Síndrome de feocromocitoma-paraganglioma de tipo 5 como causa de hipertensión arterial en una paciente colombiana: reporte de caso / Pheochromocytoma/paraganglioma type 5 syndrome as a cause of secondary hypertension in a Colombian patient: case report

Resumen El feocromocitoma es un tumor derivado de las células de la cresta neural con la capacidad de producir sustancias simpaticomiméticas y, por ende, un cuadro clínico particular. Causa menos del 1 % de los casos de hipertensión arterial sistémica y su incidencia se estima entre 0,4 y 0,6 casos por 100.000 personas cada año, con una supervivencia media de siete años. De todos los tumores sólidos, el feocromocitoma tiene un mayor componente genético, que puede heredarse hasta en el 40 % de los casos. Una vez diagnosticada la enfermedad, se debe definir el tratamiento y el pronóstico, en parte condicionados por las variantes genéticas asociadas, en especial RET, SDHx, VHL y NF1. Se presenta el caso de una mujer joven con dolor abdominal e hipertensión arterial sistémica, a quien se le diagnosticó feocromocitoma. Al secuenciar el exoma, se identificó una variante patogénica extremadamente rara y de reciente descubrimiento: SDHA: c.1A>C (p.Met1Leu). La paciente respondió adecuadamente al tratamiento quirúrgico y continuó en seguimiento sin recurrencias. El abordaje diagnóstico de los pacientes con feocromocitoma comienza con la sospecha clínica, seguida de la medición de determinados metabolitos en sangre y orina, y, finalmente, los estudios de imagenología. Los desarrollos tecnológicos actuales permiten la aplicación de la medicina de precisión en este campo. En este caso de feocromocitoma, se identificó un componente genético importante que no solo afecta al paciente, sino también, a sus familiares. La tamización adecuada del caso índice permite identificar mutaciones y caracterizar mejor la enfermedad.

Abstract Pheochromocytoma is a tumor derived from neural crest cells able to produce sympathomimetic substances and, hence, a particular clinical picture. It is responsible for less than 1% of high blood pressure cases, with an estimated incidence between 0.4 and 0.6 cases per 100,000 people each year, and an average survival of seven years. Pheochromocytoma is a solid tumor with a high genetic component, as heritability can reach 40%. Once diagnosed, its treatment and prognosis are partly conditioned by the associated pathogenic variants that can be documented, especially those related to RET, SDHx, VHL, and NF1 genes. We present the case of a young woman with abdominal pain and high blood pressure, who was found to have a pheochromocytoma. Genetic testing detected a rare and recently discovered pathogenic variant: the SDHA:c.1A>C (p.Met1Leu). The patient responded adequately to the surgical treatment and continued the follow-up without documented recurrences. The diagnostic approach for pheochromocytoma patients must start with a clinical suspicion, followed by metabolite measurement in blood and urine, and finally, imaging. Currently, technology development allows precision medicine applicability. In this case of pheochromocytoma, recent developments in precision medicine resulted in the detection of associated genetic components involving the patient and her family. Adequate screening of the index patient is required for documenting pathogenic variants and better characterizing the disease.

Feocromocitoma y paraganglioma en un hospital pediátrico de Argentina. Serie de casos / Pheochromocytoma and paraganglioma at a children's hospital in Argentina. A case series

El feocromocitoma y el paraganglioma son tumores neuroendocrinos secretores de catecolaminas. Los feocromocitomas se originan en la médula suprarrenal, mientras que los paragangliomas son extraadrenales. Se describe una serie de casos de niños con diagnóstico anatomopatológico de feocromocitoma o paraganglioma que consultaron en un hospital pediátrico de alta complejidad de Argentina. Se incluyeron 21 pacientes, 14 varones, con una mediana de edad de 11,4 años; 8 casos con feocromocitoma y 13 casos con paraganglioma. Se presentaron con hipertensión arterial 14/21. La mayoría de los paragangliomas tuvieron localización paraaórtica (9/13). Debido a que representan una causa potencialmente curable de hipertensión arterial, la sospecha clínica es muy importante. El diagnóstico temprano y la instauración de un tratamiento antihipertensivo adecuado, que permita afrontar la cirugía con normotensión arterial, aseguran la curación en la mayoría de los casos si la resección tumoral es completa.

