Plasma Metanephrines Research Articles

A Decade of Insights into Bilateral Adrenal Masses: Epidemiology, Clinical Profiles, and Therapeutic Approaches

Bilateral adrenal masses (BAMs) are rare, accounting for 10-15% of adrenal masses. Their diagnostic and therapeutic approaches differ from those of unilateral masses. This study aimed to analyze the epidemiological, clinical, paraclinical, and therapeutic profiles of BAMs. It is based on a retrospective analysis of 30 patient records from the Endocrinology, Diabetology, and Nutrition Department at CHU Hassan II in Fez, over a 12-year period. The average age of the patients was 53 years, with a male predominance (53.3%). BAMs were symptomatically revealed in 46.7% of cases, incidentally discovered in 23.3%, identified during tumor staging in 20%, and associated with a genetic syndrome in 10% of cases. Clinical examination revealed hypertension in 23.3% of patients, an abdominal mass in 10%, signs of adrenal insufficiency in 10%, hypercortisolism in 6.67%, and hyperandrogenism in 16% of cases. Biological assessment showed elevated urinary or plasma metanephrine derivatives in 9 patients, hypercortisolism in 3 patients, adrenal insufficiency in 3 patients, 11-β-hydroxylase enzyme block in 3 patients, and primary hyperaldosteronism in 1 patient. Adrenal computed tomography (CT) was performed in 29 patients. A staging workup, including PET scan, was requested in 20% of cases. MIBG scintigraphy was performed in 23.3% of patients. The investigations revealed 53% of BAMs were secreting and 47% non-secreting. There were 9 cases of pheochromocytomas, including 5 associated with a syndrome (3 MEN2a, 1 MEN2b, 1 VHL), 8 cases of non-secreting adenomas, 3 cases of congenital adrenal hyperplasia due to 11-β-hydroxylase enzyme block, 2 cases of adrenal metastases, 2 cases of adrenocortical carcinoma, 2 cases of adrenal cysts, 1 case of Conn’s adenoma, 1 case of cortisol-secreting adenoma, 1 case of primary adrenal lymphoma, and 1 case of adrenal hematoma. Treatment included the management of emergencies and preoperative preparation for patients eligible for surgery. Bilateral adrenalectomy was performed in 33.3% of patients, and unilateral adenectomy in 1 case of cortisol-secreting adenoma. Medical treatment was initiated in 16.6% of cases, and palliative treatment in 13.33% of cases. Surveillance alone was implemented in the remaining 33.3%. Prognosis depends on the type of adrenal mass, with outcomes marked by the death of one case of malignant adrenocortical carcinoma and one case of primary adrenal lymphoma. Our study, involving 30 cases of BAMs, highlights their clinical, biological, radiological, therapeutic, and prognostic characteristics. Data in the literature are limited compared to unilateral adrenal masses. Future larger studies are desirable for optimal management.

Alterations and clinical value of peripheral lymphocyte subsets and inflammatory factors in paragangliomas.

Given the pivotal role of immune and inflammatory responses in tumor patients, the present study aimed to explore alterations and the clinical value of peripheral lymphocyte subsets and inflammatory factors in pheochromocytomas/paragangliomas (PPGLs). The clinical data of 327 patients, including 102 patients with metastatic PPGLs, were retrospectively analysed. Peripheral lymphocyte subsets were determined by flow cytometry. Relationships between immune and inflammatory parameters and clinicopathological characteristics were evaluated by intergroup comparisons and correlation analyses. Univariate and multivariate logistic regression analyses were employed to identify metastatic indicators. The corresponding nomogram was constructed and evaluated for discrimination and calibration. The median age at diagnosis was 45.0 years, and duration of follow-up was 3.0 years. Compared with those in younger patients (<45.0 years), most lymphocyte subsets were significantly reduced in older patients (≥45 years) (P<0.05). The count of lymphocytes, CD3+T cells and CD4+T cells were negatively correlated with 24h-urinary epinephrine and plasma metanephrine levels (R=-0.2∼-0.1, P<0.05). In addition, patients with lymph node (n=37) or bone metastases (n=41) had a lower percentage of CD4+T cells (P<0.05). Multivariate analysis revealed that CD3+T cell≥1446.50/μl, CD4+T cell%<39.95%, CD8+T cell%<24.95%, CD4+/CD8+T cell ratio<2.88, B cell%≥8.65%, TNF-alpha<12.45pg/ml, IL8<30.50pg/ml and PLT≥269.50*109/L were significant indicators of metastatic PPGLs. The area under the curve (AUC) of the nomogram was 0.800 (95% CI: 0.736-0.865). Immunesenescence, characterized by immune dysfunction with aging, was observed in PPGLs. Higher epinephrine and metanephrine levels might impair host's immune response. Monitoring changes in peripheral lymphocyte subsets and serum cytokines could indicate patients' conditions, especially the occurrence of metastasis.

7958 Organ Of Zuckerkandl Paragangliomas

Abstract Disclosure: L. McVicker: None. S. Egan: None. K.C. Conlon: None. J. Gibney: None. J. Feeney: None. M. Whelan: None. A. Garrahy: None. Background: The Organ of Zuckerkandl (OoZ) was first described in 1901 by an Austrian anatomist Emile Zuckerkandl as a para-aortic paraganglia located laterally to the abdominal aorta at the level of the inferior mesenteric artery. It represents the largest accumulation of extra-adrenal chromaffin cells in mammals. Paragangliomas (PGL) of the OoZ are rare entities with prior retrospective study of 371 patients with phaeochromocytoma or sympathetic PGL revealing only 21 cases of OoZ PGLs of which 14 of which (66%) had metastases at diagnosis (1). 70% of cases are in association with SDHB or less commonly, SDHD mutations (2). Clinical Case: A 48-year-old female presented with a year long history of palpitations and headache. Plasma normetanephrine level was 6340 pmol/L (lab reference 0-1180), plasma metanephrine 412 pmol/L (lab reference 0-510) and plasma 3-methoxytyramine &amp;lt;100 pmol/L (lab reference 0-180). CT adrenals showed normal adrenal glands. A 4.5 cm x 2.1 cm hyper-vascular retroperitoneal mass was visualised. A 68Ga-DOTATOC PET/CT showed no abnormal uptake in the area of the mass. [1]23I-MIBG scan showed increased uptake within the mass compatible with a PGL of the OoZ. Following surgery, histology confirmed PGL of the OoZ and plasma metanephrines normalised following. Genetic testing for predisposing mutation was negative. A 38-year-old male presented with sweating episodes, palpitations, and hypertension. Plasma normetanephrine level was 2,230 pmol/L (lab reference 0-1180) and plasma metanephrines 223 pmol/L (lab reference 0-520). CT adrenals showed normal adrenal glands with no other abnormalities noted. [1]23I-MIBG showed increased uptake in the region of the origin of the inferior mesenteric artery from the aorta consistent with PGL of the OoZ. The patient underwent laparoscopic resection with resultant normalisation of metanephrine levels. Histology showed a 21 mm encapsulated tumour in keeping with PGL with a PASS Score of 7. As with the first case, genetic testing for predisposing mutations returned negative. Conclusion: OoZ PGLs represent rare presentations of phaeochromocytoma-paraganglioma disease. This small case series is notable as neither case was associated with a predisposing genetic mutation, which has previously been shown to be more common in OoZ PGLs. There was also no evidence of metastasis in either case which is more commonly associated with this OoZ disease. The first case is also remarkable in terms of the tumour’s imaging characteristics. Previous studies have shown greater sensitivity using 68Ga-DOTA-Somatostatin Analogue PET/CT in comparison to [1]23I-MIBG in the detection of PGLs (3). In the first case, the tumour did not show any significant avidity on 68Ga-DOTATOC PET/CT but was avid on [1]23I-MIBG. Reference: 1. Ayala-Ramirez et al. J Clin Endocrinol Metab. 2011 2. Lodish et al. Endocr Relat Cancer. 2010 3. Carrasquillo et al. J Nuclear Medicine. 2021 Presentation: 6/2/2024

