Adrenal Pheochromocytoma Research Articles

Laparoscopic Management of Adrenal and Extra-Adrenal Pheochromocytoma

Background and Purpose Laparoscopic management of extra-adrenal pheochromocytoma requires meticulous surgical procedures because of the variable anatomic position and/or proximity to major blood vessels and the potential catecholamine surge during operation. We present our experiences with laparoscopic management of extra-adrenal pheochromocytoma and compare the intraoperative hemodynamics with those during laparoscopic resection of adrenal pheochromocytoma. Patients and Methods We retrospectively reviewed the medical records of 3 patients who underwent laparoscopic management of extra-adrenal pheochromocytoma (retrocaval, n=1; interaortocaval, n=1; periadrenal, n=1) and 24 patients who underwent laparoscopic management of adrenal pheochromocytoma between June 2005 and June 2023. We also evaluated fluctuations in blood pressure (BP) reported during both surgeries. Results The tumors were successfully resected under laparoscopic guidance in both groups, and one patient had converted to open surgery. Intraoperative hypertension (BP>200 mm Hg) was observed in 1 extra-adrenal pheochromocytoma and 13 adrenal pheochromocytoma patients, whereas intraoperative hypotension (BP <80 mm Hg) was observed in 1 extra-adrenal pheochromocytoma and 12 adrenal pheochromocytoma patients. Conclusion Laparoscopy is the method of choice for extra-adrenal resection because it is feasible and reproducible with appropriate preoperative planning, similar to adrenal resection.

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

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

Maternal pheochromocytoma and childbirth in Sweden 1973-2015: a population-based study on short and long-term outcome.

Data guiding management of pheochromocytoma and paraganglioma (PPGL) in pregnant women is limited, and long-term effects on the child are unknown. The aim of this retrospective registry-based case-cohort study was to assess how maternal PPGL and treatment impacts maternal and fetal outcome, including long-term outcome for the child. The main outcomes were maternal and fetal mortality and morbidity at delivery and relative healthcare consumption in children born by mothers with PPGL during pregnancy. The National Birth Register identified 4,390,869 pregnancies between 1973-2015. Data was crosslinked with three Swedish national registers to identify women diagnosed with pheochromocytoma or paraganglioma within one year before or after childbirth. Hospital records were reviewed and register data was collected for five age-matched controls for each child until age 18. 21 women and 23 children were identified (incidence 4.8/1.000.000 births/year), all women with adrenal pheochromocytomas (Pc). The majority (71%) were diagnosed post-partum. Nine women (43%) were hypertensive during pregnancy. Preterm delivery was more common in Pc patients compared to controls (30% vs 6%, p < 0.001). There was no maternal or fetal mortality. Timing of tumor removal did not affect gestational weight or APGAR scores. There was no observed difference in hospital admissions between children affected by maternal Pc and controls. Pc was commonly diagnosed after delivery and raised the risk of pre-term delivery, suggesting a need for an increased awareness of this diagnosis. However, reassuringly, there was no fetal or maternal mortality or any observed long-term impact on the children.

Undiagnosed adrenal pheochromocytomas in sudden death and trauma-related death: forensic issues and legal implications

Undiagnosed adrenal pheochromocytomas in sudden death and trauma-related death: forensic issues and legal implications

Chemoenzymatic Synthesis of GAA-7 Glycan Analogues and Evaluation of Their Neuritogenic Activities.

Ganglioside GAA-7 exhibits higher neurite outgrowth than ganglioside GM1a and most echinodermatous gangliosides (EGs) when tested on neuron-like rat adrenal pheochromocytoma (PC12) cells in the presence of nerve growth factor (NGF). The unique structure of GAA-7 glycan, containing an uncommon sialic acid (8-O-methyl-N-glycolylneuraminic acid) and sialic acid-α-2,3-GalNAc linkage, makes it challenging to synthesize. We recently developed a streamlined method to chemoenzymatically synthesize GAA-7 glycan and employed this modular strategy to efficiently prepare a library of GAA-7 glycan analogues incorporating N-modified or 8-methoxyl sialic acids. Most of these synthetic glycans exhibited moderate efficacy in promoting neuronal differentiation of PC12 cells. Among them, the analogue containing common sialic acid shows greater potential than the GAA-7 glycan itself. This result reveals that methoxy modification is not essential for neurite outgrowth. Consequently, the readily available analogue presents a promising model for further biological investigations.

