24-hour Urinary Metanephrines Research Articles

Impact of commonly used drugs on 24-hour urine metanephrine excretion.

Impact of commonly used drugs on 24-hour urine metanephrine excretion.

P-06 Catecholamine-induced cardiomyopathy: A rare presentiation of pheochromocytoma

Abstract Introduction Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors. Clinical manifestations consist of various cardiovascular signs and symptoms related to excessive secretion of catecholamines. Catecholamine-induced cardiomyopathy is a rare but life-threatening complication of PPGL. Excessive discharge of catecholamines results in vasoconstriction, coronary vasospasm and myocardial ischemia. Three types of cardiomyopathies can be observed in patients with PPGL; dilated cardiomyopathy, Takotsuba cardiomyopathy and hypertrophic cardiomyopathy. Clinical Case Herein, we present a case with PPGL complicated with heart failure probably due to excessive secretion of catecholamines. A 19 years-old man was admitted to emergency department with dyspnea and hypotension. He exhibited severe signs of heart failure with very high liver function tests; ALT: 3647 U/L (8-65) and AST: 4542U/L (7-40), probably due to hepatic congestion. Echocardiogram performed in ICU reported %10 left venticular ejection fraction with diffuse akinesia. Remarkable improvement of liver function was recorded following the introduction of heart failure medicines. A computed tomography scan that was performed for abdominal pain and distension revealed a six cm tumour at the left adrenal gland compatible with pheochromocytoma. Laboratory analyses were; 24-hour urine metanephrines: 1938mcg (44-261), normetanephrines: 17934mcg (103-390). Following necessary preoperative preparations, laparoscopic left adrenalectomy was performed and a 70 mm adrenal tumor, histopathologically compatible with pheochromocytoma, was excised. His postoperative laboratory findings were; 24-hour urine metanephrines: 248 mcg (44-261), normetanephrines: 4368 mcg (103-390), chromogranin A: 554.9 ng/ml (0-100), 3-methoxytyramine: 0.34 nmol/l (0-0.17). A 68-Ga-DOTA-Peptide PET/CT following 12 weeks of surgery demonstrated hypermetabolic lesions at left suprarenal area. A second open surgery was performed and lymph node metastases were detected (Figure 1). His cardiac functions ameliorated significantly following the removal of tumors. Genetic analysis for PPGL syndromes were negative for KIF1B, SDHB, NTRK1, TMEME127, VHL, RET, SDHD genes. Work-up is still pending for the mutations of SDHA, SDHC and SDHAF2 genes. Conclusion Cathecolamine-induced cardiomyopathy is a rare entity associated with PPGL. Urgent recognition of related clinical signs and symptoms and detection of PPGL is lifesaving. It should be kept in mind in patients presenting with symptoms of heart failure, hypotension and multisystem crisis in the absence of coronary or valvular heart disease.Figure 1.Pheochromocytoma with lymph node metastasis. (H&E x100)

24-hour urine metanephrine excretion in patients diagnosed with adrenal incidentaloma: impact of commonly used drugs on a clinical decision.

Incidentaloma is an adrenal tumor detected during diagnostic imaging performed for extra‑adrenal causes. Evaluation of metanephrine concentrations in a 24‑hour urine collection can be a significant challenge in patients with multiple medications and comorbidities. The aim of this study was to evaluate the effect of commonly used groups of drugs on metanephrine levels in the 24‑hour urine collection. A total of 1051 patients with adrenal mass below 10 Hounsfield units on unenhanced computed tomography were included in the study. Patients diagnosed with Cushing or Conn syndrome, adrenal carcinoma, pheochromocytoma, active extra‑adrenal malignant neoplasms, and exacerbation of severe illnesses were excluded. Metanephrine, normetanephrine, and 3‑methoxytyramine in the 24‑hour urine collection were measured by high‑performance liquid chromatography with electrochemical detection. Information on concomitant medication (β‑blockers, calcium channel blockers [CCBs], loop diuretics, thiazide diuretics, potassium‑sparing diuretics, α‑blockers, angiotensin‑converting enzyme inhibitors / angiotensin II receptor blockers, metformin, nonmetformin antidiabetic drugs [NMADs], lipid‑lowering drugs, proton pump inhibitors, levothyroxine, thyreostatics, antidepressants, neuroleptics, benzodiazepines, glucocorticosteroids, inhaled B‑receptor agonists, and ipratropium) was collected from each patient. The urinary excretion of normetanephrine was significantly higher in the patients on β‑blockers, CCBs, loop diuretics, α‑blockers, NMADs, and neuroleptics. α‑Blockers increased urine metanephrine concentration, and NMADs, antidepressants, and glucocorticosteroids lowered it. There was no association between the analyzed drugs and urinary 3‑methoxytyramine level. Many drug groups interfere with the measurement of urinary fractionated metanephrines. These interactions should be taken into account during interpretation of a hormonal evaluation, as they can be crucial for further management, especially for making a decision on surgical treatment.