Pheochromocytomas and paragangliomas are neuroendocrine tumors producing catecholamines. Pheochromocytomas occur in the adrenal medulla, while paragangliomas are those that occur outside the adrenal gland. Here we describe a case series of children with a pathological diagnosis of pheochromocytoma or paraganglioma who consulted at a tertiary care children's hospital in Argentina. A total of 21 patients (14 males) were included; their median age was 11.4 years; 8 children had pheochromocytoma and 13, paraganglioma. Arterial hypertension was observed in 14/21. Most paragangliomas were para-aortic (9/13). Since they are a potentially curable cause of hypertension, clinical suspicion is very important. An early diagnosis and the initiation of an adequate antihypertensive treatment, which allows the patient to undergo surgery with normal blood pressure, ensure a cure in most cases if tumor resection is complete.

Evaluation of 99m Tc-HYNIC-TOC and 131 I-MIBG imaging in diagnosis of pheochromocytoma and paraganglioma / 基础医学与临床

Objective To evaluate 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging in clinical diag-nostic of pheochromocytoma and paraganglioma(PPGL).Methods This was a retrospective study.359 PPGL pa-tients diagnosed by pathology microscopy were included.The diagnostic sensitivity and influencing factors on 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging were analyzed.Results The positive rate of 99mTc-HYN-IC-TOC somatostatin receptor scintigraphy was 57.7%(184/319)and 131I-MIBG imaging was 83.2%(232/279).The positive rates of 99m Tc-HYNIC-TOC somatostatin receptor imaging in the adrenal glands,retroperitoneum,head and neck,heart and mediastinum,pelvis and bladder were 53.3%,62.5%,95.0%,66.7%,50.0%and 11.0%respec-tively and the positive rates of 131I-MIBG imaging were 86.7%,88.5%,45.4%,50.0%,75.0%and 33.3%respec-tively.The positive rate of the two imaging did not showed difference among patients with different genetic back-grounds(SDH,VHL,RET mutations).The median maximum diameter of tumors was 4.4(3.0,6.1)cm.and the diag-nostic sensitivity of somatostatin receptor imaging and 131 I-MIBG imaging for larger tumors(≥4.4 cm)was signifi-cantly higher than those for the smaller tumor group(＜4.4 cm)(64.0%vs.51.3%;92.3%vs.74.1%)(P＜0.01).Tumors in 19 patients(5.3%)failed to uptake neither imaging method.Conclusions This is the largest PPGL cohort in China concerning 99m Tc-HYNIC-TOC somatostatin receptor imaging and 131 I-MIBG imaging.The sensitivity of 131 I-MIBG imaging is higher than that of 99m Tc-HYNIC-TOC somatostatin receptor imaging,but for some tumors,such as head and neck paraganglioma,the latter has obvious advantages.These two imagings technol-ogies are complementary and the choice of them should depend the individual situation of patients.

Association of NSE level with clinical features in pheochromocytoma/paraganglioma / 基础医学与临床

Objective To study the relationship between serum neuron-specific enolase(NSE)and clinical features of pheochromocytoma/paraganglioma(PPGL).Methods Totally 501 PPGL patients diagnosed from January 2019 to December 2022 were divided into normal NSE group(NSE≤16.3 ng/mL)and elevated NSE group(NSE＞16.3 ng/mL).The clinical characteristics were compared between the two groups.Results Compared with normal NSE group,patients in the elevated NSE group had larger diameter in primary tumor(5.00 cm vs.4.60 cm),higher 24-hour urinary norepinephrine(NE)and 24-hour urinary dopamine(DA)levels,and a higher rate of metasta-sis(31.6%vs.13.7%)(P＜0.05).NSE level was positively correlated with the primary tumor size(r=0.131,P＜0.05),24-hour urinary NE level(r=0.195,P＜0.05)and 24-hour urinary DA level(r=0.119,P＜0.05).Conclusions The level of NSE is related to tumor size,secretion function and metastasis in PPGL patients.

