Catecholamine-producing Tumors Research Articles

Cardiac repolarization abnormalities and neurally mediated syncope: overlooked aspects in the diagnosis of pheochromocytoma

BackgroundPheochromocytoma is a rare catecholamine-producing tumour originating from adrenal chromaffin cells. Classic clinical presentation includes headache, diaphoresis and palpitation. Syncope is uncommon and may result from hypotension or arrhythmia. We report a case of neurally mediated syncope in pheochromocytoma associated with cardiac repolarization abnormalities, a unique presentation of the disease.Case presentationThis case report presents a 28 year-old woman, describing recurrent syncope usually preceded by prodromes such as headache, visual blurring, heart palpitations and psychomotor agitation. Firstly she was diagnosed with anxiety and depression, but there was no improvement of symptoms with psychiatric treatment. Previous Holter revealed long QT interval. Echocardiogram showed normal dimensions, preserved left ventricular function and no valvopathies. The patient was referred for a Head-up tilt test (HUTT) in order to investigate reflex syncope. The electrocardiogram (ECG) exhibited normal sinus rhythm and diffuse cardiac repolarisation abnormalities. HUTT was positive for vasodepressor type neurally mediated syncope and ECG showed U waves after a syncope episode. This electrocardiographic finding motivated further clinical investigation. The patient also described abdominal pain, increased abdominal volume, weight loss and blood pressure instability. Based on clinical history and ventricular repolarisation abnormalities uncovered by HUTT, pheochromocytoma was suspected. Urinary test was positive for catecholamines and the abdominal imaging revelead expansive lesion. She underwent surgery to remove the pheochromocytoma, confirmed by immunohistochemistry.ConclusionsAfter surgery she had no recurrency of symptoms, remaining asymptomatic after six years of follow-up, suggesting a cause-effect relationship between neurally mediated syncope and pheochromocytoma.

The great mimic: A rare clinical presentation of myocarditis and multi-organ failure secondary to phaeochromocytoma

Phaeochromocytomas are catecholamine-producing tumours derived from the sympathetic or parasympathetic nervous system. The clinical presentation is variable, ranging from adrenal incidentalomas to patients with hypertensive crisis or, rarely, with myocarditis and multiple organ failure. We present the case of a 54-year-old patient admitted to the emergency room due to sudden onset of dyspnoea and tachycardia; after a few minutes, due to the onset of oxygen desaturation and loss of consciousness, he was intubated; a coronary angiography was performed which revealed no significant stenosis; the diagnostic hypothesis therefore led us to think of a genesis of the clinical presentation due to a myocarditis which was then confirmed by cardiac MRI. The aetiology was also clarified by performing abdominal CT and urinary and serum dosage of catecholamines. Phaeochromocytoma confirms itself as an excellent simulator, which is why it is defined as the "great mimic" and is one of the diagnostic hypotheses to think about in young patients with acute multiorgan failure not explained by other causes. Contributions: VN and MUS helped in conception and design of the study, MUS, VN and PV did data collection, VN and MUS did analysis and interpretation of data; MUS and VN contributed to drafting the work and revising it critically for important intellectual content. All authors approved the final version for publication and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Conflict of interest: The authors declare they have no competing interests, and all authors confirm accuracy. Grant support & financial disclosures: None Ethical Consideration, informed consent, and Consent for publication: Informed consent was signed by patient. All mentioned ethical aspects and related consents were taken into consideration during the conduct of this study.

