Catecholamine-secreting Tumors Research Articles

Pheochromocytoma – A challenge to anesthetist

Abstract Phaeochromocytoma is a catecholamine-secreting tumor of the sympathoadrenal system. It poses a significant challenge to the anesthesiologist, as sudden and intense hemodynamic changes are common in the preoperative and intraoperative periods. Preoperative optimization with sympatholytic drugs along with fluid resuscitation and intraoperative hemodynamic stability is essential for improved patient outcome. The anatomy of the tumor and proximity to major vasculature prove a challenge to anesthetists and surgeons alike. We are presenting a case of a 53-year-old male with a phaeochromocytoma of the right adrenal gland posted for laparoscopic right adrenalectomy, with the tumor mass compressing the inferior vena cava.

Increasing Catecholamine Secretion Through NPY in Pheochromocytomas With False-Negative 123 I-MIBG Scintigraphy.

123 I-MIBG has been well established as a functional imaging tool, and 131 I-MIBG therapy is being considered for catecholamine-secreting tumors. Tumors with the characteristics of a noradrenergic biochemical phenotype, small, malignant, metastatic, extra-adrenal, bilateral, and hereditary, especially SDHx -related tumors, are reported to correlate with reduced MIBG uptake. However, the potential molecular mechanisms influencing MIBG uptake have been poorly studied. To identify critical genes that may enhance MIBG accumulation in pheochromocytomas (PCCs), we performed RNA-seq analyses for 16 operated patients with PCCs (6 MIBG-negative and 10 MIBG-positive) combined with RT-qPCR for 27 PCCs (5 MIBG-negative and 22 MIBG-positive) and examined primary cultures of the surgical tissues. In the present study, 6 adrenal nodules of 66 nodules surgically removed from 63 patients with PCCs (9%) were MIBG negative. MIBG, a guanethidine analog of norepinephrine, can enter chromaffin cells through active uptake via the cellular membrane, be deposited in chromaffin granules, and be released via Ca 2+ -triggered exocytosis from adrenal chromaffin cells. When we compared expression of several catecholamine biosynthesis and secretion-associated genes between MIBG-negative and MIBG-positive tumors using transcriptome analyses, we found that neuropeptide Y, which is contained in chromaffin granules, was significantly increased in MIBG-negative tumors. NPY stimulated norepinephrine secretion dose-dependently in primary cell culture derived from MIBG-positive PCC. In our study, MIBG-negative PCCs were all norepinephrine-hypersecreting tumors. These data indicate that NPY upregulation in PCCs may stimulate chromaffin granule catecholamine secretion, which is associated with false-negative 123 I-MIBG scintigraphy.

Bilateral pheochromocytomas: clinical presentation and morbidity rate related to surgery technique and genetic status.

Pheochromocytomas (PHEOs) are rare catecholamine-secreting adrenal tumors. Approximately 60-90% of bilateral PHEOs are hereditary. We retrospectively analyzed the clinical characteristics of patients with bilateral PHEOs and the morbidity rate (malignancy, tumor recurrence and adrenal insufficiency (AI) rate) related to surgery technique and genetic status of the patients. Fourteen patients (12.5%, nine women, five men) had synchronous or metachronous bilateral PHEOs (out of 112 PHEO patients who underwent surgery between 1976 and 2021). The median age at diagnosis was 32 years (9-76) (three were children). Nine patients (64.2%) presented synchronous bilateral tumors, five (35.7%) contralateral metachronous tumors, 2-12 years after the first surgical intervention; three (21.4%) were metastatic. Median follow-up: 5 years (1-41), IQR 19 months. A total of 78.5% had a germline mutation (eight RET gene with MEN2A syndrome, three VHL syndrome, three not tested). Post-surgery recurrence was noted in 16.6% of patients (one with MEN2A syndrome and metastatic PHEOs, one with VHL syndrome), with similar rates after total adrenalectomy or cortical-sparing adrenal surgery. AI was avoided in 40% after cortical-sparing surgery. Bilateral PHEOs are usually associated with genetic syndromes. The surgical technique for patients with hereditary bilateral PHEOs should be chosen based on a personalized approach, as they are at higher risk for developing new adrenal tumors requiring additional surgeries.

