Diagnosis Of Pheochromocytoma Research Articles

504 Diagnosis of Pheochromocytoma During First Trimester Pregnancy

504 Diagnosis of Pheochromocytoma During First Trimester Pregnancy

Constructing a Novel Amino Acid Metabolism Signature: A New Perspective on Pheochromocytoma Diagnosis, Immune Landscape, and Immunotherapy.

Pheochromocytoma/paraganglioma (PGPG) is a rare neuroendocrine tumor. Amino acid metabolism is crucial for energy production, redox balance, and metabolic pathways in tumor cell proliferation. This study aimed to build a risk model using amino acid metabolism-related genes, enhancing PGPG diagnosis and treatment decisions. We analyzed RNA-sequencing data from the PCPG cohort in the GEO dataset as our training set and validated our findings using the TCGA dataset and an additional clinical cohort. WGCNA and LASSO were utilized to identify hub genes and develop risk prediction models. The single-sample gene set enrichment analysis, MCPCOUNTER, and ESTIMATE algorithm calculated the relationship between amino acid metabolism and immune cell infiltration in PCPG. The TIDE algorithm predicted the immunotherapy efficacy for PCPG patients. The analysis identified 292 genes with differential expression, which are involved in amino acid metabolism and immune pathways. Six genes (DDC, SYT11, GCLM, PSMB7, TYRO3, AGMAT) were identified as crucial for the risk prediction model. Patients with a high-risk profile demonstrated reduced immune infiltration but potentially higher benefits from immunotherapy. Notably, DDC and SYT11 showed strong diagnostic and prognostic potential. Validation through quantitative Real-Time Polymerase Chain Reaction and immunohistochemistry confirmed their differential expression, underscoring their significance in PCPG diagnosis and in predicting immunotherapy response. This study's integration of amino acid metabolism-related genes into a risk prediction model offers critical clinical insights for PCPG risk stratification, potential immunotherapy responses, drug development, and treatment planning, marking a significant step forward in the management of this complex condition.

Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism.

Pheochromocytomas and paragangliomas (PPGLs) cause symptoms by altering the circulation levels of catecholamines and peptide hormones. Currently, the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines. In this study, we used ultra-performance liquid chromatography (UPLC)/quadrupole time-of-flight mass spectrometry (Q-TOF MS) analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients. We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla. Through conducting two steps of metabolomics analysis, we identified 111 differential metabolites between the healthy group and the patient group, among which 53 metabolites were validated. By integrating the information of differential metabolites and differentially expressed genes, we inferred that the cysteine-methionine, pyrimidine, and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm. The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma, whereas the pyrimidine pathway showed no significant difference. Finally, we developed an optimized diagnostic model of two metabolites, L-dihydroorotic acid and vanylglycol. Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.

Clinical diagnosis of pheochromocytoma and paraganglioma-induced secondary hypertension through UPLC-MS/MS analysis of plasma catecholamines and their metabolites.

This study aimed to elucidate the clinical diagnostic value of plasma catecholamines and their metabolites for pheochromocytoma and paraganglioma (PPGL)-induced secondary hypertension using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). The study population included 155 patients with PPGL that were divided into the PPGL with hypertension (n=79) and a PPGL without hypertension (n=76) groups, and 90 healthy volunteers and 90 patients with primary hypertension as the control groups. UPLC-MS/MS was performed to detect plasma levels of catecholamines and their metabolites, including dopamine, vanillylmandelic acid (VMA), norepinephrine, metanephrine, and normetanephrine. Receiver operating characteristic curves were generated to analyze the diagnostic value of the plasma levels of catecholamines and their metabolites in PPGL-induced secondary hypertension. Patients in the primary hypertension and PPGL without hypertension groups had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal group (all p<.05). On the other hand, patients in the PPGL with hypertension group had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal, primary hypertension, and PPGL without hypertension groups (all p<.05). Collectively, our findings showed that dopamine, VMA, norepinephrine, metanephrine, and normetanephrine are all effective biomarkers for the diagnosis of PPGL and PPGL-induced secondary hypertension.