8097 A Rare Case of a Renal Cell Carcinoma and Pheochromocytoma Collision Tumor

Abstract Disclosure: R. Daas: None. S. Logan: None. W. Sexton: None. V. Chumbalkar: None. M. McGettigan: None. C. Veloski: None. Background: Collision tumors are neoplasms comprised of two or more distinct tumors. A collision tumor consisting of a renal cell carcinoma and pheochromocytoma is extremely rare with less than five cases reported in the literature. Clinical Case: A 64-year-old male with a history of hypertension and type 2 diabetes presented with hematuria. The patient was on 4 anti-hypertensive medications at the time. He noted increased road rage, anxiety, tremors, and insomnia. A CT abdomen/pelvis revealed an exophytic 8.6 x 7.9 cm left upper pole renal mass and a 7.5 x 6.2 cm left adrenal mass. Contrast-enhanced MRI abdomen showed a left upper/interpolar renal mass with heterogenous peripheral enhancement, restricted diffusion, and areas of central necrosis along with a heterogenous, enhancing left adrenal mass with associated restricted diffusion and areas of cystic necrosis. Both masses had associated areas of hyperintense signal on T1 fat-suppressed MRI suggestive of hemorrhage. Lab work revealed ACTH 26.6 pg/mL (7.2-63.3), cortisol 13 ug/dL (3.7-19.4), aldosterone 23.1 ng/dL (4-31), renin 4 ng/mL/hr (0.5-4), dopamine 136 pmol/L (&amp;lt;240), epinephrine 121 pmol/L (&amp;lt;330), norepinephrine 23,666 pmol/L (1050-4800), plasma normetanephrines 12.3 nmol/L (0-0.89), plasma metanephrines &amp;lt;0.10 nmol/L (0-0.49), 24-hour urine normetanephrines 4,178 mcg (122-676) and 24-hour urine metanephrines 4,233mcg (224-832). The patient was treated with alpha blockade prior to left radical nephrectomy, left adrenalectomy and infrahilar paraaortic lymph node dissection. Despite aggressive preoperative alpha blockade with maximal doses of doxazosin, addition of metyrosine and other anti-hypertensives, he developed acute hypertension with adrenal mass manipulation during the procedure and then hypotension following removal. He was admitted to the ICU for management of hypotension with pressors and fluid resuscitation and did well. Post-operative labs showed plasma normetanephrines 0.98 nmol/L (0.00-0.89) and plasma metanephrines 0.11 nmol/L (0.00-0.49). Pathology revealed clear cell renal cell carcinoma (RCC) of the kidney. The adrenal gland showed 2 tumors; one consistent with pheochromocytoma and another intimately associated with the former consistent with metastatic RCC, morphology diagnostic of a collision tumor. Following surgical resection, the patient was referred for genetic testing, surveillance imaging and lab testing, and treated with pembrolizumab adjuvant therapy for stage IV RCC. Conclusion: Although collision tumors are rare, biochemical testing to rule out a pheochromocytoma must be performed for all indeterminate adrenal masses and presumed adrenal metastases of active malignancies. Presentation: 6/2/2024

12315 Unveiling A Paraganglioma: Catecholamine-Induced Hyperglycemia Masquerading As Type 2 Diabetes Mellitus

Abstract Disclosure: S. Salman: None. M. Hussine: None. J. Tibaldi: None. Background: Excessive catecholamines have been demonstrated to exert adverse effects on insulin homeostasis and carbohydrate metabolism, potentially resulting in the onset of secondary DM. We present a case of a patient who had been previously misdiagnosed with T2DM for an extended period. Clinical Case: A 34-year-old woman with history of T2DM, HTN, and chronic tachycardia on beta blockers, presented with complaints of palpitations, headaches, and abdominal pain for two weeks. Upon admission, she was found to be in DKA, necessitating transient administration of insulin drip. Furthermore, she exhibited persistent tachycardia and intermittent episodes of hypertensive urgency. Notably, thyroid levels revealed euthyroidism. Although DKA resolved, her fasting blood sugar levels remained elevated and refractory to escalating insulin therapy. CT abdomen with contrast revealed a large enhancing mass in the RUQ. MRI abdomen confirmed an 8.1 cm heterogeneously enhancing T2 hyperintense mass located in the RUQ, abutting the right hepatic lobe, right adrenal gland, extrahepatic biliary ducts, and adjacent vessels. Given suspicions of a neuroendocrine tumor, she was transferred to the surgical service for tumor excision. Hormonal analysis revealed elevations in plasma metanephrines (620 pg/mL, n 0-88 pg/mL), plasma normetanephrines (9954 pg/mL, n 0-210.1 pg/mL), 24-hr urine normetanephrines (10,952 μg/24hr, n 110-720 μg/24hr) and 24-hr urine metanephrines (1406 μg/24hr, n 35-278 μg/24hr). Additionally, she exhibited elevated 24-hr urine epinephrine fraction (218 μg/g Cr, 0-20 μg/g Cr) and 24-hr urine norepinephrine fraction (2775 μg/g Cr, 0-45 μg/g Cr). Preoperatively, appropriate alpha and beta blockade were administered, followed by successful retroperitoneal tumor resection. Postoperatively, her glucose levels normalized without the need for further insulin therapy, and no episodes of hypoglycemia were reported. Histopathological examination of the excised mass revealed an 11 cm sympathetic paraganglioma with retention of SDHB staining. Genetic testing for SDHB, SDHD, VHL, and RET mutations is pending. Conclusion: This case underscores the potential oversight of pheochromocytomas and paragangliomas due to their nonspecific symptomatology, often mimicking more prevalent conditions, thereby presenting diagnostic challenges. The catecholamines secreted by these tumors can lead to both impaired insulin secretion and increased insulin resistance, resulting in clinically significant manifestations. The exact mechanism underlying the glycemic dysregulation remains controversial, necessitating further investigation through large-scale multicenter prospective studies to enhance understanding and inform diagnostic and therapeutic strategies for these tumors, which can manifest with severe and potentially fatal glycemic disturbances. Presentation: 6/1/2024