Occult Pheochromocytoma and Acute Ischaemic Stroke in Young Adult: Cause or Association

Pheochromocytoma is a rare catecholamine-secreting tumours of chromaffin tissues that cause a constellation of symptoms. It is closely associated with endocrine hypertension that can be masked, sustained or paroxysmal leading to hypertensive crisis, resulting in vascular and non-vascular complications and rarely cerebral ischaemia and stroke. A healthy 22 year old male reported with acute Right upper limb(RUL) monoplegia and Motor aphasia for five days with raised blood pressure levels. hypertonia was present, deep tendon reflexes were exaggerated in RUL and Right Plantar was extensor. General and systemic findings were nonsignificant . Routine investigations showed thrombocytosis and M.R.I. Brain was suggestive of acute infarction of Left Parieto-Temporal region. Renal doppler, Carotid Intima Media Thickness, Cerebral Angiogram, 2D-E.C.H.O. and Fundoscopy were normal. AntinuclearAntibody was negative. Contrast CT of abdomen revealed right adrenal mass suggestive of isolated Pheochromocytoma. Vanyl-Mandelic Acid was positive. Patient was stabilised and managed conservatively for 4 weeks followed by adrenalectomy and appropriate medical therapy. Patient is on regular followup and does not seem to require any antihypertensives or any other intervention. Pheochromocytoma is a notorious tumor and a great masquerader specially in young adults. A keen eye, routine checkups and evaluation is the key to detecting and preventing its associated morbidity and mortality.

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.

Abstract 15836: Paraganglioma Presenting as Myocardial Infarction With Decompensated Heart Failure

Description of Case: Paragangliomas are extra-adrenal catecholamine secreting tumors, classically presenting with paroxysmal hypertension, headache, and diaphoresis. However, presentations vary significantly, and can mimic cardiac pathologies including myocardial infarction and aortic dissection. A 52-year-old male with history of hypertension and 1 year of palpitations presented for substernal chest pressure with associated dyspnea, nausea and diaphoresis. He reported two days of cough and nasal congestion, and recent addition of metoprolol for palpitations. His family history was notable for early ACS. On examination, he was tachycardic (140 bpm), hypertensive (220/140 mmHg), and hypoxic requiring non-rebreather mask. EKG revealed sinus tachycardia with 1mm J point elevations in V2 and V3. Chest X-Ray and bedside ultrasound indicated pulmonary edema and reduced systolic function. Nitroglycerin infusion was initiated and he was admitted to the Cardiac ICU. Laboratory testing showed a Troponin-T of 0.15 ng/L (normal &lt;0.01 ng/L), ntPro-BNP 2764 pg/mL, lactic acid 3.2 mmol/L, and respiratory swab positive for Influenza A. A CT Aorta ruled out acute dissection but identified several large retroperitoneal masses. Urgent cardiac catheterization demonstrated non-obstructive CAD. Echocardiography noted severely reduced ejection fraction of 30-35%. With diuresis and alpha blockade, he clinically improved and was discharged. Plasma and urine studies revealed elevated metanephrines. He underwent open paraaortic mass resection and pathology later confirmed paraganglioma. Discussion: With angina, elevated troponins, and acute decompensated heart failure, this presentation was initially concerning for ACS. However, the absence of obstructive CAD warranted further investigation. While concomitant Influenza A infection raised concern for viral myocarditis, abdominal imaging proved crucial in diagnosing paraganglioma.

Abstract 18669: Pheochromocytoma Crisis Precipitated by Carvedilol

Description of case: Pheochromocytomas are rare, catecholamine-secreting tumors of the adrenal gland. Definitive treatment is surgical, but requires pre-operative optimization with alpha, followed by beta blockade (BB). Initial treatment with BB can precipitate pheochromocytoma crisis, characterized by hemodynamic instability and end-organ dysfunction. This case describes pheochromocytoma crisis in a young, healthy female after switching from metoprolol to carvedilol. A 27-year-old woman is evaluated by an outpatient cardiologist for recurrent palpitations, “hot flashes” and headaches. Mobile telemetry monitor reveals episodes of “SVT” for which she is started on metoprolol succinate. Given her symptoms, testing for plasma free metanephrines is ordered and is markedly abnormal. Subsequently the patient is switched from metoprolol to carvedilol. Within a few hours of taking carvedilol the patient reports sudden onset dyspnea, nausea, vomiting and chest pain. On arrival, vital signs are remarkable for a resting pulse of 130 and blood pressure of 130/97. EKG shows sinus tachycardia. Labs reveal a high-sensitivity troponin of 1,816 ng/L and a 2-hour troponin of 4,560. CT shows a 5.8 cm left adrenal mass. An echocardiogram reveals a reduced LVEF of 45-50% and is suggestive of reverse takotsubo cardiomyopathy. Her carvedilol is discontinued, she is started on prazosin and her symptoms resolve within 24 hours. She later resumes metoprolol and proceeds with surgical excision. Discussion: This case reports a pheochromocytoma crisis likely precipitated by carvedilol and complicated by reverse-takotsubo cardiomyopathy. Interestingly, the patient tolerated metoprolol despite being in the same class. This switch was made knowing she tolerated BB and with the idea that she would benefit from additional alpha-blockade. Carvedilol is a racemic mixture, with S-carvedilol binding beta-1 and -2 receptors while R-carvedilol binds strictly alpha-1. There is evidence that patients catabolize the enantiomers differentially, resulting in higher concentrations of one enantiomer in an unpredictable manner. It is therefore preferred to avoid all BB before sustained alpha blockade while treating pheochromocytoma despite the patient’s previous tolerance.

