MIBG Research Articles

False-positive 123I-metaiodobenzylguanidine scintigraphy in a patient with a gastrointestinal stromal tumor presenting as a left adrenal incidentaloma.

A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. On computed tomography scan, the mass appeared to localize within the tip of the lateral limb of the left adrenal gland, and between the left adrenal gland and the posterior wall of the stomach. The plasma corticotropin and cortisol concentrations and the 24-h urine fractionated metanephrine levels were normal. 123I-metaiodobenzylguanidine scintigraphy showed tumor avidity consistent with a hormonally inactive pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal computed tomography postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a gastrointestinal stromal tumor. Clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathological analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies. Anatomic structures and tumors that develop in neighboring tissues to the adrenal glands may be confused with primary adrenal tumors. 123I- metaiodobenzylguanidine (MIBG) scintigraphy is specific for diagnosing pheochromocytomas and paragangliomas; however, it has been reported that 123I-MIBG may accumulate in neuroendocrine tumors as well as other tumors. Clinicians should recognize the limitations of imaging studies and the uncertainty of an imaging-based preoperative diagnosis.

A Report on Health Resource Use of Internal Radiation Therapy with 131I-MIBG (2nd Survey)

Internal radiation therapy using Iodine-131 metaiodobenzylguanidine (131I-MIBG) for neuroblastoma has been discussed whether a special application scheme for off-labeled drugs called "Kouchi-Shinsei" could be applied to neuroblastoma or not by the Evaluation Committee on Unapproved or Off-labeled Drug with High Medical Needs (the Committee); if the Committee determines that Kouchi-Shinsei is applicable, neuroblastoma indication is expected to be regulatory approved within a year. Since a NHI medical technical fee is not yet set for neuroblastoma, the Japanese Society of Nuclear Medicine surveyed health resource use via a questionnaire survey of medical institution that has conducted a Japanese Advanced Medical Care B clinical study in neuroblastoma. Results showed that the necessary total cost per patient is 1,847,451 JPY when calculated based on the Draft Proposal for Medical Examination Value (Ver. 7.3) of the Japanese Health Insurance Federation for Surgery. Because follow-up is necessary for 3 months after administration, it was considered that an appropriate fee per patient is 1,847,451 JPY and an appropriate NHI medical technical fee per patient is 46,186 points which can be claimed up to once a month for 4 times including the initial month of the treatment.

The Accuracy of Pre-Operative Ultrasonography in Localizing Parathyroid Adenoma for Minimally Invasive Parathyroidectomy (MIP)

OBJECTIVES To determine the sensitivity of pre-op ultrasonography in localizing parathyroid adenoma for minimally invasive parathyroidectomy (MIP) technique. METHODOLOGY The study was conducted at the department of ENT and Head & Neck Surgery, MTI Hayatabad Medical Complex Peshawar. It included a retrospective analysis of records of patients who underwent MIP from Jan 1, 2019, to July 31, 2022. All patients had pre-operative meta-iodobenzylguanidine (MIBG) scans, and serum PTH, Serum calcium levels were determined. A pre-op ultrasound scan was acquired to mark the site of the parathyroid adenoma. MIP was carried out using a 3.5 to 4 cm transverse skin incision over the marked site to expose the thyroid gland. If the marked parathyroid gland was identified without using any other aids, the result was labelled as "True positive". The sensitivity of pre-op ultrasonography was calculated using SPSS v 26.0. RESULTS A total of 53 cases were included in the study. The male: female ratio was 1:1.8. The ages of patients ranged from 23-70 years with a mean age of 48.49 years with a standard deviation of +_ 10.818. Pre-op ultrasonography accurately localizes the site of parathyroid adenoma in 49 patients. Statistical analysis showed this to be a significant finding. CONCLUSION Pre-op ultrasonography is significantly helpful in localizing the parathyroid adenoma. Therefore its routine use is recommended to help localize the adenoma in minimally invasive parathyroidectomy.

PS-BPR01-2: PHEOCHROMOCYTOMA WITH HYPERALDOSTERONISM-LINKED MUTATIONS IN THE POTASSIUM CHANNEL KCNJ5

Context: Recent advances in genetic analysis techniques have led to the genetic analysis of adrenal tumors with hormone excess. In pheochromocytomas, many genetic abnormalities have been identified. Furthermore, several causative genes have been also reported in primary aldosteronism. We performed a comprehensive genetic analysis of functional adrenal tumors using next-generation sequencing. We report here a case of pheochromocytoma with KCNJ5 gene abnormality, which is considered to be specific for primary aldosteronism. Case: A 53-year-old woman with high blood pressure since age 48, excessive sweating and weight loss since age 52, and left ventricular hypertension noted on electrocardiogram during a medical checkup presented to her previous physician. A computed tomography scan of the abdomen showed a right adrenal tumor 30 mm in diameter, and an urinary test showed high levels of urinary metanephrine and normetanephrine (1.42 mg/day) and I-123 MIBG scintigraphy showed an accumulation at the tumor. Plasma renin activity was 0.2 ng/mL/hr, plasma aldosterone concentration was 73.9 pg/mL, and a positive captopril challenge test was performed. Adrenal scintigraphy using 131 I-adosterol showed bilateral adrenal accumulation, suggesting bilateral lesions. Laparoscopic right adrenalectomy was performed for pheochromocytoma. Histology showed focal proliferation of enlarged medullary-like cells and calcification of the adjacent adrenal tissue. The tumor tissue was positive for KCNJ5 gene mutation. A postoperative captopril challenge test was performed again, which was negative. Conclusion: KCNJ5 gene abnormality is considered specific for primary aldosteronism, but was also found in pheochromocytoma. However, the contribution of KCNJ5 gene abnormality to catecholamine production is not yet elucidated. This is a case of pheochromocytoma in which coexistence of primary aldosteronism is also suspected based on the captopril challenge test and imaging findings, and the finding of a gene mutation associated with primary aldosteronism in such a case is very interesting and will warrant further investigation.