Primary perioperative haemodynamic effects of ß-receptor blockade in patients with catecholamine-secreting tumours

IntroductionGuidelines for the treatment of catecholamine-producing tumours strictly recommend starting ß-receptor blocking medication only after α-receptor blockade has been established. This recommendation is supported only by non-surgical case reports. However, in clinical practice ß-receptor blockade is often started before the diagnosis of a phaeochromocytoma is made. As we routinely treat patients with catecholamine-producing tumours without α-receptor blockade, our aim was to evaluate haemodynamic changes in such patients with and without ß-receptor blockade. MethodsPerioperative blood pressure was assessed prospectively for all patients. The primary outcome was the highest pre-, intra-, and postoperative systolic blood pressure in patients with or without a ß-receptor blockade. Secondary outcomes were the incidence of intraoperative systolic blood pressure peaks >250 mm Hg and hypotensive episodes. Subsequently, a propensity score matching (PSM) analysis was performed. ResultsOut of 584 phaeochromocytoma and paraganglioma resections, 383 operations were performed without α-receptor blockade (including 84 with ß-receptor blockade). Before operation and intraoperatively, patients with ß-receptor blockade presented with higher systolic blood pressure (155 [25] and 207 [62] mm Hg) than patients without ß-receptor blockade (147 [24] and 183 [52] mm Hg; P=0.006 and P=0.001, respectively). Intraoperatively, patients with ß-receptor blockade demonstrated a higher incidence of hypotensive episodes (25% without vs 41% with ß-blockade; P<0.001). After propensity score matching no difference between the groups could be confirmed. ConclusionOverall, patients with isolated ß-receptor blockade developed higher blood pressure before operation and intraoperatively. After propensity score matching a difference could no longer be detected. Overall, ß-receptor blockade seems to be more a sign for severe disease than a risk factor for haemodynamic instability.

The effects of perioperative dexmedetomidine infusion on hemodynamic stability during laparoscopic adrenalectomy for pheochromocytoma: a randomized study.

Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumor originating from the adrenal medulla chromaffin cells. Hemodynamic instability can occur during the induction of anesthesia and surgical manipulation of the tumor. This study investigated the effects of intraoperative dexmedetomidine administration on hemodynamic stability in patients undergoing laparoscopic adrenalectomy for pheochromocytoma. Forty patients who underwent laparoscopic adrenalectomy for pheochromocytoma were randomly assigned to the dexmedetomidine (n = 20) or control (n = 20) group. The primary outcome of this study was intraoperative hemodynamic stability, and the secondary endpoint was the plasma catecholamine concentrations, specifically of epinephrine and norepinephrine. The intraoperative maximum blood pressures were significantly lower in the dexmedetomidine group (control vs. dexmedetomidine group: 182 ± 31 vs. 161 ± 20, 102 ± 17 vs. 90 ± 10, and 128 ± 22 vs. 116 ± 12 [mean ± SD] mmHg and p = 0.020, 0.015, and 0.040 for systolic, diastolic, and mean blood pressure, respectively). The maximum heart rate during surgery was 108 ± 15 bpm in the control group and 95 ± 12 bpm in the dexmedetomidine group (p = 0.010). Other parameters of hemodynamic instability were comparable between both groups. Plasma catecholamine concentrations did not differ between the groups. Dexmedetomidine infusion following the induction of anesthesia at a rate of 0.5 μg/kg/h significantly attenuated the maximum intraoperative SBP, DBP, MBP, and HR, contributing to improved hemodynamic stability.

SAT333 A Case Of Pheochromocytoma Initially Presenting As Takotsubo-like Cardiomyopathy