Analysis of clinical features of metastatic pheochromocytoma/paraganglioma / 中华泌尿外科杂志

Objective:To explore the clinical data of patients with metastatic pheochromocytoma/paraganglioma (PPGL).Methods:The clinical data of 57 patients with metastatic pheochromocytoma/paraganglioma diagnosed and treated at Peking Union Medical College Hospital from January 2016 to June 2022 were reviewed, including 28 cases of pheochromocytoma(PCC) and 29 cases of paraganglioma(PGL). The clinical manifestations, biochemical indexes, tumour characteristics, and metastatic characteristics of the 57 patients were analysed.Results:There were 34 males and 23 females. The median age at the time of initial diagnosis was 34 (20, 54) years, 17 (29.3%) presented with concurrent metastases, and 40 (70.7%) with heterochronous metastases. The median time to presentation of metastases was 2.2 (0, 5.0) years (range 0-22 years). Adrenergic symptoms were present in 45 cases (78.6%) at the time of initial diagnosis, and the median size of the primary tumour was 6.7 (5.0, 9.0) cm. Excessive catecholamine secretion was present in 48 cases (81.4%). The most common locations of metastasis were lymph nodes (71.9%, 41/57), bone (47.3%, 27/57), lung (38.6%, 20/57), and liver (35.1%, 20/57). Metastatic PGL had more multifocal metastases than PCC [10 (34.5%) vs. 2 (7.1%), P=0.011)], was more frequently associated with SDHB mutations [13 (42.9%) vs. 3 (10.7%), P=0.008], and was more likely to have concurrent metastases [12 (41.3%) vs. 5 (17.9%), P=0.005]. Metastatic PCC primary tumours were larger compared to PGL [median length 8.9 (4.0, 17.0) cm vs. 6.1 (1.0, 15.8) cm, P=0.020]. Conclusions:Patients with PGL present with metastases over an extremely wide time span, and patients diagnosed with PPGL should be followed throughout their lives. PGL is more prone to multifocal metastases and simultaneous metastases than PCC, and PGL is more highly correlated with the SDHB mutation.

Anesthesia management of children undergoing resection of pheochromocytoma and paraganglioma / 中华麻醉学杂志

Objective:To retrospectively analyze the anesthetic management characteristics of children undergoing resection of pheochromocytoma and paraganglioma (PPGL).Methods:The clinical data from patients undergoing resection of PPGL and confirmed histologically from January 1, 2010 to June 30, 2023 were retrospectively collected. The baseline characteristics, intraoperative conditions and postoperative complications were recorded.Results:The clinical data from 47 pediatric patients were analyzed. The overall incidence of hemodynamic instability events was 68% (32 cases). Lowering preoperative blood pressure to normal levels and the maximum diameter of tumor≥6 cm was helpful in reducing the incidence of the intraoperative hemodynamic instability events ( P<0.05). Postoperative hypotension developed in 7 cases, acute left heart failure in 1 case, arrhythmia in 1 case, adrenocortical insufficiency in 4 cases, and pulmonary infection in 13 cases. Conclusions:Thorough preoperative preparation, evidence-based anesthetic management, and meticulous postoperative vital sign monitoring can increase the perioperative safety for children undergoing resection of PPGL, thereby reducing the incidence of complications.