Neuroblastoma-related severe hypoperfusion in the cerebellum of an infant: A case of opsoclonus-myoclonus syndrome.

A 2-year-old girl started to wobble without any specific triggers, so the patient was admitted to our hospital's pediatric department. The entire cerebellum showed severe atrophy on MRI and much lower uptake than that in the cerebral cortex on perfusion SPECT. The diagnosis of opsoclonus-myoclonus syndrome (OMS) was suspected. MRI visualized a small mass behind the inferior vena cava. Although its uptake on I-123 MIBG scintigraphy was inconclusive, the mass was surgically removed, and the diagnosis of neuroblastoma was pathologically confirmed. OMS is one of the paraneoplastic neurological syndromes with cerebellar ataxia, myoclonus of the trunk and extremities, and opsoclonus as its main symptoms. Approximately 50% of children cases with OMS are associated with neuroblastoma. The prognosis for neuroblastoma itself with OMS is relatively good, but the neurological prognosis is very poor. If there is decreased blood flow in the cerebellum of an infant, it may be necessary to search for neuroblastoma.

PS-BPR01-10: PHEOCHROMOCYTOMA MASQUERADING AS A LONG-TERM SEVERE ANXIETY DISORDER WITH PANIC ATTACKS REFRACTORY TO PSYCHIATRIC TREATMENT

Introduction and Objective: Pheochromocytoma is often diagnosed in the workup of a patient with severe, refractory hypertension, but nowadays many silent pheochromocytomas are diagnosed in the workup of an incidental adrenal mass. Anxiety is also a common symptom in patients with pheochromocytoma and occasionally may be the only clinical manifestation. Hereby we describe the case of a patient with a severe refractory anxiety disorder as a bizarre presentation of pheochromocytoma. Design and Methods: Review of the patient's records and of the relevant literature. Results (Case Description): A 67-year old woman was referred to our Endocrinology Clinic for the workup of an incidental left adrenal mass found in an abdominal CT ordered in the nephrolithiasis workup after a renal colic. The patient had no previous relevant history of somatic disease. She had been suffering from anxiety disorder since she was 50, beginning with climacteric symptoms (hot flashes, irritability and mood swings) followed by severe anxiety, frequent panic attacks, insomnia and inability to concentrate. Hormonal replacement therapy had been ineffective. In the following 17 years she had consulted many public and private psychiatrists and had been treated with combinations of anxiolytic and antidepressant drugs including lormetazepam, clonazepam, bromazepam, vortioxetine, quetiapine, venlafaxine, agomelatine, risperidone, mirtazapine, but the patient's anxiety symptoms kept deteriorating. BP up to 180/110 mmHg and tachycardia up to 130 bpm had been recorded during anxiety crises but ABPM ruled out sustained hypertension or tachycardia. After the finding of the adrenal lesion the diagnostic process was straightforward. It was a solid, heterogeneous mass of about 6 cm diameter, with necrotic areas and mean densitometry of 86 UH. The lab workup showed normal creatinine and potassium, suppressed cortisol after 1 mg dexamethasone, normal ACTH, aldosterone, renin and aldosterone/renin ratio, but plasma metanephrines were above 5x the upper normal limit (634/2423 pg/mL). A MIBG scan confirmed intense uptake in the left adrenal area without abnormal extra-adrenal deposits. After standard preparation, the tumor was laparoscopically removed without complications. 1 month after the surgery plasma metanephrines were normal and the anxiety symptoms had vanished almost totally, but the patient kept taking a low dose of risperidone (1.5 mg/day) as a maintenance therapy; BP and HR remained normal Conclusions: Pheochromocytoma/paraganglioma should be included in the workup of patients with severe anxiety disorder, especially when refractory to treatment.

18F]mFBG PET-CT for detection and localisation of neuroblastoma: a prospective pilot study

PurposeMeta-[18F]fluorobenzylguanidine ([18F]mFBG) is a positron emission tomography (PET) radiotracer that allows for fast and high-resolution imaging of tumours expressing the norepinephrine transporter. This pilot study investigates the feasibility of [18F]mFBG PET-CT for imaging in neuroblastoma.MethodsIn a prospective, single-centre study, we recruited children with neuroblastoma, referred for meta-[123I]iodobenzylguanidine ([123I]mIBG) scanning, consisting of total body planar scintigraphy in combination with single-photon emission computed tomography-CT (SPECT-CT). Within two weeks of [123I]mIBG scanning, total body PET-CTs were performed at 1 h and 2 h after injection of [18F]mFBG (2 MBq/kg). Detected tumour localisations on scan pairs were compared. Soft tissue disease was quantified by number of lesions and skeletal disease by SIOPEN score.ResultsTwenty paired [123I]mIBG and [18F]mFBG scans were performed in 14 patients (median age 4.9 years, n = 13 stage 4 disease and n = 1 stage 4S). [18F]mFBG injection was well tolerated and no related adverse events occurred in any of the patients. Mean scan time for [18F]mFBG PET-CT (9.0 min, SD 1.9) was significantly shorter than for [123I]mIBG scanning (84.5 min, SD 10.5), p < 0.01. Most tumour localisations were detected on the 1 h versus 2 h post-injection [18F]mFBG PET-CT. Compared to [123I]mIBG scanning, [18F]mFBG PET-CT detected a higher, equal, and lower number of soft tissue lesions in 40%, 55%, and 5% of scan pairs, respectively, and a higher, equal, and lower SIOPEN score in 55%, 30%, and 15% of scan pairs, respectively. On average, two more soft tissue lesions and a 6-point higher SIOPEN score were detected per patient on [18F]mFBG PET-CT compared to [123I]mIBG scanning.ConclusionResults of this study demonstrate feasibility of [18F]mFBG PET-CT for neuroblastoma imaging. More neuroblastoma localisations were detected on [18F]mFBG PET-CT compared to [123I]mIBG scanning. [18F]mFBG PET-CT shows promise for future staging and response assessment in neuroblastoma.Trial registrationDutch Trial Register NL8152.