A RARE PRESENTATION OF SMALL CELL LUNG CARCINOMA METASTASIZING TO PHEOCHROMOCYTOMA

Abstract Introduction/Objective Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize hematogenously into another unrelated tumor. We report an interesting case of a tumor-to-tumor metastasis of small cell lung carcinoma to pheochromocytoma of the adrenal gland. Methods/Case Report A 75-year-old female former cigarette smoker with a past medical history of hypertension presented with a two-day history of dyspnea and epigastric pain. Physical examination demonstrated elevated blood pressure only. A computerized axial tomography scan of the chest and abdomen showed an incidental 3.1 cm right adrenal mass and right hilar lymphadenopathy. Detailed biochemical workup showed elevated serum epinephrine, norepinephrine, and 24-hour urine metanephrine. Adrenalectomy showed a 5.8 cm tumor mass with solid lobulated yellow to pink-tan and focally hemorrhagic cut surfaces. Microscopic examination showed a neoplasm composed of two distinct components. The predominant component consisted of nests ("zellballen") of large polygonal cells with variable nuclear pleomorphism, abundant amphophilic to basophilic cytoplasm, and a delicate intervening fibrovascular stroma, without significant mitotic activity. The minor component was characterized by sheets and nests of "small blue cells" with round to ovoid nuclei, stippled nuclear chromatin pattern, scanty cytoplasm, patchy necrosis, and high mitotic activity (>20 mitoses per 10 HPF). Foci of small cell carcinoma deposits were also present in the lymphatic channels of pheochromocytoma. Immunohistochemical stains demonstrated cytoplasmic staining of predominant component tumor cells for synaptophysin, chromogranin, and the absence of staining for TTF-1, CK CAM 5.2, and Ki-67. However, minor component tumor cells demonstrated cytoplasmic staining for synaptophysin, membranous staining for CK CAM 5.2, and nuclear staining for TTF-1 and Ki-67(60%). A final diagnosis of composite pheochromocytoma (predominant) and small cell neuroendocrine carcinoma (minor) was rendered. The possibility of a” collision” tumor comprising primary small cell carcinoma of pulmonary origin metastatic to an adrenal pheochromocytoma in light of the patient's cigarette smoking history and the presence of right hilar lymphadenopathy was favored. The subsequent biopsy of the right subcarinal adenopathy showed small cell carcinoma. Results (if a Case Study enter NA) NA Conclusion To the best of our knowledge, this is the only case of metastasis to a pheochromocytoma from a small cell neuroendocrine lung carcinoma.

An Unusual Cause of Bilateral Adrenal Incidentaloma: A Case Report of Primary Adrenal Lymphoma

Primary adrenal lymphoma (PAL) is an extremely rare among the causes of adrenal incidentaloma. Most were diagnosed with adrenal insufficiency and B symptoms (unexplained weight loss, night sweats, fever). This article presented a 57-year-old woman who was investigated for bilateral adrenal masses found incidentally on computed tomography (CT). Physical examination and laboratory tests revealed no evidence of adrenal insufficiency or B symptoms. Only 24-hour urinary metanephrine and normetanephrine excretion were increased. Tumour F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) scan showed the greatest dimension was 14 cm in the left adrenal mass and the maximum standardized uptake value (SUV max) was 26.1 (relative to mean SUV in the normal liver parenchyma, which was 2). An adrenal biopsy was performed after taking adequate precautions against the possibility of a catecholamine crisis. Histopathology revealed high-grade B-cell lymphoma. Bone marrow involvement and brain metastasis were not observed. She received the R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen and intrathecal methotrexate therapy as central nervous system prophylaxis. The patient responded well to treatment, and close clinical follow-up continues. PAL should always be considered when a bilateral adrenal mass is detected.