Abstract Disclosure: J.S. Figueroa: None. S.W. Holland: None. J. Cheng: None. M.C. Sullivan: None. Background: Takotsubo-like cardiomyopathy (TCM) is a known but rarely seen clinical complication associated with pheochromocytoma that is important to recognize. Case Presentation: A 68 year old woman with a history of hypertension on verapamil, lisinopril-hydrochlorothiazide, clonidine, hyperlipidemia, asthma, and chronic kidney disease presents for nausea and vomiting associated with pressure like chest pain. Cardiac work up revealed elevated troponins and T wave inversion in the anterolateral leads concerning for non-ST segment elevation myocardial infarction (NSTEMI). CT Abdomen study revealed two right sided adrenal nodules 2.4 x 1.8 cm and 1.9 x1.1 cm. Coronary angiography was normal but study was concerning for TCM. She developed new onset atrial fibrillation and was treated with calcium channel blocker and beta blocker. Transthoracic echocardiography showed apical hypokinesis and a mildly decreased ejection fraction of 41%. She was discharged home on beta blocker and losartan therapy. The patient presented 5 days later with similar symptoms and a maximum elevated blood pressure 170/110 mm Hg. Labs revealed elevated plasma free metanephrines level of 505 pg/ml (ref range ≤57 pg/ml) with normal renin, aldosterone, and cortisol levels. CT adrenal protocol study showing pre-contrast density of largest nodule 39 Hounsfield units (HU), postcontrast density 81 HU, and washout density 56 HU with washout at 59.5%. The smaller nodule had pre-contrast density of 31 HU, postcontrast of 65 HU, washout density of 61 HU with washout at 11.8%. Endocrine and Endocrine surgery were consulted at this time. Alpha blocker tamsulosin was initiated and beta blocker therapy was discontinued. Patient underwent right adrenalectomy with subsequent improvement of her ejection fraction two months later. Histology was concerning for malignancy for which she is currently being followed. Conclusion: This case highlights TCM as a presenting sign for a pheochromocytoma. A study by Agarwal et al. found that a minority of patients who had TCM due to pheochromocytoma developed symptoms typical of the tumor such as headache, hypertension, palpitations, and diaphoresis. The study also found that complications such as cardiogenic shock and heart failure were higher in pheochromocytoma related TCM.¹ Consider catecholamine producing tumors as a potential cause of TCM where appropriate alpha and beta blockade may help to reduce symptoms. Earlier recognition of a potential pheochromocytoma would also have discouraged the use of a beta blocker initially until pheochromocytoma was ruled out. An individualized, multidisciplinary approach helps lead to a timely diagnosis and appropriate treatment decisions for these rare tumors. References (1) Agarwal, V.,Kant, G.,Hans N., Messerli F.H. Takotsubo-like Cardiomyopathy in Pheochromocytoma. International Journal of Cardiology 2011; Vol 153,3,241-248 Presentation: Saturday, June 17, 2023

Global trends and current status in pheochromocytoma: a bibliometric analysis of publications in the last 20 years.

Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumour originating from the chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. However, there are few bibliometric studies on Pheochromocytoma. Therefore, this study was employed to summarize the global trends and current status in pheochromocytoma by bibliometric analysis. The Web of Science (WOS) core collection database was searched for publications relating to pheochromocytoma from 2001 to 2021. Bibliometric analysis was used to examine the data, and Microsoft Excel was utilized to create bar graphs. In addition, VOSviewer was used to carry out co-authorship analysis, co-citation analysis and co-occurrence analysis. CiteSpace was used to analyze the keywords citation bursts. A total of 8,653 publications published in 1,806 journals by 38,590 authors in 6,117 organizations from 100 countries/regions were included in our study. Among them, USA was the leading countries in terms of total publications and sum of time cited, whereas Eunice Kennedy Shriver Natl Inst Child Hlth & Hum was the leading institutions. The main publications for pheochromocytoma-related articles were Journal of clinical endocrinology &metabolism. Pacak karel and Eisenhofer Graeme were the main contributing authors. The studies on pheochromocytoma could be grouped into five clusters: Treatment, Mechanism, Etiology, Radiology and Hormones study. Moreover, the radiology study, etiology study and some specific keywords such germlines mutation, mesenchymal stem-cells, autophagy, neuroinflammation, neurotoxicity, and hemodynamic instability, may become the hot spots of future. Although the number of articles on pheochromocytoma has fluctuated slightly over the past 20 years, there has been an overall upward trend. In general, precision medicine research on pheochromocytoma, especially metastatic pheochromocytoma, in terms of diagnosis, treatment, and etiology will be a hot research topic in the future. This study helps to understand the research perspectives, hot spots and trends of pheochromocytoma and provide new insight and a basis for future pheochromocytoma research quickly.