An atypical imaging characteristic of calvarial metastasis of neuroblastoma as multiple multi-loculated cystic masses with internal blood-fluid levels: a case report

As the third most common malignancy of childhood, Neuroblastoma has a great propensity to metastasize to multiple organs. The most common site of metastasis is the bone and bone marrow. Concerning the central nervous system, neuroblastoma usually involves the calvarium and the external dural surface. The skull metastases may show different appearances, including: multiple lytic bone lesions, bone thickening, hair-on-end periosteal reaction, irregular suture widening and/or plaque like epidural deposits. Here we present a case of metastatic neuroblastoma, appearing as multiple multi-loculated cystic epidural masses with internal blood-fluid levels as a rare imaging manifestation of calvarial metastasis. An 8-year-old boy with known history of autism, presented to the emergency department with a 3-month history of intermittent fever, malaise and myalgia and headache along with significant weight loss. Laboratory examination revealed elevated ESR and CRP and anemia. On Abdomino-Pelvic imaging a well-defined, 45*30*24mm, solid-cystic mass was observed, replacing the normal left adrenal gland. On brain MRI, multiple multi-loculated cystic, lentiform masses were observed on the external surface of cerebral hemispheric dura. Multiple fluid-fluid levels were noted in the locules in some of which the dependent fluid was hyperintense on T1w and FLAIR and hypointense on T2w sequences, compatible with blood, representing blood-fluid level. The wall and septa of the masses, enhanced after contrast administration. Associated abnormal marrow signal and aggressive type periosteal reactions were identified in the overlying bone. All of the lesions had increased uptake in MIBG scan. Bone marrow biopsy revealed small round cells, diagnostic for neuroblastoma. The patient underwent chemotherapy treatment. All calvarial/epidural metastatic lesions resolved after chemotherapy and residual adrenal tumor was resected. Cystic epidural lesions, especially when associated with adjacent abnormal bone marrow signal, or periosteal reaction and containing blood-fluid level should raise the suspicion of a calvarial metastasis.

Dual-phase 18 F-FP-CIT positron emission tomography and cardiac 123 I-MIBG scintigraphy of Parkinson's disease patients with GBA mutations: evidence of the body-first type?

Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA-PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta-iodobenzylguanidine (MIBG) uptake of GBA-PD in comparison to sPD. Through next-generation sequencing analysis targeting 41 genes, a total of 16 GBA-PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual-phase [18 F]-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (1 8 F-FP-CIT) positron emission tomography (PET)and cardiac 123 I-MIBG scintigraphy results were compared between the two groups. The GBA-PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early-phase 18 F-FP-CIT PETshowed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p=0.011) and part of the occipital cortex (p < 0.05) in the GBA-PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate-to-putamen ratio were similar between the two groups. The GBA-PD group had a lower heart-to-mediastinum uptake ratio in 123 I-MIBG scintigraphy than the sPD group. The GBA-PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non-motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA-PD than sPD. These findings suggest that GBA-PD patients have more widespread peripheral (extranigral) α-synuclein accumulation, representing a body-first PD subtype.

ODP042 Hereditary Pheochromocytoma with a Novel Mutation in the Succinate Dehydrogenase Subunit A gene

Abstract Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumorswith a diverse clinical presentation. Pathogenic variants in the genes encoding different subunits of the succinate dehydrogenaseenzyme complex that plays a central role in energy metabolism,have been linked to hereditary PPGL syndromes. Here wereport a rare case of hereditary pheochromocytoma with a novel mutation in the succinate dehydrogenase subunit A (SDHA) gene. A middle aged woman presented with left sided abdominal pain and was incidentally found to have bilateral adrenal lesions on abdominal imaging. She denied any symptoms of catecholamine excess but her plasma metanephrines level was elevated. Family history was significant for breast cancer in her motherand sister. Computed tomography (CT) scan of the abdomen showed bilateralbulky adrenal glands with a lesion in theleft adrenal gland. Magnetic resonance imaging (MRI) abdomen was performed for further characterization, the lesion measured approximately 2.8×2.6 cm with imaging characteristics suggestive of pheochromocytoma. Iodine-131 Metaiodobenzylguanidine (MIBG) whole body scan showed abnormal focal radiotracer uptake at the left adrenal gland, and she then underwentleft sided robotic adrenalectomy. Following surgery, the patient had symptomatic relief. Histopathology confirmed the diagnosis of pheochromocytoma measuring 2×2×1.5 cm with PASS (Pheochromocytoma of the Adrenal gland Scaled Score) score of 1/10, due to cellular monotony. Genetic testing revealed that she was positive for a pathogenic mutation in the SDHA gene consistent with the diagnosis of hereditary PPGL syndrome. Genetic testing was performed for the patient due to her presentation with bilateral adrenal masses and family history of cancers. Guidelines recommend genetic testing for patients with features that indicate a high likelihood of a hereditary cause for PPGL, including positive family history, syndromic features, and multifocal, bilateral, or metastatic disease. SDHA mutated PPGLs have diverse phenotypes and may be at high risk of metastasis. They are also associated with extra-adrenal tumors, include gastrointestinal stromal tumours (GIST), pituitary adenomas, papillary thyroid carcinoma, renal carcinoma and breast carcinoma. The detection of susceptibility genes for hereditary PPGL syndromes has key implications, for surveillance to detectextra-adrenal disease and recurrent tumors, as well as for consideration of genetic testing forfamily members. Presentation: No date and time listed