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

FRI227 Functional Transformation Of An Initially Non-functional Paraganglioma In A Patient With Cyanotic Congenital Heart Disease

Abstract Disclosure: M. McConnell: None. M. Kanin: None. M.S. Auerbach: None. R. Yu: None. Background: Most pheochromocytomas and about half of paragangliomas (P-PGLs) are functional in that they produce catecholamines. Transformation of non-functional to functional P-PGLs is exceedingly rare. We present a case of such transformation in a young male with cyanotic congenital heart disease (CCHD), resulting in catecholamine-induced cardiomyopathy. Clinical Case: A 27-year-old male with CCHD presented to the hospital with tachycardia, hypertension, and hypoxia. He had a newly depressed ejection fraction of <20% and was in florid heart failure. Despite intervention, he decompensated rapidly, requiring extracorporeal membrane oxygenation (ECMO). Five years prior to this presentation, he had had normal 24-hour urine fractionated metanephrines, vanillylmandelic acid (VMA), and homovanillic acid (HVA) levels; on imaging, he had been incidentally found to harbor a 3.3 x 1.6 x 2.5-cm nodule in the upper aortocaval space which could represent a paraganglioma. Subsequent imaging showed slow growth of this mass. Given this pertinent history, urine and plasma free metanephrine studies were repeated during the hospitalization while he was not on vasopressors. 24-hour urine normetanephrines were elevated at 2,644 mcg/d (81-667 mcg/d), metanephrines at 405 mcg/d (55-320 mcg/d) while plasma free metanephrines were elevated at 0.92 nmol/L (0-0.49 nmol/L) and normetanephrines at 11.85 nmol/L (0-0.89 nmol/L). DOTATATE PET/CT revealed a soft tissue mass measuring 4.3 x 3.1 x 4.9 cm with intense DOTATATE activity in the right paravertebral space between the aorta and cava. He was treated with alpha-adrenergic blockade with improvement in blood pressure. Two months later, he underwent resection of the mass with pathology confirming a 4.9 cm paraganglioma. Conclusion: It is very rare for a paraganglioma to undergo transformation from non-functional to functional status although it is reported in the literature. This scenario is supported by our patient’s normal 24-hour urine metanephrines, VMA, and HVA results on initial presentation followed by marked elevation in urine and plasma metanephrines 5 years later when he presented with heart failure. The functional transformation in this patient was accompanied by significant growth of the paraganglioma. We surmise that alterations in gene expression during tumor growth may be responsible for the functional transformation. It is crucial to reassess the functionality of a paraganglioma if the clinical condition suggests catecholamine excess. 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 (<= 57 pg/mL), plasma normetanephrines of 474 pg/mL (<= 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.

THU529 Challenges In The Management Of Biochemically Silent Paraganglioma

Abstract Disclosure: S. Dewan: None. A. Farooqi: None. J. Jun: None. Biochemically silent Pheochromocytoma and Paraganglioma (PPGL) are rare neuro-endocrine tumors because of which there is low quality evidence and insufficient guidelines for their management. 74-year-old Female was referred to our Endocrine clinic for incidentally discovered Retroperitoneal mass on MRI. On evaluation patient reported having concerns of escalating anxiety, difficult to control HTN and episodic flushing after physical activity in the last one year. A CT abdomen and pelvis with contrast was ordered which showed 1.7 x 1.8 cm mass anterior to the L5 vertebral body just caudal to the aortic bifurcation. The biochemical work up including 24-hour urine Metanephrines (104 ug/24 hr; n 52-341), Normetanephrines (479 ug/24 hr; n 88-444), Total Metanephrines (583 ug/24 hr; n 88-444), 3 Methoxytyramine (166 mcg/24 hr; n <242) was inconclusive. For further evaluation PET CT DOTATATE scan was ordered which showed the lesion to be DOTATAE somatostatin analogue avid, consistent with somatostatin receptor positive neuroendocrine tumor. Patient was scheduled for surgery in 2 weeks and was started on Terazosin in addition to her anti HTN medications Amlodipine, Losartan and HCTZ. The surgery had to be rescheduled due to inadequate blood pressure control. Her amlodipine and Terazosin dosage were gradually increased while the procedure was rescheduled. Eventually she underwent Laparotomy exploration and resection of the lesion. Patient tolerated the procedure well and had no major intra or post operative fluctuations in her blood pressure, heart rate or blood glucose. According to the Endocrine Surgery team, the tumor could not be sufficiently removed since it was immovable during surgery and could not be delineated from the spine. The post-operative CT scan showed nodular lesion at aortic bifurcation slightly increased in soft tissue component from prior CT scan. After discussions with surgery and oncology team, patient opted for imaging surveillance for now and will consider genetic counseling and/or radiation therapy if the tumor increases in size. Untreated PPGL carries a high risk of cardiovascular morbidity and mortality, and some may also be malignant with a propensity to cause mass effects and metastasis. Currently, there are scarce evidence-based studies comparing treatment options in biochemically silent PPGL, and there is no consensus for the most appropriate peri-operative management of biochemically silent PPGL. This case adds to the literature on how a combination of calcium channel blocker and alpha blocker can be used to achieve peri-operative blood pressure and heart rate control with no major side effects. It also demonstrates the importance of functional imaging, especially in clinically or radiologically suspected PPGL, even with a normal biochemical work up. We suggest multi-disciplinary evaluation and individualized management to ensure positive outcomes. Presentation: Thursday, June 15, 2023

Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL). To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients. Patients undergoing polysomnography for suspected OSA were recruited. Plasma free and 24-hour urinary metanephrines were measured by HPLC-MS/MS. Patients with elevated levels had repeat measurements, abdominal imaging, and follow-up to diagnose or exclude a PPGL. Seventy-six patients completed polysomnography and biochemical testing; 68 (89.5%) patients had OSA, of whom 19 (27.9%) had elevated plasma and/or urinary metanephrines. On follow-up, one patient had a bladder paraganglioma, while PPGL was excluded in the remaining patients. OSA patients had more false-positive urinary metanephrines (17 of 67, 25.4%) than plasma metanephrines (2 of 67, 3.0%), P < .01, and this was more common in severe OSA (13 of 34, 38.2%), compared to moderate/mild OSA (4 of 33, 12.1%), P < .01. Both plasma and urinary metanephrines decreased after treatment with continuous positive airway pressure. On multivariable analysis, severe OSA, obesity, and family history of hypertension were positive predictors for false-positive urinary metanephrines in patients with suspected OSA. In OSA patients, plasma metanephrines are less likely to yield false-positive results for the diagnosis of PPGL than 24-hour urinary metanephrines. In patients with suspected OSA, obesity, or a family history of hypertension, plasma metanephrines may be the preferred first-line test to avoid unnecessary anxiety or follow-up.

Immunohistochemically ACTH positivity in an adrenal adenoma that mimicks pheochromocytoma in terms of clinical and radiological findings

Abstract Introduction Ectopic ACTH secretion is a rare cause of endogenous hypercortisolism. Herein, a case of an immunhistochemically ACTH (+) adrenocortical adenoma with typical pheochromocytoma-like clinical and imaging findings on admission is presented. Clinical Case A 41 years-old male was admitted because of an incidentally detected adrenal mass. He complained about attacks of hypertension, headache and facial flashing that occurred unregularly for the last four years although he was on candesartan. Hypertension was common in his family with no sudden death. BMI was 36.61kg/m2, blood pressure was 130/80mmHg. The only pathologic finding was fire-red flashing at his face. Abdominal MRI exhibited a mass, 91×89×86mm in size, at left adrenal gland, compatible with pheochromocytoma. His 24 hours urinary metanephrine was 375.49mcg (44–261), normetanephrine was 786.26mcg (119–451). Routine laboratory tests, electrolytes were normal. Following two-weeks of preparation with hydration and doxazosin, an open-left adrenalectomy was performed safely. His postoperative follow-up was uneventful. Hypertension resolved completely. 24-hour urinary metanephrines returned to normal, 5-HIIA was normal, as well. Pathological examination of the operation specimen was reported as adrenocortical neoplasia, 420 gr. in weight. Only necrosis was positive considering about Weiss criteria. Chromogranin-A and synaptophysin were positive. Ki-67 index was below 1%. The unexpected pathological results alarmed us for measurement of adrenal steroids. DHEA-S was low [60.60mcg/dl (80–560)], total testosterone normal [3.08ng/ml (2.41–8.27)], early-morning cortisol was 9.56µg/dL. Short synacthen test was performed, stimulated cortisol was 12.14µg/dL, which was compatible with adrenal failure. Prednisolon 5mg/day was introduced. He was considered as adrenal Cushing syndrome and preoperative mildly high metanephrines were attributed to induction of Phenylethanolamine N Methyltransferase activity in adrenal medulla by high cortisol in neighbourhood. At follow-up visits, he seemed well with any complaints. His periodic abdominal imagings were normal. He was compliant to glucocorticoid replacement, but surprisingly his baseline cortisol levels kept being low, dropped to lower levels; even to 2.7mcg/dl. At third post-operative year, he still required prednisolon, his plasma ACTH was 320pg/ml and early-morning cortisol was 4.8mcg/dl. His baseline medical records were re-evaluated, contralateral adrenal seemed normal at diagnosis. ACTH immunohistochemical staining of operation specimen was performed and was found positive. Conclusion This case has serious take home messages. First, glucocorticoid axis should be evaluated for each adrenal mass regardless of clinical and imaging findings. Second, although it is very rare, ectopic ACTH secretion should be kept in mind in cases, who exhibit long-lasting adrenal failure with even worsening cortisol levels following adrenalectomy.

