Pheochromocytoma Patients Research Articles

Bilateral pheochromocytomas: clinical presentation and morbidity rate related to surgery technique and genetic status.

Pheochromocytomas (PHEOs) are rare catecholamine-secreting adrenal tumors. Approximately 60-90% of bilateral PHEOs are hereditary. We retrospectively analyzed the clinical characteristics of patients with bilateral PHEOs and the morbidity rate (malignancy, tumor recurrence and adrenal insufficiency (AI) rate) related to surgery technique and genetic status of the patients. Fourteen patients (12.5%, nine women, five men) had synchronous or metachronous bilateral PHEOs (out of 112 PHEO patients who underwent surgery between 1976 and 2021). The median age at diagnosis was 32 years (9-76) (three were children). Nine patients (64.2%) presented synchronous bilateral tumors, five (35.7%) contralateral metachronous tumors, 2-12 years after the first surgical intervention; three (21.4%) were metastatic. Median follow-up: 5 years (1-41), IQR 19 months. A total of 78.5% had a germline mutation (eight RET gene with MEN2A syndrome, three VHL syndrome, three not tested). Post-surgery recurrence was noted in 16.6% of patients (one with MEN2A syndrome and metastatic PHEOs, one with VHL syndrome), with similar rates after total adrenalectomy or cortical-sparing adrenal surgery. AI was avoided in 40% after cortical-sparing surgery. Bilateral PHEOs are usually associated with genetic syndromes. The surgical technique for patients with hereditary bilateral PHEOs should be chosen based on a personalized approach, as they are at higher risk for developing new adrenal tumors requiring additional surgeries.

Clinico-pathologic profile and outcomes of pediatric endocrine patients managed by endocrine surgeons: Experience over three decades in a tertiary center in India.

Pediatric endocrine disorders requiring surgical intervention are rare and so are experienced surgeons dealing with these. The aim of the current study was to investigate disease profile and perioperative outcome of pediatric patients with surgical endocrine disorders in an endocrine surgery unit. This retrospective study (Sep 1989-Aug 2019) consisted of pediatric endocrine surgery patients (<18years) who were managed by a team of pediatric endocrinologists and endocrine surgeons at our center. Patients were divided into three cohorts consisting of a decade each. Clinico-pathologic variables, perioperative events operative and follow-up details were recorded. A total of 332 children were included and their mean age was 14.6±3.9years (M:F=1:1.6). Thyroid disorders were most prevalent (59.8%), followed by adrenal (28.2%), parathyroid (10.4%), and pancreas (1.5%). Incidence of benign, malignant, and congenital/developmental disorders were 65.4, 28.1 and 8.3, respectively. Familial association was observed in 8.9% children, which is highest among pheochromocytoma patients. Overall, 201 thyroidectomies+associated procedures, 35 parathyroidectomies, 96 adrenal and paraganglioma resections, and 5 pancreatic procedures were performed. Median hospital stay was 5.6±4.1days. The number of cases increased significantly over 3decades. Clinical profile and outcome did not vary except for significant decrease in incidence of malignant pathology (p=0.04) and increase in VHL cases (p=0.04) in the last decade though overall increase in familial cases was nonsignificant (p=0.11). No perioperative mortality was observed except for 3% after adrenalectomy. A team of dedicated endocrine surgeons and pediatric endocrinologists is effective in management of pediatric endocrine surgery.

Does Genotype-Specific Phenotype in Patients with Multiple Endocrine Neoplasia Type 2 Occur as Current Guidelines Predict?