FRI270 A Rare Case Of Giant Benign Pheochromocytoma

Abstract Disclosure: M.S. Hossain: None. B. Gautam: None. K. Mandal: None. H. Liao: None. D.S. Rosenthal: None. S.C. Kumar: None. Background: Pheochromocytomas are Catecholamine-secreting tumors that arise from the adrenal medulla. These tumors are rare however giant pheochromocytomas (&amp;gt;7 cm) are even rarer entities, which are thought to be more aggressive and malignant. Here we present a case of incidentally found giant but benign pheochromocytoma. Case Report: A 40-year-old female with no PMH presented to the hospital with fever &amp; cough for 1 month which was associated with weight loss (10lb). Patient was started on antibiotics and CT revealed right-sided adrenal incidentaloma while searching for sources of infection. CT &amp; MRI abdomen were done for better characterization, showed a round circumscribed right adrenal mass measuring 11.3 x 11.4 x 12.8 cm. Mass had irregular central necrosis, peripheral enhancement &amp; neovascularization. Patient denied headache, sweating &amp; palpitation; no personal or family history of pheochromocytoma. On physical examination BP: 103/70, HR: 98, Temp: 98F, BMI:25.9, unremarkable for cushingoid features, virilization &amp; hirsutism. Hormonal workup showed elevated free normetanephrine 185 (&amp;lt;148pg/ml) &amp; chromogranin A 801 (&amp;lt;311ng/ml), but normal free metanephrine &amp;lt;25 (&amp;lt;57pg/ml) &amp; total metanephrines 185 (&amp;lt;205pg/ml). 24hr Urine study: elevated total metanephrines 1661 (182-739mcg/24h) &amp; normetanephrine 1482 (88-649mcg/24h) but normal metanephrine 179(58-203mcg/24h), urine volume 2360ml/24h, urine creatinine 0.87(0.50-2.15g/24h). Patient Cortisol, ACTH, Aldosterone, Renin activity, DHEA-S, Androstenedione was normal. Patient was started on alpha-blockers. Patient underwent successful right-sided adrenalectomy &amp; nephrectomy with IVC resection. Pathology reported pheochromocytoma stage II T2Nx, Ki 67 &amp;lt;5%. No vascular and extracapsular invasion &amp; no mitosis. Post operative outpatient follow up showed elevated plasma free normetanephrine 199(&amp;lt;148pg/ml) &amp; normal free metanephrine &amp;lt;25 (&amp;lt;57pg/ml) &amp; total metanephrine 199 (&amp;lt;205pg/ml). 24hr urine study: normal metanephrine 61 (58-203mcg/24h), Normetanephrine 268 (88-649mcg/24h) &amp; total metanephrines 329 (182-739mcg/24h). Patient was advised for Ga68 DOTATE/PET scan, genetic counseling &amp; lifelong follow-up with endocrinology for surveillance. Discussion: Pheochromocytoma symptoms may vary regardless of tumor size. Giant pheochromocytoma may not have high secretory potential due to central necrosis resulting in reduced chromaffin cells or catecholamines that are restricted to capsular mass which may release into the bloodstream intraoperatively1. Therefore, initiating alpha-blockers before surgery in these cases may prevent perioperative complications.1. Minei S, Yamashita H, Koh H, Satoh T, Kobayashi S, Furuhata M, et al. Giant cystic pheochromocytoma A case report. Hinyokika Kiyo. 2001;47:561-3. Presentation: Friday, June 16, 2023