PS-C22-5: PLASMA METANEPHRINES PROVIDE GREATER SPECIFICITY THAN URINARY METANEPHRINES IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA: A PROSPECTIVE TRIAL

Introduction: Pheochromocytoma and paraganglioma (PPGL), and obstructive sleep apnea (OSA) are important secondary causes of hypertension. Both plasma and urinary metanephrines have high diagnostic sensitivity and specificity for diagnosis of PPGL. Patients with OSA have increased nocturnal catecholamine release, which can lead to increased metanephrines production over 24 hours. We hypothesized that morning plasma metanephrines have a higher diagnostic accuracy than 24-hour urinary metanephrines in patients with OSA. Methods: We recruited patients undergoing polysomnography for suspected OSA. Plasma and 24-hour urinary metanephrines were measured. Patients with elevated metanephrines had repeated measurements of metanephrines, imaging and follow-up, to diagnose, or exclude, PPGL. Results: Seventy-six patients completed polysomnography and biochemical testing, of which 68 had OSA. One patient had a PPGL, while PPGL was excluded in the remaining patients. At baseline, OSA patients were more likely to have falsely-elevated urinary (17 of 67, 25.4%), than falsely-elevated plasma metanephrines (2 of 67, 2.9%) (P &lt; 0.01). Seven patients had normal metanephrines on repeat testing. Nine patients with persistently elevated metanephrines underwent abdominal imaging: six patients had no PPGL, one had lipid-rich adrenal adenomas, one had indeterminate adrenal adenoma, and one had bladder tumor. This final patient with biopsy-proven bladder PPGL had marginally-elevated urinary metanephrines, but false-negative plasma metanephrines, due to the small tumor size. Falsely-elevated urine metanephrines were more common in patients with severe OSA (13 of 3, 38.2%), compared to moderate OSA (1 of 13, 7.7%) and mild OSA (3 of 20, 15%), P &lt; 0.01. Falsely-elevated plasma and urine metanephrines were all due to elevation of normetanephrine, while metanephrine was normal in all patients. Declines in metanephrines were observed only in patients with OSA treated with continuous positive pressure ventilation, while those untreated had no improvements. Conclusion: In patients with OSA, metanephrines measured in plasma provide better specificity than those measured in urine for the diagnosis of PPGL. However, one patient with a small PPGL was missed by plasma metanephrines.

PS-R04-4: A CASE OF PHEOCHROMOCYTOMA IN A 17-YEAR-OLD MALE

Background: Pheochromocytoma is a rare catecholamine secreting tumor arising from the adrenal medulla and produces signs and symptoms due to excessive catecholamine secretion from the tumor. It is a rare cause of secondary hypertension and a delay in recognition and treatment can present serious consequences to the patient. Case Summary: We present a case of a 17-year-old male with a history of hypertension for 4 years with episodic headache, palpitations, and sweating. He does not have any history of serious illnesses, hospitalizations, or trauma. He was not on any medications. He has a family history of hypertension. He does not drink alcohol, smoke cigarettes, or do any illicit drugs. Upon arrival to the ER, he was conscious, coherent with BP of 170/140mmHg, PR 111bpm, RR 26cpm, and afebrile. Laboratory work-up showed proteinuria, elevated BUN and creatinine levels, hyponatremia, hypokalemia, and hypocalcemia. A 2D echocardiography showed left ventricular hypertrophy. The whole abdominal CT scan demonstrated a fairly defined hypodense mass in the left suprarenal measuring 4.8 x 6.4 x 4.7 cm. Pheochromocytoma was confirmed by biochemical tests that showed elevated plasma normetadrenaline and 24-hour urine metanephrine. The patient was initially started on an alpha-adrenergic blocker, Terazosin, and a beta-blocker, Propranolol. Blood pressure was still uncontrolled hence calcium-channel blocker, Nicardipine drip was also given to control the blood pressure. During surgery, they noted the mass to be 8x5 cm invading the superior pole to mid pole and renal hilum hence the patient underwent left open adrenalectomy with left radical nephrectomy. Immediately upon removal of the mass, the patient had a hypotensive episode, which was addressed immediately. The histopathologic finding showed no extension of the mass to the kidneys and it is consistent with pheochromocytoma. Blood pressure control without medication was achieved 13 days post-operatively. The patient is regularly monitored for the recurrence of hypertension due to the increased risk of recurrence. The patient is now living with a solitary kidney hence should also be followed up through. Conclusion: Although it is a rare condition, pheochromocytoma should be considered a differential diagnosis in young patients presenting with unexplained hypertension, headache, and palpitations. A multidisciplinary approach is the best way to achieve success in the management of a patient with pheochromocytoma.