The clinical manifestation of multiple endocrine neoplasia type 2 (MEN2) in terms of developing medullary thyroid cancer (MTC), pheochromocytoma (PCC), and/or primary hyperparathyroidism (PHPT) is related to the respective pathogenic variant of the RET proto-oncogene. The aim of this study is to retrospectively analyze the individual, genotype-dependent clinical manifestations of a large cohort of MEN2 patients. By comparing their clinical profile with currently existing evidence-based knowledge, an optimal therapy and prevention strategy in terms of prophylactic thyroidectomy and clinical follow-up could be ensured. This is a retrospective single-center study of 158 MEN2 patients who were diagnosed and/or surgically treated at a tertiary referral care center between 1990 and 2022. All participants were categorized according to their pathogenic variant of the RET proto-oncogene. Subsequently, the clinical manifestation of the disease and its time of occurrence was documented. Our analysis showed results in line with existing studies, except for a considerably lower-than-predicted occurrence of PCC in patients with V804M/L mutations. This study supports the current recommendation regarding the pathogenic variant-dependent management of this rare cancer-associated syndrome.

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.

Abstract 18626: Cardiac Malformations in a Pheochromocytoma and Paraganglioma Syndrome: Reconsidering the Origins of Structural Cardiovascular Disease

Introduction: Structural cardiovascular (CV) disease and heart failure in patients with pheochromocytoma/paraganglioma is thought to develop from catecholamines and hypertension. A syndrome of polycythemia, catecholamine-releasing paragangliomas, and resultant hypertension caused by pathogenic mosaic variants in hypoxia-inducible factor 2-alpha (HIF2A or EPAS1 ) was described. Hypothesis: We hypothesized this syndrome may have both developmental and secondary causes of structural CV disease. Methods: We evaluated CV structure and function in syndromic patients (n=10), hypertensive pheochromocytoma patients without a known syndrome (n=29), and polycythemic patients (n=29) using cardiac magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT) and compared their findings to normal volunteers. We also evaluated the mouse model via vascular casting and subsequent micro-CT or ex vivo 14 tesla MRI at embryonic, post-natal, and adult stages. We tested affected tissue from the mouse model for the genetic variant. Results: Compared to normal volunteers, hypertensive pheochromocytoma, and polycythemic patients, syndromic patients had enlarged left and right atrial appendages relative to respective atria (LAA/LA ratio 0.18 ± 0.04 p&lt;0.001; RAA/RA: 0.20 ±0.10 p=0.005) [ Table ]. We observed similar abnormalities in the mouse model and confirmed the genetic variant in the affected cardiac tissue ( Figure ). Conclusions: This study identifies a signature for distinguishing primary from secondary causes of CV disease in patients with pheochromocytoma and paraganglioma using an atrial appendage to atrial volume ratio.

FRI207 Challenges Of Pheochromocytoma Management In A Heart Failure Patient

Abstract Disclosure: M. Novitskaya: None. M. Sonbol: None. S. Jafri: None. J. Monye: None. E. Japp: None. Introduction: Successful management of pheochromocytoma in patients with heart failure requires a careful balance between blood pressure control and appropriate perioperative volume resuscitation. Clinical Case: A 38-year-old male with heart failure with reduced ejection fraction (EF 15-20%), HTN, and polysubstance use disorder presented with dyspnea and subsequent in-house PEA arrest. Whole body CT showed an incidental 7.3 cm left adrenal mass. Laboratory work-up was notable for elevated plasma free metanephrines 47.30 nmol/L (n&amp;lt;0.89) and normetanephrines 39.8 nmol/L (n&amp;lt;0.49). Medical management of presumed pheochromocytoma was initiated with doxazosin. Left and right heart catheterization showed elevated intracardiac filling pressures (mmHg): RA 10, RV 66/5 (12), PA 55/29 (43), PCWP 35. Subsequent coronary angiogram was aborted due to hypertensive emergency and flash pulmonary edema for which he required IV hydralazine 20 mg, furosemide 80 mg, labetalol 30 mg, verapamil 5 mg, nitroglycerin 800 mg bolus then gtt at 100 mcg/min to achieve hemodynamic stability. He reached the preoperative BP goal after up titration of doxazosin to 12 mg daily and carvedilol to 25 mg twice daily. He subsequently underwent left adrenalectomy. Intraoperatively, the patient’s abdomen was insufflated to 13 mmHg given his reduced EF, and he received 2 L crystalloid prior to adrenal vein division. After a left adrenalectomy, he developed hypotension despite receiving an additional 3 L crystalloid, and was started on norepinephrine, epinephrine, and vasopressin gtt. Postoperatively, he remained intubated for two days due to distributive shock. With continued diuresis, mean arterial pressure recovered to &amp;gt;65 mmHg and he was extubated. He was successfully discharged on metoprolol succinate 25 mg, spironolactone 25 mg and losartan 25 mg daily. Clinical Lessons: Preoperative management of pheochromocytoma involves alpha-adrenergic blockade followed by beta-adrenergic blockade to target a BP of &amp;lt;130/80. A high sodium diet is recommended after adequate alpha-adrenergic blockade, and volume resuscitation is started preoperatively due to vasodilation after adrenalectomy. Successful management of patients with pheochromocytoma and heart failure requires extra attention to BP and volume status. Our patient’s case was complicated by severe HTN during cardiac catheterization resulting in flash pulmonary edema, and postoperative hypotension requiring vasopressor support due to loss of circulating catecholamines. His estimated risk of morbidity/mortality from adrenalectomy was &amp;gt;25% due to these factors. Multidisciplinary collaboration among endocrinologists, cardiologists, anesthesiologists, surgeons, and perfusionists is crucial to optimize patient outcomes. This patient case adds to the literature in presenting a positive adrenalectomy outcome in a patient with heart failure. Presentation: Friday, June 16, 2023