Hereditary pheochromocytoma/paraganglioma and associated syndromes:a clinical and genetic study / 陆军军医大学学报

Objective To summarize and analyze the clinical phenotypes,hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas(PCC/PGL)and related syndromes.Methods Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled,and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection,and Sanger sequencing was applied to verify the mutation of the probands and family members.Results There were 15 patients diagnosed with hereditary PCC/PGL,including 7 cases of von Hippel-Lindau(VHL)syndrome,3 cases of multiple endocrine neoplasia type 2(MEN2),and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A(c.500G＞A),VHL2B(c.239G＞T and c.444_457del),and VHL2C(c.293A＞G)according to their clinical manifestations.All probands received surgical treatment,and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G＞C,c.1832G＞A,and c.1901G＞A missense mutations,respectively,and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy,including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families,4 patients carried SDHB mutations(SDHB:c.343C＞T,c.541-2A＞G,c.575G＞A,c.268C＞T)and 1 patient carried an SDHD mutation(SDHD:c.337_340del).Sporadic retroperitoneal PGL were most common.Conclusion More than 1/3 of PCC/PGL patients carry germline gene mutations,showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up,and genetic counseling.

Neoplasia endocrina múltiple tipo 2B: un enfoque de diagnóstico genotipo-fenotipo y abordaje terapéutico / Multiple endocrine neoplasia type 2B: A genotype-phenotype diagnostic and therapeutic approach

Resumen La neoplasia endocrina múltiple tipo 2B (MEN 2B) es un síndrome genético poco común, con una prevalencia estimada de 0,9 a 1,6 por millón de individuos y una incidencia de 1,4 a 2,6 por millón de nacidos vivos por año. Es causada por una mutación en el protooncogén RET y se caracteriza por la presencia de carcinoma medular de tiroides (CMT) en el 100 % de los casos, feocromocitoma hasta en el 50 % y características extraendocrinas como un fenotipo marfanoide, alteraciones musculoesqueléticas y dentales, neuromas mucosos, alacrimia y ganglioneuromatosis intestinal difusa con síntomas de dismotilidad esofágica y gastrointestinal. Este síndrome se asocia con una calidad de vida deteriorada y una supervivencia deficiente, debidas principalmente a la agresividad del CMT, enfermedad que usualmente es de aparición temprana o metastásica. El diagnóstico generalmente se realiza de forma tardía, lo cual retrasa el enfoque integral, que incluye tipificación genética, tratamiento quirúrgico temprano del CMT y terapias específicas como inhibidores de tirosina quinasa (ITK) en caso de CMT avanzado. La cirugía es el tratamiento principal y la única posibilidad de cura, aunque el advenimiento de las terapias dirigidas parece estar mejorando la supervivencia libre de progresión en los casos avanzados.

Abstract Multiple endocrine neoplasia type 2B (MEN 2B) is a rare genetic syndrome with an estimated prevalence of 0.9 to 1.6 per million individuals and an annual incidence of 1.4 to 2.6 per million live births. It is caused by a mutation in the RET proto-oncogene and is characterized by the presence of medullary thyroid carcinoma (MTC) in 100% of cases, pheochromocytoma in up to 50%, and extraendocrine features such as a marfanoid phenotype, musculoskeletal and dental abnormalities, mucosal neuromas, alacrimia, and diffuse intestinal ganglioneuromatosis with symptoms of esophageal and gastrointestinal dysmotility. This syndrome is associated with a diminished quality of life and poor survival, primarily due to the aggressiveness of MTC, which often presents at an early or metastatic stage. Diagnosis is often delayed, resulting in a delayed comprehensive approach that includes genetic profiling, early surgical management of MTC, and specific therapies such as tyrosine kinase inhibitors (TKIs) for advanced MTC. Surgery remains the mainstay and the only potential cure, although the advent of targeted therapies appears to improve progression-free survival in advanced cases

The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management

ABSTRACT Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.