PSAT006 Two Cases of Pheochromocytoma Associated Takotsubo Syndrome- Importance of Early Recognition and Treatment

Abstract Introduction Pheochromocytoma is a rare catecholamine producing adrenal medullary tumor that classically presents with hypertension. Takutsubo cardiomyopathy (TC) is a rare but increasingly recognized presentation of pheochromocytoma. We present two cases of TC likely caused by pheochromocytoma. Case 1 A 60 y/o male who presented with acute onset nausea, vomiting and abdominal pain. Systolic BP was 150-160 mm Hg, and diastolic BP was 100 mmHg. Troponin was elevated (4.15 ng/ml; nl = 0-0.04). An echocardiogram showed a reduced left ventricular ejection fraction (LVEF) of 15-20% (nl = 50-75%), a mildly dilated left ventricle, and apical ballooning suggestive of TC. Coronary arteries were normal on cardiac catheterization. CT scan identified a 5.3×5.6×5.7 cm adrenal mass of 50 HU pre-contrast. Further evaluation revealed markedly elevated plasma metanephrine concentration of 858 pg/ml (nl&amp;lt;57) and normetanpehrine concentration of 1729 pg/ml (&amp;lt;148). His presentation was strongly suggestive of pheochromocytoma associated TC. He was prepared for surgery with doxazosin 2 mg twice daily followed by metoprolol succinate and metyrosine up to 500 mg/d. Final pathology revealed a 5.3 cm left pheochromocytoma with negative surgical margins. Germline genetic testing was negative for pheochromocytoma/paraganglioma pathogenic gene mutations, and an MIBG scan did not reveal metastatic disease. Echocardiogram one month after adrenalectomy showed a marked improvement in LVEF to 55-60% with no regional wall motion abnormalities, and plasma metanephrine concentrations normalized. Case 2 A 61 y/o female smoker with type 2 diabetes mellitus, hypertension, Graves disease and obesity presented with sudden onset of nausea followed by chest discomfort, bilateral shoulder discomfort and shortness of breath. Troponin was 0.6 ng/ml (nl = 0-0.04), EKG showed ST elevations in leads I, 2, V5 V6 with hyperacute T waves. Coronary arteries were normal on catheterization. She required intubation, and systolic BP ranged from 110 to 200 mm Hg. On echocardiogram the LVEF was 35% to 40% (nl = 50-75), and there was diffuse hypokinesis of the mid to apical LV myocardium with hypercontractility of the LV base, suggestive of TC. The plasma metanephrine concentration was 3.31 nmol/l (nl= 0-0.49), and normetanephrine concentration was 5.02 nmol/l (nl= 0-0.89). CT imaging revealed a 2.9 cm left adrenal mass. She underwent successful left adrenalectomy after preparation with alpha, beta blockade and metyrosine. Germline genetic testing was negative for pheochromocytoma/paraganglioma pathogenic gene mutations . Echocardiogram nine months post-adrenalectomy showed normal EF of 50-55% and resolution of apical hypokinesis. Discussion We present two pheochromocytoma patients presenting with TC that reversed following appropriate pheochromocytoma management. Few case series report the association of pheochromocytoma and TC. These patients usually present acutely without prodromal stressors commonly found with classic TC. Conclusion In the setting of TC, pheochromocytoma should be considered. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT015 A Rare Case of Incidental Massive Pheochromocytoma with Ectopic Parathyroid Hormone Secretion

Abstract Background Pheochromocytoma (PC) is a rare neuroendocrine tumor with an annual incidence of 2 to 8 cases per million that can secrete excess catecholamines precipitating hyper-adrenergic symptoms. In rarer instances, PCs can also secrete substances other than catecholamines. Case A 51-year-old female underwent MRI lumbar spine that demonstrated an incidental 13 cm right adrenal mass. History was significant for newly diagnosed hypertension and a five-year history of episodic headaches, diaphoresis, palpitations and anxiety. A previous cardiac evaluation including Holter monitor, echocardiogram, and stress test was unrevealing. Physical exam was significant only for chronic back pain and BMI 20.4. Labs revealed elevated serum catecholamines with metanephrines and normetanephrines &amp;gt;40x and &amp;gt;65x the upper limit of normal respectively, elevated urine catecholamines and elevated chromogranin A suggestive of PC. Labs also demonstrated mild hypercalcemia &amp;gt;10.3 mg/dL (8.6-10.4 mg/dL) with elevated PTH 78 pg/mL (14-64 pg/mL) and low vitamin D 25-OH 25 ng/mL (30-100 ng/mL). Calcitonin, albumin and phosphorus were normal. She was treated with non-competitive alpha and beta-blockade and metyrosine before undergoing successful right adrenalectomy. Post-operative labs demonstrated normalization of catecholamines, PTH and calcium. Surgical pathology confirmed the diagnosis of PC and demonstrated tumor cells which stained for PTH confirming ectopic PTH secretion, a rare phenomenon. The PC was very large with an elevated PASS (Pheochromocytoma of the Adrenal Gland Scaled Score) indicating increased risk for malignancy/recurrence; however, there was low Ki-67 activity and no capsular involvement, which suggested benign behavior. Furthermore, an MIBG scan was negative for metastatic disease, and an extensive genetic workup for familial PC/PGL (including MEN, RET, SDHx) was negative. Conclusion PC is a rare neuroendocrine tumor that can secrete excess catecholamines precipitating hyper-adrenergic symptoms and potentially fatal complications including hypertensive crises, cardiovascular disease, ischemia and multi-organ failure if untreated. Consequently, early recognition of PCs is imperative. The patient in this case had a five-year history of symptoms seen with PC and newly diagnosed hypertension despite normal BMI and negative cardiac workup. However, she had no evaluation for secondary causes of hypertension. Despite the large tumor size and significantly elevated catecholamines, she functioned without significant morbidity potentially due to adrenergic receptor desensitization. This case also highlights the rare phenomenon of ectopic secretion in PCs, specifically ectopic PTH secretion. A 2019 systemic review identified only 150 cases of pheochromocytomas/paragangliomas with ectopic hormone secretion – of those, only 17 secreted PTH or PTH-related peptide [1]. It is important to consider ectopic secretion in patients with PCs as they may have additional clinical manifestations associated with the hormone or substance secreted. Fortunately, this patient had no overt manifestations of hyperparathyroidism or hypercalcemia.