Pediatric malignant pheochromocytoma with atypical presentation as vision changes, lung metastasis, and recurrence: a case report

BackgroundThis case report documents a case of malignant pheochromocytoma manifested as vision changes with lung metastasis and recurrence.Case presentationA 10-year-old Han Chinese girl presented with vision changes and was eventually diagnosed with pheochromocytoma by contrast-enhanced computed tomography, urine vanillylmandelic acid. After medication for hypertension and surgery, clinical symptoms disappeared. Malignant pheochromocytoma with lung metastasis was confirmed histologically using the Pheochromocytoma of the Adrenal Gland Scaled Score scoring system and genetically with succinate dehydrogenase complex iron sulfur subunit B mutation, and 3 months later, unplanned surgery was performed because of the high risks and signs of recurrence. She is asymptomatic as of the writing of this case report. Our patient’s case highlights the importance of considering a diagnosis of malignant pheochromocytoma, and long-term follow-up for possible recurrence.ConclusionAlthough there are well-recognized classic clinical manifestations associated with pheochromocytoma, atypical presentation, such as vision changes in children, should be considered. In addition, malignant pheochromocytoma children with a high Pheochromocytoma of the Adrenal Gland Scaled Score and succinate dehydrogenase complex iron sulfur subunit B mutation require a long-term follow-up or even unplanned surgery because of the higher risk of recurrence.

Cascaded nanozyme-based high-throughput microfluidic device integrating with glucometer and smartphone for point-of-care pheochromocytoma diagnosis

The development of point-of-care (POC) diagnostics devices for circulating tumor cells (CTCs) detection plays an important role in the early diagnosis of pheochromocytoma (PCC), especially in a low-resource setting. To further realize the rapid, portable, and high-throughput detection of CTCs, an Au@CuMOF cascade enzyme-based microfluidic device for instant point-of-care detection of CTCs was constructed by combining a smartphone application and a commercial portable glucose meter (PGM). In this microfluidic system, DOTA and norepinephrine (NE) modified Au@CuMOF signal probes and Fe3O4@SiO2 capture probes were used for the dual recognition and capture of rare PCC-CTCs. Then, the targeted binding of the Au@CuMOF cascade nanozymes to the CTCs endowed the cellular complexes with multienzyme mimetic activities (i.e., glucose oxidase-like and peroxidase-like activity) to catalyze glucose reduction as signal output for colorimetric and personal glucose meter (PGM) dual-mode detection of CTCs. The developed method has a linear range of 4 to 105 cells mL−1 and a detection limit of 3 cells mL−1. This method allows the simultaneous detection of six samples and demonstrates good applicability for CTCs detection in whole blood samples. More importantly, the combination of PGM, smartphone app and array microfluidic chips enables the rapid, portable, and high-throughput diagnoses of PCC, and providing provide a convenient and reliable alternative to traditional liquid biopsy diagnosis of various cancers.

Carbon dot-based fluorescent probe for early diagnosis of pheochromocytoma through identification of circulating tumor cells

Pheochromocytoma (PCC), as a rare neuroendocrine tumor, is often missed or misdiagnosed because of its atypical clinical manifestations. To realize the early accurate diagnosis of PCC, we have selected circulating tumor cells (CTCs) with more complete biological information as biomarkers and developed a simple and novel fluorescence cytosensor. Octreotide-2,2′,2′′,2′’’- (1,4,7,10 -tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) modified magnetic Fe3O4 and signal amplification CDs@SiO2 nanospheres are prepared to capture and detect PCC-CTCs from peripheral blood via binding to the somatostatin receptor SSTR2 overexpressed on the surface of PCC cells. During the detection process, the target cells were separated and enriched by magnetic capture probes (Fe3O4-DOTA), and then signal probes (CDs@SiO2-DOTA) could also specifically bound to target cells to form the sandwich-like structure for fluorescence signal output. The proposed fluorescence cytosensor has revealed good sensitivity and selectivity for quantitative analysis of PCC-CTCs in the concentration of 5–1000 cells mL−1 with a LOD of 2 cells mL−1. More importantly, designed fluorescence cytosensor has shown good reliability and stability in complex serum samples. This strategy provides a new way for detection of PCC-CTCs.