Síndrome de feocromocitoma-paraganglioma tipo 5 asociado a mutación en el complejo de la succinato deshidrogenasa tipo A (SDHA), a propósito de un caso / Pheochromocytoma-paraganglioma type 5 syndrome associated with mutation in the succinate dehydrogenase type A complex (SDHA), a case report

Resumen Los feocromocitomas y paragangliomas son neoplasias neuroendocrinas infrecuentes que pueden producir catecolaminas. Tienen una incidencia menor a un caso por millón de habitantes. Son histológicamente benignas y muestran mínimas diferencias respecto a sus contrapartes malignas. Asimismo, son dos de las neoplasias humanas con mayor carga genética. La mutación más común es en la vía del complejo de la succinato deshidrogenasa (SDH) y, de esta, una de las que menos se reportan son las variantes de la SDH subunidad A (SDHA). Se describe el caso de un paciente con feocromocitoma y paraganglioma asociados a una mutación en SDHA y se señala su comportamiento y buena respuesta clínica al manejo quirúrgico y vigilancia activa.

Histogram analysis in the differentiation between adrenal adenomas and pheochromocytomas: the value of a single measurement / Análise por histograma para diferenciação entre adenomas da adrenal e feocromocitomas: o valor de uma medida única

Abstract Objective: To assess the diagnostic accuracy of histogram analysis on unenhanced computed tomography (CT) for differentiating between adrenal adenomas and pheochromocytomas (PCCs). Materials and Methods: We retrospectively identified patients with proven PCCs who had undergone CT examinations between January 2009 and July 2019 at one of two institutions. For each PCC, we selected one or two adenomas diagnosed within two weeks of the date of diagnosis of the PCC. For each lesion, two readers scored the size, determined the mean attenuation, and generated a voxel histogram. The 10th percentile (P10) was obtained from the conventional histogram analysis, as well as being calculated with the following formula: P10 = mean attenuation - (1.282 × standard deviation). The mean attenuation threshold, histogram analysis (observed) P10, and calculated P10 (calcP10) were compared in terms of their diagnostic accuracy. Results: We included 52 adenomas and 29 PCCs. The sensitivity, specificity, and accuracy of the mean attenuation threshold were 75.0%, 100.0%, and 82.5%, respectively, for reader 1, whereas they were 71.5%, 100.0%, and 81.5%, respectively, for reader 2. The sensitivity, specificity, and accuracy of the observed P10 and calcP10 were equal for both readers: 90.4%, 96.5%, and 92.6%, respectively, for reader 1; and 92.3%, 93.1%, and 92.6%, respectively, for reader 2. The increase in sensitivity was significant for both readers (p = 0.009 and p = 0.005, respectively). Conclusion: For differentiating between adenomas and PCCs, the histogram analysis (observed P10 and calcP10) appears to outperform the mean attenuation threshold as a diagnostic criterion.

Resumo Objetivo: Avaliar a acurácia diagnóstica da análise por histograma na tomografia computadorizada (TC) sem contraste para a diferenciação entre adenomas adrenais e feocromocitomas (FCCs). Materiais e Métodos: Identificamos, retrospectivamente, pacientes com diagnóstico de FCC confirmado que foram submetidos a exames de TC entre janeiro de 2009 e julho de 2019 em duas instituições distintas. Para cada FCC, selecionamos um ou dois adenomas diagnosticados em até duas semanas da data do diagnóstico do FCC. Para cada lesão, dois leitores pontuaram o tamanho, determinaram a atenuação média e geraram um histograma com os voxels das imagens. O percentil 10 (P10) foi obtido a partir da análise convencional do histograma, além de ser calculado com a seguinte fórmula: P10 = atenuação média - (1,282 × desvio-padrão). O limiar de atenuação média, o P10 da análise por histograma (P10 observado) e o P10 calculado (P10calc) foram comparados em termos de acurácia diagnóstica. Resultados: Foram incluídos 52 adenomas e 29 FCCs. A sensibilidade, especificidade e acurácia do limiar de atenuação média foram de 75,0%, 100,0% e 82,5% para o leitor 1, respectivamente, e de 71,5%, 100,0% e 81,5% para o leitor 2, respectivamente. A sensibilidade, especificidade e acurácia do P10 observado e do P10calc foram idênticas para os dois leitores: 90,4%, 96,5% e 92,6%, respectivamente, para o leitor 1; e 92,3%, 93,1% e 92,6%, respectivamente, para o leitor 2. O aumento da sensibilidade foi significativo para ambos os leitores (p = 0,009 e p = 0,005, respectivamente). Conclusão: Para a diferenciação entre adenomas e FCCs, a análise por histograma (P10 observado ou P10calc) parece superar o limiar de atenuação média como critério diagnóstico.

