Urinary Normetanephrine Research Articles

7439 Mercury toxicity presenting as Pheochromocytoma

Abstract Disclosure: A. Ansar: None. K. McNerney: None. B.A. Marshall: None. Background: Mercury intoxication is a rare cause of hypertension in children and can mimic other endocrinopathies such as pheochromocytoma. Mercury affects catecholamine metabolism and can cause elevated catecholamine levels, thereby incorrectly suggesting a catecholamine-secreting tumor. Clinical Case: An 8-year-old girl presented to the ED with progressive night sweats, intractable migratory myalgias, hypertension and tachycardia. Patient was in her usual state of health until 2 weeks before presentation when she started to have worsening intermittent pains in her chest, arms, back, and knees. She also experienced restlessness and inability to sleep. On presentation she was hypertensive, with blood pressure of 146/116 mm Hg while calm, heart rate 125 bpm, afebrile. She was anxious, irritable, and seemed uncomfortable. Her skin was dry and rough with a scaly eczematous rash on the arms and legs. She had persistently elevated blood pressure in upper and lower extremities, unremarkable echocardiogram and electrocardiogram, and a normal result on fundoscopic examination. Her initial electrolytes, creatinine, and urinalysis were all normal and remained so on serial evaluations. Urine drug screen was negative. Thyroid function panel showed normal TSH with slightly elevated Free T4 2.28 ng/dL (0.9-1.7), but a normal Free T3 3.9 pg/mL (2.0-4.4) and Free T4 by equilibrium dialysis 1.8 ng/dL (0.8 - 2.0). CT of the chest, abdomen and pelvis was negative and did not show any lesions. Plasma renin activity was 4.6 ng/mL/hour, supine, (<2.0) and plasma aldosterone level < 4.0 ng/dL (< 40 supine) were normal. 24-hour urinary norepinephrine was 90 μg/24h (13-65), epinephrine 37 μg/24h (0.2-10), urine metanephrines 195 μg/24h (18-144), urine normetanephrines 305 μg/24h (29-145), all elevated. Further history taking revealed that patient was taking Ayurvedic supplements prepared by hand by medicinal personnel in India for 3 months prior to presentation. These were stopped 2 weeks prior to her presentation, when she first became symptomatic. Her blood mercury level was 11 ng/mL (n <9), and urinary mercury excretion 67 μg/24 hours (n<10), both obtained 3 weeks after stopping supplementation. She was started on oral chelation therapy with succimer 10 mg/kg/day. Her hypertension was controlled with doxazosin. One week after initiation of therapy, her symptoms improved, and she became normotensive. Her acrodynia and irritability resolved. Urine metanephrine levels will be repeated at upcoming clinic follow up. Conclusion: Mercury toxicity should be considered in the differential of pheochromocytoma to avoid extensive diagnostic testing and morbidity associated with it. Lead, mercury, and arsenic have been detected in traditionally prepared Ayurvedic supplements. A careful history of intake of supplements can be important in cases with unusual symptomatology. Presentation: 6/3/2024

Is It Enough to Diagnose Pheochromocytoma by Measuring Urine Metanephrines Levels?

This study aimed to evaluate the diagnostic value of plasma and urinary metanephrines and determine their sensitivity, specificity, and correlation among patients with adrenal lesions, which required a multidisciplinary approach because of size, functional state, or malign appearance. This retrospective study of 152 patientswith adrenal lesions was conducted at the Outpatient Clinics of Ankara Bilkent City Hospital at the Department of Endocrinology and Metabolism Diseases betweenAugust 2019and February 2022. These patients were discussed at the Endocrinology and Surgery multidisciplinary council because of their adrenal lesions.Among them, 94 patients underwent adrenal surgery. Thirty patients with histologically proven pheochromocytoma, 36 with cortical nodular hyperplasia, four cases of adrenocortical carcinoma and 24 cases with angiomyolipoma were detected. According to the analysis, the most sensitive test in diagnosing pheochromocytoma was urinary fractionated metanephrine (90%), followed by plasma free metanephrines at 84 %. Conversely, the most specific test was plasma free normetanephrine (91.4%).A statistically significant correlation exists between plasma and urinary metanephrine; plasma normetanephrine levels were alsosignificantly correlated with urine normetanephrine. These findings indicate that plasma and urine metanephrines are sensitive for detecting pheochromocytoma and can be used interchangeably.