PSAT013 Elevated Plasma Free Metanephrines with No Evidence of Pheochromocytoma in a Patient with Multiple Endocrine Neoplasia Type 2A

Abstract Background Adrenal medullary hyperplasia (AMH) is arbitrarily defined by adrenal medullary proliferation measuring less than 1 cm while larger lesions are considered pheochromocytoma. Some patients with MEN2 present with adrenal medullary hyperplasia (AMH), which is a precursor of pheochromocytomas. Clinical Case A 22-year-old female with a past medical history of MEN2A. She is positive for germline mutation in RET proto-oncogene at 10q11.2 exon 11, position 634 from cysteine to arginine. She was evaluated for a 1cm left thyroid nodule, which required total thyroidectomy for Medullary Thyroid Cancer. Pathology revealed a 0.5cm deposit on the largest dimension, clear margins, and no angiovascular, or lymphovascular invasion, surgery was complicated by hypoparathyroidism. She complained of intermittent anxiety and fatigue but was otherwise asymptomatic. Physical examination is unremarkable except for thyroidectomy scar and multiple exostoses. On 8/5/2011 plasma-free metanephrines were elevated at 83 pg/ml (&amp;lt;57pg/ml) and Free normetanephrine was 45 pg/ml (&amp;lt;145pg/ml). Over the next years, her plasma-free metanephrine levels have been checked approximately every 6 months ranging between 63-106pg/ml with free plasma normetanephrine in normal ranges (30-81pg/ml). However, on 2/2021, her plasma normetanephrine level increased to 304pg/ml. More recently, on 11/30/2021 her free normetanephrine levels reached 671pg/ml and free Metanephrine 131pg/ml. She had two MRIs of the abdomen and pelvis over the years and both showed unremarkable adrenal glands. NM I-123 MIBG scintigraphy reported physiologic symmetric activity in the adrenal glands. Finally, she had GA-68 DOTATATE PET/CT with no suspicious radiotracer avid lesion in the abdominopelvic organs. Given the persistent elevation on plasma metanephrines, we decided to start the patient on Doxazosin prophylactically while we continue biochemical and imaging surveillance. Conclusion Our patient has a persistent elevation in plasma-free metanephrines with no evidence of pheochromocytoma in abdominal imaging. The earliest abnormality in the adrenal medulla in patients with MEN 2 is diffuse hyperplasia with a reduction in the cortical/medullary ratio (1). This hyperplasia is considered to be a precursor of pheochromocytoma in patients with MEN 2 and in our case the most likely explanation for the progressive elevation in plasma-free metanephrines (1). There is a strong molecular relationship between AMH and Pheochromocytoma (2), close monitoring for progression to pheochromocytoma is necessary for all patients with AMH. The presence of markedly elevated plasma metanephrines in an asymptomatic patient with no evidence of pheochromocytoma poses a therapeutic dilemma for preemptive use of alpha blockade and the potential need for a medical alert bracelet. References (1) Cho, K et al "Adrenal Medullary disease in Multiple Endocrine Neoplasia II". AJR 134: 23-29. (2) Korpershoek, E et al "Adrenal Medullary Hyperplasia Is a Precursor Lesion for Pheochromocytoma in MEN2 Syndrome". Neoplasia. 2014 Oct; 16(10): 868–873 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT008 Pheochromocytoma Management: Considerations for Cardiac Stress Testing

