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.

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.

Familial hyperaldosteronism type Ⅲ(FH-Ⅲ) is extremely rare, and there are no reported cases in China. Herein, we reported two cases with FH Ⅲ, both of which presented with severe hypertension and hypokalemia in their early childhood. One patient had significantly enlarged adrenal glands and developed clinical manifestations of Cushing′s syndrome at the age of 20. Complete relief of symptoms was achieved after bilateral adrenalectomy. The other case had normal adrenal imaging, and with spironolactone treatment, blood pressure and potassium levels were well-controlled. Both cases had germline mutation of KCNJ5 gene which were c. 433G>C(p.Glu145Gln) and c. 452G>A(p.Gly151Glu), respectively.

Von Hippel-Lindau disease(VHL disease)is a hereditary tumor syndrome caused by VHL mutations.VHL disease-related tumors are often multiple and mostly treated by surgery.However,they often relapse after surgery.The VHL gene functions as a tumor suppressor through both hypoxia-inducible factor(HIF)dependent and HIF-independent pathway.Research on the genetic mechanisms of VHL disease has laid the foundation for the treatment of the disease.In recent years,the targeted drugs based on the genetic mechanism of VHL disease have provided a new approach for the treatment of the disease.Small molecule tar-geted drugs such as belzutifan and tyrosine kinase inhibitors,which act on the hypoxia signaling pathway,have shown excellent prospects for the treatment of VHL disease.The study aimed to summarize the genetic mechanisms and advances in related treatment of VHL disease.More in-depth clinical research on targeted drugs for VHL disease will provide more treatment options for the patients.

Pheochromocytomas/Paragangliomas(PPGLs)are rare neuroendocrine tumors with a high hereditary predisposition.The pseudo-hypoxic PPGLs dominated by SDHx mutations show a higher potential of metastasis.Ap-proximately 10%-17%of PPGLs develop metastasis and patients with metastatic diseases have restricted treatment options and a poor prognosis.Tumor immune microenvironment(TIME)plays a crucial role in the development and progression of tumors as well as predicting patients'prognosis and their response to immune checkpoint inhibitors.Several studies have initially characterized the immune landscape of PPGLs.This review focuses on the infiltration of immune cells,the expression of immune checkpoints in the TIME of PPGLs and their relationships with genetics and metastasis of tumors in order to better understand the mechanisms of tumor immune evasion in PPGLs and pro-vide insights to support novel treatment strategy for metastatic PPGLs.

Aldosterone-producing adenoma(APA)is one of the main causes of primary aldosteronism(PA).Cur-rent researches on its autonomous secretion of aldosterone mainly focus on the detection of somatic driver genetic mutations.However,the specific mechanisms underlying the death and proliferation of adrenal cortical cells and the occurrence and development of adenomas are still unclear.This study aims to review the research progress on the mechanisms of cell death and proliferation of APA by combining previously published studies on genomics,tran-scriptomics,metabolomics,and epigenetics related to adrenal tissues.

Objective To explore the clinical characteristics of renal paraganglioma(PGL).Methods The clinical data of a rare case of renal paraganglioma in a pediatric patient were reported and published cases of renal paragan-gliomas both domestically and internationally were reviewed.Results A 12-year-old male patient underwent surgery for a right renal mass,with histopathological confirmation revealing a renal paraganglioma.Immunohistochemical staining results were positive for CgA and S-100,while Ki-67 index showed positivity in hot spots at 20%.The SDHB stain was negative.Germline genetic testing detected a heterozygous mutation in exon 6 of the SDHB gene,c.641A＞C(p.Gln214Pro).Following surgery,local radiotherapy was administered to the operative area.A posto-perative 18 F-FDG-PET/CT scan did not reveal any metastatic lesions.A total of 15 cases of renal paraganglioma have been reported at home and abroad since 2001,of which 8 were male and 7 were female,with an average age at diagnosis being(42±17)years old.Only 5 patients had hypertension preoperatively,and only 2 pres-ented with typical clinical symptoms.Out of 8 patients who underwent catecholamine testing before surgery,only 4 demonstrated elevated levels.The maximum tumor diameter was(9.9±7.3)cm,with 67%(10 out of 15 cases)having tumors larger than or equal to 5 cm in diameter.In this group,30%(3 out of 10 cases)had tumors that were S-100 negative,and 50%(2 out of 4 cases)had tumors with a Ki-67 index of≥3%.Conclusions Renal paraganglioma is extremely rare,and some patients present without clinical symptoms and with normal catecholamine,making misdiagnosis more likely.Due to the frequent occurrence of large tumors and high Ki-67 indexes,such tumors carry a relatively higher risk of recurrence and metastasis.Therefore,close follow-up is essential after the operation.