8355 Pheochromocytoma In The Elderly: A Mini Case Series

Abstract Disclosure: S. Nabi: None. A. Golash: None. P. Panwar: None. G. Powner: None. C. Schiteanu: None. C. George: None. M. Vallabhaneni: None. B.G. Issa: None. A. Clark: None. D. Bailey: None. J. Waldron: None. F.W. Hanna: None. Diagnosis and management of pheochromocytoma in the older population is challenging due to the co-morbidities and general age-related frailty. We present a mini case series of four patients aged 72 to 86 years who presented to our tertiary referral center at the University Hospitals of North Midlands UK, between 2019 and 2022.The case series documents the challenges of managing pheochromocytoma in this population, emphasizing how close monitoring, regular follow ups and collaboration between different members of the multidisciplinary team helped to achieve the desirable outcomes in these cases. Case 1: Adrenal incidentaloma in 84-year-old female. Background of hypertension and diabetes mellitus. History of occasional palpitations. Investigations showed raised plasma and urinary metanephrines. MIBG scan confirmed pheochromocytoma and after adequate alpha and beta blockade underwent successful laparoscopic surgery. No intra or post operative complications and showed good recovery. Discharged on the 5th day post operative. Case 2: 82-year female under cardiology with non-ST elevation myocardial infarction. Background of hypertension, chronic kidney disease and gastroesophageal reflux disease. Initial presentation with shortness of breath, sweating and swelling lower limbs. Normal coronary arteries on angiography, so investigated for possible excess catecholamine production. Had significantly raised 24-hour urinary normetadrenaline. Paraaortic paraganglioma confirmed on MIBG SPECT scan. Initially opted for medical treatment however quality of life worsened over the next year and eventually underwent robot assisted excision. Procedure was uneventful with good post-operative recovery. Was able to go home 2 days after the procedure. Case 3: 72-year-old female referred with right adrenal incidentaloma. Background of hypertension, diabetes mellitus, hypothyroidism, asthma, arthritis and Ca breast treated 10 years ago. Results showed raised plasma metanephrines, subsequently, MIBG scan revealed a 3 cm right adrenal nodule with increased uptake. Full alpha and beta blockade achieved before she underwent surgical treatment with no complications. Discharged on the 3rd day post op. Case 4: An 80-year-old male was referred with left adrenal incidentaloma. History of diabetes, chronic kidney disease, ischemic heart disease and heart failure, recent myocardial infarction and atrial fibrillation. Biochemical and radiological investigations confirmed pheochromocytoma. He was started on alpha blockade that proved difficult to achieve due to underlying co-morbidities. The patient needed close monitoring by the endocrine team and was finally established on adequate alpha and beta blockade. Due to significant risks associated with the procedure, the patient decided not to proceed with the surgery and opted for medical management. Remains under active follow up. Presentation: 6/2/2024

8081 Case report of sympathetic paraganglioma presenting as chronic catecholamine induced cardiomyopathy

Abstract Disclosure: Z. Tan: None. A. Taiwo: None. Background: Sympathetic paragangliomas are rare neuroendocrine tumors (&amp;lt;1/100,000) arising from extra-adrenal autonomic paraganglia, generally in the thorax, abdomen, and pelvis. They secrete catecholamines predominantly norepinephrine, which can cause a rare complication of catecholamine-induced cardiomyopathy. Clinical Case: A 33-year-old male, with history of obesity and borderline hypertension not on medication, presented with dyspnea on exertion, worsening paroxysmal nocturia dyspnea of 1 month duration and sudden onset of severe right flank pain. Work up for his chronic shortness of breath revealed: Troponin negative. EKG showed sinus tachycardia. Echocardiogram revealed enlarged left ventricle, severely decreased LV systolic function of 25-30%. Given the absence of angina symptoms, negative troponin, and EKG findings, his new-onset cardiomyopathy was presumed to be non-ischemic. CT chest, abdomen and pelvis was performed for the new onset right flank pain, which revealed a 4.1 cm x 4.0 cm centrally necrotic aortocaval soft tissue mass. This raise a concern about malignancy. A CT-guided Fine-Needle Aspiration of the retroperitoneal mass suggested paraganglioma. Further investigation showed plasma normetanephrine at 5.56 nmol/L (Reference range: 0-0.89 nmol/L), 24 hour urine normetanephrine at 2411 ug/d (Reference range: 114-865 ug/d), and 24 hour urine norepinephrine at 179 ug/d (Reference range: 14-20 ug/d). Plasma metanephrines and plasma dopamine were within the normal range. A gallium DOTATE PET/CT revealed a necrotic aortocaval mass with peripheral uptake, consistent with the known paraganglioma. He was diagnosed with sympathetic paraganglioma complicated with chronic catecholamine-induced cardiomyopathy and had exploratory laparotomy excision of his paraganglioma. Preoperatively, he was treated with phenoxybenzamine and carvedilol. However, his post-surgical course was complicated by acute on chronic heart failure and pneumonia, and he subsequently passed away from a pulseless electrical activity arrest. Conclusion: Although sympathetic paragangliomas rarely presents as catecholamine-induced cardiomyopathy, this case emphasizes the importance of considering hormonal abnormalities in patients who present with non-ischemic cardiomyopathy without high risk factors. Reference: 1. Alessandra Giavarini, Antoine Chedid et al. Acute catecholamine cardiomyopathy in patients with phaechromocytoma or functional paraganglioma. Heart 2013; 99: 1438-1444. Presentation: 6/2/2024

8275 Recurrent Retroperitoneal Paraganglioma

Abstract Disclosure: J. Kang: None. V. Gupta: None. J.S. Subauste: None. Paragangliomas are rare, highly vascular neuroendocrine neoplasms that may originate from sympathetic or parasympathetic paraganglia and may secrete catecholamines. They are closely related to pheochromocytomas which are considered to be their intra-adrenal counterparts. A 65-year-old African American male with type 2 diabetes and tobacco use presented to his primary care physician with night sweats and unintentional weight loss of about 30 pounds in 3 months. Review of systems and laboratory workup was unremarkable. CT Chest/Abdomen/Pelvis with contrast showed a homogenous, well-circumscribed 4.6cm retroperitoneal mass causing mass effect on portal vein, Inferior vena cava, and right renal artery. Interventional radiology performed fine needle aspiration with intra-procedural blood pressure rising to 201/70 mmHg. Pathology showed paraganglioma, staining positive for synaptophysin, chromogranin A, CD 56 and S-100 protein. Plasma metanephrines were elevated at 2818 pg/mL, plasma normetanephrines at 1247 pg/mL with consistent 24-hour urine results. Workup for other adrenal hormones was negative. No family history of pheochromocytoma/paraganglioma or any clinical manifestations of Von-Hippel-Lindau syndrome or Neurofibromatosis were present. He was started on alpha blockade followed by beta blocker and surgical resection was planned. In the interim, escalating requirements of insulin were noted. Intra-operative course was complicated by systolic blood pressure rising to 290s which resolved after mass was removed. Immunohistochemical studies sent to Mayo, Rochester showed retained cytoplasmic SDHB expression in tumor cells. Hence, no further genetic testing was performed. Post excision, plasma-free metanephrines normalized with significant improvement in blood pressure and diabetes. He was followed with yearly plasma-free metanephrines for surveillance. Although asymptomatic, a three-fold rise of plasma metanephrines was noted five years later. CT Abdomen was concerning for recurrence. Dotate/PET scan showed dotate-avid para-aortic soft tissue lesion measuring 2.3 cm between the celiac artery and the superior mesenteric artery which was surgically excised with pathology consistent with paraganglioma (Ki67&amp;lt;1%). Diagnosis of paragangliomas is often in 3rd - 5th decade. About 30% are hereditary and associated with Von-Hippel-Lindau, Neurofibromatosis-1, MEN2A/B among other syndromes. They are mostly benign but SDHB pathogenic variants are likely to be malignant. Genetic testing should be considered in all paraganglioma patients to screen for germline pathogenic variants in SDH and other genes. Diagnosis of secretory paraganglioma is by urinary and/or plasma fractionated metanephrines and catecholamines. Treatment of choice is surgery when amenable to resection with preoperative medical blockade to prevent perioperative complications. Presentation: 6/1/2024

