IRRs according to county of residence for either PHEO, PGL, or ACC. Conclusions: Malignant PHEO, PGL, and ACC remain rare cancers in California, with disease-specific differences in IRR’s by sex and race/ethnicity but not by urban versus suburban/rural county of residence. We report novel findings of a higher incidence of malignant PHEO in non-Hispanic Black Californians and a lower incidence of malignant PGL in Hispanic and Asian/Pacific Islander Californians. We also confirm higher incidence of ACC in women and non-Hispanic White Californians. Additional research is needed to clarify whether these differences reflect disparities in access to care. Citation Format: Claire K. Mulvey, Alan Paciorek, Brandon Shih, Meg McKinley, Dawn Pearson, Iona Cheng, Li Zhang, Ann Griffin, Quan-Yang Duh, Sanziana Roman, Julie Ann Sosa, Insoo Suh, Chienying Liu, Katherine Van Loon, Emily Bergsland. Differences in incidence by sex and race/ethnicity of adrenocortical carcinomas and malignant pheochromocytomas and paragangliomas in California [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A108.

Pheochromocytoma and Paraganglioma: From Epidemiology to Clinical Findings.

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Pheochromocytomas arise from chromaffin cells in the adrenal medulla, and PGLs arise from chromaffin cells in the ganglia of the autonomic nervous system. Paragangliomas originate from sympathetic or parasympathetic ganglia in the abdomen, thorax, and pelvis. The majority of PCC and sympathetic PGL are endocrine active tumors causing clinical symptoms by secreting excess catecholamines (norepinephrine, epinephrine, dopamine) and their metabolites. The incidence of PCC and PGL ranges between 2 and 8 per million, with a prevalence between 1:2500 and 1:6500. It peaks between the 3rd and 5th decades of life, and approximately 20% of cases are pediatric patients. The prevalence among patients with hypertension in outpatient clinic ranges between 0.1-0.6% in adults and between 2-4.5% in the pediatric age group. 10-49% of these tumors is detected incidentally in imaging techniques performed for other reasons. However, 4-8% of adrenal incidentalomas are PCCs. Of these neuroendocrine tumors, 80-85% are PCCs and 15-20% are PGLs.Up to 40% of patients with PCC and PGL has disease-specific germline mutations and the situation is hereditary. Of 60% of the remaining sporadic patients, at least 1/3 has a somatic mutation in predisposing genes. 8% of the sporadic cases, 20-75% of the hereditary cases, 5% of the bilateral, adrenal cases, and 33% of the extra-adrenal cases at first presentation are metastatic. Although PCCs and PGLs have scoring systems for histological evaluation of the primary tumor, it is not possible to diagnose whether the tumor is malignant since there is no histological system approved for the biological aggressiveness of this tumor group. Metastasis is defined as the presence of chromaffin tissue in non-chromaffin organs, such as lymph nodes, liver, lungs and bone. Although most of the PCC and PGL are benign, the metastatic disease may develop in 15-17%. Metastatic disease is reported between 2-25% in PCCs and 2.4-60% in PGLs. The TNM staging system of the American Joint Committee on Cancer (AJCC) was developed to predict the prognosis, based on the specific anatomical features of the primary tumor and the occurrence of metastasis.

Analysis of risk factors for intraoperative hemodynamic instability in adrenal incident pheochromocytoma

Objective To evaluate the risk factors for intraoperative hemodynamic instability (HI) in patients with adrenal incident pheochromocytoma. Methods Perioperative clinical parameters of patients undergoing surgery for adrenal incident pheochromocytoma at the First Hospital of Peking University from January 2001 to July 2018 were analyzed. There were 39 males and 41 females, with mean age of 45.1 years (13-76 years old). The median tumor length was 5.1 cm (1.5-14.0 cm), with 25 cases (31.3%) on the left side , 55 cases (68.8%) on the right side. There were 37 cases combined with coronary heart disease or diabetes or BMI≥24 kg/m2. Patients were divided into hemodynamic instability (HI group) and hemodynamic stability group (HS group) by whether intraoperative hemodynamic instability occurred. The differences of demographic characteristics and clinical parameters between the two groups were compared. Logistic regression analysis was done for seeking the risk factors for hemodynamic instability during surgery. Results There were 54 cases (67.5%) in the HS group and 26 cases (32.5%) in the HI group. Univariate analysis showed that there was no significant difference in age [(44.06±13.58) years old vs. (47.35±16.11) years old], combined with coronary heart disease or diabetes or BMI≥24 kg/m2 [50.0% (27/54) vs. 38.5% (10/26)], tumor long diameter [median 5.0 cm(1.5-14.0 cm) vs. 6.0cm(1.5-13.5 cm)], tumor location[left: 29.6% (16/54) vs. 34.6% (9/26)], preoperative catecholamine test positive [44.4% (20/45) vs. 50.0% (10/20)], open surgery [27.8% (15/54) vs. 34.6% (9/26)]and preoperative non-alpha blockers[13.0%(7/54) vs. 30.8%(8/26)] between HS group and HI group (P>0.05). Further logistic regression analysis was used to analyze the risk factors of intraoperative hemodynamic instability. Multivariate analysis found that patients who preoperative non-alpha blockers before surgery were independent risk factor for HI (OR=4.574, 95%CI 1.273-16.432, P=0.020). Conclusions Preoperative non-alpha blocker in patients with adrenal incidental pheochromocytoma could be independent risk factor for intraoperative hemodynamic instability. Therefore, it is recommended that patients with adrenal incidental tumors, especially those who fail to rule out pheochromocytoma, take preoperative alpha blockers. Key words: Pheochromocytoma; Adrenal incidentaloma; Hemodynamic; Alpha blocker