P050 PITFALLS IN ESTABLISHING THE DIAGNOSIS OF PHEOCHROMOCYTOMA ILLUSTRATED BY THREE CASE REPORTS

Background and Objective: Pheochromocytoma is a rare cause of secondary hypertension. Because of the low incidence, any diagnostic test has a low positive predictive value. Methods: We report three example cases with diagnostic pitfalls. Results: First case: A 72-year old Caucasian women was admitted for the evaluation of a right adrenal mass, measuring 4 cm. The patient was asymptomatic, never hypertensive. Standard endocrinological evaluation of the adrenal mass revealed significantly elevated plasma and urine normetanephrine (>2 fold upper normal range) and metanephrine levels (>10 fold upper normal range). Subsequent functional imaging with MIBG SPECT/CT confirmed catecholamine storage in the left adrenal mass. After pretreatment with phenoxybenzamine (causing hypotension) the mass was removed surgically and a pheochromcytoma confirmed histologically. Second case: A 59-year old Caucasian women with repetitive hypertensive crises for several years was screened for pheochromocytoma and significantly elevated plasma and urine normetanephrine levels (> 5 fold upper normal range) were observed. MRI demonstrated a small left adrenal mass of 2 cm. Although no relevant tracer uptake was observed on MIBG SPECT/CT, subsequent somatostatin receptor imaging with DOTA-TATE PET/CT suggested adrenal pheochromocytoma (Fig.). After pretreatment with doxazosine the mass was removed surgically and a pheochromocytoma confirmed histologically, blood pressure normalized after surgery. Third case: A 67 year old Asian woman was admitted for the evaluation of a large left adrenal mass measuring 7.5 cm. She had well controlled hypertension with dual antihypertensive medication and did not suffer from paroxysmal hypertensive crises. Plasma normetanephrine levels were substantially elevated (>20 fold upper normal range). MIBG SPECT/CT confirmed catecholamine storage in the adrenal mass that was partly necrotic. After pretreatment with doxazosine the mass was removed surgically, a largely necrotic pheochromocytoma was confirmed histologically. No further antihypertensive treatment was necessary. Conclusions: These cases demonstrate that a pheochromocytoma may be asymptomatic, any adrenal mass needs standard endocrinological workup. Standard functional imaging has a limited sensitivity, additional approaches have to be considered.

P001 AN UNCOMMON CAUSE OF HIGH BLOOD PRESSURE IN YOUNG BASKETBALL PLAYER

Paragangliomas are rare neuroendocrine tumors that affect approximately 1.5–9 patients per million. They originate from chromaffin cells of the adrenal medulla or sympathetic and parasympathetic ganglia. Paragangliomas account for 10%–20% of retroperitoneal tumors and can manifest at any age. These tumors can secrete catecholamines, leading to symptoms such as hypertension, headaches, and diaphoresis.However, palpitations or tachycardia may also be present. Definitive treatment entails surgical resection, with acceptable rates of morbidity and mortality, necessitating careful patient preparation and intraoperative management. Case Presentation: We present the case of a 29-year-old man with a BMI 26,5 kg/m2, who is physically active and without other cardiovascular risk factors, episodic hypertension, headaches and blush. A contrast CT scan of the abdomen revealed a retroperitoneal intercavoaortic mass and 24-hour urine Normetanephrines were significantly elevated, indicating a functional paraganglioma. Laboratory tests revealed an elevated plasma normetanephrine level of 1838 pg/ml (reference values 0 - 180 pg/ml). The patient was prepared for surgery with alpha blockers, followed by beta blockers. Intraoperative blood pressure elevation was managed with intravenous beta blockers. Postoperatively, the patient did not require anti-hypertensives. The tumor, measuring 6x4x3.5 cm, histopathology and immunohistochemistry confirmed the diagnosis of a normetanephrine producing paraganglioma. The genetic study revealed a pathogenic variant in the SDHB gene, specifically the c.166_170delCCTCA (p.Pro56Tyrfs*5) in heterozygosity. This variant is associated with a 49% risk of Pheochromocytoma and Hereditary Paraganglioma, a 14% risk of Renal Carcinoma and susceptibility to Gastrointestinal Stromal Tumors. The c.166_170delCCTCA variant follows an autosomal dominant inheritance pattern, indicating a 50% risk of recurrence. Conclusions: The diagnosis of extra-adrenal retroperitoneal paragangliomas remains challenging due to the silent evolution of the condition. It is essential to consider screening patients who are young, and present with resistant arterial hypertension for secondary hypertension.