Comparison of Patients with Atrial Fibrillation Without Structural Heart Disease and Normal Population In Terms of Urine Catecholamines.

This study aimed to compare the sympathetic nervous system activity of atrial ���brillation patients without structural heart disease and the normal population in terms of urinary metanephrine levels. Our study was conducted with 40 paroxysmal or persistent patients without structural heart disease and CHA2DS2VASc score of 0 or 1 and 40 healthy controls. Laboratory parameters, demographic characteristics, and 24-hour urine metanephrine levels were compared between the 2 groups included in the study. Metanephrine value in urine was found to be signi���cantly higher in the atrial ���brillation group (atrial ���brillation group 97.50 �� 17.19 ��g/day vs. control group 74.27 �� 15.55 ��g/day; P < 0.001). The body mass index of the atrial ���brillation group was found to be signi���cantly higher than the control group (atrial ���brillation group 27.26 �� 2.97 kg/m2 vs. control group 24.05 �� 2.24 kg/m2; P < 0.001). In multivariate linear regression analysis, body mass index (beta: 0.266, P =.02) and urinary metanephrine level (beta: 0.522, P = 0.002) were found to be independent risk factors. According to receiver operating characteristic analysis, it was determined that urinary metanephrine value (area under the curve = 0.834, P < 0.001) and body mass index (area under the curve = 0.803, P < 0.001) predicted the development of atrial ���brillation. Our study found that urinary metanephrine levels were higher in patients with atrial ���brillation without structural heart disease than those without atrial ���brillation, and metanephrine values predicted the development of atrial ���brillation.

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.

226: THE PHEO-HEPATO PHENOMENON: TRANSAMINITIS IN THE SETTING OF ACTIVE PHEOCHROMOCYTOMA

Introduction: Pheochromocytomas are neuroendocrine tumors that cause release of excess catecholamines. This release causes commonly known signs and symptoms of hypertension, tachycardia, headache, flushing, and palpitations. Less commonly seen is abdominal pain with transaminitis. Description: A 47-year-old woman with no medical history presented with one day of severe abdominal pain, nausea, vomiting, palpitations, and symptoms of feeling flushed. Initial evaluation found the patient to be hypertensive, tachycardic, and tachypneic. On CT imaging, the patient was found to have a 6.5cm ovoid adrenal mass and lab work showed elevated 24-hour urine and plasma metanephrines, consistent with pheochromocytoma. The patient’s course was complicated by the development of transaminitis (had been normal on initial lab work), with elevation to AST 4882 U/L, ALT 4183 U/L, with normal alkaline phosphatase and bilirubin. Both ultrasound and CT imaging showed intrinsic fatty liver disease with patent vasculature, though no underlying pathology in the setting of no personal history of alcohol abuse, IV drug use, and non-reactive hepatitis panel. Hepatology consulted, and etiology thought to be in the setting of poor perfusion due to catecholamine storm. With medical treatment of the pheochromocytoma, AST and ALT significantly down-trended (75% within one week), and had normalized by the patient’s adrenalectomy and have remained normal in the post-operative period. Discussion: Pheochromocytoma is a rare neuroendocrine tumor, which has varying symptomatology on presentation, though commonly includes severe hypertension with headache, sweating, and palpitations related to catecholamine surge. A less common, though still reported presenting symptom, is abdominal pain. There have been cases in the literature wherein patients with pheochromocytoma present with abdominal pain and transaminitis, though not to the degree that has been seen in our patient. The pathogenesis of this in the setting of pheochromocytoma is not completely understood, though is thought to be related to increased vascular resistance due to catecholamine release, leading to decreased blood flow and oxygenation. With medical and ultimate surgical management of pheochromocytoma, liver function tests can be expected to return to baseline values.

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.