Abstract Introduction Pheochromocytomas, though rare, can have dire consequences and should be treated with timely surgical resection. Left untreated, there is high risk for developing cardiomyopathy, hemorrhagic stroke, pulmonary edema, etc. However, the resection itself has a high risk for hemodynamic instability and cardiac complications. We present a case of pheochromocytoma in a patient with multiple comorbidities who required pre-op cardiac clearance and discuss the considerations for appropriate stress test selection. Case A 60-year-old male with PMH of HTN, T2DM, CKD, OSA, and PAD s/p bilateral LE amputations was incidentally found to have a 6×5×5cm left adrenal mass on CT A/P done after a motor vehicle accident. MRI confirmed 6.6cm left adrenal mass. Lab testing showed elevated plasma fractionated catecholamines with free metanephrines 2246 (&amp;lt;57 pg/mL), free normetanephrines 1014 (&amp;lt;148 pg/mL), total metanephrines 3260 (&amp;lt;4-fold ULN of MN+NMN), aldosterone 11 (&amp;lt;28 ng/dL), plasma renin activity 0.28 (0.25-5.82 ng/mL/h), post-DST cortisol 2.7 (&amp;lt;2.0 ng/dL; 2-10 is equivocal), and chromogranin A 1449 (&amp;lt;311 ng/mL). 24-hour urine showed metanephrines 4114 (90-315 mcg/24H), normetanephrines 1174 (122-676 mcg/24H), and total metanephrines 5288 (224-832 mcg/24H). I-123 MIBG scan confirmed suspicion for pheochromocytoma. BP was elevated despite doxazosin 4mg BID, lisinopril 20mg daily, amlodipine 10mg daily, and carvedilol 37.5mg BID. He was referred to urology who planned for surgical resection pending cardiac clearance. Cardiology requested stress test to assist with pre-op risk stratification given multiple cardiac risk factors. Exercise stress test was not possible due to h/o LE amputations. Dobutamine stress test was initially recommended as this is the default testing modality at our institution but after multi-disciplinary discussion, regadenoson stress test was later selected due to concern for catecholamine surge and pheochromocytoma crisis with dobutamine use. Stress test was completed without complications and showed small reversible perfusion defect. Cardiac clearance was obtained for semi-urgent surgery. Patient tolerated left adrenalectomy and pathology confirmed pheochromocytoma. BP is now well-controlled on carvedilol 25mg BID alone. Discussion Cardiac stress testing with an underlying pheochromocytoma requires thoughtful decision making. Case reports describe cardiogenic shock, hypertensive crisis, or even death after exercise or dobutamine stress testing, possibly secondary to catecholamine surge resulting in pheochromocytoma crisis. Dobutamine is a synthetic catecholamine that stimulates both β and α1 receptors to increase inotropy and chronotropy, whereas regadenoson is a selective α2a receptor agonist that increases coronary vasodilation. In pheochromocytoma patients who require pre-op cardiac clearance, it is important to consider mechanism of action of various stress test modalities to avoid potential complications or consequent fatalities related to hemodynamic instability. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP052 Recurrent Pheochromocytoma Concerning For Surgical Seeding From Prior Partial Adrenalectomy

Abstract Introduction Surgery for a sporadic pheochromocytoma does not always lead to long-term cure, even in patients with a benign tumor, with an estimated recurrence rate of 3% (1). We present a patient with a history of pheochromocytoma s/p partial adrenalectomy 10 years prior found to have recurrence not within the adrenal parenchyma, but in the prior resection bed and diaphragm, concerning for seeding of the surgical bed from prior surgery. Clinical Case A 56-year-old man with a history of pheochromocytoma s/p a laparoscopic left partial adrenalectomy 10 years prior, with no detected rupture of the capsule at time of surgery, presented with symptoms of palpitations and anxiety. The patient had previously tested negative for SDHB, SDHD, MEN2, and VHL. Repeat labs were concerning for recurrence: 24-hour urine normetanephrines 1192 μ g (156-729 μ g) and metanephrines 204 μ g (58-276 μ g), plasma normetanephrine 479.4 pg/mL (0. 0-136.8 pg/mL), metanephrines 38.2 pg/mL (0. 0-88. 0 pg/mL), and chromogranin A 129. 0 ng/mL (0. 0-101.8 ng/mL). MRI with contrast showed a mildly enhancing mass in the left adrenalectomy postsurgical bed with no changes noted in the liver, and an I-123 MIBG scan showed focal uptake in the left adrenal gland corresponding to the mass seen on MRI as well as heterogeneous uptake in the left hepatic lobe. A DOTATE PET scan done prior was negative. The patient underwent laparoscopic left adrenalectomy; the left adrenal gland was dissected and the patient was found to have multiple satellite lesions along the left diaphragm which were excised. On pathology, immunostains were positive for chromogranin and synaptophysin. Multiple nodules of pheochromocytoma/paraganglioma were seen involving the soft tissue of the diaphragm (&amp;lt;0.1-0.6 cm) and the periadrenal soft tissue and prior resection bed (&amp;lt;0.1-2.5 cm), with no tumor seen within the residual adrenal parenchyma. The tumor extended to the cauterized tissue edges and no lymphovascular invasion was seen. No necrosis, no increased mitotic activity, no atypical mitotic figures were noted, and Ki-67 proliferation index was &amp;lt;1%. Testing done six weeks postoperatively showed plasma normetanephrine 49.9 pg/mL, metanephrine &amp;lt;10 pg/mL, and chromogranin A 87.9 ng/mL. Repeat genetic testing was negative for SDHB, SDHD, VHL, and MEN2. One year postoperatively, the patient's blood pressures are well-controlled on a small dose of doxazosin, kept on as a prophylactic measure. Conclusion This case demonstrates a rare presentation of recurrent pheochromocytoma found in the diaphragm, periadrenal tissue, and surgical bed from a prior partial adrenalectomy, concerning for recurrence in setting of surgical seeding from prior surgery. This case highlights the importance of perhaps considering a total adrenalectomy rather than partial when possible. Reference: (1) Holscher I, et al. Recurrence Rate of Sporadic Pheochromocytomas After Curative Adrenalectomy: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2021 Jan 23;106(2): 588-597. Presentation: No date and time listed

LBSAT62 Incidental Diagnosis Of Pheochromocytoma With Left Ventricle Hypertrophy And Bradycardia In A Normotensive Patient