Development and validation of a simple, fast and sensitive liquid chromatography-tandem mass spectrometry method to establish reference intervals for 24-h urinary free normetanephrine, metanephrine and methoxytyramine

ObjectiveTo develop and validate a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect urinary free metanephrines and methoxytyramine, establishing reference intervals. MethodsUrine samples were diluted with isotope internal standard solution, then analyzed directly using tandem mass spectrometry with multiple reaction monitoring measurement and electrospray ionization source in positive ion mode. Analytical parameters including linearity, lower limit of quantitation, imprecision and accuracy of the method were evaluated. The reference intervals for urinary catecholamine metabolites were established by analyzing 24-h urine samples collected from 81 apparently healthy volunteers. ResultsThe analytical times for MN, NMN, and 3-MT were at 2.79, 2.80, and 2.74 min, respectively. The method displayed excellent linearity (r > 0.99) in the range of 1-1000 ng/mL, with lower limits of quantification (LLOQ) at 0.50 ng/mL for MN and NMN, and 0.25 ng/mL for 3-MT. The method's intra-day and inter-day imprecisions were less than 8 %. The method recovery ranged from 96.8% to 105.8 % for MN, 89.7%–106.4 % for NMN, and 93.5%–106.2 % for 3-MT. No carry-over was observed during the analysis of all analytes. The LC-MS/MS method was used to establish reference intervals in 24-h urine samples from 81 apparently healthy volunteers. There was no association of sex with urinary free metabolites. ConclusionThis study established a novel, fast and sensitive LC-MS/MS method for determining urinary free catecholamine metabolites, which could facilitate screening and diagnosis for catecholamine-related tumors more conveniently and quickly.

Single Stage Bilateral Adrenalectomy (Cortical-Sparing) and Pancreatectomy (Corpus-Sparing) in a Patient with Von Hippel-Lindau Disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome and affects many organs. We aim to report an adult patient with VHL disease having bilateral adrenal pheochromocytoma and multiple neuroendocrine tumors of the pancreas who was successfully treated with simultaneous function-preserving adrenalectomy and pancreatectomy. A 27-year-old woman was admitted to hospital with hypertension. The computed tomography of the abdomen revealed a solid tumor in both adrenal glands with the sizes of 12x7 cm on the right and 4x4 cm on the left. She also had two pancreatic solid masses in the head and three in the tail with varying sizes. The laboratory tests are all within normal limits except elevated 24-hour urinary metanephrine and normetanephrine. I-123 MIBG scanning showed increased uptake in both adrenal glands. Fine needle aspiration biopsy of the tumor on head of pancreas via endoscopic ultrasonography showed neuroendocrine tumor. Those findings were compatible with bilateral pheochromocytoma and multiple pancreatic neuroendocrine tumors and genetic tests revealed the mutation which confirmed the diagnosis of VHL disease. After suppression with alpha-1 inhibitor, right total, left cortical-sparing adrenalectomy, Whipple procedure for the pancreatic head lesions and spleen-preserving distal pancreatectomy were performed and pancreatic corpus was preserved. This case showed that multiple function-preserving procedures can be safely performed with oncological principles in patients with VHL disease.

Giant left pheochromocytoma with vascular anomalies and pelvic horseshoe kidney: a case report