Erythrocyte membrane-coated nanocarriers modified by TGN for Alzheimer's disease

Alzheimer's disease (AD) is an aging-related neurodegenerative disease, and the main pathological feature was β-amyloid protein (Aβ) deposition. Recently, bioactive materials-based drug delivery system has been widely investigated for the treatment of AD. In this study, we developed a red blood cells (RBC) membrane-coated polycaprolactone (PCL) nanoparticles (NPs) loading with a therapeutic agent for AD, curcumin (Cur). A functional peptide TGNYKALHPHN (TGN) was conjugated to the surface of membrane for blood-brain barrier (BBB) transport (TGN-RBC-NPs-Cur). TGN peptide can be recognized by receptors on the BBB and has great potential for brain transport. To confirm the targeted delivery of Cur to the brain, a cell co-culturing immortalized human cerebral microvascular endothelial cells and human brain astrocytes glioblastoma (hCMEC/D3 and U-118MG) in vitro model was established. As a result, the BBB transporting ratio of TGN-RBC-NPs-FITC was 29.64% at 12 h which was approximately eight-fold than RBC-NPs-FITC. The improvement of drug accumulation in the AD lesion was confirmed by the NPs modified with the BBB-penetrating peptide in the fluorescence imaging and quantitative analysis with UPLC-MS/MS in vivo. The neuroprotective effects were evaluated with new object recognition behavioral test, in vitro AD cell model, dendritic spine stain, GFAP and IBA1 immunofluorescence stain. The spatial learning and memory abilities of the AD model mice treated with TGN-RBC-NPs-Cur were obviously enhanced compared with the AD control mice and were also better than Cur at the same dosage. These results were consistent with the values of protection index of rat adrenal pheochromocytoma cells (PC12 cells) treated by Aβ25–35. TGN-RBC-NPs-Cur increased the dendritic segments densities and restrained activation of microglia and astrocytes of AD mice, as well as reversed cognitive function of AD mice. All of the results demonstrated TGN-RBC-NPs-Cur a promising therapeutic strategy for delaying the progression of AD by designing biomimetic nanosystems to deliver drugs into the brain.

Physical Stimulation Methods Developed for In Vitro Neuronal Differentiation Studies of PC12 Cells: A Comprehensive Review.

PC12 cells, which are derived from rat adrenal pheochromocytoma cells, are widely used for the study of neuronal differentiation. NGF induces neuronal differentiation in PC12 cells by activating intracellular pathways via the TrkA receptor, which results in elongated neurites and neuron-like characteristics. Moreover, the differentiation requires both the ERK1/2 and p38 MAPK pathways. In addition to NGF, BMPs can also induce neuronal differentiation in PC12 cells. BMPs are part of the TGF-β cytokine superfamily and activate signaling pathways such as p38 MAPK and Smad. However, the brief lifespan of NGF and BMPs may limit their effectiveness in living organisms. Although PC12 cells are used to study the effects of various physical stimuli on neuronal differentiation, the development of new methods and an understanding of the molecular mechanisms are ongoing. In this comprehensive review, we discuss the induction of neuronal differentiation in PC12 cells without relying on NGF, which is already established for electrical, electromagnetic, and thermal stimulation but poses a challenge for mechanical, ultrasound, and light stimulation. Furthermore, the mechanisms underlying neuronal differentiation induced by physical stimuli remain largely unknown. Elucidating these mechanisms holds promise for developing new methods for neural regeneration and advancing neuroregenerative medical technologies using neural stem cells.