Transferrin receptor levels and its rare variant are associated with human obesity.

Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown. To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon-sequencing and genetic assessments were conducted of a case-control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole-exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis. TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild-type. Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.

Expression of endocan and vascular endothelial growth factor and their correlation with histopathological prognostic parameters in pheochromocytoma.

Endocan and vascular endothelial growth factor (VEGF) are markers expressed in various cancer types that are highly vascular, and they have prognostic significance for these cancers. In this study, we aimed to show the expression of endocan and VEGF in pheochromocytoma tumor tissues and to evaluate their correlations with histopathological parameters. Thirty-eight patients who had been operated for pheochromocytoma were included in the study. As the control group, 28 subjects whose specimens contained normal adrenal medulla tissue were included. The formalin-fixed paraffin-embedded specimens of pheochromocytoma patients were evaluated for Pheochromocytoma of the Adrenal gland Scaled Score (PASS). Sections were then stained for immunohistochemical analysis. The degree of endocan and VEGF positivity was determined by the proportion of stained cells on a negative to strong scale. Endocan (p < 0.001) and VEGF (p = 0.004) expressions were found to be significantly higher in the pheochromocytoma group than in the control group. In the pheochromocytoma group, total PASS score (r = 0.714; p < 0.001) and most of the PASS score components were positively correlated with the level of endocan expression. Median Ki-67 index (p = 0.010), total PASS score (p < 0.001), tumor cell spindling (p = 0.048), and nuclear pleomorphism (p = 0.030) were higher in pheochromocytoma with VEGF expression than in those without. If our findings are supported by studies with a larger sample size, we think that endocan has the potential to be used both as a tumor marker and in predicting malignancy potential in patients with pheochromocytoma, and that the detection of VEGF expression in these tumors is also associated with an increase in malignancy potential.

The role of MIBG scan in the diagnosis of pheochromocytoma.