P-05 Malignant pheochromocytoma with a negative biomarker hormonal assay: A case report

Abstract Description Malignant pheochromocytoma is a rare, predominantly sporadic, but also familial disease, with a malignancy frequency of about 10%. Clinical Case A 25-year-old male was referred to us by the general surgeon after he had a hypertensive crisis during the appendectomy surgery and then accidentally discovered a left adrenal gland mass by CT scan. Assessment of the patient done by physical examination, the height 168cm, weight 53 kg and the BMI 19 kg/m2 and the vital sign was Bp 200/110, and PR 87 b/min. Investigations: normal renal function test and negative metanephrines, normetanephrine and aldosterone, renin and aldosterone renin ratio also normal serum electrolytes. Imaging abdomen CT shows a mass measuring 4.8 X3.7X6.2 cm in its (AP, TS&amp;CC dimension) in the left adrenal gland (encircle), density 40-50 HU. with central hypo density represented cystic necrosis. Right adrenal is normal limbs following intravenous contrast, the left adrenal mass enhances brightly (130-140HU) with central cystic necrosis … consisting with typical features of pheochromocytoma. The patient referred to expert surgeon and there was some preoperative preparation inform of the patient received phenoxybenzamine (alpha blocker) the receive propranolol to control reflux tachycardia and normalized the blood pressure, resection of left adrenal mass was done and the gross tissue biopsy was sent to histopathologist, and the result revealed a diagnosis of malignant pheochromocytoma, after two weeks from operation CT images post operatively after total resection of left adrenal mass revealed clear bed no residual SOL with surgical clips seen. Conclusion Marker-negative Pheochromocytomas are an uncommon form of the illness. Even more dangerous forms, malignant pheochromocytomas typically release metabolites. However, a doctor must be alert to patients with negative markers who exhibit typical symptoms and must make a diagnosis using a combination of clinical, radiologic, and biochemical testing. When choosing patients for presurgical alpha blockade, this is extremely important. Table 1  

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.

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 (&amp;gt;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.

SAT332 Genetic Characterization Of A Case of Pheochromocytoma In A Pulmonary Transplant Patient

Abstract Disclosure: F. Perreault: None. S. Parisien-Lasalle: None. J. Morisset: None. C. Poirier: None. C. Beauregard: None. R. Agnès: None. P. Ferraro: None. I. Bourdeau: None. Background: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) (PPGLs) are rare tumors arising from the chromaffin cells. Approximately 40% of PPGL patients carry germline mutations in susceptibility genes, including pseudohypoxic related SDHx and VHL genes. An association was described between hypoxemia and PPGLs, notably in higher altitude exposition and cyanotic congenital heart disease. In the latter, a chronic hypoxemic state can lead to gain of function somatic mutations in the EPAS1 gene that encodes for hypoxia-inducible factor 2-alpha (HIF-2) (1). Objective: To describe a rare case of PHEO in a pulmonary transplant patient and characterize the genetic background of the tumor. Clinical Case: A 66 year-old man underwent an unilateral lung transplant at the age of 47 for chronic obstructive pulmonary disease associated with alpha-1 antitrypsin deficiency. He required home oxygen therapy for 3 years prior to transplant and was known for new onset diabetes after transplant, chronic kidney disease, hypertension and paroxysmal atrial tachycardia. His family history was non-contributing. Nineteen years after transplant, a thoracic CT-scan showed a 6.1 cm x 3.9 cm right adrenal mass (HU of 7). Retrospectively, the mass had been present for the last seven years, and increased progressively in size. Diagnosis of PHEO was confirmed by the 24-h urinary catecholamines (norepinephrine 713 nmol/d (N&amp;lt; 650), epinephrine 588 nmol/d (N &amp;lt; 145), normetanephrines 900 nmol/d (N &amp;lt; 600) and metanephrines 1191 nmol/d (N &amp;lt; 370)). Chromogranin A was elevated (3297 ng/mL (N &amp;lt; 104)). The adrenal mass showed no uptake at 18F-FDG PET/CT imaging but fixation at MIBG scintigraphy. The patient received alpha blockers and underwent a laparoscopic right adrenalectomy. The pathology report confirmed a PHEO with a PASS score of 8 to 10. Eighteen months following the surgery, the patient showed no signs of biochemical or radiological recurrence. Genetic studies: 1) Germline PPGL multigene panel: After consent, the patient underwent a panel of 14 susceptibility genes for PPGLs (INVITAE, CA, USA) that revealed no pathogenic variants. 2) Somatic genetic analysis for EPAS1 gene: PHEO DNA was extracted and exons 9, 12 and 16 of the EPAS1 gene were studied by Sanger Sequencing. No pathogenic variants were identified.Conclusion: We report a rare case of PHEO in a pulmonary transplant patient. Our genetic analyses demonstrated the absence of a pathogenic germline variant in known susceptibility PPGL genes and no somatic mutations in the EPAS1 gene. Further work is needed to better understand the genetic and molecular events leading to PHEO in this specific case and determine its possible relationship with hypoxemia. (1) Vaidya A, Flores SK, Cheng Z-M, Nicolas M, Deng Y, Opotowsky AR, et al. EPAS1 Mutations and Paragangliomas in Cyanotic Congenital Heart Disease. New England Journal of Medicine. 2018;378(13):1259-61. Presentation: Saturday, June 17, 2023