FRI264 A Case Of Composite Pheochromocytoma And Ganglioneuroma

Abstract Disclosure: D. He: None. J. Pullman: None. S. Stefan: None. B.Y. Wong: None. Background: Pheochromocytomas are catecholamine-secreting tumors that arise from chromaffin cells in the adrenal medulla or paraganglia. Representing 1-9% of pheochromocytomas, composite pheochromocytomas are rare tumors composed of pheochromocytoma and neural tumor components such as neuroblastoma, ganglioneuroblastoma, ganglioneuroma or peripheral nerve sheath tumor1. We present a case of composite pheochromocytoma and ganglioneuroma. Clinical Case: A 69-year-old man presented with recurrent dyspnea at rest, diaphoresis and tachycardia. He was diagnosed with heart failure with reduced ejection fraction and management included metoprolol 50 mg daily. On work-up, he was incidentally found to have a 1.2 cm left upper lobe lung lesion and an indeterminate 2.4 cm right adrenal mass on CTA chest. PET/CT scan showed an intensely avid left upper lobe lung nodule and a right adrenal mass with mild FDG uptake (SUV max 3.8). MRI abdomen demonstrated a 3.1 cm right adrenal lesion with a mildly thickened enhancing rim and a central enhancing nodular component suspicious for pheochromocytoma, metastases, schwannoma or ganglioneuroma. He then had a stroke with mild residual right-sided weakness. Oncological work-up of his lung and adrenal lesions eventually directed tissue sampling to biopsy of the adrenal lesion and pathology was consistent with pheochromocytoma. Subsequent biochemical evaluation revealed elevated plasma metanephrines of 194 pg/mL (&amp;lt;= 57 pg/mL), plasma normetanephrines of 474 pg/mL (&amp;lt;= 148 pg/mL), 24-hour urine metanephrines of 389 mcg (90-315 mcg) and 24-hour urine normetanephrines of 428 mcg (122-676 mcg). Pre-operatively, he was placed on phenoxybenazmine 10 mg twice daily and metoprolol 62.5 mg every 8 hours. The patient then underwent right adrenalectomy. The tumor nodule was adherent to and dissected off the inferior vena cava. Pathology showed composite pheochromocytoma with a small component of ganglioneuroma. Conclusion: This rare case of a composite pheochromocytoma with ganglioneuroma was diagnosed through histopathology as composite pheochromocytomas are clinically and radiographically indistinguishable from pheochromocytomas1. Management of composite pheochromocytomas with ganglioneuroma is similar to the management of pheochromocytomas, and surgical resection remains the first line treatment. Combined alpha and beta-adrenergic blockade is recommended to prevent intraoperative hypertensive crisis. However, more studies are needed to further understand these rare composite pheochromocytomas.

FRI265 I123-MIBG Positive, CU64-Dotatate PET Negative Pheochromocytoma In A Patient With Bilateral Adrenal Incidentalomas

Abstract Disclosure: P. Pagadala: None. V. Patel: None. Bilateral incidental adrenal nodules represent 10-23% of all incidental adrenal nodules. Most are benign nonfunctioning adenomas however these can be catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla called pheochromocytomas. Identifying pheochromocytoma using anatomic imaging alone in cases of bilateral adrenal nodules is challenging. Functional imaging with radioisotope tracers can be helpful such as MIBG (meta-iodobenzylguanidine) and DOTATATE scans. We describe a case of pheochromocytoma, which was negative on DOTATATE but positive on MIBG scan which localized the pheochromocytoma. A 65-year-old male with a history of hypertension, chronic kidney disease and obstructive sleep apnea was found to have bilateral adrenal nodules on routine imaging. MRI abdomen showed a right adrenal nodule 1.7cm x 1.8cm x 1.7cm and a left adrenal nodule 2.3 cm in maximum dimension. He had no apparent symptoms of catecholamine excess. Biochemical testing revealed elevated total plasma metanephrines on serial assessments along with elevated 24-hour urine dopamine levels. A CT scan with adrenal protocol further characterized the right adrenal nodule with precontrast density of 43 Hounsfield Units (HU) with a rapid washout of 75% within 5 minutes, consistent with benign adrenal adenoma. The left adrenal gland had 2 nodules. A smaller superior nodule 1.3 cm AP x 1.0 cm transverse x 0.9 cm craniocaudal in size, density of -3 HU on the precontrast images, with approximately 85% washout most consistent with a benign adrenal adenoma. A larger inferior nodule was 2.3 cm AP x 2.2 cm transverse x 2.3 cm craniocaudal in size and precontrast density of 32 HU, rising to 58 HU during the portal venous phase and remaining at about 58 HU on the delayed images, indicating no significant washout and is indeterminate. A Cu64 labeled DOTATATE scan showed the 1.6 cm right adrenal nodule demonstrated activity similar to that of contralateral background adrenal activity. There was no comment regarding the two left adrenal nodules. A I123 MIBG scan showed the larger of the two left adrenal nodules had a strong uptake of the MIBG highly likely to be a pheochromocytoma. The smaller left adrenal nodule and the right adrenal nodule had no significant MIBG uptake, making these adrenal adenomas. The patient underwent left robotic adrenalectomy and pathology confirmed a 2.3 cm pheochromocytoma in addition to adrenocortical nodular disease. Three months post-surgery, plasma and 24-hour urinary measurements for metanephrines and catecholamines had normalized. Further research is needed to assess the benefit of I123MIBG when DOTATATE is negative. A potential cause of false negatives on DOTATATE is variability in somatostatin receptor subtype expression. Better imaging modalities for pheochromocytomas and guidelines for the management of bilateral adrenal nodules would assist in treatment decisions. Presentation: Friday, June 16, 2023

FRI194 Pheochromocytoma Presenting As Catecholamine-Induced Cardiomyopathy: A Case Report