7652 Functional Adrenocortical Carcinoma Presenting As Uncontrolled Hypertension

Abstract Disclosure: B.R. Bedell: None. M. Fariduddin: None. J. Sanchez Perez: None. S.C. Kukreja: None. R.M. Sargis: None. Adrenocortical carcinoma is a rare malignancy, with approximately 2,000 cases reported in the United States since 1970.[1] Many secrete excess adrenocortical hormones, adding to morbidity and mortality. Surgery can be curative or prolong survival if diagnosis is made early, but prognosis remains poor due to delayed detection.[2] We present a case of metastatic functional adrenocortical carcinoma that presented with consequences of long-standing uncontrolled hypertension. A 59-year-old male with history of hypertension and CAD presented to the hospital with worsening bilateral pitting edema, dyspnea on exertion, palpitations, headaches, and proximal muscle weakness over for multiple months. His hypertension (HTN) was noted to be uncontrolled despite use of multiple antihypertensives (daily Lasix 20 mg, Lisinopril 40 mg, Metoprolol Succinate 100 mg and Amlodipine 10 mg). Hypokalemia of 3.0 mmol/l (3.5 - 5.2 mmol/l) was noted. Echocardiogram revealed new heart failure with preserved ejection fraction. A subsequent nuclear stress test incidentally revealed a right-sided 15 cm retroperitoneal mass, invading the IVC and the right hepatic lobe. An AM dexamethasone suppression test was notable for a cortisol of 39 ug/dl (&amp;lt;1.8 ug/dl) and an undetectable ACTH level of &amp;lt;1.5 pg/ml (7.2 - 63.3 pg/mL), suggestive of primary hypercortisolism. 24-hour urine cortisol was 930.6 ug/d, (&amp;lt;=60.0 ug/d), DHEA-s 1105 ug/dL (52 - 295 ug/dL), Androstenedione 2.641ng/mL (0.230 - 0.890 ng/mL), and 17-Hydroxyprogesterone 299.87 ng/dL (&amp;lt;=138.00 ng/dL). Plasma metanephrines were normal and aldosterone levels were undetectable, confirming cortisol and its precursor excess as the cause of hypertension. Biopsy of the mass was consistent with adrenocortical carcinoma. Due to disease extent, the patient was not a candidate for surgical debulking, and radiation therapy was commenced. Ketoconazole 200 mg and Spironolactone 150 mg twice daily led to improvement in HTN and hypokalemia. His course was further complicated by bacteremia and acute pulmonary embolism. The patient eventually elected to pursue hospice care. Adrenocortical carcinoma remains challenging to detect at early stages given a paucity of symptoms. This case highlights the need to have a high index of suspicion for hypercortisolism in patients with uncontrolled HTN and hypokalemia, as this may be indicative of a functional adrenal cancer. This could be a potential strategy for earlier diagnosis, thereby increasing survival rates by improving disease amenability to surgical intervention. (1.) Sharma E, Dahal S, Sharma P, et al. The Characteristics and Trends in Adrenocortical Carcinoma: A United States Population Based Study. J Clin Med Res. 2018;10(8):636-640. doi:10.14740/jocmr3503w (2.) Vaidya A, Nehs M, Kilbridge K. Treatment of Adrenocortical Carcinoma. Surg Pathol Clin. 2019;12(4):997-1006. doi:10.1016/j.path.2019.08.010 Presentation: 6/2/2024

8204 Rare Asymptomatic Presentation Of A Large Pheochromocytoma

Abstract Disclosure: A. Lorin: None. C.K. Persaud: None. M.H. Kemm: None. Background: Pheochromocytoma is a rare neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. It is associated with excessive release of catecholamines causing symptoms of hypertension, palpitations, diaphoresis, and headaches. These symptoms are particularly prominent with larger pheochromocytomas. We present the case of a large 13 cm pheochromocytoma (PCC) without the typical associated symptoms. Clinical Case: A 45-year-old male with medical history of osteoarthritis and gastroesophageal reflux presented to his primary care doctor with 2 months of intermittent right upper quadrant abdominal pain associated with nausea. Work up with CT abdomen/pelvis found a 9.3 cm heterogeneous right adrenal mass with mass effect on the right liver lobe, superior pole of the right kidney, duodenum, and pancreatic head. Hormonal testing was notable for plasma metanephrine 257.8 pg/mL (0-88), plasma normetanephrine 12063.7 pg/mL (0.0-218.9), 24 hr urine metanephrine 159 mcg/24 hr (58-276), 24 hr urine normetanephrine 22575 mcg/24 hr (156-729), and chromogranin A 5387 mg/mL (0-101.8). Given lab evaluation, diagnosis was made of pheochromocytoma, and patient was initiated on alpha blockade with doxazosin. Patient’s blood pressure and heart rate were at goal prior to doxazosin initiation and patient needed to be decreased from 1 mg daily to 0.5 mg daily due to side effects of low blood pressure and orthostatic hypotension. Patient had an uncomplicated open right adrenalectomy with pathology showing a 13 cm pheochromocytoma with invasion through the capsule into the periadrenal adipose tissue. Genetic testing revealed no known mutation variants associated with PCC. Labs drawn two weeks postoperatively showed resolution of elevated plasma metanephrine, normetanephrine, and chromogranin A. Conclusion: While the patient had an elevated plasma metanephrine, the normetanephrine was predominantly elevated. Such a hormone profile is more common in extra-adrenal PCCs, consistent with cluster 1 associated genes. This noradrenergic phenotype is likely a reason the patient did not have typical symptoms, despite the size of his pheochromocytoma. A proposed pathophysiologic mechanism for this is the dissociation of renal medulla from the cortex given the large size of the tumor. This would lead to lower local availability of corticosteroid to potentiate the conversion of norepinephrine to epinephrine, thus decreasing likelihood of classical PCC symptoms. Despite lack of expected symptoms and an imaging initially concerning for adrenocortical carcinoma, we should recognize the potential for a large adrenal tumor to represent PCC and evaluate accordingly. Presentation: 6/1/2024