Efficacy and safety of anlotinib monotherapy and combinated therapy in the treatment of advanced pheo-chromocytoma/paraganglioma / 实用医学杂志

Objective To evaluate the efficacy and safety of anlotinib monotherapy and combined therapy in patients with advanced pheochromocytoma/paraganglioma.Methods Nine patients with advanced pheochromo-cytoma/paraganglioma(PPGL)who were admitted to the Department of Urology,Sun Yat-sen University Cancer Center from January 2018 to June 2023 were collected.Patients were divided into four groups according to different treatments:anlotinib monotherapy group(3 patients),anlotinib combined with PD-1 monoclonal antibody immuno-therapy group(3 patients),anlotinib combined with immunotherapy and chemotherapy group(2 patients),and anlotinib combined with chemotherapy group(1 patients).The effectiveness and safety of different treatment regiments of anlotinib were analyzed.Results Objective response rate(ORR):(44%),Partial response(PR):(44%),Stable disease(SD):(44%),Progressive disease(PD):(11%),Disease control rate(DCR):(89%).The ORR of 2 patients with SDH gene mutation,SDHB and SDHD respectively,was 100%.Median overall survival time(OS)was 16.3 months(IQR:11.3～21.8 months).Median progression-free survival(PFS)was 16.3 months(IQR:9.8～20.8 months).There were 2 patients with adverse events grade≥3/4,all of which were hypertension.Conclusions Anlotinib monotherapy and combined therapy have preliminary efficacy and manageable safety in the treatment of advanced pheochromocytoma/paraganglioma.

Progress in genetic research on metastatic pheochromocytoma and paraganglioma / 实用医学杂志

Metastatic pheochromocytoma and paraganglioma(MPPGL)is a rare neuroendocrine tumour in which genetic factors play an important role.In recent years,with the continuous progress of genetic testing technol-ogy,more and more susceptibility genes have been proved to be associated with MPPGL,making early identifica-tion of MPPGL possible.Recent studies have shown that genes associated with the development of MPPGL include SDHA,SDHB,SDHC,SDHD,SDHAF2,FH,MDH2,VHL,IDH1,PDH1/2,SLC25A11,GOT2,DLST,CSDE1,MAML3,H3F3A,MERTK,PCDHGC3,and KIF1B,with SDHA,SDHB,SDHC,SDHD,and SDHAF2 being the common pathogenic genes.Potential mutations affect the clinical manifestations of MPPGL,such as malignant potential and genetic prediction,which can help to better understand the clinical course and treat accordingly.Genetic testing for pheochromocytomas and paragangliomas allows for early detection of genetic syndromes and facilitates close follow-up of high-risk patients.This article provides a review of the progress of research on susceptibility genes identified in MPPGL in recent years,with a view to providing a certain theoretical basis for further related research.

Automatic radiolabeling of the norepinephrine transporter targeted tracer 18F-mFBG and evaluation of 18F-mFBG PET/CT imaging in pheochromocytoma / 中华核医学与分子影像杂志

Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.