SAT329 Case Series Of Patients With FGFR-1 Related Pheochromocytoma With A Focus On Biochemical And Imaging Signatures

Abstract Disclosure: S. Jhawar: None. J. Del Rivero: None. K. Pacak: None. Introduction: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal gland and neural crest, respectively. 40% of cases are associated with germline mutations and 30-40% somatic driver mutations. Here, we present two patients with PCC who were found to have somatic FGFR1 mutation. FGFR signaling is involved in regulation of tissue repair, angiogenesis, and inflammation. Patient 1: A 70-year-old female with a history of resistant hypertension, episodic palpitations and sweating presented with diffuse abdominal pain and chest tightness. She was noted to have a blood pressure of 220/160 mm Hg. CT scan showed a 4.2 x 3.9 cm left adrenal mass, suspicious for malignancy and a &amp;lt;1 cm retroperitoneal mass. Blood work revealed elevated plasma normetanephrine (NM) 3543 pg/mL (normal 0- 145) and metanephrine (MN) 871 pg/mL (normal 0-62). 18F-FDG PET/CT showed a left adrenal mass without abnormal FDG activity. 68Ga-DOTATATE PET/CT was compatible with left PCC (SUVmax 28). 18F-DOPA PET/CT showed left PCC and a small retroperitoneal PGL. Two weeks after initiating phenoxybenzamine, she underwent total left adrenalectomy. Pathology was consistent with PCC. Molecular testing revealed FGFR1 pathogenic somatic mutation (c.1638C&amp;gt;G p.Asn546Lys). Patient 2: A 73-year-old male with known left renal cell carcinoma presented to our institution for management of recurrent right PCC. He was found to have a 3.8 cm right adrenal incidentaloma eight years ago and elevated plasma NM 6.3 nmol/L (normal &amp;lt;0.9), MN 1.5 nmol/L (normal &amp;lt;0.5). He underwent total right adrenalectomy, and the diagnosis of PCC was confirmed on histopathology. Two years later, he developed a 5.1 x 4.7 cm nodular mass in the right adrenal fossa and a &amp;lt;1 cm liver lesion on CT scan. The adrenal lesion showed intense avidity on 68Ga-DOTATATE PET/CT and 18F-DOPA PET/CT and mild avidity on 18FDG-PET/CT. 18F-DOPA PET/CT also showed avidity towards the liver lesion. He was started on doxazosin and underwent laparoscopic right adrenalectomy. Pathology demonstrated PCC. Whole exome sequencing of the tumor showed pathogenic FGFR1 mutation (c.1638C&amp;gt;G, p.Asn546Lys). Discussion: Activating FGFR1 mutations are associated with sporadic PCC. The biochemical phenotype of our patients showed higher levels of NM than MN. The imaging profile revealed that 18F-DOPA PET/CT was more sensitive than 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT as it showed avidity towards other extra-adrenal lesions. Further studies in larger cohorts are needed to enhance understanding of pathogenesis, biochemical and imaging phenotype, which will help tailor the treatment and potential development of novel targeted therapies. 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

FRI200 Severe Cushing Syndrome Due To An ACTH-producing Pheochromocytoma

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

THU591 HyperAldosteronism In Pregnancy Predicted Impacts (H.A.P.P.I.): A Retrospective Cohort Study