6891 Exclusive Normetanephrine Secreting Pheochromocytoma In A Young Male

Abstract Disclosure: E. Askar: None. H. Moran: None. IntroductionPheochromocytomas and paragangliomas arise from chromaffin cells and produce excessive catecholamines. Hypertension is their primary clinical symptom. they differ in their catecholamine secretory phenotype; paragangliomas typically secrete norepinephrine, while pheochromocytomas typically secrete epinephrine. Here, we present a case 21-year-old male with pheochromocytoma with elevated norepinephrine but normal epinephrine levels.Case presentationA 21 -year-old male with no past medical history presented with episodes of palpitations, sweating, and elevated blood pressure. He also reported abdominal pain. On admission, his blood pressure was 143/92 mmHg, pulse was 71/min, respiration was 16/min, and oxygen saturation was 100% in room air. The rest of physical exam was not significant. His electrolyte panel was normal. Computed tomography (CT) abdomen and pelvis with contrast was performed and showed a right adrenal mass measuring 4.9 x 4.0 x 6.5 cm which is predominantly hypoattenuating (approximately 30 Hounsfield units) with thick nodular rim of enhancement. Hormonal workup showed normal serum testosterone, DHEA-S, AM cortisol, ACTH, aldosterone, plasma metanephrine, and urine metanephrine, but profoundly high plasma normetanephrine 3641.6 (0.0-210.1) pg/mL. His 24-hour urinary normetanephrine was elevated at 14874 (80-440) ug/24hr, confirming a pheochromocytoma. The high norepinephrine level in the setting of normal epinephrine raised suspicion for Von Hippel Lindau (VHL). He was started on alpha and beta blockage and had laparoscopic removal of the right adrenal gland. The pathology report confirmed the diagnosis of pheochromocytoma confined to right adrenal. The patient was then referred for genetic testing. Conclusion: Pheochromocytoma can be a part of familial disorders, although being sporadic in nature most of the time. As demonstrated in our case, the hallmark of pheochromocytoma associated with VHL is nearly exclusive normetanephrine secretion and a high ratio of normetanephrine to metanephrine. Confirmation and testing of genes aid in proper monitoring and follow-up. The preferred course of treatment is radical resection. Presentation: 6/2/2024

8688 Pseudopheochromocytoma Due To Severe Obstructive Sleep Apnea

Abstract Disclosure: L.M. José: None. M. Ataide: None. F. Aratani: None. S. Beeby: None. G.F. Fagundes: None. F. Coelho: None. F. Ledesma: None. A. Latronico: None. B.B. Mendonca: None. M.C. Fragoso: None. M.Q. Almeida: None. Background: Obstructive sleep apnea (OSA) represents an independent risk factor for cardiovascular disease, and it is associated with a wide range of conditions, such as resistant hypertension and primary aldosteronism (PA). Patients with sleep apnea have a higher sympathetic activity during wakefulness due to chronic hypoxia. We present the case of pseudopheochromocytoma caused by severe OSA in an obese patient with RH and PA.Clinical Case: A 58-year-old female Brazilian patient was referred to an endocrinologist to investigate a 1.8 cm right adrenal nodule at computed tomography (CT) performed to investigate abdominal pain. Her medical history includes resistant hypertension diagnosed at 27 years of age, type 2 diabetes, dyslipidemia, Class II obesity, a previous acute myocardial infarction, and severe OSA (apnea-hypopnea index 61.6/hour). She has used irregularly the continuous positive airway pressure (CPAP) therapy at night. She is currently using carvedilol 50 mg bid, chlorthalidone 25 mg, olmesartan 40 mg, amlodipine 10 mg, spironolactone 50 mg, clonidine 0.2 mg tid, hydralazine 50 mg every 6 hours, acetylsalicylic acid 100 mg, atorvastatin 80 mg, and metformin XR 1000 mg. At physical examination, she had BMI 37 kg/m2, BP 150 x 90 mmHg, HR 64 bpm, and no signs of Cushing syndrome. Abdominal CT revealed a right adrenal nodule measuring 1.8 cm with 18 Hounsfield unit (HU) in the pre-contrast phase, reaching a density of 117 HU at the arterial phase and showing an absolute washout of 65% and a relative washout of 56%. A nodular thickening of 1.4 cm (-4 HU) at the left adrenal gland was also displayed at CT scan. Hormone evaluation showed basal cortisol 7 µg/dL, ACTH 15.7 pg/mL, DHEAS 1152 ng/mL (189-2050 ng/mL), 1 mg overnight dexamethasone suppression test 2.3 ug/dL, aldosterone 9.9 ng/dL, direct renin concentration 36.8 uIU/mL, plasma metanephrines 0.3 nmol/L (&amp;lt;0.5 nmol/L) and plasma normetanephrines 1.3 nmol/L (&amp;lt;0.9 nmol/L). It was not possible to change anti-hypertensive medications to investigate PA. A 0.3 mg clonidine suppression test did not suppress normetanephrine levels, confirming the biochemical diagnosis of pheochromocytoma. Then, alpha-blockade with doxazosin 4 mg was started and the patient underwent right adrenalectomy. Pathological examination revealed an adenoma with immunohistochemistry positive for CYP11B2. BP control was achieved with only two medications and aldosterone decreased to 3 ng/dL confirming PA. Plasma normetanephrine levels remained elevated post-surgery and only normalized after the CPAP regular use.Clinical lessons: Chronic activation of sympathetic autonomic drive in OSA can increase norepinephrine and normetanephrine levels. OSA is a very prevalent disease and it is frequently associated with RH. Therefore, OSA should be considered a possible cause of pseudopheochromocytoma in hypertensive patients. Presentation: 6/3/2024