BackgroundPheochromocytoma is a neuroendocrine tumor, and its treatment is dependent on surgical resection. Due to the wide availability of cross-sectional imaging, pheochromocytomas are commonly seen as small tumors less than 10 cm in size and are mostly treated with minimally invasive surgery. Their concomitant presence with horseshoe kidney or other anatomical and vascular anomalies is rare. Herein, we present a surgically complex giant pheochromocytoma case who underwent an open left radical adrenalectomy.Case presentationA 41-year-old Hispanic female presented with a 12 × 8 cm left hypervascular adrenal mass, pelvic horseshoe kidney, and severely dilated large left retro-aortic renal vein which branched into a left adrenal vein, congested left ovarian vein, and left uterine plexus. She was managed with insulin and metformin for uncontrolled diabetes with an A1c level of 9% and doxazosin for persistent hypertension. Clinical diagnosis of pheochromocytoma was confirmed with elevated urine and serum metanephrine and normetanephrine. The pre-operative ACTH was within normal range with a normal dexamethasone suppression test and 24-hour urine free cortisol. The adrenalectomy of the highly aggressive adrenal mass was performed via open approach to obtain adequate surgical exposure. Due to the large size of the tumor and its significant involvement with multiple adjacent structures, coordination with multiple surgical teams and close hemodynamic monitoring by anesthesiology was required for successful patient outcomes including preservation of blood supply to the pelvic horseshoe kidney. The histopathological diagnosis was pheochromocytoma with negative surgical margins. The patient was followed at 1, 4, 12, and 24 weeks postoperatively. She had a normal postoperative eGFR and was able to discontinue antihypertensive and antidiabetic medications at four weeks. She had transient adrenal insufficiency, which resolved at five months. The horseshoe kidney was intact except for a minimal area of hypo-enhancement in the left superior renal moiety due to infarction, which was significantly improved at six months.ConclusionOur patient had a giant pheochromocytoma with anatomical variations complicating an already surgically challenging procedure. Nonetheless, with multiple provider collaboration, detailed pre-operative surgical planning, and meticulous perioperative monitoring, radical resection of the giant pheochromocytoma was safe and feasible with successful postoperative outcomes.

Cystic pheochromocytoma: a rare variant of adrenal gland tumor case report

Abstract Introduction/Objective Pheochromocytoma is the primary adrenal medullary tumor in adults. Patients usually present with sustained or sporadic hypertension. The tumors are almost always solid. Cystic pheochromocytoma (CP) is extremely rare with only a few cases reported in the literature. Patients with CP may be asymptomatic and normotensive and be diagnosed incidentally on imaging or intraoperatively. Methods/Case Report We report a case of an 82-year-old male with a large CP who presented with back pain. The patient was hypertensive preoperatively (140/85 mmHg). Imaging showed a 5.4 cm complex right adrenal mass that could not be further classified. Labs showed markedly increased 24hr urine normetanephrine (1342 ug/24hr). The patient was presumed to have a pheochromocytoma and was preoperatively treated with an alpha-blocker. At surgery an 8.0 cm multiloculated cystic adrenal mass was removed, and grossly the specimen consisted of a brown, multicystic mass filled with brown liquid. Histology revealed the septa to contain nests of polygonal cells with vacuolated to basophilic granular cytoplasm with moderate nuclear pleomorphism . Immunohistochemical staining was positive for synaptophysin, chromogranin and S-100, which confirmed the diagnosis of CP. Patient’s postoperative blood pressure was 130/60 mmHg. Results (if a Case Study enter NA) NA Conclusion Cystic pheochromocytoma has to be in the differential for a retroperitoneal cystic mass in order that clinicians, radiologists as well as pathologists undertake proper patient management and diagnosis.

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.

FRI224 A Rare Case Of Recurrent Paraganglioma Presented With Liver Metastasis

Abstract Disclosure: E. Gupta: None. M. Al Mushref: None. Malignant Paragangliomas (PGLs) and Pheochromocytomas (PCC) are extremely rare. Approximately 10% of PCCs and 25% of PGLs are metastatic. Metastatic PGLs typically occur in patients with predisposing genetic mutations. We present a case of recurrent metastatic PGL in a young female with no known genetic predisposition to metastatic disease occurring after surgical resection. Our patient is a 28-year-old female with a history of PGL status post left adrenalectomy and nephrectomy two and a half years prior who presented to the ED for abdominal pain. She was first diagnosed after being admitted for hypertensive emergency. During time of diagnosis, plasma and urinary metanephrines were significantly elevated at 1.13 nmol/L and 907 ug/gCr respectively and plasma and urinary normetanephrines were elevated at 80.2 nmol/L and 52043 ug/gCr respectively. MRI showed a 16 cm left retroperitoneal mass and MIBG scan showed increased uptake in the mass however no evidence of metastatic disease was noted then. The patient had immigrated from Haiti. Her mother had passed away at age 20 of unknown cause and her father has no known history. Genetic testing was negative for hereditary gene mutations including multiple SDHDs, VHL, NF1, MEN1 and MAX. Surgical exploration showed a giant left retroperitoneal neoplasm involving the left kidney and left adrenal and both organs were resected. Pathology revealed PGL, focally extending to peripheral specimen margin and benign retroperitoneal lymph nodes and soft tissues. Post-resection meta- and normetanephrines levels were normal. Unfortunately, the patient was lost to follow up after surgery. On this admission, she endorsed right lower quadrant abdominal pain. Plasma normetanephrine was 1.72 nmol/L, metanephrine was normal, and chromogranin A level was elevated at 545 ng/mL. CT scan revealed multiple hepatic lesions and MIBG scan further showed new increased uptake suggesting metastasis. The patient was asymptomatic and blood pressure remained normal during her hospitalization. Due to concerns of recurrent PGL with metastasis, she established care with Oncology for initiation of treatment. PGL is an extremely rare neuroendocrine tumor and is closely related to PCC. Sympathetic PGLs cause catecholamine surge symptoms but low volume disease may remain asymptomatic. Genetic predisposition is common in malignant PGL particularly succinate dehydrogenase mutation subunit B. Patients should be closely followed up to screen for recurrence and genetic testing should also be done. In our patient’s case, despite surgical resection and negative genetic testing, she developed recurrence of the PGL with new metastasis emphasizing the importance of close surveillance in the case of PGL to monitor for recurrence. Presentation: Friday, June 16, 2023