Approach to the patient with adrenal incidentaloma. Case series

The formations of the adrenal glands are often detected accidentally during instrumental methods of examination of the abdominal cavity and retroperitoneal space, performed for some other reasons. Over the past 2 decades, the frequency of detection of adrenal gland formations has increased 10-fold, and most of them are diagnosed in old age. The tactics of observation and treatment depend both on hormonal activity and on the malignant potential of the detected formation. Up to 58% of patients with adrenal incidentalomas have a malignant nature, with a higher risk in young patients, with a size of more than 4 cm, as well as with a history of other malignant neoplasms. The frequency of detection of the classical clinical and laboratory picture of hypercorticism, hyperaldosteronism or catecholamine-producing tumor is less than 15%, however, the phenomenon of functionally autonomous cortisol production according to the results of studies conducted in the last few years is much more common up to 3050% of patients. Despite the absence of vivid clinical symptoms in some cases, autonomous cortisol secretion is associated with increased cardiovascular morbidity and metabolic disorders, therefore, all patients with adrenal incidentalomas need to exclude this condition. This article presents clinical cases of patients with adrenal gland formations, describes in detail the examination algorithm and the choice of treatment tactics, taking into account the results of studies conducted since the release of the latest clinical recommendations for the management of patients with adrenal gland incidentalomas in 2016.

Adrenal Incidentaloma With the Diagnosis of Normotensive Pheochromocytoma: A Case Report

Background: Pheochromocytomas (PCCs) are catecholamine-producing neuroendocrine tumors that originate from the adrenal medulla. Their clinical presentations most commonly include hypertension, headache, palpitations, and sweating; however, PCCs are sometimes normotensive and clinically silent. Case Presentation: A female patient with abdominal pain as well as persistent and crushing left flank pain for the past six months was examined. The imaging studies revealed a mass in the upper pole of the left kidney indicative of a potential adrenal gland tumor; however, she had normal blood pressure (BP). Histopathologic examination of the mass from exploratory laparotomy showed that it was a PCC. Findings from sonography and computed tomography (CT) scan of the left adrenal tumor, along with elevated urinary normetanephrine level and positive iodine-123 metaiodobenzylguanidine (MIBG) scan led to preoperative diagnosis of PCC in our case. Conclusion: This study highlighted the importance of imaging and biochemical testing in diagnosing PCCs in patients with adrenal incidentalomas (AIs), even though they were normotensive and entirely asymptomatic.

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

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

Tumour microenvironment in pheochromocytoma and paraganglioma.

Pheochromocytomas and Paragangliomas (Pheo/PGL) are rare catecholamine-producing tumours derived from adrenal medulla or from the extra-adrenal paraganglia respectively. Around 10-15% of Pheo/PGL develop metastatic forms and have a poor prognosis with a 37% of mortality rate at 5 years. These tumours have a strong genetic determinism, and the presence of succinate dehydrogenase B (SDHB) mutations are highly associated with metastatic forms. To date, no effective treatment is present for metastatic forms. In addition to cancer cells, the tumour microenvironment (TME) is also composed of non-neoplastic cells and non-cellular components, which are essential for tumour initiation and progression in multiple cancers, including Pheo/PGL. This review, for the first time, provides an overview of the roles of TME cells such as cancer-associated fibroblasts (CAFs) and tumour-associated macrophages (TAMs) on Pheo/PGL growth and progression. Moreover, the functions of the non-cellular components of the TME, among which the most representatives are growth factors, extracellular vesicles and extracellular matrix (ECM) are explored. The importance of succinate as an oncometabolite is emerging and since Pheo/PGL SDH mutated accumulate high levels of succinate, the role of succinate and of its receptor (SUCNR1) in the modulation of the carcinogenesis process is also analysed. Further understanding of the mechanism behind the complicated effects of TME on Pheo/PGL growth and spread could suggest novel therapeutic targets for further clinical treatments.