e15064 Background: Pheochromocytoma is an uncommon adrenal medulla tumor. Metaiodobenzylguanidine (MIBG) scintigraphy is the current gold standard functional imaging method for evaluating pheochromocytoma, due to its excellent 100% specificity, 80% sensitivity, and general availability. In addition to establishing an extension evaluation and monitoring medication efficacy, MIBG scintigraphy is essential to confirm the diagnosis of suspected pheochromocytoma, especially when there is a tumor-like adrenal mass whose etiology is to be determined and biopsy is contraindicated given the risk of catecholamine discharge with hypertensive flare and the risk of bleeding. Our aims are to determine the efficacy of scintigraphy in the diagnosis of pheochromocytoma by examining the epidemiological characteristic and uptake patterns of the disease. Methods: In a retrospective analysis from January 2010 to December 2020, we examined pheochromocytoma patients medical records who had been referred for MIBG scintigraphy to the regional western Algerian Nuclear Medicine department at the University Hospital Center of Tlemcen. Prior to a progressive intravenous injection of 40–80 MBq of l-MIBG, patients underwent preparation (discontinuation of interfering drugs with I-MIBG especially antihypertensive treatment, thyroid blocking, and hydration). Imaging acquisition was carried out 48 and 72 hours later. Results: Fifty patients with probable pheochromocytoma (sex ratio = 0,78; mean age = 43 [17-74] years) completed I-MIBG scintigraphy prior to adrenalectomy. The MIBG scan has a high specificity and positive predictive value (100%). It confirms the presence of pheochromocytoma in 21 cases (42%), even if the metanephrine is normal in a patient with a non-secreting pheochromocytoma. In 18 cases, the main pattern is a single, homogenous, and intense intra-abdominal uptake. For the three remaining patients, a voluminous and heterogeneous uptake with a photopenic center that was associated to a necrotic adrenal mass larger than 10 cm in size, seen on abdominal Computerized Tomography (CT). In this retrospective analysis, no cases of metastatic or multiple diseases were documented. The sensitivity and negative predictive value are 84% and 86%, respectively. In 29 patients (58%), the scan reveals no abnormalities in uptake. This is attributed, in part, to 30% false positive biology (sampling conditions of urinary and/or plasmatic metanephrines and/or normetanephrines), 20% false positive CT imaging (differential diagnosis of adrenal mass: benign or malignant adrenal nodule), and 8% false negative MIBG scintigraphy (subcentimetric, cystic and necrotic lesion). Conclusions: Due to its exceptional specificity, robust sensitivity, and whole-body staging, MIBG scintigraphy—along with biology and morphology imaging—is a crucial noninvasive diagnostic method for the management of pheochromocytoma prior to adrenalectomy.

Adipose tissue plasticity in pheochromocytoma patients suggests a role of the splicing machinery in human adipose browning

Adipose tissue from pheochromocytoma patients acquires brown fat features, making it a valuable model for studying the mechanisms that control thermogenic adipose plasticity in humans. Transcriptomic analyses revealed a massive downregulation of splicing machinery components and splicing regulatory factors in browned adipose tissue from patients, with upregulation of a few genes encoding RNA-binding proteins potentially involved in splicing regulation. These changes were also observed in cell culture models of human brown adipocyte differentiation, confirming a potential involvement of splicing in the cell-autonomous control of adipose browning. The coordinated changes in splicing are associated with a profound modification in the expression levels of splicing-driven transcript isoforms for genes involved in the specialized metabolism of brown adipocytes and those encoding master transcriptional regulators of adipose browning. Splicing control appears to be a relevant component of the coordinated gene expression changes that allow human adipose tissue to acquire a brown phenotype.

Pheochromocytomas in patients with Parkinson's disease: a diagnostic and therapeutic challenge

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Adrenal Incidentaloma With the Diagnosis of Normotensive Pheochromocytoma: A Case Report

Background: Pheochromocytomas (PCCs) are catecholamine-producing neuroendocrine tumors that originate from the adrenal medulla. Their clinical presentations most commonly include hypertension, headache, palpitations, and sweating; however, PCCs are sometimes normotensive and clinically silent. Case Presentation: A female patient with abdominal pain as well as persistent and crushing left flank pain for the past six months was examined. The imaging studies revealed a mass in the upper pole of the left kidney indicative of a potential adrenal gland tumor; however, she had normal blood pressure (BP). Histopathologic examination of the mass from exploratory laparotomy showed that it was a PCC. Findings from sonography and computed tomography (CT) scan of the left adrenal tumor, along with elevated urinary normetanephrine level and positive iodine-123 metaiodobenzylguanidine (MIBG) scan led to preoperative diagnosis of PCC in our case. Conclusion: This study highlighted the importance of imaging and biochemical testing in diagnosing PCCs in patients with adrenal incidentalomas (AIs), even though they were normotensive and entirely asymptomatic.