SAT337 Maternal Cell free DNA Testing Reveals Incidental Finding Of Adrenocortical Carcinoma

Abstract Disclosure: F. Akanbi: None. S. Raja: None. T. Else: None. Maternal Cell-free DNA Testing Reveals Incidental Adrenocortical Carcinoma IntroductionAdrenocortical carcinoma (ACC) is rare; with 1 to 2 cases per million. It is unclear if ACC in pregnancy represents a specific association though 150 cases have been reported. We report a case of ACC detected during fetal sex determination using cell free DNA (cfDNA). Case Report: A 30 year old G1P0 woman presented at GA of 25 weeks with results of non-invasive prenatal screening (NIPS) done for fetal sex determination, which noted atypical findings concerning for possible maternal neoplasm. Pregnancy had been uncomplicated; she had no significant past medical history or features of hypercortisolism. Family history was positive for lung and prostate cancer. Physical examination revealed healthy looking female with no Cushingoid facies, abdomen matched stated GA. Full body MRI revealed 5.5 cm right adrenal mass with lymph nodes metastases. CT-guided retroperitoneal lymph node biopsy showed ACC.She was asymptomatic with significantly elevated urine free cortisol 3648 (3.5-45 mcg/24 hour), serum cortisol 67.5 (5-25 ug/dl), 11-deoxycortisol 3910 (10-79 ng/dl), and suppressed ACTH <5 (5-52 pg/ml). Electrolytes were normal, DHEAS 342 (35-430 ug/dl), aldosterone < 3 (4-31 ng/dl), renin mass 5 (4-44pg/ml), urinary free normetanephrine 0.23 (< 0.9 nmol/l), urinary free metanephrine < 0.2 (< 0.5 nmol/l). MRI of the chest and brain did not show metastases. She developed at GA 29 weeks, hypertension, proteinuria, and transaminitis. Cesarean section was done at GA 30 weeks followed the next day by right adrenalectomy, IVC repair and retroperitoneal lymph node resection. Pathology showed high-grade adrenal cortical carcinoma (12 cm size) with negative margins, vascular invasion and lymph node involvement (T3, N1, M0), no caval involvement, stage III ACC. During chemotherapy planning, metastases were noted, mitotane and pembrolizumab were initiated, but discontinued after 2 cycles on account of generalized rash and elevated liver enzymes. The tumor progressed on etoposide, doxorubicin and cisplatin (EDP), and second line therapy (gemcitabine and capecitabine) was initiated. Conclusion: Physiologic changes of pregnancy mimic clinical features of ACC and pregnancy associated changes in the HPA axis also make ACC diagnosis challenging. Short fragments of DNA (cfDNA) released into the maternal bloodstream can be detected after 7 weeks of gestation. Approximately 2-20% of total cfDNA is placental, it is used for sex determination and detection of congenital genetic abnormalities, cfDNA can also originate from maternal neoplasms and has been shown to detect lung, breast and colon while case series in patients with ACC showed detection of only 1 out of 3 cases. Surgery remains first line therapy for ACC, but adjuvant therapy, surveillance and hormone replacement are also vital in ACC management. Presentation: Saturday, June 17, 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

FRI217 False Negative Plasma Metanephrines In A Patient With A Bladder Paraganglioma