Familial bilateral pheochromocytoma: a case report / 中华泌尿外科杂志

Familial pheochromocytoma belongs to autosomal dominant inheritance, and has complex and variable clinical manifestations. A child with bilateral PHEO was admitted to our hospital. His grandmother, father and brother were all diagnosed with PHEO, and his aunt was diagnosed with paraganglioma. The child underwent laparoscopic left partial adrenalectomy and open surgery for the contralateral tumor, and was in good postoperative condition. The blood pressure returned to normal and there was no local recurrence and metastasis during the follow-up of 8 months after the second operation.

Construction of a clinical-radiomic nomogram model for the differential diagnosis of adrenal adenoma and small diameter pheochromocytoma / 现代泌尿外科杂志

【Objective】 To effectively differentiate adrenal adenoma (AA) and small diameter pheochromocytoma (PCC) by establishing a clinical-radiomic nomogram model before surgery. 【Methods】 A total of 132 pathologically confirmed patients (45 PCC cases, 87 AA cases) were enrolled. After the features of enhanced CT were assessed, the radiomic features and related clinical indicators were extracted. Based on multiple Logistic regression, a clinical-radiomic nomogram with radiomic features and independent clinical predictors was developed. The area under the receiver operating characteristic (ROC) curve (AUC) was used for internal evaluation to compare the diagnostic effectiveness of the three models. The clinical effectiveness of the nomogram was verified with decision curve analysis (DCA). 【Results】 One of the 108 candidate features was used to construct the radiological feature score. Individualized clinical-radiomic nomogram included independent clinical factors (24 h urinary vanmandelic acid/renin/angiotensin I) and original first-order median radiological feature scores. Internal evaluation of the prediction model showed that the AUC was 0.945 (95%CI:0.906-0.984), superior to the single clinical model or radiological model in precise differentiation. DCA showed that the nomogram had the best clinical use. 【Conclusion】 The clinical-radiomic nomogram model can effectively differentiate adrenal adenoma from small diameter pheochromocytoma, which can improve the preoperative differential diagnosis and preparation.

Research advances in the clinical diagnosis and treatment of pheochromocytoma and paranganglioma / 现代泌尿外科杂志

Pheochromocytoma and paranganglioma (PPGL) is a rare neuroendocrine tumor. In recent years, the continuous development of multimodal imaging, pathonomics, genomics, transcriptomics, epigenomics, metabolism and proteomics have provided us with ideas to better understand the complex transfer mechanism of PPGL. This paper will review the precise typing system of PPGL, current research advances in the diagnosis and clinical prognosis.

Anesthetic management of a patient with type 1 neurofibromatosis and an occult pheochromocytoma: a case report

Abstract Neurofibromatosis type 1 is a complex genetic disorder affecting multiple organ systems. Cardiovascular manifestations include hypertension, often associated with concomitant pheochromocytoma. We present a hypertensive crisis during induction of anesthesia in a patient with neurofibromatosis type 1, scheduled for abdominal myomectomy, which revealed an undiagnosed pheochromocytoma. The case highlights the importance of assessing all patients with neurofibromatosis type 1 for pheochromocytoma, because if it is left undiagnosed, it can be disastrous in the setting of anesthesia and surgery.

Modified 30-Degree Head-Up Tilt Park Bench Position in Semielective Posterior Fossa Surgery in a Patient with Pheochromocytoma / Posição de banco de apoio de inclinação de cabeça para cima de 30 graus modificada em cirurgia de fossa posterior semieletiva em paciente com feocromocitoma

Von Hippel­Lindau (VHL) disease is a rare genetic disorder associated with the central nervous system and visceral organs. Pheochromocytomas occur in 10% of VHL patients, while cerebellar tumors are common tumors in VHL syndrome, with an incidence of 60%. The most common position for posterior fossa operations is the park bench or lateral decubitus position. These positions have primarily replaced the sitting position. However, the advantages of the supine position cannot be overlooked. The coexistence of pheochromocytoma and the cerebellar tumor may require modification in surgical position and anesthesia management in line with possible pathophysiological changes. We present the anesthesia management in posterior fossa surgery in patients with postponed pheochromocytoma surgery. The present case highlights the importance of a multidisciplinary team approach and anesthetic management.