Pheochromocytoma with Type 2 Diabetes Mellitus and Subclinical Cushing's Syndrome

Pheochromocytoma is a catecholamine-producing tumor that originates from adrenal medullary chromaffin cells. It affects 1–8 per million people annually and accounts for 5% of adrenal incidentalomas. Here, we report a 62-year-old man with sudden excessive sweating, palpitations, and headaches. He has a history of type 2 diabetes mellitus, hypertension, and an adrenal mass found incidentally by ultrasonography. Clinical history and further imaging suggest a pheochromocytoma; however, the presence of subclinical Cushing's syndrome and a normal urine vanillylmandelic acid level have led to diagnostic challenges. Finally, the patient underwent a left adrenalectomy. Histopathology showed the tumor as thick nests of cells, positive chromogranin A staining, and negative inhibin staining that confirmed the diagnosis of pheochromocytoma. In conclusion, our patient had pheochromocytoma that was thought to produce adrenocorticotropic hormone ectopically, resulting in subclinical Cushing's syndrome.

Epigenetic drugs in somatostatin type 2 receptor radionuclide theranostics and radiation transcriptomics in mouse pheochromocytoma models.

Pheochromocytomas and paragangliomas (PCCs/PGLs) are catecholamine-producing tumors. In inoperable and metastatic cases, somatostatin type 2 receptor (SSTR2) expression allows for peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE. Insufficient receptor levels, however, limit treatment efficacy. This study evaluates whether the epigenetic drugs valproic acid (VPA) and 5-Aza-2'-deoxycytidine (DAC) modulate SSTR2 levels and sensitivity to [177Lu]Lu-DOTA-TATE in two mouse PCC models (MPC and MTT). Methods: Drug-effects on Sstr2/SSTR2 were investigated in terms of promoter methylation, mRNA and protein levels, and radiotracer binding. Radiotracer uptake was measured in subcutaneous allografts in mice using PET and SPECT imaging. Tumor growth and gene expression (RNAseq) were characterized after drug treatments. Results: DAC alone and in combination with VPA increased SSTR2 levels along with radiotracer uptake in vitro in MPC (high-SSTR2) and MTT cells (low-SSTR2). MTT but not MPC allografts responded to DAC and VPA combination with significantly elevated radiotracer uptake, although activity concentrations remained far below those in MPC tumors. In both models, combination of DAC, VPA and [177Lu]Lu-DOTA-TATE was associated with additive effects on tumor growth delay and specific transcriptional responses in gene sets involved in cancer and treatment resistance. Effects of epigenetic drugs were unrelated to CpG island methylation of the Sstr2 promoter. Conclusion: This study demonstrates that SSTR2 induction in mouse pheochromocytoma models has some therapeutic benefit that occurs via yet unknown mechanisms. Transcriptional changes in tumor allografts associated with epigenetic treatment and [177Lu]Lu-DOTA-TATE provide first insights into genetic responses of PCCs/PGLs, potentially useful for developing additional strategies to prevent tumor recurrence.

Correlation between the size of pheochromocytoma and the level of metanephrines.

Objective. Pheochromocytomas (PHEO) and paraganglioma (PGLs) are rare neuroendocrine catecholamine-producing tumors that arise from the chromaffin cells of either the adrenal medulla or extra-adrenal paraganglionic tissues. Despite the recent advances in imaging technologies, biochemical evidence of excessive catecholamine production by the tumor is considered the most important test for the diagnosis of these tumors. The aim of the present study is to investigate the role of the catecholamine metabolites (normetanephrine and metanephrine) levels in the diagnosis of PHEO/PGLs and to evaluate if their levels correlate with the size of these tumors. Patients and Methods. Twenty-five patients were included in the study during the time period of 10 years. Their data were compared with another set of 25 patients to obtain the sensitivity and specificity of metanephrine and normetanephrine in the diagnosis of PHEO/PGLs. The tumor size was reviewed in every patient to obtain the correlation coefficient between the tumor sizes and the plasma/24-hour urinary metanephrine levels. Results. The sensitivity and specificity rates for plasma metanephrine were 80-92% and 92-96%, respectively; while for 24-hour urinary metanephrine were 80-90% and 95-100%, respectively. We found a strong positive relationship between the tumor size and the plasma levels of normetanephrine (r=0.518, p<0.01), and metanephrine (r=0.577, p<0.01). While the relation with the 24-hour urinary concentrations of normetanephrine (r=0.384, p=0.01) and 24-h urinary meta-nephrine (r=0.138, p<0.01) was low. Conclusion. The determination of plasma and 24-hour urinary levels of metanephrines is a reliable test for the diagnosis of PHEO, as they are continuously produced by the tumor cells in contrast to catecholamines.