Objective:To evaluate the ability of 68Ga-Pentixafor (nuclide ligand imaging agents for chemokine receptor 4) PET/CT to differentiate between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), and to assess how well this imaging method correlates with clinical features and postoperative outcomes. Methods:This was a cross-sectional study involving 73 APA and 12 NFA patients who received 68Ga-Pentixafor PET/CT imaging at Peking Union Medical College Hospital from August 2018 to October 2021. The receiver operating characteristic (ROC) curve was used to evaluate the differential value of visual analysis and the maximum standard uptake value (SUV max) of the focus on APA and NFA. The related factors of SUV max, and its predictive effect on postoperative outcomes were analyzed using Pearson or Spearman analysis and χ2 text. Results:68Ga-Pentixafor PET/CT imaging was positive in 64 APA patients (sensitivity=87.7%) and negative in all 12 NFA patients (specificity=100%). The area under the ROC curve with SUV max differentiating APA and NFA was 0.932 ( P<0.001). When the SUV max cut-off point was 6.23, the sensitivity was 80.8% and the specificity was 100%. The SUV max correlated positively with lesion size ( r=0.598) and aldosterone/renin activity ratio ( r=0.313) and correlated negatively with potassium level ( r=-0.286), renin activity ( r=-0.240) and age of diagnosis ( r=-0.273) (all P<0.05). Of the patients who underwent adrenalectomy and received more than 6 months of post-surgical follow-up, the clinical complete remission rate was higher for 68Ga-Pentixafor PET/CT imaging-positive patients than imaging-negative patients (24/39 vs. 0/4, P=0.031). Conclusions:68Ga-Pentixafor PET/CT is effective at differentiating between APA and NFA. The SUV max of 68Ga-Pentixafor PET/CT correlates with age at onset, lesion size, and the severity of clinical manifestations, and is able to predict postoperative outcomes.

Objective:To explore the clinical value of 68Ga-pentixafor PET/CT targeting for CXCR4 in the diagnosis and prognosis evaluation of primary aldosteronism (PA). Methods:Retrospective analysis was performed on information of 72 patients diagnosed with PA who received operations according to the results of 68Ga-pentixafor PET/CT in our hospital. There were 37 males and 35 females, with the average age of (48.3±9.5) years old. The average lesion diameter was (1.60 ± 0.54)cm. The preoperative systolic and diastolic blood pressure were (177.3 ± 23.9)mmHg and (107.6 ± 13.2)mmHg, respectively. The average preoperative potassium level was (2.62 ± 0.56)mmol/L. The average aldosterone concentration was (17.98 ± 4.66)ng/dl, and the median plasma renin activity was 0.01 (0.01, 0.09) ng/(ml·h). All patients underwent 68Ga-pentixafor PET/CT examination, which lead to the decision of surgical strategies. For those patients with single lesion, multiple lesions in one side or positive lesion in one side but negative in the opposite side, surgical resection of the positive side lesion or total adrenalectomy was considered. For those patients with bilateral positive lesions, surgical resection of the side with more significant positive lesions or total adrenalectomy was considered. For those with negative multiple lesions, the surgical strategy was designed according to the results of CT examination or AVS. The positive rate of 68Ga-pentixafor PET/CT and its relationship with the clinical characteristics and prognosis of patients were analyzed. Results:The results of 68Ga-pentixafor PET/CT were positive in 62 of 72 patients diagnosed with PA (86.1%), and the median SUVmax value was 11.1 (7.1, 16.2). The SUVmax value was positively correlated with the maximum diameter of adrenal lesion ( r=0.468) and negatively correlated with blood potassium levels ( r=-0.437), while not significantly correlated with other clinical characteristics. The positive rate of adenoma by 68Ga-pentixafor PET/CT was higher than that of nodular hyperplasia [90.5%(57/63) vs. 55.6%(5/9), P=0.018], and the SUVmax value in adenoma was also higher than that in nodular hyperplasia [11.9(7.8, 16.2) vs. 4.3(3.4, 11.3), P=0.022]. 32 cases were cured after operations, and 37 cases were improved. And 3 cases were not cured. The SUVmax value of lesions in the cured patients was higher than that in the improved patients [15.4(8.1, 22.7) vs. 10.1(6.8, 13.3), P=0.013]. Among 59 cases of PA patients with single adrenal lesions, 50 cases represented positive results of 68Ga-pentixafor PET/CT. 23 cases in 50 positive cases were cured and 27 cases were improved after resection of positive lesions. In the 13 PA patients with multiple adrenal lesions who underwent surgery according to the results of 68Ga-pentixafor PET/CT, 12 patients (92.3%) showed postoperative prognosis in line with preoperative expectations. Conclusions:68Ga-pentixafor PET/CT showed high positive rate in the diagnosis of PA, especially for adenoma.The SUVmax value of the adrenal lesion was correlated with the blood potassium level, the size of the lesion and the postoperative prognosis. In addition, 68Ga-pentixafor PET/CT could effectively guide the surgical decision of PA.

Objective:To analyze KCNJ5 mutation of adenomas in patients with aldosterone-producing adenoma (APA) companying with hypokalemia, and to compare the clinical characteristics of patients with and without KCNJ 5 mutations.Methods:Clinical data of 144 APA patients were retrospectively analyzed. DNA were extracted from adenoma tissues, and amplified and sequenced for KCNJ5 gene. The serum potassium level and cardiac complications in patients with and without KCNJ5 gene mutation were compared.Results:Among 144 tumors, 131 tumors (91%) had KCNJ5 mutation, including 68 tumors with G151R, 56 tumors with L168R, 5 tumors with E145Q, and two tumors with novel mutations, V156_K160delITE and G151delinsVR. Compared with patients without KCNJ5 mutation, patients with KCNJ5 mutation had lower preoperative serum potassium levels, more cardiac complications, lower postoperative systolic blood pressure, and better postoperative hypertension relief. There were no statistical differences in age, gender, blood pressure, serum potassium level, plasma renin activity or plasma aldosterone concertration.Conclusion:91% adenomas in patients with APA and hypokalemia had KCNJ5 mutation, suggesting that KCNJ5 mutation is the main cause in these patients.