8358 A Diagnostic Challenge: Occult Paraganglioma Misdiagnosed as Pheochromocytoma Leading to Unnecessary Adrenalectomy

Abstract Disclosure: A.R. Kasireddy: None. S. Alshami: None. S. Gummalla: None. C. Balasubramaniapandian: None. J.A. Henske: None. A. Albashaireh: None. Background: Pheochromocytomas and paragangliomas are rare neuroendocrine tumors. Catecholamine-secreting paragangliomas, like pheochromocytomas, can present with hypertension, sweating and episodic headaches. Thoughtful consideration must be given to distinguish between the two and potentially avoid a critical misdiagnosis. Case: A 61-year-old woman with hypertension and diabetes presented for evaluation of glomus jugulare discovered on CT of the head during evaluation of worsening hearing loss and tinnitus. She reported a longstanding history of episodic headaches, palpitations, anxiety spells and excessive sweating with more recent onset of ear fullness. When symptoms first presented, she had a left adrenalectomy 3 years prior. CT abdomen at that time showed 1.8 x 2.2 cm left adrenal nodule with a density of 12.2 HU and early contrast washout. Plasma metanephrines were normal but normetanephrines were elevated at 5.1 nmol/L (nl: less than 0.9 nmol/L). 24-hour urine metanephrines were normal but normetanephrines were elevated to 892mcg/24h (nl: 122-676 mcg/24h). MIBG scan was done and showed increased activity in the left adrenal nodule. Decision was made to proceed with left adrenalectomy. Surgical pathology was benign. Present evaluation after discovery of the glomus tumour with worsening symptoms showed normal plasma metanephrines, elevated plasma normetanephrines at 1529.9 pg/ml (0- 285.2 pg/ml), elevated plasma norepinephrine at 3280 pg/ml (0-874 pg/ml), with normal dopamine and epinephrine levels. CT head showed a 3 x 2.7 x 2.1 cm lytic destructive mass within the petrous temporal bone at the left skull base containing multiple internal calcifications. Given the lab and imaging findings, paraganglioma was diagnosed. Genetic testing revealed SDHB mutation. Neurosurgery consultants determined that the tumour was not amenable to resection. She was treated with radiation therapy, alpha blockade, and close blood pressure monitoring. Discussion: This case highlights the importance of reviewing the degree of hormonal elevations as well as the pattern of elevation to obtain a correct diagnosis. Paragangliomas commonly secrete normetanephrines rather than metanephrines and are often not immediately localized. Understanding the most likely genetic mutations when a paraganglioma is suspected can direct appropriate choice of radionuclide scanning agents. In this case, an earlier diagnostic scan may have prevented unnecessary adrenalectomy and facilitated earlier discovery of the paraganglioma. Presentation: 6/2/2024

8365 Bilateral Adrenal Hemorrhage Unveiling Adrenal Metastases In A Patient With Retroperitoneal Sarcoma

Abstract Disclosure: R.J. Shah: None. A.C. Goldberg: None. S. Jasim: None. Introduction: Metastatic disease to the adrenal gland is the most commonly occurring malignancy of the adrenal glands. Adrenal hemorrhage (AH) however is a rare but potentially fatal manifestation of malignancy. This case report highlights the unusual presentation of retroperitoneal sarcoma, manifesting as bilateral adrenal hemorrhage in the context of underlying metastases. Case Presentation: A 53-year-old man presented with a 4-week history of fatigue, intermittent abdominal pain radiating to the back, and vomiting. CT revealed bilateral adrenal masses measuring up to 8.5cm on the left side, with Hounsfield units (HU) 27, and 5.9cm on the right, HU 27, consistent with large areas of bilateral adrenal hemorrhage later confirmed on MRI. Biochemical evaluation included ACTH-stimulated cortisol, which was borderline at 17.4mcg/dl (recommended above 18-20mcg/dl), with a significantly elevated ACTH level of 103.8pg/nl (reference range 7.0-63.0pg/ml). Plasma metanephrines, electrolytes, aldosterone, and DHEA-S were normal. Although hemodynamically stable, he was started on prednisone 5mg daily as he was at high risk for primary adrenal insufficiency (AI). He was referred to endocrine surgery and further workup with PET/CT demonstrated a new FDG-avid periaortic retroperitoneal mass, with an interval increase in the size of the adrenal masses and development of hypoattenuating lesions in the kidneys and pancreas favoring aggressive metastatic disease. He underwent biopsy of the retroperitoneal mass, and pathology was consistent with high-grade sarcoma. Oncology started treatment with dexrazoxane and doxorubicin. His adrenal masses remained unchanged in size, and the patient died related to rapid progression of disease. Discussion: Spontaneous bilateral adrenal hemorrhage is rare with a reported incidence of 0.14 to 1.8%. Although most cases have been associated with sepsis, anticoagulation, hematologic disorders and trauma, it is important to maintain a high level of suspicion for underlying adrenal tumors and metastatic disease. AH can be a diagnostic challenge because of its non-specific presentation, and imaging is vital for timely recognition. Patients with bilateral AH should be managed with corticosteroids to avert AI-related fatalities. Presentation: 6/1/2024

8769 A Case of Metastatic and Catecholamine Producing Bilateral Pheochromocytoma in a Patient with RET Gene Mutation

Abstract Disclosure: R.A. Mayers: None. A. Szafran-Swietlik: None. RET mutation, observed in multiple endocrine neoplasia type 2 syndromes, is implicated in the development of pheochromocytomas of the kinase signaling cluster. Such tumors have lower metastatic risk and adrenergic production compared to the ones from the other clusters. We present a case of a metastatic, bilateral, small and biochemically active pheochromocytoma .This is the case of a 27-year-old man diagnosed with MEN 2A. He underwent total thyroidectomy due to medullary thyroid carcinoma at 2 years old. He was deemed cured and started on levothyroxine replacement. Since then, his plasma metanephrines by liquid chromatography-mass spectrometry and urine metanephrines done in a yearly basis as screening, were always within range of normality. Over the years, he developed substance abuse disorder with use of Kratom and methamphetamines and was admitted in a rehabilitation center multiple times in the last three years. During this time, the patient was reported to be slightly tachycardiac which was initially attributed to the use of substances. On the last year, an echocardiogram done as evaluation of his tachycardia showed an ejection fraction of 35%. Later, his annual metanephrine levels were markedly elevated (free metanephrine: 137 pg/mL and free normetanephrine : 157 pg/mL, normal ranges reported as less than 57 pg/mL and less than 148 pg/mL respectively). Abdominal tomography showed a right adrenal nodule of 1.2 cm and a left adrenal nodule of 1.6 cm, both with more than 10 Hounsfield Units. A Metaiodobenzylguanidine scan revealed a left adrenal nodule of 1.8 cm with diffuse radiotracer uptake, a right adrenal nodule of 1.2 cm with radiotracer activity and 3 subtle areas of focally increased radiotracer activity in the liver, two in left hepatic lobe and other in posterior right upper lobe. He underwent bilateral adrenalectomy with cortical sparring. Pathology results evidenced a left adrenal with a unifocal mass of 1.8 cm and a right adrenal with a mass of 1.2 cm , both without lymphovascular, capsular, local invasion or necrosis, a mitotic rate of 1-2 without atypical mitosis, not encapsulated with clean margins and positive for synaptophysin , chromogranin and S100 stains. An additional mass of 0.7 cm on the right adrenal gland was described with similar characteristics to the described before except for the involvement of the surgical margins. Currently on the literature there are different opinions regarding screening approach for pheochromocytomas in the presence of RET mutations. There are not strong recommendations regarding the use of imaging as a screening tool in this group of patients. It is important to consider that there are cases, as the one described in this report, that might present metastatic disease even with the presence of small pheochromocytomas that belong to the cluster of kinase signaling. Presentation: 6/3/2024