Abstract Introduction Pheochromocytoma is a rare catecholamine secreting tumor. It can be associated with multiple endocrine neoplasia type 2(MEN 2), neurofibromatosis type 1 and von hippel-lindau syndromes(1). Case 36 year old afro american male with no pervious medical or surgical history. Drinks alcohol occasionally. no regular medications or known allergies. Family history is positive for mother with hypertension. He was referred to endocrinology clinic after incidental finding of a left adrenal mass in CT scan. The CT abdomen and pelvis with contrast showed heterogenous enhancing mass in the left adrenal gland of 5.5×4.1×5.3centimeters compressing the anterior margin of left kidney with necrotic and cystic foci. Review of systems was negative, denied headache,palpitations, seizure, sweating and weight loss. Physical examination was remarkable for bradycardia with heart rate of 50BPM. Laboratory work up was significant for high plasma metanephrine 2070 pg/ml normal less than 88, normetanephrine 1983pg/ml normal less than 110, chromogranin A 1259ng/ml normal less than 101.8, 24hr urine metanephrine 13342ug/24hr normal between 58 and 276 and 24hr urine normetanephrine 6596 ug/24hr normal between 156 and729. Thrombocytosis and macrocytic RBCs.12 Lead electrocardiogram showed sinus bradycardia 50BPM with left ventricle hypertrophy Sokolow-Lyon criteria. MRI abdomen showed 4.9×3.8×5.3 centimeters solid mass in the left adrenal gland. MIBG Scan showed intense radiotracer accumulation in the left adrenal gland. He was kept on alpha blockers for three weeks and beta blocker was added in the last week with intravenous fluids on the day of surgery. He underwent uneventful left laparoscopic adrenalectomy. Histopathology showed a 6cm focal non neoplastic pheochromocytoma in the left adrenal gland with negative surgical margins. Genetic test for MEN2A/B-RET was negative. Conclusion pheochromocytoma has a variable clinical presentations. The classis triad of episodic headache, sweating and palpitations is infrequent. It can present with electrocardiogram changes of left ventricle hypertrophy without high blood pressure. Rare cases have bradycardia. The secreted interleukins and inflammatory markers can cause thrombocytosis. Treatment is surgical resection with preoperative alpha and beta blockage. Long term follow up is recommended for the recurrence(2).

PSUN382 Hold Still – A Large Neck Paraganglioma Limiting Head Movement

Abstract Background A head and neck paraganglioma is a rare diagnosis with most cases found incidentally or diagnosed due to mass effect symptoms. Only 3.5% of them are found to secrete catecholamines leading to episodic symptoms. Herein, we present a rare case of a functioning neck paraganglioma with head movement induced hyperadrenergic paroxysms. Clinical Case A 79-year-old Caucasian man, with previous left neck mass found incidentally on imaging after a motor vehicle accident, presented to the ER with syncope. While the mass had been growing for 10 years, he sought medical attention when he could no longer turn his head to the left due to worsening symptoms. He reported recurrent brief syncopal attacks along with intermittent episodes characterized by profuse sweating, headaches, palpitations, and flushed skin. Upon evaluation, he was afebrile, tachycardic and had labile blood pressure readings (high of 340/150 mmHg and a low of 70/40 mmHg). He was oriented to time and place but appeared lethargic and underweight. A solid non-tender neck mass, with an audible bruit, was apparent at the Level II of the left neck. A CT scan of the neck showed a 7.7cm left glomus vagale tumor with partial encasement of the left internal and external carotid artery. He was admitted to the intensive care unit for close blood pressure monitoring via an intra-arterial line. Due to high suspicion for a catecholamine driven process, he was started on Doxazosin 1 mg every 12 hours which stabilized his blood pressure and improved his symptoms. CT scan of the abdomen and pelvis showed a 1.1 cm left adrenal nodule with an intensity of 4 Hounsfield units. A trial of Hyoscyamine was done to help with hypotension and symptoms of dizziness and bradycardia. Labs showed plasma catecholamines that were significantly elevated to ten times the upper limit of normal. An MIBG scan showed uptake in the left carotid mass. He was a poor surgical candidate because of the proximity of the mass to the neuro-vascular bundle and was treated with radiation during hospitalization. The patient was discharged home on Doxazosin with improvement in his blood pressure. Genetic testing was negative for a pathogenic variant but detected a variant of uncertain significance (VUS) in CDKN2A, c.373G&amp;gt;C (p.Asp125His). Unfortunately, three months later the patient was admitted with an intracranial hemorrhage secondary to a fall and was transitioned to hospice care. There was no change in the tumor size noticed during that admission. Conclusion To our knowledge, this is the first case to describe hypertension paroxysms triggered by movements of the neck in the setting of a functional neck paraganglioma. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Prognostic value of [18F]FDG-PET prior to [131I]MIBG treatment for pheochromocytoma and paraganglioma (PPGL).