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

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

Calycosin Protects against Focal Cerebral Ischemia/Reperfusion Injury via Inhibiting the HMGB1/TLR4/NF-κB Signaling Pathway

Background The rate of disability and mortality associated with cerebral ischemia/reperfusion injury (CIRI) is high due to limited treatment options, making it a major challenge to clinical management. Calycosin is a biologically active compound hostile to inflammatory, neuroprotective, and tumor effects. Whether calycosin has an ischemia/reperfusion effect or mechanism is unclear. Materials and Methods For in vivo experiments, we randomly divided rats into five groups: blank control group, middle cerebral artery occlusion/reperfusion (MCAO/R) surgical group, calycosin + MCAO/R group (5 mg/kg), calycosin + MCAO/R group (10 mg/kg), and calycosin + MCAO/R group (20 mg/kg). Molding of the middle cerebral artery was performed. Calycosin’s neuroprotective effects were evaluated using the neurological deficit score, brain edema rate, and cerebral infarct volume. For in vitro experiments, we divided PC12 cells into five groups: blank control group, oxygen and glucose deprivation/reperfusion (OGD/R) group, calycosin + OGD/R group (1 × 10−6 mol/L), calycosin + OGD/R group (4 × 10−6 mol/L), and calycosin + OGD/R group (16 × 10−6 mol/L). The optimal concentration of calycosin on PC12 cells was determined using the cell counting kit-8 (CCK-8) cell activity assay. The expression of nuclear factor kappa-B (NF-κB)-related factors was detected using real-time quantitative polymerase chain reaction and Western blotting. Results In rats, the MCAO/R model resulted in elevated neurological deficit scores, increased brain infarct volumes, and increased brain edema rates. The OGD/R model decreased rat adrenal pheochromocytoma (PC12) cell activity, and calycosin had a significant cerebral protective effect on PC12 cells under OGD/R conditions. In addition, calycosin can inhibit the activation of the NF-κB pathway, and its neuroprotective effect may be related to the NF-κB pathway. Conclusion Calycosin can reduce focal CIRI, and the neuroprotective effect of calycosin may be related to the inhibition of the high mobility group protein 1/toll-like receptor 4 (TLR4)/NF-κB signaling pathways.

Bilateral pheochromocytoma in patients with von Hippel–Lindau syndrome: clinical and molecular genetic features

Bilateral adrenal pheochromocytoma (PCС) is extremely rare in children, with major predisposing factors being multiple endocrine neoplasia type 2 and von Hippel–Lindau syndrome. In case of bilateral PCC with underlying von Hippel–Lindau syndrome, organ-preserving surgery is preferred in view of the low malignant potential of such neoplasms. We aimed to study clinical and molecular genetic features of patients with bilateral adrenal PCCs treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation. The study included 20 patients with paraganglioma (PGL)/PCC (PPGL) who had received treatment (n = 17) or outpatient care (n = 3) at the Center over the period from 2012 to 2023. Bilateral adrenal PCC was diagnosed in 4 (20%) patients. In all these cases, the diagnosis was confirmed by histology. Molecular genetic testing was carried out at the Laboratory of Molecular Biology at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation in order to search for germline pathogenic variants in PCC/PGL susceptibility genes. The median age of the four patients with bilateral adrenal PCC was 9.5 years (range 4.5–14.6 years). All the patients were male. In one patient, synchronous bilateral PCC/PGL was observed. In 100% of the cases, arterial hypertension was diagnosed at the onset of the primary disease and was treated with alpha-blockers as part of preparation for surgery. According to the results of a 24-hour urine biochemistry test, all the patients had at least a 4-fold increase above the upper limit of normal for normetanephrine levels. Molecular genetic testing using the multiplex ligation-dependent probe amplification method revealed a pathogenic germline variant in exon 3 of the VHL gene in all the children (4/4). Hereditary PPGL was proven in 2/4 (50%) patients. In all the cases, R0/R1 resection was achieved. Organ-sparing surgery on one/two adrenal glands was performed in 3/4 cases. One out of four (25%) patients developed a local relapse 18.4 months after diagnosis. The overall survival rate in this group was 100%, with a median follow-up time of 8.1 months (range 0.8–50.2 months). Bilateral adrenal PCC is a very rare childhood tumor. A medical genetic consultation is necessary to identify tumor predisposition syndromes. A multidisciplinary team discussion of a surgical strategy is recommended, with organ-sparing surgery on one or two adrenal glands being the treatment of choice that should be carried out at centers specializing in pediatric surgical oncology. Here, we report a rare clinical case of bilateral retroperitoneal PCC/PGL in a patient with von Hippel-Lindau syndrome. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