Abstract Disclosure: D. Oprea: None. F. Lefrançois: None. A.C. Côté: None. M. Roy-Lacroix: None. M. St-Jean: None. N. Sauvé: None. Introduction: Hypertensive disorders of pregnancy (HDP) are increasing worldwide and are associated with a high rate of maternal and fetal morbidity and mortality. Primary aldosteronism (PA) is a frequent and reversible cause of secondary hypertension in young non-pregnant women (18%) (1). Until now, no studies have detailed the prevalence, nor the outcomes associated with PA during pregnancy. Research Question: In HDP, are cases of PA associated with different impacts on maternal-fetal health compared to pregnant women without PA? Methods: This retrospective cohort study compared 252 pregnancies according to their PA status. We included pregnancies that were followed at the Centre Hospitalier Universitaire de Sherbrooke (CHUS) between 2011 and 2022, and who had had an aldosterone/renin ratio (ARR) screening for PA, in a five-year period before or after the analyzed pregnancy. Monofetal and twin pregnancies were included. Concomitant diagnoses of pheochromocytoma, hyperthyroidism or Cushing syndrome were excluded. The primary objective of this study was to describe the occurrence of HDP in women with PA. Secondary objectives were to describe maternal, fetal and neonatal outcomes and compare them according to PA status. Results: Among 252 pregnancies, 15 were diagnosed with a PA (concerning 12 women). Our preliminary analysis showed a greater prevalence of advanced maternal age (53.3% vs 24.5, p = 0.028) and Afro-American ethnicity (60.0 % vs 10.1%, p &amp;lt; 0.001) in the PA group, in addition to a tendency towards class I obesity (40.0% vs 13.1%, p = 0.166) in this group. There were no differences in terms of prevalence of chronic hypertension (26.7% vs 25.7 %, p = 0.936), delivery mode and overall fetal morbidity and mortality. Although not statistically significant, preeclamspia tended to be more frequent (40.0% vs 27.0%, p = 0.276) and gestational hypertension less frequent (0.0 % vs 16.0%, p = 0.092) during pregnancy in the PA group. 40.1% (vs 19.0%, p = 0.052) of PA-associated HDP were diagnosed in post-partum (including 33.4 % of preeclampsia in this group) and required intravenous hypertensive treatment (40.0% vs 23.2%, p = 0.209). Also, 13.3% of pregnancies in the PA group (vs. 3.0 %, p = 0.093) required hospitalization at the intensive care unit (ICU). All cases of PA were diagnosed within 5 years pre-conception or post-partum. Conclusion: Pregnancies with PA diagnosis within a five-year period tended to present more frequently with HDP as preeclampsia, especially in the post-partum period, and often required more intensive antihypertensive treatment and ICU hospitalization. The upcoming second prospective phase of this study will better assess the prevalence of PA in pregnant women experiencing HDP. Reference: (1) Alam S. et al., Clin Endocrinol, June 2021;94(6):895903. Presentation: Thursday, June 15, 2023

FRI219 Pheochromocytoma Presenting As A Case Of Worsening Diabetes Mellitus

Abstract Disclosure: J. Eapen: None. E. Sedlis Singer: None. T.X. Lu: None. J.N. Shapiro: None. Introduction: Pheochromocytoma is often diagnosed incidentally during unrelated abdominal imaging, in patients with a family history of known disease, or in patients presenting with the classic triad of symptoms: episodic headache, sweating, and tachycardia. We describe an atypical case of pheochromocytoma presenting as acute decompensation of DM. Case presentation: A 79 year old female with DM previously well-controlled on glimepiride for 4 years presented with an acute worsening of symptoms notable for abdominal fullness, weakness and weight loss. Laboratory results revealed an increase in HbA1c from 6% to 14% (nl &amp;lt;5.7%) since 3 months prior. Metformin and basal insulin were added to her regimen with a subsequent improvement in HbA1c. An abdominal CT scan was done given the acuity of progression in her DM, which revealed a 5.8cm adrenal mass. The patient denied easy bruising, striae, mood changes, dizziness, or hypertension. Biochemical evaluation demonstrated normal potassium level 3.7 (3.5-5.3 mmol/dL) and aldosterone 8ng/mL (&amp;lt;28), non-suppressed cortisol 7.8mcg/dL after dexamethasone 1mg given the night prior, but Cushing’s Disease was ruled out by normal salivary cortisol 0.08 mcg/dL (nl 0.04-0.56 mcg/dL) and urine free cortisol 22.8 mcg/ 24h (nl 4-50 mcg/24h), and further testing revealed elevated metanephrines and catecholamines during 24 hour urine collection, Epinephrine 129 mcg/24h (nl 2-24 mcg/24h), Metanephrine 7121 mcg/24h (nl 90-315 mcg/24h) and Normetanephrine 2078 mcg/ 24h (nl 122-676 mcg/24h).Repeat CT scan again showed an indeterminate 5.4 x 3.8 x 5.5 cm right adrenal mass, a 6.9mm lipid-rich left adrenal adenoma, and left adrenal gland hyperplasia. Consequently, the patient underwent laparoscopic right adrenalectomy with pathology revealing a diagnosis of pheochromocytoma. Post-op plasma fractionated metanephrines normalized and have remained normal. Immediately post-op, all diabetes medications (including insulin, glimepiride, and metformin) were stopped and she has had resolution of diabetes with HbA1c 6 on no medications when 1-year post-op. Discussion: Excess catecholamines are known to cause disruption of glucose and insulin homeostasis from desensitization of the beta-adrenergic receptor and increased insulin resistance1. Despite this, less than a handful of pheochromocytoma cases have been reported to be presenting as an acute glycemic derangement as in our patient.