A doença de Von Hippel-Lindau (VHL) é uma doença genética rara associada ao sistema nervoso central e órgãos viscerais. Feocromocitomas ocorrem em 10% dos pacientes com VHL, enquanto os tumores cerebelares são tumores comuns na síndrome de VHL, com incidência de 60%. A posição mais comum para operações da fossa posterior é o banco do parque ou posição de decúbito lateral. Essas posições substituíram principalmente a posição sentada. No entanto, as vantagens da posição supina não podem ser negligenciadas. A coexistência de feocromocitoma e tumor cerebelar pode exigir modificação da posição cirúrgica e manejo da anestesia de acordo com possíveis alterações fisiopatológicas. Apresentamos o manejo da anestesia na cirurgia da fossa posterior em pacientes com cirurgia de feocromocitoma adiada. O presente caso destaca a importância de uma abordagem de equipe multidisciplinar e do manejo anestésico.

Manifestaciones endocrinológicas en la enfermedad de Von Hippel-Lindau: revisión narrativa

La enfermedad de Von Hippel-Lindau es un síndrome neoplásico, autosómico dominante, caracterizado por una mutación germinal del gen VHL que codifica para la proteína VHL en el cromosoma 3. Esta mutación predispone al desarrollo de tumores benignos y malignos que afectan diferentes órganos, a causa de una ausencia de la inhibición de la vía de la tumo-rigénesis mediada por el factor inducible por hipoxia. La prevalencia de esta enfermedad es de 2 a 3 por 100 000 personas y las neoplasias se localizan con mayor frecuencia en retina, sistema nervioso central, cabeza y cuello, páncreas, riñón, glándula suprarrenal y órgano reproductor. Se clasifica en 2 tipos dependiendo de la presencia o ausencia de feocromocitoma. El feocromocitoma y las neoplasias pancreáticas constituyen las manifestaciones endocrinas más frecuentes. El feocromocitoma se presenta entre el 10-30% de los casos. Puede cursar desde una entidad asintomática hasta una sintomatología variable que incluye la triada clásica de cefalea, palpitaciones y diaforesis. El diagnóstico se realiza mediante pruebas bioquímicas o sus metabolitos que confirman niveles elevados de catecolaminas, y estudios imagenológicos. Las lesiones pancreáticas son con frecuencia asintomáticas y se detectan de forma incidental en estudios de imagen realizados en los pacientes con VHL. Aunque las características clínicas y bioquímicas de estas neoplasias no son patognomóni-cas, pueden ser útiles para sugerir la enfermedad VHL como la etiología subyacente.

Von Hippel-Lindau disease is an autosomal dominant neoplastic syndrome characterized by a germline mutation of the VHL gene encoding the VHL protein on chromosome 3. This mutation predisposes to the development of benign and malignant tumors that affect different organs, due to an absence of inhibition of the hypoxia-inducible factor-mediated tumorigenesis pathway. The prevalence of this disease is 2 to 3 per 100,000 people, and neoplasms are most frequently located in the retina, central nervous system, head and neck, pancreas, kidney, adrenal gland, and the organ. It is classified into 2 types depending on the presence or absence of pheochromocytoma. Pheochromocytoma and pancreatic neoplasms are the most frequent endocrine manifestations. Pheochromocytoma occurs in 1030% of cases. It can range from an asymptomatic entity to a variable symptomatology that includes the classic triad of headache, palpitations and diaphoresis. The diagnosis is made through biochemical tests that confirm high levels of catecholamines and imaging studies. Pancreatic lesions are frequently asymptomatic and are detected incidentally in imaging studies performed in VHL patients. Although the clinical and biochemical characteristics of these malignancies are not pathognomonic, they may be useful in suggesting VHL disease as the underlying etiology.