A RARE PRESENTATION OF SMALL CELL LUNG CARCINOMA METASTASIZING TO PHEOCHROMOCYTOMA

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

Panaxadiol carbamate derivatives: Synthesis and biological evaluation as potential multifunctional anti-Alzheimer agents

It is reported that panaxadiol has neuroprotective effects. Previous studies have found that compound with carbamate structure introduced at the 3-OH position of 20 (R) -panaxadiol showed the most effective neuroprotective activity with an EC50 of 13.17 μM. Therefore, we designed and synthesized a series of ginseng diol carbamate derivatives with ginseng diol as the lead compound, and tested their anti-AD activity. It was found that the protective effect of compound Q4 on adrenal pheochromocytoma was 80.6 ± 10.85 % (15 μM), and the EC50 was 4.32 μM. According to the ELISA results, Q4 reduced the expression of Aβ25-35 by decreasing β-secretase production. Molecular docking studies revealed that the binding affinity of Q4 to β-secretase was −49.67 kcal/mol, indicating a strong binding affinity of Q4 to β-secretase. Western blotting showed that compound Q4 decreased IL-1β levels, which may contribute to its anti-inflammatory effect. Furthermore, compound Q4 exhibits anti-AD activities by reducing abnormal phosphorylation of tau protein and activation of the mitogen activated protein kinase pathway. The learning and memory deficits in mice treated with Q4in vivo were significantly alleviated. Therefore, Q4 may be a promising multifunctional drug for the treatment of AD, providing a new way for anti-AD drugs.

Primary adrenal diffuse large B cell Lymphoma with Tumor thrombus in central adrenal vein: a case report and literature review

BackgroundPrimary adrenal lymphoma (PAL) is a rare disease confined wholly or chiefly to extramural involvement. Tumor thrombus in the central adrenal vein, renal vein, and inferior vena cava has been reported in adrenal pheochromocytoma, adrenocortical carcinoma, adrenal metastasis carcinoma, and adrenal leiomyosarcoma. Primary adrenal diffuse large B cell lymphoma with tumor thrombus in the central adrenal vein has rarely been reported in the current study. ( We searched in PubMed, Web of Science databases, Embase, and Medline in the English language from 1970 to December 2022. The keywords used were “Primary adrenal lymphoma " and " tumor thrombus”.)Case presentationIn this report, we discuss the case of a 57-year-old woman who complained of abdominal discomfort following cold stimulation, low back pain, anorexia, fatigue, and weight loss for 1 year. Contrast-enhanced spiral computed tomography (CT) showed mild-to-moderate enhancement of the bilateral masses and central adrenal vein tumor thrombus. After an exhaustive study, the patient was diagnosed with primary adrenal diffuse large B-cell lymphoma. In the diagnosis of PAL, the possibility of a tumor embolism in the central adrenal vein, renal vein, or inferior vena cava should be considered, although this is rare.

Evaluation of adrenal masses using 18F-FDOPA PET/CT in patients suspected with pheochromocytoma.