6661 Critical Limb Ischemia - An Unusual Presentation Of A Pheochromocytoma

Abstract Disclosure: S. Hassan: None. Background: Pheochromocytomas can lead to vasoconstriction and its various clinical manifestations due to excess catecholamine release. Critical limb ischemia as a clinical manifestation of pheochromocytoma has been reported sparsely. Clinical Case: A 43 year old female with a past medical history of type 2 diabetes mellitus, Turner syndrome, and hypertension presented to the emergency department with acute on chronic left leg pain. She underwent workup with a CT angiography of the abdomen with runoff for evaluation of her vessels, which revealed an occlusion of her left superficial femoral artery with chronic stenosis of the right femoral system. Multiple unsuccessful attempts were made at revascularization of her left lower extremity, including femoropopliteal bypass, with eventual left above knee amputation, multiple fasciotomies, and angiogram and stenting of multiple vessels. The patient was on a combined OCP (norethindrone-ethinyl estradiol) for hormone replacement for Turner syndrome for the past 30 years, and did not have a personal or family history of clotting disorders. She underwent a hypercoagulable workup which was negative. Echocardiogram was negative for thrombi and was otherwise unremarkable. Incidentally discovered on her initial CT angiography was a heterogeneously enhancing right adrenal mass, which was further delineated on a dedicated CT of the adrenals, which showed a 3.7 cm right adrenal mass with pre-contrast Hounsfield units measuring 46. Biochemical workup revealed a normal plasma renin activity and aldosterone, plasma metanephrine elevated to 5.20 nmol/L (range 0.00 – 0.49 nmol/L), plasma normetanephrine elevated to 4.95 nmol/L (range 0.00 – 0.89 nmol/L), 24 hour urine metanephrine elevated to 3830 ug/d (range 36-229 ug/d), and 24 hour urine normetanephrine 1733 ug/d (range 95 – 650 ug/d). She reports a diagnosis of hypertension at age 36, with no secondary workup pursued; she had suboptimal control on three separate medications, lisinopril, metoprolol, and hydrochlorothiazide. Her blood pressure and heart rate were noted to be labile during her aforementioned surgery. Alpha blockade with doxazosin was started based on her significantly elevated plasma and urine metanephrines and normetanephrines, with improvement in her blood pressure control. She was not found to have a definitive cause of her critical limb ischemia; she was noted to have atherosclerosis in the vessels of her lower extremities, and her chronic oral contraceptive use may also have played a role. However, OCPs are often reported to cause venous rather than arterial thrombi. Therefore, it can be inferred that the catecholamine excess from her presumed pheochromocytoma caused vasoconstriction which may have played a role in the development of her critical limb ischemia. Conclusion: Catecholamine excess that is resultant from a pheochromocytoma may manifest as critical limb ischemia. Presentation: 6/1/2024

7183 Histoplasmosis Of Adrenal In An Immunocompetent Patient From Arizona: A Surprising Biopsy

Abstract Disclosure: R. Habibi: None. S. Penquite: None. N. Ebrahimi: None. R. Cardenas Lara: None. Introduction: Histoplasmosis of adrenal gland in the context of disseminated infection is a rare entity in a non-endemic area. Early diagnosis and treatment can save one’s life. Here we present a case of a patient from Arizona who was referred to us with a large adrenal mass initially resembling malignancy. Presentation: A 58-year-old male with no significant medical history from Bisbee Arizona presented to our clinic with significant weight loss of 120 pounds in 8months, jaundice, fatigue, nausea and vague abdominal pain. He had an abdominal CT scan in a rural area hospital which showed a left adrenal 4.2 x 4.3 x 3.7 cm mass with average HU=40, with interval development from a CT scan 6months prior to that which showed left adrenal 1.5 x 1.3 x 1.3 cm mass. He had the initial CT scan after a mechanical fall. He was experiencing sweating, dizziness and low blood pressure of 90/60 mmhg, but used to have hypertension. Physical examination revealed diffuse jaundice in an ill appearing cachectic individual. Laboratory data were significant for total bilirubin of 4.9, direct bilirubin 0.7. Plasma metanephrines and normetanephrines, 24-hour urine free cortisol, morning cortisol levels and DHEA sulfate were normal. Other findings on the CT scans of head, chest and abdomen were soft tissue thickening between the right posterior 10th and 11th ribs along with hepatosplenomegaly, nodular lung lesions with calcified granuloma, sub centimeter brain lesions within the left putamen/external capsule junction with corresponding mild edema. During the following month after initial visit he developed bilateral tongue masses with dysphagia along with enlarging bilateral adrenal lesions, measuring up to 4.4 cm on the right and 5.2 cm on the left. The patient was admitted to hospital for further extensive work up. He underwent biopsies of left adrenal mass and tongue lesions which demonstrated necrotizing granulomatous inflammation with fungal elements compatible with histoplasmosis. Liposomal amphotericin B was started, which was quickly switched to itraconazole 200mg twice a day once lumbar puncture result was normal. His transient low blood pressures resolved. He was seen in clinic after few weeks with overall improving symptoms. Follow up with imaging of adrenal in few months is planned. He is currently in his third month of treatment for histoplasmosis with itraconazole. Discussion: The presentation of disseminated histoplasmosis can resemble malignancy as illustrated in this case. Southwest of the United States is an unusual geographical area for such infection. Initial unilateral involvement of adrenal as a mass in an immunocompetent individual is also uncommon. Considering dramatic response to antifungal treatment, a clinician should suspect such rare infections when seeing a nonfunctional adrenal mass with rapidly progressive constitutional symptoms. Presentation: 6/3/2024

6645 Paraganglioma or Benign Ectopic Thyroid Tissue?

Abstract Disclosure: J.A. Dower: None. R. MacLeod: None. B. Cardoso: None. C. Matouk: None. S. Mehra: None. G. Riccio: None. L. Williams: None. S.K. Majumdar: None. Introduction: During gestation, cells destined to form the thyroid descend through the thyroglossal duct; ectopic thyroid tissue may deposit anywhere along this route from tongue base to mediastinum (1). Less commonly, thyroid tissue can be found lateral to the duct, either alone or in association with a lymph node (2). We present a case of lateral ectopic thyroid tissue mimicking paraganglioma. Clinical Case: A healthy 32-year-old woman presented to ENT with cervical adenopathy persisting for several months after a flulike illness. FNA showed no evidence of malignancy. A neck CT with contrast ordered for further evaluation revealed a 3.2 x 2.3 x 1.5 cm enhancing mass within the right carotid space, splaying the external and internal carotid artery branches, most concerning for paraganglioma. A second, smaller lesion was noted inferiorly. Neck MRI confirmed these findings and revealed a subcentimeter T2 lesion within the right thyroid lobe. The patient was referred to endocrine for further workup. She had no symptoms of sympathetic hyperactivity and no family history suggestive of pheochromocytoma or paraganglioma. Biochemical workup was largely within normal limits: plasma metanephrines 53 pg/mL (57), normetanephrines 94 pg/mL (148), calcitonin &amp;lt;2 pg/mL, TSH 1.210 uIU/mL (0.27-4.2), FT4 1.52 ng/dL (0.8-1.7). Follow-up 24-h urine studies were also unremarkable: metanephrines 166 mcg (36-190), normetanephrines 159 mcg (35-482). Brain MRI, chest CT, and abdomen/pelvis MRI were negative for additional masses. DOTATATE PET/CT was completed to determine if the thyroid lesion was another potential paraganglioma requiring resection versus a nodule amenable to biopsy; uptake was confined to the carotid space lesions, so FNA of the thyroid nodule was considered safe. Thyroid FNA revealed FLUS with genetic testing indicating low likelihood of malignancy. The patient underwent tumor embolization followed by neck dissection with successful removal of both the larger and smaller masses identified on imaging. Frozen and permanent tissue section revealed that both masses consisted of benign thyroid tissue without associated lymphoid tissue. The patient experienced jaw pain with eating after surgery and is under consideration for Botox injection. Conclusion: Benign thyroid tissue can deposit in unexpected places, mimicking malignancy and paraganglioma, alike. Even a very thorough workup can mistake the identity of a mysterious mass; only the tissue itself can make the diagnosis.