ODP280 A Unique Case of Coexisting Paraganglioma, Primary Hypoaldosteronism and Primary Hyperparathyroidism in a Single Patient

Abstract Introduction To date, case reports have shown an association between paraganglioma and primary hyperaldosteronism, and primary hyperparathyroidism with primary aldosteronism, but not for all three of the aforementioned endocrinopathies combined. Clinical Case A 54-year-old woman with history of uncontrolled HTN, hypokalemia, DM2, CKD stage III, Takotsubo cardiomyopathy and primary hyperparathyroidism presented to the hospital with back pain. CT scan showed a 4.3 cm necrotic retroperitoneal mass. Due to her labile blood pressure, ranging from 194/102 mmHg to 106/60 mmHg, endocrinology was consulted for evaluation of secondary hypertension. Plasma normetanephrines were 3447 pg/mL (n ≤ 57 pg/mL), 24-hour urine normetanephrines 5954 mcg/24 hours (n 122-676 mcg/24 hours) and 24-hour urine norepinephrines 476 mcg/24 hours (n 15-100 mcg/24 hours). 24-hour urine cortisol and 24-hour urine metanephrines were within normal limits. Plasma aldosterone level and plasma renin activity (PRA) were 19 ng/dL and 0.78 ng/mL/h (n 0.25-5.82 ng/mL/h),. However, the patient was also taking spironolactone and telmisartan which interfered with results, and withdrawal of interfering medications was considered unsafe. 68Ga-DOTATATE PET/CT showed mild uptake in a left para-aortic mass. Genetic testing did not show pathogenic mutations of AP2S1, CASR, MEN1, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, TMEM127 or VHL genes. The patient was started on doxazosin and underwent successful removal of the left retroperitoneal mass consistent with paraganglioma. Six months later, surveillance testing showed normalization of fractionated plasma metanephrines and of 24-hour urine metanephrines. However, due to blood pressure of 152/100 mmHg and K of 2.8 mmol/L (n 3.5-4.7 mmol/L), concern was raised for primary hyperaldosteronism. After potassium repletion, labs showed plasma aldosterone of 37 ng/dL, PRA of 0.2 ng/mL/h (n 0.25-5.82 ng/mL/h) and ARR of 185 with potassium of 4.1 mmol/L (n 3.5-4.7 mmol/L) consistent with primary hyperaldosteronism. MRI of adrenal glands showed a left adrenal gland that was thickened and nodular but without discrete nodules &amp;gt; 1 cm. The patient was referred for adrenal vein sampling. Five years previously, the patient had been diagnosed with primary hyperparathyroidism, with PTH of 188.5 pg/mL (n 14-64 pg/dL), Calcium of 10.6 mg/dL (n 8.5-10.1 mg/dL) and GFR of 39. Pre-operative imaging with MRI neck had shown enlargement of two parathyroid glands. She had undergone two-gland parathyroidectomy with intraoperative PTH decrease of &amp;gt; 50% and normalization of calcium. However two weeks later, her PTH returned to pre-operative levels (with normal 25(OH)D) and continues to remains elevated. This has been attributed to underlying secondary hyperparathyroidism from her chronic kidney disease. Conclusion To our knowledge, this is a unique case of combined paraganglioma, primary hyperaldosteronism and primary hyperparathyroidism, as thorough literature review has not shown such a coexistence in the past. Presentation: No date and time listed

ODP050 Oncocytic Adrenocortical Carcinoma Presenting with Hematuria

Abstract Introduction Adrenocortical carcinoma (ACC) is rare and aggressive endocrine tumor. It is commonly noticed due to symptoms of hormone excess, mass-effect, or incidentalomas. Different histological variants are noted, which include: oncocytic, myxoid, sarcomatoid, and the conventional subtype. The oncocytic variant is usually seen on the left side, and usually presents with symptoms of mass-effect. Only around 17% were noted to be functional. We present an interesting case of ACC (oncocytic type) which presented with hematuria. Case Presentation 70-year-old female with a history of morbid obesity, hypertension, anxiety, GERD, tubular adenoma, hyperlipidemia, and lumbar radiculopathy came in to see her primary care for hematuria and back pain. She has a long-standing history of back pain, for which she has had an EMG, which showed mild axonal polyneuropathy and bilateral L5 radiculopathy. Apart from hematuria, she denies any other urinary complaints. Additionally, she denied any fever, chills, nausea, abdominal pain, sweating, tremor, headache, palpitations, easy bruising, fractures, muscle weakness, hirsutism, or changes in her weight. She has a family history of pancreatic cancer and is currently retired, and denies alcohol, tobacco, or recreational drug use. A KUB X-ray was ordered which showed calcification in the left upper quadrant, concerning for a splenic artery aneurysm; this led to a CTA abdomen, which showed a large 7.2 cm heterogenous enhancing solid left adrenal mass, concerning for primary adrenal carcinoma, which was new compared to imaging 2 years ago. Also seen was a 0.7 cm enhancing right hepatic lobe lesion, along with a 1.5 cm splenic artery aneurysm. Following this, an abdomen MRI with contrast showed a 7×7×7 cm solid heterogeneously enhancing left upper quadrant mass beside the left adrenal gland and pancreas. Subsequently, a CT guided needle biopsy was done, which revealed scant adrenal tissue. PET scan showed a hypermetabolic mass, arising from the left adrenal, consistent with adrenal carcinoma. At this point, an endocrinology referral was placed, and other lab work including 24-hour urine free cortisol, DHEA-S, 24-hour urine metanephrine, and aldosterone/renin ratio was done. DHEA-S level was elevated at 264 mcg/dl (12-133). She was then transferred to a tertiary care facility, where she underwent a left adrenalectomy, para-aortic lymphadenectomy, nephrectomy, splenectomy, and distal pancreatectomy. Pathology confirmed adrenal cortical carcinoma (oncocytic type), with negative margins, Ki-67 labelling index of 25%, and no lymphovascular invasion, pT2pNO. She was then discharged home with visiting nurses. Conclusion Oncocytic ACC is an infrequent tumor, which presents with symptoms of mass effect, and definitive diagnosis requires histopathological assessment. The Lin–Weiss–Bisceglia (LWB) system and Helsinki score help establish malignant potential. Fortunately, it has a decreased tendency to metastasize and a better prognosis than other ACC subtypes. Further studies to understand oncocytic ACC are needed. Presentation: No date and time listed