Abstract Disclosure: T.F. King: None. G. Sng: None. T. Puar: None. Introduction: Both plasma free metanephrines and urinary metanephrines have high (>90%) sensitivity to detect phaeochromocytoma and paragangliomas (PPGL). False positive urine metanephrines are seen in many conditions including obstructive sleep apnoea (OSA), and plasma metanephrines have been proposed to be a useful diagnostic tool in this patient population. Clinical Case: A 53 year old female was recruited into a study evaluating the utility of plasma and urine metanephrines in the diagnosis of PPGL in patients with OSA. She had a 6 year history of hypertension that was well controlled with amlodipine 5mg daily. She had no headache, palpitations or paroxysmal symptoms. She had 3 previous uneventful pregnancies and there was no significant family history of note. She was overweight (BMI 28.3 Kg/m2) and blood pressure was 130/80 mmHg. Sleep studies revealed severe OSA. Screening plasma and 24 hour urine metanephrines were performed at baseline and again after 6 months (Table 1). 24 hr Urinary normetanephrine, mcg/day (Upper Reference interval 423): Baseline 437, Visit 2 (Six Months later) 535, Post-operative 235. Table 1. Serial measurements of urine and plasma metanephrines. In view of the persistently elevated urinary normetaneprine, a CT abdomen and pelvis was performed. This revealed normal adrenal glands, but an avidly enhancing 2cm focal nodular lesion was seen at the left lateral posterior wall of the urinary bladder. Transurethral biopsy revealed a tumour with immunohistochemistry positive for synaptophysin and GATA3, consistent with a paraganglioma. A CT/PET Ga68 dotatpeptide scan showed intense uptake in the same area with no evidence of lymphadenopathy or distant disease. Amlodipine was changed to terazosin pre-operatively and the patient went on to have an uneventful robot assisted excision and partial cystectomy. Histology was consistent with a bladder paraganglioma with clear tumour margins. Genetic analysis for hereditary PPGL was negative for mutations in SDHx, VHL, RET, NF1, but there was a variant of uncertain significance in the MUTYH gene, namely c.767C>T (p.Thr245Ile). At two months post-operative review, the patient remained well and home blood pressure readings were all >120/80mmHg on 5mg amlodipine. Repeat urine and plasma metanephrines were normal. Conclusions: Plasma metanephrines may not be sensitive enough to detect small asymptomatic bladder paragangliomas. Further studies are warranted to elucidate the optimal diagnostic tests in patients with sleep apnoea and suspected PPGL. Interval measurements of metanephrines may be useful in the diagnosis of small PPGL that may manifest with time. Presentation: Friday, June 16, 2023

FRI245 Non-classic CAH Presenting As Bilateral Adrenal Incidentalomas

Abstract Disclosure: Y.A. Chin: None. T. Puar: None. T. King: None. Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an autosomal recessive disorder. Non-classic CAH usually presents in late childhood or asymptomatic may remain undiagnosed. Adrenal incidentalomas have been reported as a presentation of CAH. Clinical Case: A 56-year-old man presented with a 4-day history of epigastric pain associated with chest discomfort and diaphoresis. There was no postural giddiness, vomiting, paroxysm or constitutional symptoms. He was a smoker, his parents were non-consanguineous and he had fathered 2 children. He was tachycardic at 114 bpm, but normotensive (129/89 mmHg) with no postural hypotension and no abnormal pigmentation. He had evidence of heart failure with bibasal crepitations and pedal oedema. Secondary sexual characteristics were normal and testicular volume was 15 mls bilaterally with no palpable mass. CT abdomen showed grossly enlarged bilateral adrenal glands with heterogenous nodular appearance with several focal hypodense cystic components, with absolute washout <60%. Biochemistry was consistent with primary adrenal insufficiency (PAI); 8am serum cortisol 188 nmol/L, with peak cortisol post 250mcg synacthen of 195 nmol/L. Serum ACTH was elevated at 254.6 ng/L, aldosterone and renin were normal and 24hr urinary normetanephrine was mildly elevated at 1982 nmol/d (NR 600-1900 nmol/d). Echocardiography revealed severe global hypokinesia (EF 20%) but myocardial perfusion imaging was negative for ischemia. In view of suspicion for tuberculosis, malignancy or infiltrative disease, CT guided adrenal biopsy was performed. Histology showed hyperplastic adrenal cortex with lipofuscin pigments, focal lymphohistiocytic infiltrates. No lymphoplasmacytic infiltrate with IgG 4 plasma cells, granuloma, malignant cells or amyloid deposits were seen. Serum 17-OHP level later came back elevated at 39.7 nmol/L (NR 1.8-10.4 nmol/L). DNA sequencing of CYP21 revealed compound heterozygous mutations in c.292+1G>A and c.518T>A, both of which have been reported to be causative of CAH. He was transitioned from stress dose to physiological glucocorticoid replacement and ACTH normalised on subsequent outpatient visits. Follow up imaging after 6 months and 2 1/2 years revealed no change in size or morphology of the adrenal glands. Follow up echocardiography showed no improvement in ejection fraction despite intensive heart failure treatment. Conclusion: Nodular adrenal hyperplasia is well described among CAH individuals, especially in those with inadequate glucocorticoid replacement and chronically elevated ACTH levels. There was no change in size of the adrenal lesions despite adequate glucocorticoid replacement. Improvement of cardiac function with glucocorticoid replacement has been reported in paediatric patients with CAH, but our case did not show any improvement on serial echocardiography. 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