Pheochromocytomas (PHEOs) are chromaffin cell-derived adrenal tumors. 6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine (18F-FDOPA) is a radiotracer taken up in neuroendocrine chromaffin cells via the L-type amino-acid transporter. 18F-FDOPA is useful in patients with PHEO. However, more information about the use of 18F-FDOPA PET/CT scan is needed. Thus, the current study investigated various PET parameters on preoperative 18F-FDOPA PET/CT scan. The 18F-FDOPA PET/CT scan findings of 29 patients who underwent adrenalectomy after PET/CT scans were evaluated according to their pathologic diagnosis. Thereafter, the patients were classified under different risk groups which were compared based on the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). In terms of histopathologic results after surgery, 24 patients presented with PHEO. The remaining 5 patients were diagnosed with adrenal cortical adenomas or adrenal medullary hyperplasia. The maximum standardized uptake value, mean standardized uptake value, tumor-to-liver ratio, and tumor-to-contralateral adrenal gland ratio of PHEOs on preoperative 18F-FDOPA PET/CT scan were higher than those of other tumors. The metabolic tumor volume (MTV) and total lesion uptake of PHEOs in the intermediate-risk group (n = 19) were higher than those in the low-risk group (n = 5). The MTV and total lesion uptake were significantly correlated with the GAPP score. Preoperative 18F-FDOPA PET/CT is helpful to identifying PHEOs. In addition, imaging interpretation using the standardized uptake value of the suspected tumor or the tumor-to-liver/contralateral adrenal gland ratio can be effective. The metabolic parameters of PHEOs are positively correlated with the GAPP score.

FRI263 Challenges In Management Of Biochemically Silent Pheochromocytoma

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

FRI179 Etiology And Morphology Of Adrenal Calcifications: Single Center Retrospective Study Of 540 Patients

Abstract Disclosure: A. Kittithaworn: None. P. Dogra: None. L. Rahimi: None. R. Sandooja: None. I. Bancos: None. Background: Adrenal calcification is discovered incidentally on imaging performed for reasons other than adrenal pathology and represents &amp;lt;1% of benign adrenal lesions. Data on the etiology and morphology of adrenal calcifications are scarce. Objective: To determine the etiology and imaging characteristics of adrenal calcification. Methods: We conducted a single-center retrospective study of patients with adrenal calcification on abdominal computed tomography between January 1st,2017 and December 31st, 2021. Medical records were reviewed for demographics, discovery mode, etiology and morphology. Subgroup analysis of patients with calcification/s associated with an adrenal mass was performed. Results: Adrenal calcification was reported in 540 patients (245, 45% women, median age 65 years (IQR 54-74). Only a minority of patients with adrenal calcifications were evaluated by an endocrinologist (167, 31%). Adrenal calcifications were discovered incidentally in 472 (87%) patients, during cancer staging imaging in 66 (12%), and evaluation of other symptoms in 2 (&amp;lt;1%). The etiology of adrenal calcification was most commonly idiopathic (390, 72%), followed by adrenal mass (112, 21%), hemorrhage (20, 6%), and granulomatous disease (8, 1.5%). Adrenal calcifications were bilateral in 34 (6%) patients and unilateral in 506 (94%), with a similar left and right distribution. Unilateral calcifications were more frequently single (399, 79%) with punctate (60%), coarse (28%), linear/curvilinear (9%), or eggshell (3%) morphology. Bilateral adrenal calcifications presented more frequently with multiple lesions (53% vs 21% in unilateral calcifications, p &amp;lt;0.0001), and were coarse (59%), punctate (29%), or linear (9%). When associated with either unilateral or bilateral adrenal mass, calcifications were either central (50, 45%), peripheral (44, 39%), septal (10, 9%), or both central and peripheral (7, 7%) in relation to the adrenal mass. Adrenal masses associated with adrenal calcifications were: adrenal adenomas in 63 (56%), myelolipomas or cysts in 28 (23%), metastases in 12 (11%), adrenal carcinomas in 4 (4%), pheochromocytomas in 2 (2%), and other rare masses in 3 (3%) patients. Patients with adrenal calcifications associated with an adrenal mass were younger at the time of diagnosis (median of 63 vs 66 years, p=0.014), and had a higher proportion of women (61% vs. 41%, p=0.0002), and were more likely to be discovered during cancer staging imaging (21% vs. 10%, p=0.003). Adrenal mass-associated calcifications were more frequently multiple rather than single lesions (46% vs. 17%, p&amp;lt;0.0001). Conclusion: Adrenal calcifications are usually unilateral single punctate or coarse lesions of unclear etiology. The majority of the adrenal masses that demonstrated calcifications were benign, however adrenal malignancy or pheochromocytomas were diagnosed in 17% of cases. Presentation: Friday, June 16, 2023