8683 Composite Pheochromocytoma/Paraganglioma-Ganglioneuroma: Biochemical And Radiological Features

Abstract Disclosure: S. Agarwal: None. A.P. Dackiw: None. F. Nwariaku: None. J.E. Mosquera: None. L. Jia: None. M.G. Roden: None. O. Hamidi: Advisory Board Member; Self; Corcept Therapeutics. Introduction: Composite pheochromocytoma/paraganglioma with ganglioneuroma (PHEO-GN or PGL-GN) is a rare tumor consisting of chromaffin cells or ganglia tissue combined with a developmentally related neurogenic tumor. Composite tumors can be present in up to 10% of PHEO and are rare with just over 100 cases reported in published literature. We present a case series of patients with PHEO-GN and PGL-GN seen at our tertiary care center to examine their natural history, clinical, radiological, and biochemical characteristics. Methods: We conducted a retrospective longitudinal follow-up study of consecutive adult patients with histologically-proven PHEO-GN and PGL-GN seen between 2013 and 2023. We collected and summarized data on demographics, laboratory findings, radiological results, and clinical outcomes. Results: The cohort comprised 10 patients (60% women): 8 with PHEO-GN (1 diagnosed on autopsy), 1 with PGL-GN, and 1 with PHEO-ganglioneuroblastoma. The median age at diagnosis was 47 years (interquartile range [IQR], 35-60). Most (80%) tumors were discovered incidentally. The prevalence of a genetic syndrome was 40% and included multiple endocrine neoplasia (MEN) 2A, MEN 4, Neurofibromatosis 1, and hereditary PHEO-PGL syndrome due to succinate dehydrogenase type B gene mutation. Nine patients (90%) had biochemically functional tumors with adrenergic biochemical phenotype in 89% and noradrenergic in 11%. The tumor associated with MEN 4 also had dopamine secretion. The median elevation above the upper normal limit of plasma metanephrine was 7.4 (IQR, 1.6-12), 24-hour urine metanephrine was 7.12 (IQR, 3.7-8.8), plasma normetanephrine was 1.7 (IQR, 1.5-1.9), and 24-hour urine normetanephrine was 2.9 (IQR, 2.4-3.5). The median tumor size at the time of diagnosis was 4.2 cm (IQR, 3.3-5.2). The median pre-contrast HU on CT imaging was 37 HU (IQR, 20-40). The median time to surgical excision from the diagnosis was 2.7 months (IQR, 1.9-4.6). All patients that underwent surgery were alive without recurrence of disease at last follow-up visit with a median follow-up of 14.5 months (IQR, 0.5-18.4). Conclusions We present a series of 10 consecutive patients with composite PHEO-GN and PGL-GN. The prevalence of genetic syndrome (40%) was much higher than previously reported (up to 25% in prior reports). PHEO or PGL component of these tumors is commonly biochemically functional with metanephrine and normetanephrine elevation commonly seen. Metastatic or recurrent disease was not observed in our cohort, suggesting favorable outcomes after surgical resection. Presentation: 6/2/2024

12293 Dynamic Clinical Evolution: Why Patients Require Long-Term Follow-up Over Time

Abstract Disclosure: A. Attre: None. A. Syeda: None. A. Khan: None. B. Esayag-Tendler: None. Dynamic Clinical Evolution: Why Patients Require Long-Term Follow-up Over Time Introduction Primary Hyperaldosteronism (PHA) is an increasingly recognized cause of secondary hypertension amenable to specific therapy. We describe a case of PHA with change in management trajectory over time. Case A 48-year-old woman was diagnosed with PHA in 2009 based on an aldosterone level of 42.7 ng/dL, plasma renin activity of &amp;lt;0.1 ng/mL/hr, and a low potassium of 3.4 mmol/L. At that time, simultaneous adrenal venous sampling (AVS) had revealed a bilateral etiology of aldosterone excess. Original imaging with CT scan had shown fullness on both adrenal glands, and she was treated with 50mg daily spironolactone. Follow-up with CT scan in 2018 revealed similar imaging phenotype. When she established care with us in 2020, the abdomen MRI revealed a 2.5 cm x 1.9 cm right adrenal nodule. In addition, the blood pressure readings were noted to be high despite increasing doses of spironolactone to 150mg. Her laboratory results revealed aldosterone 151 ng/dL [&amp;lt; 31 ng/dL], cortisol 0.8 µg/dL, plasma renin activity 0.8 ng/mL/hr [0.2 ng/mL/hr - 1.6 ng/mL/hr], ACTH 12.5 pg/mL [7.2 pg/mL - 63.3 pg/mL], normal plasma metanephrine and a normal thyroid panel. A decision was made to repeat AVS in 2023 following Dr. Doppman’s protocol. The patient’s spironolactone was held before AVS and the plasma renin activity before the procedure was 0.4-0.8 ng/mL/hr. Results: Repeat AVS in 2023 showed mean pre-ACTH right to left lateralization index (LI) of 29.9 and mean post-ACTH LI of 9.7 (cutoff &amp;gt;4). This is concordant with the right adrenal nodule noted on imaging. The selectivity index confirmed adequate adrenal venous sampling data. Analysis of our findings confirmed right adrenal excess and left adrenal suppression compared to the IVC results. This patient underwent a laparoscopic right adrenalectomy in 2023. This patient's aldosterone levels were measured two days postoperatively and were found to be 4.2 ng/dL, showing immediate improvement. Six months postoperatively, our patient’s home and clinic blood pressures are in 120s/60s mmHg range without any medications. The aldosterone remains less than 6 ng/dL and the plasma renin activity is no longer low. Her potassium remains around 4.9 mmol/L. Discussion Based on current literature, surgical treatment is preferred when there is a confirmed unilateral cause of PHA. Adrenalectomy is recommended in patients with confirmed unilateral hyperaldosteronism especially when they do not achieve clinical and biochemical goals (renin plasma activity &amp;gt;1 ng/mL/hr, resolution of hypokalemia and optimal BP control) despite the use of MRA at appropriate doses. Suppressed renin is known to be associated with increased cardiovascular morbidity. This case serves as an important example of the need to follow patients long-term because PHA is a dynamic clinical entity that affects quality of life. Presentation: 6/3/2024