THU514 Atypical Presentation Of Birt-Hogg-Dubé Syndrome With Poorly Differentiated Follicular Thyroid Cancer And Paraganglioma

Abstract Disclosure: K. Lertdetkajorn: None. J. Haw: None. J.E. Paysour: None. Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare genetic disorder typically presenting with skin hamartomas, renal tumors, and lung cysts. BHD is caused by germline mutations of the folliculin (FLCN) gene. We present the case of a patient with follicular thyroid cancer and paraganglioma diagnosed with BHDS. Case: A 64-year-old female was noted to have progressive enlargement of a neck mass over six months following admission for a hypertensive emergency. CT neck demonstrated a heterogeneous mass centered within the left thyroid lobe measuring 10.4 x 8.6 x 7.6 cm with internal calcifications. TSH was normal. FNA of this mass was suspicious for follicular neoplasm, and she underwent a total thyroidectomy. The pathology reported poorly differentiated adenocarcinoma of the thyroid gland, follicular variant, pT3aN0M0 with positive margins, and lymph-vascular space invasion (LVI). FDG-PET/CT scan showed postsurgical changes of a total thyroidectomy with ill-defined FDG uptake along the left thyroid bed, 3 x 2.8 cm portacaval lymph node (SUV of 9.6) and focal soft tissue FDG avid rectal abnormality. MRI abdomen demonstrated a 4.0 x 4.1 x 3.2 cm soft tissue mass characterized by arterial hyperenhancement and washout in the portacaval region broadly interfacing with the IVC, main portal vein, and left renal vein. EGD was unremarkable, but an EUS demonstrated 3.7 x 3.5 hypoechoic, well-circumscribed, mild-vascular hypoechoic portocaval mass. FNA of this mass was consistent with paraganglioma. Laboratory results supported the diagnosis of paraganglioma with urine metanephrine 9661 mcg/24 h (224 - 832 mcg/24 h) and urine normetanephrine 9457 mcg/24 h (122 - 676 mcg/24 h). The patient was referred for genetic testing to investigate whether the co-existence of follicular thyroid cancer and paraganglioma was secondary to a genetic disorder. The germline genetic testing revealed the pathogenic variant, c.1436dup (p.Thr481Hisfs*5), identified in the FLCN gene with no detections of VHL or SDH complex variants, confirming the diagnosis of BHDS. The patient later underwent a colonoscopy and was found to have stage I colon cancer. Some early reports have shown an association between BHDS and colon tumors. The patient decided not to have any surgery at this time. She continues to follow up in the clinic and takes levothyroxine for suppressive goals. Octreotide LAR, along with blood pressure medications including phenoxybenzamine, was started to treat her paraganglioma. Conclusion: Patients with BHDS may present with atypical clinical manifestations. Genetic testing will aid in diagnosing a germline mutation in the FLCN gene. The association between thyroid cancer and BHDS has been reported previously; however, paraganglioma as a spectrum of BHDS has not been published. Further reported cases and research may provide additional data to investigate the relationship between BHDS and paraganglioma. Presentation: Thursday, June 15, 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.