Pseudopheochromocytoma — an epidemic of the modern world? Case series and review of literature

Background: Pseudopheochromocytoma is a condition that occurs more frequently than other diseases presenting with similar symptoms such as: paroxysmal hypertension, diaphoresis, pallor, palpitations. However, due to the lack of specific guidelines and awareness among physicians, it is widely underdiagnosed. Conventional antihypertensive treatment is ineffective in controlling symptoms which leads to decreased quality of life in patients affected by this disorder. Case presentation: In our paper, we present three female patients with paroxysmal hypertension who were admitted to the Department of Endocrinology for an investigation of suspected pheochromocytoma. The biochemical findings and imaging carried out at the hospital ruled out the diagnosis of an adrenal tumor in all three of the patients. Given the proposed criteria the clinical features of the patients were suggestive of pseudopheochromocytoma. In all three cases, the anxiolytic or SSRI treatment was applied with satisfactory symptom control. Conclusions: After ruling out pheochromocytoma in patients presenting with paroxysmal hypertension, physicians should consider a diagnosis of pseudopheochromocytoma. Management of the disorder should include anxiolytic, antidepressant, α-adrenoceptor blockers, and β-adrenoceptor blockers treatment, with close cooperation between hypertension specialist and psychiatrist or psychologist. Early proper diagnosis can reduce emotional distress related to an extensive diagnostic process as well as the overall cost of healthcare in patients with pseudopheochromocytoma.

Deliberate Compensated Vasoplegia-A Novel Pharmaceutical Approach for Controlling Blood Pressure During Surgery for Pheochromocytoma.

The most dreaded adverse event of pheochromocytoma surgery is operative severe blood pressure fluctuations. Preoperative protocols with alpha-blockade have achieved controversial results. No study to date evaluated the use of operative protocols in pheochromocytoma patients. Deliberated compensated vasoplegia (DCV) is a novel pharmaceutical regimen developed at our institution to decrease severe hypertensive events. The aim of this study is to compare outcomes of pheochromocytoma resection with and without DCV protocol. A retrospective analysis of all pheochromocytoma resections between the years 2012 and 2021 was performed. Resections performed with and without DCV protocol were compared. The primary outcome measured was the incidence of severe hypertension (MAP > 150mmHg) during surgery. Secondary outcomes included other abnormal blood pressure measurements as well as perioperative data and complications. A total of 41 resections were included, 21 performed under DCV protocol, and 20 without the protocol. Analysis demonstrated no significant difference in preoperative parameters including tumor size, catecholamine levels, and preoperative alpha-blockade protocol. The use of DCV protocol resulted in significant decrease in severe hypertension incidence from 1.95 ± 3.6 to 0.03 ± 0.13 events/h, p = 0.008. Application of the DCV protocol was not associated with any other adverse events. This study suggests that DCV anesthesia protocol significantly decreases the incidence of severe hypertensive episodes during pheochromocytoma resection. This is the first study that describes a highly effective protocol for controlling hypertension in pheochromocytoma patients.

Association Between Surgical Indication and Outcomes for Outpatient Adrenalectomy

IntroductionDespite a favorable risk-benefit profile, inpatient admission postoperatively for minimally invasive adrenalectomy (MIA) has remained common. Prior studies have shown that outpatient MIA was not associated with an increased 30-day complications or readmission. However, this has not been explored in-depth by adrenalectomy indication. We aimed to examine whether the safety profile of outpatient MIA varies by adrenal indication. Materials and MethodsClinicopathologic parameters were examined for all MIAs entered into an adrenal database at our institution from 2012 to 2021. Predictor variables included patient demographics, surgical indication, and operative time. Outcomes were 30-day emergency department visit, readmission, and complication rates between surgical indications, comparing outpatient and inpatient groups. Statistical analyses were performed using Kruskal–Wallis, Wilcoxon, Mann-Whitney, and Chi-squared tests, as appropriate. ResultsA total of 185 MIA patients were included. Outpatient MIA was performed in 53 patients (28.6%). Outpatient discharge post-MIA was related to both surgical indication and operative time. Pheochromocytoma (PC) patients were less likely to be discharged as an outpatient postoperatively when compared to all other indications (13.0% versus 33.8%, P = 0.007). Among all patients with operations 2-3 h in length, PC patients were less likely to be discharged home as an outpatient (10% versus 33.3%, P = 0.040). No significant differences were identified between outpatient and inpatient MIA groups for complications, emergency department visits, or readmission (P > 0.05 for all). Only six outpatient MIA patients had any complication (11.3%) and six were readmitted (11.3%). ConclusionsOutpatient MIA was demonstrated to be associated with similar, low complication and readmission rates compared to inpatient MIA, although it was used less often for patients with PC or prolonged operative times. Our study highlights potential evidence that outpatient MIA can be safely used in selected patients across all indications for adrenal surgery.

