Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism. / è‚¾ä¸Šè ºå—œé“¬ç»†èƒžç˜¤å½±å“ä¸‰æ¡ä¸»è¦ä»£è°¢é€šè·¯ï¼šåŠèƒ±æ°¨é ¸-è›‹æ°¨é ¸ä»£è°¢ã€å˜§å•¶ä»£è°¢å’Œé ªæ°¨é ¸ä»£è°¢é€šè·¯.

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.

Paraganglioma of the Neck: A Rare Case With Spinal Metastasis.

Paragangliomas are rare neuroendocrine tumors that arise from the paraganglia, which are clusters of neuroendocrine cells associated with the autonomic nervous system. These tumors are commonly found in the adrenal medulla but can also occur in other locations outside the adrenal gland. Here, we present a case report of a slow-growing paraganglioma in the left neck with spinal metastasis in a 60-year-old man. This case highlights the importance of considering paraganglion tumors in the differential diagnosis of neck masses and the need for early diagnosis and management to prevent potential complications. Importantly, both the clinical picture and anatomical location of these tumors is important when determining treatment plans.

Paraganglioma of the Right Recurrent Laryngeal Nerve Presenting as a Thyroid Nodule.

Paragangliomas are abnormal growth cells of neuroectodermal origin that arise from the autonomic nervous system. Head and neck paragangliomas are rare, commonly benign and often have a hereditary origin. Head and neck paragangliomas most commonly arise in the carotid bodies, vagus and glossopharyngeal nerves, and the sympathetic chain. However, we present a case of a paraganglioma arising from the recurrent laryngeal nerve, a phenomenon that has been reported only three times before in the literature. The patient is a 49-year-old female with a past medical history of bilateral carotid body paragangliomas and Hashimoto's disease. She has a family history of paragangliomas in her father and distant relatives and carries a pathogenic variation in the succinate-dehydrogenate subunit D (SDHD) gene, which was first identified through the original linkage studies involving her family. She presented with a mild swelling sensation in her neck. A thyroid ultrasound revealed a right lobe nodule measuring 3.3 x 2.2 x 2.1 cm. Fine needle aspiration of the nodule revealed an atypia of undetermined significance with a risk of malignancy judged as 50%. A total thyroidectomy was performed due to concern for malignancy. During the operation, the thyroid was nodular and hypervascular. At the right thyroid lobe, there was a pearlescent tubular structure approximately 4-5 mm in size. This was stimulated via intraoperative nerve monitoring and was consistent with being a part of the right recurrent laryngeal nerve. Pathology of the tubular structure revealed a 2.8 cm paraganglioma of the right recurrent laryngeal nerve. An incidental 0.1 cm papillary thyroid microcarcinoma within the left thyroid lobe was also noted. Our patient presented with a history of paragangliomas at a very young age and bilaterality, features that are highly characteristic of hereditary disease. Through the original linkage studies involving her family, her father was recognized as being an obligate carrier at risk of bearing occult paragangliomas. Imaging showed that he carried three paragangliomas. Identification of the familial SDHD syndrome as well as SDHD testing has now become widely available. Recognizing hereditary paraganglioma and other cancer susceptibility syndromes can help foster more knowledge on the subject and improve clinical outcomes. More attention should be put on the presentation of paragangliomas in an atypical location, such as in our case.

Paragangliomas Arising From the Laryngeal Paraganglia: Thyroid and Laryngeal Paragangliomas With Radiology-Pathology Correlation.

Paragangliomas are neuroendocrine tumors that arise from the embryonic neural crest cells of the extra-adrenal chromaffin and non-chromaffin cellular system. Paragangliomas arising from the laryngeal paraganglia, which occur in the thyroid and larynx, are a rare subset of paragangliomas compared to the more common locations of the carotid body, vagale, jugular, and tympanic paragangliomas. The preoperative diagnosis of both thyroid and laryngeal paragangliomas may pose a challenge due to cytological, pathological, and imaging non-specificity that overlaps with many other neoplasms. These lesions may be associated with significant intraoperative bleeding and complicated excision with adherence to nearby structures, including the recurrent laryngeal nerve. This article discusses the imaging appearance, pathological features, clinical and operative considerations and manifestations, and management of head and neck paragangliomas, as seen in two patients at our institution.

Genetic changes in the FH gene cause vagal paraganglioma.