ODP271 Primary Aldosteronism and Primary Hyperparathyroidism: A Report of Dual Endocrine Hypertension

Abstract Background Primary aldosteronism (PA) is one of the common causes of secondary hypertension. Primary hyperparathyroidism (PHPT) is a less common etiology of secondary hypertension. The concomitance of both PA and PHPT is very rare, with a possible bilateral positive feedback loop between the adrenal cortex and the parathyroid gland[1]. Clinical case: A 64-year-old female was referred to the endocrine clinic for secondary hypertension assessment. She was diagnosed with hypertension 30 years earlier, poorly controlled on three antihypertensive medications, nifedipine 90 mg daily, lisinopril 40 mg daily, and atenolol 50 mg daily. She started experiencing muscle cramps two years prior to the referral and was found to be hypokalemic on multiple occasions, with potassium ranging between 2.5 to 3 mmol/L. She also had multiple admissions to the emergency department for hypertensive urgencies within the last year. Family history was positive for poorly controlled hypertension in the patient's mother. Physical examination showed class I obesity with a BMI of 31, but otherwise unremarkable. Workup showed elevated aldosterone concentration of 38 ng/dl and suppressed renin concentration (&amp;lt;1 pg/ml) with an aldosterone/renin ratio of 38. Overnight dexamethasone suppression test was normal (cortisol of 1.5 mcg/dl, suppressed ACTH of 5.5 pg/ml, and appropriately elevated dexamethasone of 324 ng/dl). 24-hour urine metanephrine and normetanephrine levels were normal. Imaging showed bilateral adrenal adenomas of about 13-14 mm in widest diameter, with an average density of 10 Hounsfield units. Adrenal venous sampling revealed hyperfunctioning left adrenal with normal right adrenal. The left adrenal gland was removed laparoscopically, and blood pressure normalized postoperatively on the single antihypertensive agent (lisinopril). Interestingly, during the initial workup, the patient also had elevated calcium of 11 mg/dl and low phosphate at 2.5 mg/dl. In addition, parathyroid hormone (PTH) was elevated at 103 and 95 pg/ml on two occasions, with normal 25-OH vitamin D levels. 24-hoururine calcium was 240mg/dl, and creatinine in urine was 76.4 mg/dl. The calcium creatinine clearance ratio was 2.5%. Diagnosis of primary hyperparathyroidism was made. She had no renal stone, chronic kidney disease, or fractures, with a normal DEXA scan. There was no current indication for parathyroidectomy, and the patient continued to be followed up in the clinic. Clinical lesson: Recent evidence shows cross-talk between the adrenal cortex and parathyroid gland. Our patient may represent such a case, with concomitance of two rare endocrinopathies resulting in difficult-to-control hypertension [1,2]. Thus it is essential to investigate multiple etiologies of secondary hypertension. Reference: Brown JM, Vaidya A. Interactions between adrenal-regulatory and calcium-regulatory hormones in human health. Curr Opin Endocrinol Diabetes Obes . 2014;21(3): 193-201. doi: 10.1097/MED. 0000000000000062 Maniero C, Fassina A, Guzzardo V, et al. Primary hyperparathyroidism with concurrent primary aldosteronism. Hypertension. 2011 Sep;58(3): 341-6. doi: 10.1161/HYPERTENSIONAHA.111.173948. Epub 2011 Aug 8. PMID: 21825220. Presentation: No date and time listed