СИНДРОМ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ ПРИ ФЕОХРОМОЦИТОМЕ И ГОРМОНАЛЬНО-НЕАКТИВНОЙ АДРЕНОКОРТИКАЛЬНОЙ АДЕНОМЕ НАДПОЧЕЧНИКА

Introduction. The syndrome of arterial hypertension (AH) can be in patients with functioning and non-functioning masses of the adrenal glands which requires a thorough examination to exclude secon¬dary AH of origin. Aim. Identification of clinical, laboratory and radiological features of the AH syndrome in pheochromocytoma (PCC) and adrenocortical adrenal adenoma (incidentaloma). Materials and methods. A retrospective analysis of the clinic, biochemical, hormonal, radiological methods of examination was carried out in 15 patients referred for surgical treatment with a diagnosis of pheochromocytoma. During the postoperative histological examination of the removed masses of the adrenal glands, the diagnosis of PCC was confirmed in 8 out of 15 patients, in 7 patients instead of PCC, adrenocortical adenoma of was diagnosed. Results. Comparative analysis of the results of clinical, laboratory and radiological examination of patients with PCC and non-functioning adrenocortical adenoma with arterial hypertension syndrome showed that arterial hypertension syndrome in PCC has the following features: a crisis course of hypertension with its characteristic symptoms (headache, tremor, profuse sweating, palpitations), passing without treatment with the development of severe weakness after the crisis. Patients with PCC, compared with patients with adrenocortical adenoma, had a lower body mass, high levels of metanephrine, and on computed tomography (CT), the tumors were larger with high contrast uptake in the unenhanced and delayed phases. The reasons for the overdiagnosis of PCC in patients with adrenocortical adenoma in the presence of hypertension were: underestimation of clinical manifestations and an increase in the level of normetanephrine in daily urine, as well as a slight increase in the unenhanced density of contrast uptake on CT in 2 of 7 patients.

PSAT011 Biochemically Silent Pheochromocytoma in an Asymptomatic Patient with a Unilateral Lipid Poor Adrenal Adenoma