Pheochromocytoma: Intricate Cardiovascular Manifestations

Abstract We present the case of a 60-year-old female patient, dyslipidemic, obese, diabetic and hypertensive, with a history of resected right adrenal pheochromocytoma (1999 - no subsequent surgical or endocrinological re-evaluation), presenting for increased blood pressure values and the recurrence of symptoms (headaches, palpitations, sweating), with progressive accentuation in the last months. The patient associates pain in the right costovertebral angle and weight loss. The clinical examination revealed facial erythrosis, excessive sweating, tachycardic heart sounds, increased blood pressure and orthostatic hypotension. Electrocardiography reveals sinus tachycardia, signs of left ventricular hypertrophy, with repolarization abnormalities, morphological aspect confirmed by the transthoracic echocardiography. An ultrasound of the abdomen and pelvis ultrasound objectified a large tumor formation at the level of the right adrenal gland and a liver nodule. In the context of the symptoms, the suspicion of recurrent pheochromocytoma was raised, confirmed biochemically by the increase in urinary normetanephrines and through imagistic methods (CT scan of the abdomen and pelvis), the patient having an indication for curative surgical treatment. After completing the preoperative assessment (ECG Holter monitor, ABPM), during the hospitalization period, the antihypertensive regimen was adjusted by combining 4 antihypertensive drugs, episodes of orthostatic hypotension being managed by administering glucocorticoids and colloidal solutions for volume repletion. The patient was referred to the general surgery clinic for resection of the tumor, following the antihypertensive preparation protocol. Although the post-procedural evolution was favorable, the patient presents a high risk of tumor recurrence, requiring annual evaluation for a period of 10 years. Also, due to the association of cardiovascular risk factors and target organ damage, the patient requires periodic cardiological evaluation.

Relapse of Pheochromocytoma with Hipertensive Heart Disease Mildly Reduced Left Ventricle Ejection Fraction

Pheochromocytoma is a tumor originating from the medulla of the adrenal gland. This tumor is rare and is caused by excessive production of catecholamines. There are three classic triads of pheochromocytoma: diaphoresis, palpitations and headaches. Elevated metanephrines and normetanephrine in plasma or urine confirm the diagnosis. At the same time, radiological examination helps in the tumor's location and the presence of local invasion or metastasis. Hypertension is a health problem that is quite dangerous worldwide because it is a significant risk factor for cardiovascular diseases such as heart attack, heart failure, stroke, and kidney disease. Hypertension can cause Hypertensive Heart Disease, which is a significant cause of morbidity and mortality due to cardiovascular disease. This scientific report presents a case study of a 19-year-old woman diagnosed with relapsed pheochromocytoma and hypertensive heart disease with mildly reduced left ventricular ejection fraction. This patient was previously diagnosed at the age of 13 with pheochromocytoma, where the patient experienced symptoms of headache, sweating, especially in the forehead area, trembling hands, and hypertension. Hence, the patient had to be treated. The patient underwent further examination and found a right adrenal tumor, so an adrenalectomy was performed on the patient. Similar complaints appeared again in the patient, and further examination was carried out. Moreover, an increase in plasma metanephrine and normetanephrine levels was found. A CT scan of the abdomen revealed a right adrenal tumor, so this patient underwent another adrenalectomy.

The Role of Chromogranin A Assay in the Diagnosis of Pheochromocytomas

Background: Pheochromocytomas (Pheo) are rare neuroendocrine tumors with a suggestive clinical picture, characterized by hypersecretion of catecholamines and other neuroendocrine biomarkers. Methods: The purpose of the study was to analyze the diagnostic features of Pheo and investigate the role played by different neuroendocrine and hormonal markers in diagnosing Pheo.The retrospective study involved a group of 69 patients diagnosed and treated with Pheo, who had both urinary and plasma catecholamines and neuroendocrine markers measured pre- and postoperatively. Results: After comparing pre- and postoperative hormonal parameters and neuroendocrine biomarker changes, numerous statistically significant findings were found. The analysis of the relationships between chromogranin A (CgA) levels, plasma and urine metanephrines, and normetanephrine and Pheo tumor size was included in the study. Additionally, we evaluated Cg A's diagnostic efficacy in comparison to plasma metanephrines, normetanephrine, and neuron-specific enolase (NSE) for Pheo. Conclusions: We obtained statistically significant data on pre- and postoperative differences for plasma and urinary catecholamines, CgA and NSE. Pheo tumor size is interdependent with serum levels of Cg A, plasma and urinary metanephrines, and normetanephrine. The best diagnostic power for Pheo was plasma normetanephrine, followed by plasma metanephrines and CgA.