Abstract Disclosure: M. Tsikala Vafea: None. D. Lee: None. Introduction: Pheochromocytoma (PCC) is a rare catecholamine-secreting neuroendocrine tumor presenting with the classic triad of episodic headache, sweating and tachycardia. Catecholamine-induced cardiomyopathy (CICMP) can occur as a complication of PCC in 7-11% of patients. It presents more commonly as dilated cardiomyopathy and inverted Takotsubo cardiomyopathy but also as hypertrophic or unspecified cardiomyopathy. Following appropriate pharmacologic treatment and resection of PCC, these cardiac complications usually resolve. Case report: 36 year old man with history of hypertension presented to the hospital with worsening orthopnea and cough. Following antibiotic treatment failure for suspected pneumonia, he was re-admitted with hemoptysis, tachycardia, hypoxia, and hypertensive emergency. Troponin and brain natriuretic peptide were found to be elevated. CT chest and abdomen showed pulmonary nodules and a large left adrenal mass measuring 9.6x9.3x9.4 cm, concerning for metastatic PCC. He was subsequently started on doxazosin. Transthoracic echo showed bi-atrial enlargement, diffuse severe left ventricle hypokinesis, reduced ejection fraction 25% and diastolic dysfunction. Stress cardiac MRI showed non-ischemic cardiomyopathy, corroborating the diagnosis of CICMP. After achieving adequate alpha-adrenergic blockade, he was started on goal-direct medical therapy consisting of valsartan, metoprolol and empagliflozin. His pulmonary nodular opacities improved on repeat imaging, congruent with pulmonary edema rather than metastases. Plasma and 24-hour urine metanephrines (2,964 pg/mL and 23,310 mcg/24 hr, respectively) and normetanephrines (9,266 pg/mL and 33,927 mcg/24 hr, respectively), as well as dopamine (493 pg/mL), epinephrine (3,205 pg/mL) and norepinephrine (above reportable range of 4,800 pg/mL) eventually came back significantly elevated, confirming his diagnosis of PCC. A month after presentation, he underwent left adrenalectomy, which revealed an 11 cm composite PCC ganglioneuroma. One-month postoperatively, urine metanephrines and normetanephrines were normal but his ejection fraction remained unchanged. Discussion: CICMP should be considered in patients presenting with acute heart failure and an incidental adrenal mass to avoid delays in treatment. Acute pulmonary edema may resemble pulmonary nodules on CT, so interpretation of these findings should correlate with the clinical presentation. Timely initiation of alpha-adrenergic blockade upon suspicion of PCC is crucial as it can significantly improve hemodynamics, and biochemical markers take time to result. 96% of CICMP cases improve after resection of PCC within a variable time frame ranging from one week to several months. Our patient’s CICMP had not improved one month after his adrenalectomy, but it remains to be seen whether he eventually recovers his cardiac function. Presentation: Friday, June 16, 2023

SAT311 A Time And Place For Metyrosine: Successful Treatment Of A Pheochromocytoma Presenting With Hypotension And Multisystem Organ Failure

Abstract Disclosure: R. Shafiq: None. J. Giordano: None. Pheochromocytomas are rare neuroendocrine catecholamine-secreting tumors. The surgical excision of pheochromocytoma is definitive management which requires presurgical preparation with an alpha blocker, beta blocker, and sometimes metyrosine to reduce perioperative hemodynamic instability. We present a case of pheochromocytoma complicated with acute on chronic renal failure and acute on chronic heart failure with hypotension requiring metyrosine in presurgical preparation due to hypotension and intolerance to alpha-blocker with successful surgical excision of the tumor. Case: 67 yo M admitted for acute on chronic heart failure and acute on chronic renal failure. He was noted to have an incidental right adrenal mass of 4.3 x 4.5 cm on the CT chest. He denied any prior history of hypertension, episodes of flushing, sweating, palpitations, headaches, or any family history of adrenal malignancies. His labs were consistent with significantly elevated plasma metanephrines to 4.5 nmol/L (normal range &amp;lt; 0.5 nmol/L) and normetanephrine 36 nmol/L (normal range &amp;lt; 0.9 nmol/L). Levels were repeated with slight worsening of metanephrines to 5.6 and normetanephrine to 42. He was hypotensive on presentation initially on milrinone drip that was slowly tapered off. His echo on admission showed left ventricle global hypokinesis with EF 25-30%. He had a worsening renal function on admission and required a few dialysis sessions before being referred to our hospital. He had an MRI adrenal done w/o contrast in the setting of renal failure with a heterogenous mass concerning for pheochromocytoma. PET CT was done which was negative for metastatic disease. Due to strong suspicion of uncontrolled pheochromocytoma as a cause of his heart failure and acute on chronic renal failure, the team and patient opted for unilateral adrenalectomy. He was started on metyrosine pre-surgically as he could not tolerate alpha blockade due to hypotension. His metanephrine levels improved from 5.6 to 1.8 and normetanephrine from 43 to 15 with metyrosine prior to surgery. He had a successful right adrenalectomy and pathology confirmed pheochromocytoma. Of note, he had a history of diabetes with uncontrolled hyperglycemia during admission. Hyperglycemia resolved after adrenalectomy. His plasma metanephrine levels normalized post-adrenalectomy and remained normal on the follow-up visit. Conclusion: Preoperative medical stabilization is a crucial step before surgical resection of pheochromocytoma that traditionally includes an alpha blocker followed by a beta-blocking agent to reduce intra-operative hypertensive crisis. Metyrosine is an often-overlooked agent due to cost, however, should remain in our armamentarium for pheochromocytoma crisis complicated with hypotension when the patient is unable to tolerate an alpha-blocking agent. Presentation: Saturday, June 17, 2023