Abstract Introduction Pheochromocytomas are rare catecholamine-secreting tumors arising from the adrenal medulla, which can occur in asymptomatic patients. Diagnosis is primarily through biochemical evidence of catecholamine over secretion, however, in rare cases catecholamine levels are within normal limits. These are known as "biochemically silent" pheochromocytoma. The lack of biochemical evidence makes diagnosis particularly challenging in cases presenting as adrenal incidentalomas. We present a patient with a left adrenal incidentaloma, initially identified 10 years ago which has been slowly growing and gradually becoming biochemically active. This case illustrates how radiologic findings can alert providers to the presence of pheochromocytoma and the importance of not immediately attributing mild biochemical abnormalities to medications. Case A 50-year-old Caucasian female presented to the clinic for evaluation of a left adrenal incidentaloma discovered 10 years ago. Past medical history is significant for hypothyroidism, dyslipidemia, anxiety and depression. Patient had undergone surveillance of the adrenal nodule both radiographically and biochemically since its discovery. First available imaging is a CT Abdomen/Pelvis in 2016 that noted a 1.7cm left adrenal nodule with unenhanced attenuation value of 25.6 HU. Most recent CT Abdomen/Pelvis in June 2021 reported a 2.6cm mixed density enhancing left adrenal gland nodule with less apparent macroscopic fat, concerning for a lipid poor adenoma. Biochemical work up done previously was reported to be non-functional. In 2018, elevated 24-hr urine normetanephrine of 859mcg/24h (88-649mcg/24h) and elevated 24-hr urine total metanephrines of 955mcg/24h (182-739mcg/24h) were noted. No intervention was done at that time. In August 2021, elevated plasma normetanephrine of 308.6 pg/ml (0-136.8pg/ml), elevated urine 24hr norepinephrine of 165mcg/24h (0-135mcg/24h), and elevated urine 24 hr urine normetanephrine of 1015mcg/24h (131-612mcg/24h) were noted. Rest of the biochemical work up was negative for hyperaldosteronism, hypercortisolemia and hyperandrogenemia. Although elevations were noted in the above values, they were &amp;lt;2 fold and the patient was also taking Effexor which can falsely elevate the normetanephrine levels. However, given the increasing size of the lipid poor adenoma, the patient was referred for endocrine surgery evaluation. She was preoperatively placed on doxazosin and underwent laparoscopic surgical removal. Pathology was consistent with a 2.4cm pheochromocytoma. Postoperatively, plasma metanephrines and normetanephrines were within normal limits. Subjectively, patient reports improvement of her hot flashes, insomnia and anxiety. Conclusion This case emphasizes the importance of surveillance for a lipid poor adrenal nodule. Providers should have a high level of suspicion for pheochromocytoma in patients with a lipid poor adenoma even if they are biochemically silent. A knowledge of medications causing falsely elevated catecholamine levels is necessary, however, these should be considered along with other clinical and radiological findings. Early diagnosis is important, if pheochromocytoma remains unrecognized it can lead to high morbidity and mortality. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

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.

ODP039 Giant Cystic Pheochromocytoma and GIST in a Patient With NF-1

Abstract Introduction Neurofibromatosis-1 (NF-1) is a genetic condition known to be associated with pheochromocytoma. We report a case of giant cystic pheochromocytoma in a patient with NF-1 and hypertensionincidentally found to have gastrointestinal stromal tumor (GIST) at operation. Clinical case: A 60-years old woman presented with a 5-week history of left sided abdominal lump. Her history is significant for NF-1, flank surgery age 5 and hypertension managed by amlodipine. Examination revealed a large nontender left upper quadrant abdominal mass crossing the midline. Computed tomography showed a20. 0×13.1×21.1 cm septate cystic and/or necrotic lesion arising from the left retroperitoneum versus adrenal gland, displacing the kidney anteromedially. Plasma free metanephrine was 3.38 nM (0-0.49) normetanephrine 3.47 nM (0-0.89),urine metanephrine 2605 mcg/day (36-229), urine normetanephrine 1215 mcg/day (95-650). There were no prior images or screens for pheochromocytoma. After preoperative blockade with phenoxybenzamine, open left adrenalectomy was performed. Intraoperative blood pressure fluctuated significantly. Exophytic firm nodules were incidentally noted and removed from the jejunum. Pathology revealed a22.5×21. 0×11.9 cm pheochromocytoma weighing 3058.9 g and five 0.2-0.7 cm gastrointestinal stromal tumors, spindle type. One-month postoperative metanephrine was 0.16 with normetanephrine 0.53 nM. The blood pressure remained normal without antihypertensives. Discussion Giant cystic pheochromocytomas are rare and may be silent. In populations with NF-1 the prevalence of pheochromocytoma is 0.1-7.7% and GIST 1.2% 1–3 . Their co-existence is seen less frequently. Recommendations for pheochromocytoma screening in NF-1 vary, from only hypertensive or symptomatic patients to routinely every 3 years 2–5 . There is no screening test for GIST 1 . Our patient presented at age 60 with the rare combination of clinically giant unilateral cystic pheochromocytoma, with incidental GIST in the setting of NF-1 and hypertension . Conclusion Routine screening for pheochromocytoma in patients with NF-1, especially those with hypertension may lead to earlier diagnosis and treatment.

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.