FRI263 Challenges In Management Of Biochemically Silent Pheochromocytoma

Abstract Disclosure: G. Gannamani: None. T. Gourdin: None. J.K. Fernandes: None. Background: Incidental adrenal tumors are a common radiological finding. Biochemical work up is important as functioning adrenal tumors increase mortality and morbidity. Missing diagnosis of Pheochromocytoma can result in fatal outcomes. There have been case reports with asymptomatic and mildly elevated biochemical markers or symptomatic but no biochemical evidence which pose challenges in diagnosis. Here we describe a case of Metastatic Pheochromocytoma which was biochemically silent. Case Description: 61-year-old female with incidental finding of left adrenal mass measuring 8.7 x 5.6 x 5.7 cm on CT (Computed Tomography) scan for back pain 10 years prior to presentation. She was told no further testing was needed then as she was asymptomatic. She now has uncontrolled hypertension requiring multiple anti-hypertensives that prompted further work up. Biochemical work up at outside facility reported as normal aldosterone, renin activity, AM cortisol, ACTH, DHEA-S, plasma metanephrine and normetanephrine, epinephrine, norepinephrine, and dopamine. Elevated Chromogranin A of 5608 (normal &amp;lt; 93 ng/mL). Repeat CT Abdomen showed multiple enhancing lesions in liver, large lobulated adrenal mass measuring 15 x 10 x 14 cm (previously 8.7 x 5.6 x 5.7 cm) with central necrosis, absolute washout is 63%. This mass extended into gastro-hepatic space, obliterating fat space between the left adrenal mass and tail of pancreas was also reported. Imaging was concerning adrenal malignancy vs Pheochromocytoma. Further work up with MRI (Magnetic Resonance Imaging) Abdomen showed 14 cm centrally necrotic mass suggestive of adrenal neoplasm with loco-regional involvement. CT chest with bilateral pulmonary nodules and diffuse sclerotic and lucent bone lesions concerning osseous metastatic disease. Liver biopsy positive for metastatic neuroendocrine neoplasm consistent with Pheochromocytoma, immunohistochemical stains positive for Synaptophysin, Chromogranin, S100, GATA3, Inhibin. Dotatate PET CT with large centrally necrotic left adrenal mass. Abnormal radiotracer uptake in left kidney, stomach, gastrohepatic lymph nodes, widespread osseous lesions suggesting metastatic disease. She was not a surgical candidate given extension of mass and metastasis to multiple organs. Treatment started with Sunitinib (Tyrosine kinase inhibitor), plan to repeat imaging in 4-6 months hoping for tumor shrinkage.