Pheochromocytoma and Extraadrenal Paraganglioma: Case Report and Review of the Laparoscopic Approach

The reported percentage of catecholamine-producing tumors is around 80-85% in pheochromocytomas and 15- 20% in paragangliomas. The case of a 34-year-old female patient with a clinical, imaging and histopathological diagnosis of pheochromocytoma with paraganglioma with successful laparoscopic surgical resolution with a retroperitoneal approach is described. The cardinal symptom is uncontrolled hypertension despite medical management with multiple antihypertensives. The initial diagnostic approach is with the measurement of metanephrines in plasma and urine, if this is not conclusive, the clonidine test can be performed. With a positive laboratory result, an imaging study should be performed for localization and finally surgical resolution with a preference for the laparoscopic approach, with less risk of post-surgical complications.

ODP041 Hearing Loss Reveals Dopamine-secreting Metastatic Paraganglioma

Abstract Background Paragangliomas are neuroendocrine tumors arising from chromaffin cells in extra-adrenal parasympathetic or sympathetic tissues. Frequently they produce catecholamines such as epinephrine and norepinephrine which cause adrenergic symptoms. Rarely, paragangliomas produce only dopamine. These tumors carry a worse prognosis than other types of paragangliomas, especially when associated with loss of SDH-B. Case A 41 year old African American female with developmental delay, allergic rhinitis, OSA, and obesity presented to a primary care clinic for evaluation of hearing loss and left ear pain. Patient was treated for acute otitis media but symptoms failed to resolve. She was referred to audiology where she was found to have a mixed conductive and sensorineural hearing loss on the left. Despite using hearing aids, a year later the patient presented to an ENT clinic with several weeks of worsening left aural fullness and decreased hearing. On otoscopy, a mass was visualized in the middle ear. CT scan identified a lytic lesion at the jugular foramen extending into the middle ear; MR of the inner auditory canal was concerning for a paraganglioma. PET CT revealed widely metastatic disease including FDG avid cervical and supraclavicular lymph nodes, pulmonary nodules, hepatic lesions, and sclerotic lesions in the vertebral column and right humerus. Biopsy of an hepatic lesion confirmed metastatic paraganglioma with loss of SDH-B. Labs were consistent with dopamine excess. A 24 hour urine dopamine was 1020 mcg/24 hour (normal 65-400) with plasma dopamine elevated at 191 pg/mL (normal &amp;lt;30). A 24 hour urine norepinephrine level was mildly elevated at 85 mcg/24 hours (normal 15-80) but plasma norepinephrine and epinephrine were both normal. The patient denied any history of palpitations, flushing, headaches, or chest pain. She was briefly started on doxazosin but this was later discontinued as metanephrines and normetanephrines were not significantly elevated. The tumor was not amenable for surgery. Ultimately after discussion with oncology, the patient opted to proceed with temozolomide and capecitabine chemotherapy. Discussion It is important to recognize differences in treating dopamine secreting paragangliomas compared with other catecholamine producing tumors. Preoperative alpha blockade is not routinely recommended as it may cause hypotension and postoperative cardiovascular collapse. While chemotherapy with Cyclophosphamide–dacarbazine–vincristine has historically been used for metastatic paragangliomas, temozolomide is now showing benefit in cases with SDH-B mutation. Sources cited: Foo, S. H., et al. "Dopamine-secreting phaeochromocytomas and paragangliomas: clinical features and management." Singapore Med J 51.5 (2010): e89-e93. Hadoux, J., Favier, J., Scoazec, J. -Y., et al (2014),SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma. Int. J. Cancer, 135: 2711-2720. https://doi.org/10.1002/ijc.28913. Presentation: No date and time listed