MON-389 Normotensive Pheochromocytoma

Background: Pheochromocytoma is a rare neuroendocrine tumour arising from chromaffin cells of the adrenal medulla that produce catecholamines and their metabolites. It accounts for up to 5-9% of adrenal incidentalomas (AI). Lack of hemodynamic features including hypertension has been reported in 13.5% to 55% of incidental pheochromocytoma series. It is postulated that normotensive pheochromocytoma (NP) silent presentation might be caused by reduction in secretion of catecholamines. Adrenalectomy is the treatment of choice for normotensive pheochromocytoma. Pre-operative pharmacological blockade for NP is still controversial. Clinical case: A 39 years old lady Admitted with perforated Appendix was referred to the endocrine service for incidentally discovered left adrenal mass .Patient has no history suggestive of adrenal hyper functioning. No family history of endocrine disorders. Physical examination showed blood pressure of 90/60 mmHg with no signs of adrenal hyper functioning. CT scan showed, left adrenal mass measuring 6 X 4.1 x 4.7 cm with multiple central necrotic areas and heterogenous enhancement. MIBG scan showed a large focus of uptake in the left adrenal area. Laboratory investigations showed normal DST. Plasma metanephrines were 1850 ng/l (normal less than 90 ng/l) and normetanephrines were 3050 ng/l (normal less than 129 ng/ml). 24 hours urine adrenaline was more than 213 nmol/24 h (normal less than 147), metanephrines was more than 17.7 umol/l (normal is less than 2.04) and normetanephrine more than 15.79 umol/l (normal is less than 4.40). Patient had left laparoscopic adrenalectomy with no complications. She did not receive any pre-operative pharmacological blockade as she couldn't tolerate any. Histopathology showed pheochromocytoma 7 cm in diameter with no central necrosis, mitotic count was 1% per HPF, no Atypical mitosis, no vascular or capsular invasion, no extension. Genetic screen was negative. Conclusions: Screening for pheochromocytoma is mandatory for all adrenal incidentaloma even in the absence of hypertension as Lack of hemodynamic features has been reported in 13.5% to 55% of incidental pheochromocytoma series.

Associated factors of intraoperative hemodynamic instability in patients with incidental pheochromocytomas

Objective: To analyze the associated factors of intraoperative hemodynamic instability (HI) in patients with incidental pheochromocytomas. Methods: The data of 104 patients with a pathological diagnosis of pheochromocytoma at Chinese PLA General Hospital between January 2011 and December 2016 was retrospectively analyzed. The patients were divided into hemodynamic stability (HS) group (n=56) and HI group (n=48) according to hemodynamic characteristics. The clinical features, biochemical test, preoperative and intraoperative hemodynamics were analyzed. Multivariate logistic regression analysis was used to explore the associated factors of HI. Results: The age [(44.7±12.7) years vs (52.1±12.8) years], tumor diameter [(47.9±16.3) mm vs (57.9±21.6) mm], preoperative blood pressure [(121.3±11.5) mmHg vs (127.2±13.3) mmHg] in HS group were less than those in HI group (all P<0.05). The proportion of age ≥ 50 years (28.6% vs 64.6%), tumor diameter ≥ 45 mm (48.2% vs 68.8%) and hematocrit < 0.38 (25.0% vs 51.3%) in HS group were less than that in HI group (all P<0.05). Multivariate logistic regression analysis indicated that age ≥ 50 years (OR=7.940, 95% CI: 2.480-25.417, P<0.001), tumor diameter ≥ 45 mm (OR=5.042, 95% CI: 1.482-17.156, P=0.010), blood pressure ≥ 130/80 mmHg (OR=3.127, 95% CI: 1.034-9.463, P=0.044) and hematocrit < 0.38 (OR=6.273, 95% CI: 1.893-20.788, P=0.003) were independent associated factors of HI. The proportion of HI ( χ(2)=9.033, P=0.003) and intensive care unit (ICU) admission ( χ(2)=16.641, P<0.001) increased along with increasing associated factors. Conclusion: Adequate preoperative medical preparation and volume expansion for appropriate blood pressure are important for elder patients with large tumor to prevent HI in patients with incidental pheochromocytomas.