FRI200 Severe Cushing Syndrome Due To An ACTH-producing Pheochromocytoma

Abstract Disclosure: G.A. Stamatiades: None. A. Bikas: None. H.J. Shah: None. K. Wong: None. A. Vaidya: None. M. Nehs: None. S.S. Basaria: None. Background: Pheochromocytomas are rare catecholamine-secreting tumors that arise from sympathetic adrenomedullary chromaffin tissue. Rarely, pheochromocytomas co-secrete ACTH and patients present with Cushing syndrome. Due to its rarity, clinicians may not consider this etiology of Cushing syndrome. We report a case of a man with ACTH-producing pheochromocytoma in whom methodic systematic approach led to its diagnosis and successful treatment. Clinical Case: A 48-year-old man presented with altered mental status. His family confirmed depressed mood, paucity of thought, and occasional blank stares. The patient was diagnosed with type-2 diabetes mellitus and hypertension 3 months ago, which were not controlled despite being on multiple anti-hypertensives and anti-diabetic agents. His EEG, head CT, and brain MRI were normal. On admission, his laboratory tests were notable for hypokalemia (3.0 mmol/L, n&amp;lt;5.3 mmol/L) and metabolic alkalosis (HCO3 33 mmol/L, n&amp;lt;32 mmol/L). Physical examination showed facial plethora, multiple ecchymoses and profound proximal muscle weakness. CT scan of the abdomen showed a 3.4 cm left adrenal nodule with a density of 33 Hounsfield units and a 73% absolute washout. The right adrenal gland was hyperplastic. Plasma and urinary metanephrines were significantly elevated (plasma metanephrines 1.6 nmol/l, n &amp;lt; 0.50 nmol/l, urinary metanephrines 1,685 mcg/24h, n &amp;lt;646 mcg/24h). Midnight salivary cortisol was 11,500 ng/dl (n&amp;lt;100 ng/dl) and 24h urinary free cortisol was 13,099 mcg/24h (n &amp;lt; 45 mcg/24h). ACTH was 450 pg/ml (n&amp;lt;63pg/ml) with a serum cortisol of 93 ug/dl (n&amp;lt;18.4 ug/dl). His serum cortisol after 8 mg Dexamethasone Suppression test was 100 ug/dl. DOTATATE PET CT scan showed uptake in the left adrenal nodule. The workup was suggestive of left-sided pheochromocytoma producing ectopic ACTH. The patient underwent laparoscopic left adrenalectomy. Postoperative ACTH was undetectable, indicating surgical cure. His blood pressure and plasma glucose gradually improved and remained normal after discontinuation of all medications. Surgical pathology was consistent with pheochromocytoma with positive staining for ACTH, confirming the diagnosis of ACTH-producing pheochromocytoma. He was discharged home after successful rehabilitation. Clinical Lessons: Pheochromocytomas are a rare cause of ectopic ACTH production, resulting in clinical Cushing syndrome. Imaging of the contralateral adrenal gland provides a valuable clue in making the diagnosis of ectopic ACTH production (as the gland is enlarged rather than atrophic). Reference: (1) Elliott PF, Berhane T, Ragnarsson O, Falhammar H. Ectopic ACTH- and/or CRH-Producing Pheochromocytomas. J Clin Endocrinol Metab. 2021 Jan 23;106(2):598-608. doi: 10.1210/clinem/dgaa488. PMID: 32710791. Presentation: Friday, June 16, 2023