Pheochromocytomas and paragangliomas (PPGLs) are rare tumors arising from the neural crest cells that form the sympathetic and parasympathetic nervous systems. Radiotherapy with [131I]metaiodobenzylguanidine (MIBG) is recommended for unresectable PPGLs. We investigated the usefulness of the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) for predicting the prognosis of patients with unresectable PPGL(s) before receiving [131I]MIBG therapy. We retrospectively analyzed the cases of 25 patients with unresectable PPGLs treated with [131I]MIBG at our hospital between 2001 and 2020. The MTV and TLG were measured in reference to liver accumulation. We divided the patients into two groups based on median values for the maximum standardized uptake value (SUVmax), MTV, and TLG, and evaluated between-group differences using log-rank tests. Cox proportional hazards models were used to determine whether there were significant differences in prognosis with respect to tumor type (pheochromocytoma vs. paraganglioma), site of metastasis, age, past treatment (chemotherapy, external radiation or [131I]MIBG treatment before the current [131I]MIBG treatment), urinary catecholamine, SUVmax, MTV, and TLG. The median follow-up time was 42months (range 2-136months). The median overall survival was 63months. The overall survival (OS) was significantly shorter in the high-MTV group (log-rank test, p = 0.049) and the high-TLG group (p = 0.049), with no significant difference between the high- and low-SUVmax groups (p = 0.19). Likewise, there was no significant difference in prognosis according to pheochromocytoma or paraganglioma, metastasis location, age, or prior chemotherapy. A history of external radiation before [131I]MIBG treatment was associated with a significantly worse prognosis (hazard ration [HR] = 7.95, p = 0.0018). Urinary adrenaline and noradrenaline were not significant prognostic factors (p = 0.70, p = 0.25, respectively), but urinary dopamine did predict a worse outcome (p = 0.022). There was no increased risk of death for higher SUVmax or TLG (p = 0.63 and 0.057, respectively), but higher MTV did predict a worse outcome (HR = 7.27, p = 0.029). High MTV and high TLG were significantly associated with a poor prognosis after [131I]MIBG therapy for PPGLs. Other treatment strategies for such patients may need to be explored.

Montreal Cognitive Assessment Predicts the Short-Term Risk of Lewy Body Disease in Isolated REM Sleep Behavior Disorder with Reduced MIBG Scintigraphy.

Long-term follow-up of isolated rapid eye movement (REM) sleep behavior disorder (IRBD) patients reveals a high risk of α-synucleinopathies. We explored the early clinical predictive factors of phenoconversion from IRBD to Parkinson's disease (PD) or dementia with Lewy bodies (DLB). We assessed baseline office-based cognitive test scores (Montreal Cognitive Assessment [MoCA-J], Mini-Mental State Examination [MMSE], and Frontal Assessment Battery [FAB]), motor function, and olfactory function in 36 consecutive polysomnography (PSG)-confirmed IRBD patients with reduced metaiodobenzylguanidine (MIBG) accumulation. PD or DLB was confirmed by medical chart review retrospectively. Of 36 IRBD patients, 19 (n=19, 52.8%) with abnormal MoCA-J score (< 26) had significantly lower scores in trail making B, phonetic verbal fluency sub-items in the executive domain, and in delayed recall in the memory domain. In total, 12 (33.3%) patients developed PD or DLB; seven of 12 patients (58.3%) developed DLB at a mean follow-up period of 6.8 years. In the normal MoCA-J group (n=17, 47.2%), two patients developed PD, but none developed dementia. Furthermore, in the abnormal MoCA-J group, seven patients developed DLB and three developed PD without dementia. The phenoconverter group had significantly lower scores in delayed recall in the memory domain compared to the disease-free group. Cox hazard analysis showed that MoCA-J was superior to MMSE. Among IRBD patients with reduced cardiac MIBG accumulation, MoCA-J score of <26 (Mild Cognitive Impairment-Lewy body) and a low sub-item score for delayed recall predicted short-term progression to probable DLB.

Patterns of Failure in High-Risk Neuroblastoma with or without Metastatic Site Irradiation

<h3>Purpose/Objective(s)</h3> Neuroblastoma is the most common extracranial malignancy diagnosed in childhood. Despite recent improvements in outcomes and an overall 5-year survival of >80%, the majority of children with high-risk neuroblastoma will relapse despite aggressive treatment. As part of their treatment paradigm, radiation treatment (RT) is recommended to the primary site after surgery, as well as to metastatic sites of disease that continue to be metaiodobenzylguanidine (MIBG)-avid post-induction chemotherapy. While there is an abundance of data supporting the former, data is limited on the role of RT to metastatic sites and thus our practice has generally been to withhold RT to metastatic sites. The aim of this study is to examine patterns of failure in patients with high-risk metastatic neuroblastoma to better determine the value of metastatic site RT. <h3>Materials/Methods</h3> We performed an IRB-approved retrospective review from our institutional database of patients with high-risk neuroblastoma who were treated from 2010-2020. The included patients had MIBG-avid metastatic disease at the time of diagnosis, as well as first relapse. These patients achieved a partial or complete response before first relapse, and did not receive total body radiation or therapy with ¹³¹I-MIBG prior to first relapse. We analyzed the patients who failed and compared the anatomical location of all sites at initial relapse to sites that were MIBG-avid on post-induction chemotherapy scan. <h3>Results</h3> With a median follow up of 38 months, 13 of the 41 patients (32%) treated during this time recurred, and 5 (12%) died. 3 patients who recurred were excluded from the analysis as they did not have sufficient records. Of the 10 patients analyzed with recurrent disease, there were 70 MIBG-avid metastatic sites on post-induction chemotherapy scan, and of these only 11 (16%) received RT. There were 13 total MIBG-avid metastatic sites at time of first recurrence, of which 6 (46%) were in original site present on post-induction chemo MIBG scan, 1 which received radiation treatment and the other 5 (38%) did not. Of the sites that did receive radiation treatment, 10/11 (91%) did not recur. In analysis per patient, 4/10 (40%) recurred initially in metastatic sites that were MIBG-avid on post-induction scan, while the remaining majority recurred in both initial and new sites or new sites only. <h3>Conclusion</h3> In this unique cohort of high-risk neuroblastoma patients who mostly did not receive RT to post-induction chemotherapy MIGB-avid metastatic sites, a little less than half of the patients and sites relapsed in initial areas, while the remaining relapsed at new sites. Those sites that were treated with RT had excellent local control >90%, consistent with prior reports. While this data suggests that RT to metastatic sites on post-induction chemotherapy MIBG scan may improve outcomes, the sample size is limited and caution must be taken to balance potential benefits with risks, especially in situations with several metastatic sites.