The characteristics of peroperative blood pressure and heart rate in patients with normotensive incidental pheochromocytomas

Objective To investigate the characteristics of peroperative blood pressure and heart rate in patients with normotensive incidental pheochromocytomas in order to provide the basis for peroperative treatment. Methods This retrospective study collected the data of 104 patients with a pathological diagnosis of unilateral pheochromocytoma at PLA General Hospital during January 2011 to December 2016. They were divided into normotensive incidental pheochromocytomas(NIP)group(n=50)if the patients were normotensive and HIP group(n=54)if the patients were with hypertension. The clinical features, imaging features and peroperative hemodynamics were analyzed. Results (1)The age, urinary norepinephrine, daily dosage and duration of phenoxybenzamine in NIP group were less than those of HIP group(all P<0.05). (2)Preinduction blood pressure, maximum blood pressure, and total fluid intake in NIP group were lower than those in HIP group(all P<0.05). The blood pressure range, heart rate range, increased blood pressure, minimum mean arterial pressure, vasoactive medication were without statistical significance between these two groups.(3)The times and rate of intraoperative systolic blood pressure more than 30% baseline, 200 mmHg(1 mmHg=0.133 kPa), 180 mmHg, 160 mmHg, intraoperative tachycardia, bradycardia, intraoperative hypotension and postoperative hypotension were without statistical significance between these two groups.(4)Stratified analysis of age(50 years), phenoxybenzamine(40 mg/d), tumor diameter(50 mm)and preinduction blood pressure(130/80 mmHg)showed that intraoperative blood pressure and heart rate were without statistical significance between these two groups.(5)There was no correlation between phenoxybenzamine(daily dosage or duration)and peroperative hypotension. Applying phenoxybenzamine or vasoactive medication was not correlated with peroperative hypotension in NIP group. Conclusion The peroperative blood pressure and heart rate of patients with NIP are similar to those of patients with HIP. Adequate peroperative treatment should be applied to NIP to avoid hemodynamic instability. (Chin J Endocrinol Metab, 2018, 34: 466-471) Key words: Pheochromocytoma; Hypertension; Peroperation; Blood pressure; Heart rate

Comparative study between incidental and symptomatic pheochromocytoma

Comparative study between incidental and symptomatic pheochromocytoma

Incidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: A nationwide study and systematic review

IntroductionRecent years have seen major changes in clinical practice which may have affected the incidence rates of pheochromocytoma(PCC)/sympathetic paraganglioma(sPGL). There is, however, a lack of up-to-date information describing trends in these incidence rates. MethodsWe searched the Dutch pathology registry to identify all histopathologically confirmed cases of PCC/sPGL diagnosed between 1995 and 2015. We calculated incidence rates according to age category as well as age-standardized incidence rates (ASR). We also searched Medline and Embase to find data on nationwide incidence rates of PCC/sPGL. ResultsThe nationwide pathology study revealed a total of 1493 patients with either PCC or sPGL. The ASR for PCC increased from 0.29 (95% CI: 0.24–0.33) to 0.46 (95% CI: 0.39–0.53) per 100,000 person-years in the periods 1995–1999 and 2011–2015, respectively. For sPGL the ASR in these same periods were 0.08 (95% CI: 0.06–0.10) and 0.11 (95% CI: 0.09–0.13) per 100,000 person-years, respectively. Concomitantly, PCC size decreased (β −0.17; P < .001) and age at diagnosis increased (β 0.13; P = .001). Our systematic search yielded 3 papers reporting on a total of 530 PCC/sPGL cases, showing a combined annual incidence rate varying from 0.04 to 0.21 per 100,000 person-years. ConclusionIncidence rates of PCC/sPGL have increased significantly over the past two decades. This trend coincides with a higher age and a smaller tumor size at diagnosis. Most likely these observations are at least in part the result of changes in clinical practice during the study period, with a more intensified use of both imaging studies and biochemical tests for detecting PCC/sPGL.