FRI230 Cystic Pheochromocytoma

Abstract Disclosure: S. Saberi: None. A 67-year-old woman presented with right abdominal tenderness, abdominal distention, gas and belching. Her blood pressure was 134/70, pulse 84 with no palpable abdominal mass. Her medical history includes depression and anxiety which developed 17 years prior and later resolved. She was diagnosed with hypertension approximately 20 years earlier initially well-controlled with candesartan-hydrochlorothiazide 16-12.5 mg daily and metoprolol succinate ER 50 mg daily. Two years prior to presentation her blood pressure rose to the 180s/90s requiring doubling of her candesartan-hydrocholorothiazide. An abdominal ultrasound was obtained which showed an abdominal mass. Subsequently, a CT of the abdomen and MRI of the abdomen with and without contrast were obtained revealing a 10 cm predominantly cystic adrenal mass with partial irregular wall thickening and nodularity causing mass effect on the inferior vena cava, liver and right kidney. Results of lab testing revealed an elevated plasma free metanephrines 1187 pg/ml (normal &amp;lt; 57 pg/ml), plasma free normetanephrines 1911 pg/ml (normal &amp;lt; 148 pg/ml), total free metanephrines and normetanephrines 3098 pg/ml (normal &amp;lt; 205 pg/ml). Her other adrenal biochemical evaluation was normal. She underwent open right adrenalectomy after adequate pre-operative blockade. Post-operatively her plasma free normetanephrines decreased to 0.47 nmol/L (normal &amp;lt; 0.90 nmol/L) and plasma free metanephrines were less than 0.20 nmol/L (normal &amp;lt; 0.50 nmol/L). Cystic Pheochromoctyoma: Spontaneous rupture of cystic pheochromocytoma can cause an adrenergic crisis. Cystic pheochromocytoma may develop due to hemorrhage within the lesion, necrosis and subsequent cyst formation (1). Patients may present with abdominal pain, GI symptoms or palpable masses rather than classic symptoms of pheochromocytoma (2).The differential diagnosis of cystic adrenal lesions includes lymphangiomas, pseudocysts of other surrounding structures (such as liver, pancreas, kidney, spleen, retroperitoneal and urachal and mesenteric cysts), dermoids, adrenal carcinoma, hydatid cysts of the adrenal glands (3).Small case series report the incidence of adrenal cysts in adrenal disease as 5.1% (4). A female predominance has been reported in prior studies (4). More commonly cystic adrenal lesions are unilateral and present in persons aged 30s-50s (2). Adrenal cysts are classified based on their origin as endothelial cysts derived from malformation of the lymphatic or arteriovenous systems, pseudocysts derived from prior hemorrhage, epithelial cysts with thin wall and serous fluid, or parasitic cysts. Necrosis and liquefaction in the adrenal lesion may lead to fluid accumulation and a cystic appearance. Large cysts are at risk for hemorrhage and rupture. All adrenal cysts require biochemical evaluation. Particular attention should be paid to predominantly cystic masses with any solid component as up to 7% of these may be malignant (5). Uniform guidelines for surgical management of these lesions have not been well established. Patients with symptoms such as abdominal pain, biochemical abnormalities, complications such as pressure on adjacent organs or rupture with cyst content leakage, suspicion of malignancy, cysts larger than 5 cm or increasing size of the cyst should be considered for surgical intervention (5, 6). In patients presenting with abdominal pain and hypertension who are found to have a cystic adrenal lesion pheochromocytoma should be considered. Presentation: Friday, June 16, 2023