ODP307 Does Size Matter: A Case of a 16cm Pheochromocytoma

Abstract Background Pheochromocytomas are catecholamine producing tumors that arise from chromaffin cells. The incidence is of 0.6 cases per 100,000 person-year. Although rare, it is an unpredictable and dangerous tumor that can lead to a fatal catecholamine induced cardiovascular accident. Typical symptoms include profuse sweating, palpitations, headaches, paroxysmal hypertension, anxiety, chest pain. Occasionally, the tumor can present as an asymptomatic incidentaloma. Case A 55-year-old patient with no significant past medicalor family history presented to the emergency department (ED) with right lower quadrant abdominal pain. CT abdomen/pelvis demonstrated acute appendicitis and an incidental finding of a 15×10×11.8 cm left adrenal mass. The patient denied episodic headaches, palpitations, diaphoresis, chest pain, and anxiety. On exam, patient's vital signs included a blood pressure of 112/77 mmHg and pulse rate of 88 bpm. Further, there was no evidence of hypercortisolism including moon facies, acanthosis, hirsutism, abdominal striae, or proximal muscles weakness. He subsequently underwent biochemical testing which revealed 24-hour urine metanephrines of 1131 ug/d (55-320ug/d), normetanephrine of 6450 ug/g (0-330 ug/g), mildly elevated urine cortisol of 130.6 ug/d (&amp;lt;60 ug/d) and DHEAS of 73 ug/dL (70-130 ug/dL). In preparation for surgery, alpha blockade was initiated. He underwent successful left adrenalectomy with pathology revealing pheochromocytoma of 16 cm, focally invading the extra-adrenal adipose tissue and with a pheochromocytoma of the adrenal gland score (PASS) of 11, suggestive of high-risk disease. Biochemical testing, including a 24-hour urine and serum metanephrines, obtained approximately 6 weeks post-operatively were normal. Genetics evaluation is currently pending. Conclusions Although pheochromocytomas are known to manifest as the classic triad of palpitations, sweating and headaches, up to 20% can be asymptomatic. Giant pheochromocytomas, defined as size greater than 10 cm, are commonly asymptomatic, hence biochemical testing should be done regardless of absence of symptoms.

RF33 | PSUN04 Luteinizing Hormone-Chorionic Gonadotrophin Receptor in Pheochromocytomas

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

PSAT021 Hemorrhagic Pheochromocytoma Presenting With Cardiogenic Shock: Challenges in Diagnosis and Treatment.