FRI218 Von Hippel-Lindau With Pheochromocytoma And Severe Orthostatic Hypotension

Abstract Disclosure: N. Ebrahimi: None. C.G. Rivas Pajuelo: None. R. Habibi: None. S. Tariq: None. S.A. Penquite: None. Introduction: Von Hippel-Lindau (VHL) syndrome clinically manifests with benign and malignant tumors across multiple organ systems including the cerebellum, retina, kidney, and adrenal glands. Pheochromocytoma occurs in 25-30% of patients with VHL. Up to 50% of patients with pheochromocytoma present with hypertension or paroxysmal hypertension, although patients can be normotensive on presentation. Patients with pheochromocytoma are often severely volume depleted due to chronic vasoconstriction. Here we present a case of VHL with pheochromocytoma complicated by profound orthostatic hypotension after initiation of alpha-blockade. Case Presentation: A 32-year-old man presented for evaluation of progressive headache and diplopia. Patient was normotensive on initial presentation with BP 129/80mmHg. Brain MRI with contrast subsequently revealed a posterior fossa cystic mass with an avidly enhancing central nodule concerning for hemangioblastoma. Given these findings, a CT chest/abdomen/pelvis was obtained, which demonstrated a 4.6 x 5.0 cm right adrenal mass, several enhancing renal lesions, and multiple cystic lesions throughout the pancreas. This constellation of radiological findings was clinically concerning for VHL. Further endocrinologic work-up revealed plasma metanephrines 663 pg/mL (insert reference range here), plasma catecholamines 770 pg/mL (insert reference range here), which confirmed the diagnosis of pheochromocytoma. Alpha blockade was initiated with doxazosin 4 mg BID, and a high sodium diet (insert g/day). Shortly after initiation of doxazosin, patient developed severe orthostatic hypotension despite salt loading and volume resuscitation. Ultimately doxazosin was discontinued, and surgery was postponed due to severe symptomatic orthostatic hypotension limiting patient’s ability to get out of bed. High sodium diet was continued on hospital discharge and alpha-adrenergic blockade was later re-initiated which patient is tolerating well. Patient is pending adrenalectomy in the coming weeks. Discussion: Orthostatic hypotension in pheochromocytoma is expected due to volume depletion from chronic vasoconstriction. Alpha adrenergic blockade is required to alleviate hypertension, allow for adequate volume expansion, and to prevent a hypertensive crisis intraoperatively. Clinicians should be aware of the commercially available alpha-adrenergic antagonists and when they should be temporarily discontinued. There is no preferred alpha-adrenergic antagonist agent, however doxazosin has shown to cause less orthostatic hypotension and does not have such an antihypertensive effect as of Phenoxybenzamine. Presentation: Friday, June 16, 2023

Image-Guided Precision Medicine in the Diagnosis and Treatment of Pheochromocytomas and Paragangliomas.

In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment. Despite major medical improvements, PPGLs, as with other neuroendocrine tumors (NETs), leave clinicians facing several challenges; their inherent particularities and their diagnosis and treatment pose several challenges for clinicians due to their inherent complexity, and they require management by multidisciplinary teams. The conventional concepts of medical imaging are currently undergoing a paradigm shift, thanks to developments in radiomic and metabolic imaging. However, despite active research, clinical relevance of these new parameters remains unclear, and further multicentric studies are needed in order to validate and increase widespread use and integration in clinical routine. Use of AI in PPGLs may detect changes in tumor phenotype that precede classical medical imaging biomarkers, such as shape, texture, and size. Since PPGLs are rare, slow-growing, and heterogeneous, multicentric collaboration will be necessary to have enough data in order to develop new PPGL biomarkers. In this nonsystematic review, our aim is to present an exhaustive pedagogical tool based on real-world cases, dedicated to physicians dealing with PPGLs, augmented by perspectives of artificial intelligence and big data.

Sonographic Findings of Pheochromocytoma in an Adolescent Female During an Evaluation for Possible Renal Artery Stenosis

A 16-year-old female initially presented to urgent care, with a 2-day history of nausea, vomiting, headache, and abdominal pain. After falling and having a tonic/clonic seizure at urgent care, the patient was transferred to an emergency room and subsequently admitted to the pediatric intensive care unit within the hospital for monitoring. Due to persistent tachycardia and hypertension, a renal Doppler examination was performed to evaluate for possible renal artery stenosis. Instead, a 4.0-cm right adrenal mass was discovered, prompting catecholamines and metanephrines testing, and subsequent endocrinology assessment. The diagnosis of pheochromocytoma was made, and a full diagnostic evaluation was completed to exclude extra-adrenal tumor growth and genetic association. Surgical resection of the tumor was successfully accomplished, and the patient was scheduled for annual metanephrine monitoring. This case highlights the significance of a thorough evaluation of the adrenal glands in pediatric patients presenting with atypical hypertension, where renal artery stenosis is suspected.