FRI208 Treating Pheochromocytoma For Glycemic And Blood Pressure Control

Abstract Disclosure: A.M. Santiago Carrion: None. A.N. Gonzalez Bossolo: None. Pheochromocytomas are catecholamine-secreting tumors of the adrenal medulla chromaffin cells. They account for 0.2-0.6% of hypertension (HTN) in patients of general outpatient clinics. In addition, is known that this excess of catecholamine production is associated with impaired insulin release from pancreatic beta-cells leading to hyperglycemia. However, pheochromocytoma as a cause of diabetes and HTN is frequently overlooked. A 60-year-old woman with medical history of arterial HTN and type 2 diabetes mellitus since 10 years ago was referred to the Endocrine clinic by Nephrology for glycemic control. Her medical regimen consisted of linagliptin 5mg daily, metformin 1000mg twice daily, insulin glargine 40 units daily, losartan 50mg twice daily, amlodipine 10mg daily and hydrochlorothiazide 25mg daily. Physical examination was unremarkable, including adequate vital signs with blood pressure 110/64 mmHg and heart rate 93/min. Laboratories were notable for glycated hemoglobin 8.7%, fasting blood glucose 118 mg/dL, and urine albumin-creatinine ratio (UACR) 4622 mg/g with adequate glomerular filtration rate. Upon further investigation of nephrotic-range proteinuria, patient was incidentally found with a right adrenal mass on ultrasound, which was confirmed to have absent signal dropout on MRI and measured 5 cm. On retrospective, patient revealed feeling episodic palpitations, diaphoresis, and occasional headaches which she attributed to menopausal symptoms. Plasma free metanephrines were negative, but free normetanephrines were elevated at 2160 pg/mL (range &amp;lt;148 pg/mL). Patient underwent successful right adrenalectomy and pathology confirmed a right 5 cm pheochromocytoma with negative margins. Unfortunately, she wished to defer genetic testing. Four weeks after surgery, plasma normetanephrines fell to normal levels 141.8 pg/mL. Furthermore, patient was able to wean off basal insulin completely and HTN remained controlled with losartan monotherapy. Glycated hemoglobin improved to 6.7%. Additionally, UACR improved to 1352.94 mg/g and empagliflozin was added to avoid diabetic kidney progression. In this case we presented a patient with common comorbidities encountered in the clinic, but with an unusual etiology. Moreover, this patient presented with nephrotic-range proteinuria that has significantly improved after removal of the tumor, which has only been seen in case reports. Some authors propose a possible immunological pathogenesis or glomerular hyperfiltration. Detection of resistant HTN should had prompted earlier detection of pheochromocytoma in this patient. As physicians, we should be aware of endocrine causes of diabetes and HTN, such as Cushing syndrome, Acromegaly, Primary Aldosteronism, and Pheochromocytoma and Paraganglioma, as treating these may lead to better quality of life, and less disease-related complications and polypharmacy. Presentation: Friday, June 16, 2023

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

Management of a Complex Case of a Recurrent Paraganglioma.

Paragangliomas are rare, slow-growing, hypervascular, catecholamine-secreting neuroendocrine tumors arising from the paraganglia. Paragangliomas are rarely found in the head and neck and are typically benign, presenting as a painless, slow-growing mass. Surgical extirpation in combination with long-term surveillance has been long regarded as the standard of care; however, the advances in imaging, radiation therapy, and embolization techniques have improved diagnostic and therapeutic modalities. We present a case of an 87-year-old female who had previously undergone resection of a paraganglioma in 1998, with no evidence of disease in 2002. Eighteen years later, the patient presented to the clinic with otogenic complaints. Imaging showed an expansive mass from the jugular foramen with bone destruction and opacification within the ear canal. The patient opted for observation. The patient eventually presented to the emergency room with neurologic manifestations. Imaging showed a cerebellar abscess prompting emergency drainage. Intraoperative cultures grew Prevotella loescheii and S. intermedius, and the patient was started on 6 weeks of IV antibiotic therapy. Debulking of the paraganglioma was performed followed several months by mastoid and ear canal obliteration; however, the patient experienced complications, including dehiscence of the external auditory canal and Clostridium difficile infection. The patient was eventually treated successfully, marked by a reduction in complaints, a return to baseline activities, and imaging showing no increase in tumor size.

Pheochromocytoma: Clinical Experience From a Single Tertiary Care Center in India.

Pheochromocytoma is a catecholamine-secreting tumor arising from adrenomedullary chromaffin cells that has a varied clinical presentation. Identification of this tumor, which has episodic symptoms, is a diagnostic challenge for clinicians. Diagnosis at an appropriate time is important because it is associated with significant morbidity and mortality. This study aims to mitigate the limited availability of data in our geographical area. To assess the clinical, biochemical, and radiological features and outcomes of patients diagnosed with pheochromocytoma at our center. This is a retrospective study. Patients diagnosed with pheochromocytoma during 2015-2023 were included in the study. Clinical, biochemical, and radiological data were collected at presentation, post-surgery, discharge, and until the last follow-up; data were retrieved from hospital records. Statistical analysis was done using IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. This study included 19 patients, of whom 10 (52.6%) were female. The most common clinical presentation was a hypertensive crisis in patients with pre-existing hypertension (63.1%), followed by headache (47.3%). The classical triad of headache, palpitation, and sweating was seen in only three patients (15.7%). The mean tumor size was 5.01±2.06 cm, with a range of 2.5 to 12 cm. All patients underwent adrenalectomy; six patients (31.5%) had perioperative complications, with post-operative hypotension being the most common at 21% (n = 4), followed by an acute coronary event during alpha blockade in one patient (0.05%) and an intra-operative hypertensive crisis in one patient (5%). A biochemical remission rate post-surgery was achieved in 17 (89.47%) patients. Hypertensive crisis in patients with pre-existing hypertension was the predominant presenting feature in most of our patients. Female predominance was noted (52.3%) compared to males. Perioperative complications were observed in 31.5% of patients, with post-operative hypotension being the most common complication.