Abstract Introduction Pheochromocytomas are rare catecholamine producing tumors with heterogenous clinical presentations. Although acute catecholamine-induced cardiomyopathy is well described in the literature, it is rarely suspected as a cause of cardiogenic shock. Timely diagnosis is challenging and appropriate preoperative treatment is crucial for successful management, as this condition carries a high mortality rate. We describe a case of hemorrhagic pheochromocytoma presenting with refractory hypotension and discuss the difficulties in diagnosis and treatment we encountered. Case Presentation A 57-year-old man presented with pallor, severe headache, and hypotension. After administration of intravenous fluids, the patient developed flash pulmonary edema and was found to have acute systolic heart failure. He was taken for emergent left heart catheterization, which did not show any evidence of coronary obstruction. Therefore, he was treated for presumed myocarditis and received stress dose steroids. His condition quickly deteriorated to cardiogenic shock and was further complicated by cardiac arrest. He required extracorporeal membrane oxygenation (ECMO) treatment for 2 days, during which time his systolic blood pressures were extremely labile (47–270 mmHg). CT angiography incidentally noted a 4.3 cm right para-adrenal lesion, at which time urine metanephrines were ordered and noted to be markedly high. Ga-68 DOTATATE scan was negative, however, dedicated abdominal CT revealed a likely hemorrhagic right adrenal mass. With supportive care, the patient's cardiac function recovered by the fifth hospital day, and labetalol was slowly introduced, followed by doxazosin. Sixteen days after the initial presentation, laparoscopic right adrenalectomy was successfully performed. Pathology confirmed pheochromocytoma with few positive cells in a hemorrhagic and necrotic adrenal lesion. Discussion Our case underlines several important points in the diagnosis and management of pheochromocytoma. First, it is crucial to have a high level of suspicion for a catecholamine-secreting tumor in the setting of labile blood pressures and acute cardiomyopathy, especially in cases without evidence of coronary artery or valvular disease. Notably, steroids should be used cautiously, as they may further precipitate catecholamine crisis and have been associated with hemorrhagic pheochromocytomas. While catecholamine-induced cardiomyopathy is associated with a high mortality rate, the majority of cases are reversible with timely management. Treatment is complex, as standard initial pheochromocytoma management with alpha-blockers and hydration is often precluded due to cardiogenic shock, and vasopressors such as norepinephrine and epinephrine can worsen cardiomyopathy. Furthermore, early initiation of mechanical circulatory support (specifically ECMO) was a life-saving modality, as it facilitated cardiac function recovery and enabled bridging with alpha blockers. Better prognosis is associated with surgery performed after improvement of cardiomyopathy and alpha blockade. And finally, a multidisciplinary approach is crucial for the successful treatment of pheochromocytoma in emergency situations. Given this rare presentation of pheochromocytoma more, data are needed to define an optimal strategy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Fluorescence/Colorimetry/Smartphone Triple-Mode Sensing of Dopamine by a COF-Based Peroxidase-Mimic Platform.

Simple and accurate monitoring of urinary dopamine (DA) concentration is significant, which is helpful for the assessment or exclusion of catecholamine-producing tumors, such as pheochromocytoma and paraganglioma. Herein, a fluorescence/colorimetry/smartphone triple-mode sensing platform for DA determination was constructed using copper ion (Cu2+)-modified hydrazone-linked covalent organic frameworks (Cu-BTA-COF). Cu-BTA-COF with 21.67 wt % copper content exhibited peroxidase-mimic activity. After adding H2O2 and 1,3-dihydroxynaphthalene, the Cu-BTA-COF platform can sensitively and selectively detect DA in three modes with consistent results. In fluorescence/colorimetry/smartphone modes, the linear ranges of DA were 1-10, 0.2-40, and 1-10 μM, with related detection limits of 7.2, 8.6, and 23 nM, respectively. Moreover, the Cu-BTA-COF platform can be explored for DA determination in human urine samples with satisfactory recoveries (97.6-100.4%) in all the three modes, suggesting the potential practical application of the Cu-BTA-COF platform for DA detection in urine.

Pheochromocytoma and paraganglioma during childhood and adolescence

Pheochromocytoma and paraganglioma belong to the group of rare catecholamine-producing tumours during childhood and adolescence. They occur most frequently in patients with tumour predisposition syndromes. Imaging is essential to assess tumour stage and to plan therapy initiation. The aim of this review is asummary of the most important characteristics of the aforementioned tumour entities with aspecial focus on imaging. In particular, magnetic resonance imaging (MRI) as well as nuclear medicine techniques are presented. Diagnostic methods in patients with pheochromocytoma and paraganglioma are presented based on the literature and own case reports. The radiologic modality of choice for the staging of catecholamine-producing tumours during childhood and adolescence is MRI, due to the lack of ionizing radiation and high soft tissue contrast. In addition, 123-I-meta-iodo-benzyl-guanidine (MIBG) scintigraphy and positron emission tomography/computer tomography (PET/CT) are performed. Whole-body MRI is particularly important as ascreening tool in patients with atumour predisposition syndrome. Radiologic imaging and nuclear medicine techniques are important for the assessment of disease stage and therapy planning in patients with catecholamine-producing tumours. Detection of metastatic disease is essential, as there are no known histopathologic markers, which can predict the metastatic potential of the tumours.