FRI203 A Case Of Pseudoadrenal Tumor Mimicking Left Adrenal Pheochromocytoma

Abstract Disclosure: A. Tanabe: None. E. Sugito: None. H. Kajio: None. Approximately 50% of adrenal incidentalomas are non-functional cortical adenomas, and 25% are adrenocortical hormone-secreting adenomas and pheochromocytomas. Adrenocortical carcinomas, and pheochromocytomas which have malignant potential, need to be differentiated and removed even if the tumors are hormonally inactive. In addition to these adrenal origin tumors, anatomic structures and tumors that develop in tissues neighboring the adrenal glands (pseudoadrenal tumors) may be confused with primary adrenal tumors. The larger the tumor, the more difficult it is to determine continuity with the adrenal glands. Herein we report a patient with gastrointestinal stromal tumor (GIST) that mimicked a left adrenal pheochromocytoma. 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. The mass appeared to be in the tip of the lateral limb of the left adrenal gland and was located between the left adrenal gland and the posterior wall of the stomach. The patient had no abnormal findings other than general obesity. The blood pressure was 106/72 mmHg with antihypertensive agents. The plasma corticotropin and cortisol concentrations were normal and suppressed normally after a 1-mg overnight dexamethasone suppression test. The plasma aldosterone concentration and renin activity were increased with angiotensin receptor blocker and diuretic therapy. The 24-h urine fractionated metanephrines levels were at the upper limit of the reference range. Because the tumor showed unenhanced computed tomography (CT) attenuation of 40-50 Hounsfield units, hormonally-inactive adrenocortical carcinoma or pheochromocytoma had to be differentiated. I-123-metaiodobenylguanidine (I-123-MIBG) scintigraphy showed tumor avidity consistent with a pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal CT 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 GIST. Although it has been reported that I-123-MIBG may accumulate in tumors other than neuroendocrine tumors, reports on GISTs are rare. Lessons learned from our case include the importance of clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathologic analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies. Presentation: Friday, June 16, 2023

Pheochromocytoma: Intricate Cardiovascular Manifestations

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

Huangdi Anxiao Capsules-containing serum protects cell model from cognitive dysfunction in diabetes via inhibiting NLRP3-mediated pyroptosis

This study aims to investigate the effects and the molecular mechanism of Huangdi Anxiao Capsules(HDAX)-containing serum in protecting the rat adrenal pheochromocytoma(PC12) cells from diabetes-associated cognitive dysfunction induced by high glucose and whether the mechanism is related to the regulation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis. The PC12 cell model of diabetes-associated cognitive dysfunction induced by high glucose was established and mcc950 was used to inhibit NLRP3. PC12 cells were randomized into control, model, HDAX-containing serum, mcc950, and HDAX-containing serum+mcc950 groups. Methyl thiazolyl tetrazolium(MTT) assay was employed to determine the viability, and Hoechst 33258/PI staining to detect pyroptosis of PC12 cells. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1 beta(IL-1β) and IL-18. Western blot was employed to determine the protein levels of postsynaptic density protein 95(PSD-95), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), GSDMD-N, and cleaved cysteinyl aspartate specific proteinase-1(caspase-1), and RT-PCR to determine the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1. The immunofluorescence assay was adopted to measure the levels and distribution of NLRP3 and GSDMD-N in PC12 cells. Compared with the control group, the model group showed decreased cell proliferation, increased PI positive rate, down-regulated protein level of PSD-95, up-regulated protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1, up-regulated mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and elevated levels of IL-1β and IL-18. Compared with the model group, HDAX-containing serum, mcc950, and the combination of them improved cell survival rate and morphology, decreased the PI positive rate, down-regulated the protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1 and the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and promoted the secretion of IL-1β and IL-18. The findings demonstrated that HDAX-containing serum can inhibit the pyroptosis-mediated by NLRP3 and protect PC12 cells from the cognitive dysfunction induced by high glucose.