Change in Perioperative Management of 14 Consecutive Patients with Pheochromocytoma – Is Alpha Blockade Still Necessary?

Abstract Background Pretreatment with alpha-blockers before surgery for pheochromocytoma or paraganglioma is considered the gold standard and is recommended in the 2014 Endocrine Consensus Guidelines. Meanwhile, there is evidence at specialized clinics that alpha blockade does not provide any benefit preoperatively. Due to an index case with severe side effects from alpha blockade and the recent evidence, we have refrained from preoperative alpha blockade before planned surgery for a catecholamine-secreting tumor in our hospital since 2018. Aims The aim of the study is to evaluate the outcome after change of perioperative management. Methods A retrospective analysis of patients was performed using data prospectively collected in the Eurocrine quality registry of all patients with pheochromocytomas and paragangliomas operated on at our hospital from 2018 to 2022. Results During this period, 14 patients with pheochromocytomas (n=10) and paragangliomas (n=4) underwent surgery. 21% (3 of 14) patients were pretreated by alpha blockers for 7-14 days, 79% (11/14) patients did not receive preoperative alpha blockade after interdisciplinary discussion. All patients with alpha blockade had significant orthostasis symptoms, and 2 patients experienced syncope despite adequate volume delivery. One of these patients suffered a traumatic brain injury after a fall. Intraoperatively, 50% (7 of 14) of the patients experienced a hypertensive crisis &amp;gt;200 mmHg, which was resolved with rapid anesthetic intervention. The 3 patients with alpha blockade had prolonged hypotension postoperatively, so catecholamines had to be administered after extubation in 2 patients. No relevant complications occurred. Conclusions In our hospital, no relevant complications occurred despite omission of alpha blockade for pretreatment in pheochromocytomas and paragangliomas. However, the number of cases in these rare tumors is low, nevertheless this seems to be feasible in a good interdisciplinary setting.

Abstract 2199: Novel urinary marker for diagnosis and prognosis of neuroblastoma

Abstract Background and Aim: Urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA) concentrations are widely used for diagnosis of neuroblastomas, which are catecholamine-secreting tumors. As recent advances in mass spectrometry have facilitated the measurement of metabolites present at extremely low concentrations, urinary metabolites with better diagnostic or prognostic utility for detection of neuroblastomas could be identified. This study utilized quantitative analyses using liquid chromatography-mass spectrometry (LC-MS) to evaluate the diagnostic and prognostic performance of a novel biomarker candidate: 3-methoxytyramine sulfate [3-MTS]. Materials and Methods: The concentrations of the three urinary metabolites (HVA, VMA, and 3-MTS) in urine samples of 41 patients with primary neuroblastoma and urine samples of 155 control participants were measured using LC-MS. The cut-off values for these metabolites were the mean + 2 standard deviation values of the control. Linear discriminant analysis was used to evaluate the association of urinary marker candidates with unfavorable risk factors such as the International Neuroblastoma Pathology Classification and MYCN amplification. Results: The sensitivity and specificity were as follows: 3-MTS 90.2%, 94.2%; HVA 87.8%, 96.1%; VMA 87.8%, 96.1%; VMA or HVA+3-MTS 97.6%, 92.3%; HVA+VMA 87.8%, 94.8%; respectively. 3-MTS could differentiate between the cases with favorable and unfavorable histology (AUC =0.950). 3-MTS+VMA differentiated between the cases with MYCN amplification and nonamplification (AUC=0.952). Conclusions: 3-MTS might be a useful urine marker for both diagnosis and prognosis of neuroblastoma. Citation Format: Akinari Hinoki, Hizuru Amano, Hiroo Uchida, Atsushi Narita, Shun Kumano, Mayumi Abe, Minoru Sakairi, Chiyoe Shirota, Wataru Sumida, Satoshi Makita, Yoshiyuki Takahashi, Tsuyoshi Osawa. Novel urinary marker for diagnosis and prognosis of neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2199.

132 Resistant Hypertension Secondary to Catecholamine-Secreting Glomus Tumor

132 Resistant Hypertension Secondary to Catecholamine-Secreting Glomus Tumor