Vagal paraganglioma (VPGL) is a rare neuroendocrine tumor that originates from the paraganglion associated with the vagus nerve. VPGLs present challenges in terms of diagnostics and treatment. VPGL can occur as a hereditary tumor and, like other head and neck paragangliomas, is most frequently associated with mutations in the SDHx genes. However, data regarding the genetics of VPGL are limited. Herein, we report a rare case of a 41-year-old woman with VPGL carrying a germline variant in the FH gene. Using whole-exome sequencing, a variant, FH p.S249R, was identified; no variants were found in other PPGL susceptibility and candidate genes. Loss of heterozygosity analysis revealed the loss of the wild-type allele of the FH gene in the tumor. The pathogenic effect of the p.S249R variant on FH activity was confirmed by immunohistochemistry for S-(2-succino)cysteine (2SC). Potentially deleterious somatic variants were found in three genes, SLC7A7, ZNF225, and MED23. The latter two encode transcriptional regulators that can impact gene expression deregulation and are involved in tumor development and progression. Moreover, FH-mutated VPGL was characterized by a molecular phenotype different from SDHx-mutated PPGLs. In conclusion, the association of genetic changes in the FH gene with the development of VPGL was demonstrated. The germline variant FH: p.S249R and somatic deletion of the second allele can lead to biallelic gene damage that promotes tumor initiation. These results expand the clinical and mutation spectra of FH-related disorders and improve our understanding of the molecular genetic mechanisms underlying the pathogenesis of VPGL.

Success and safety of endoscopic versus microscopic resection of temporal bone paraganglioma: a meta-analysis.

PURPOSE: Temporal bone paraganglioma (TBP) are the most common tumors of the middle ear. They pose a challenge in otologic surgery due to their extensive vascularity and intricate location within the middle ear. This meta-analysis aimed to compare the safety and efficacy of two surgical approaches, microscopic middle ear surgery (MMES) and endoscopic middle ear surgery (EMES), in the resection of TBP. METHODS: Eligible studies published after 1988 were identified through systematic searches of "PubMed", "Scopus" and "Google Scholar". Retrospective studies and randomized/non-randomized control trials reporting on surgical approaches for TBP with a minimum of five adult patients were included. RESULTS: A total of 595 records were initially identified. After removing 229 duplicates, 349 articles were excluded based upon article subject, title and abstract. Following the review of full texts, 13 articles were assessed for eligibility. The pooled analysis included a total of 529 ears, with a complication rate of 7.8% for EMES and 14.2% for MMES. Subgroup differences indicated no significant variation between the two methods (p = 0.2945). CONCLUSION: Both EMES and MMES demonstrated favorable surgical outcomes with low complication rates for TBP resection. These findings suggest that EMES is a safe and effective method for TBP resection and one that is comparable to MMES. Since the risk of bleeding is significant in these tumors, a third-hand technique, endoscopic bipolar cautery or laser-assisted hemostasis should be considered. Conversion to MMES is another option when visibility is critically affected by bleeding.

Computed tomographic findings in canine and feline heart base tumors (25 cases).

Tumors located at the heart base are rare in dogs and cats and aortic body tumors (chemodectoma/paraganglioma), hemangiosarcoma, ectopic thyroid carcinoma, lymphoma, and other uncommon neoplasia can be found at that location. The objective of this retrospective case series was to describe the CT characteristics of canine and feline heart base tumors. CT studies of 21 dogs and four cats with histologically or cytologically confirmed heart base tumors were reviewed for size, location, shape, margination, contrast enhancement, adjacent neovascularization, invasion, mass effect, cavitary effusions, and metastasis. Neuroendocrine tumors (15 aortic body tumors, three ectopic thyroid carcinoma, and three nonspecific neuroendocrine) were more commonly observed than hemangiosarcoma (4) and were frequently located between the cranial vena cava and aortic arch (12/21; 57%) and or dorsal to the pulmonary trunk bifurcation/pulmonary arteries (10/21; 48%). Hemangiosarcoma was more commonly found cranioventral to the aortic arch and cranial to the right auricular appendage (3/4; 75%). Mediastinal and peritumoral neovascularization was associated with 16/21 (76%) neuroendocrine tumors but none of the hemangiosarcoma. Median postcontrast attenuation in Hounsfield units (HU) was higher in neuroendocrine (110 HU) than in hemangiosarcoma (51 HU). Pericardial effusion was frequently observed with hemangiosarcoma (3/4; 75%) and infrequently in neuroendocrine (3/21; 14%). In four cases (all neuroendocrine), concurrent cranial mediastinal masses were present. CT provides useful information regarding the characteristics of heart base tumors, indicating differences between the appearance of neuroendocrine tumors and hemangiosarcoma. However, no differences were found between aortic body tumors and ectopic thyroid carcinoma.

Seventy years of pheochromocytomas and paragangliomas in Argentina. The FRENAR database.

Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors characterized by the excessive production of catecholamines. This study aims to describe the clinical characteristics of PPGL cases in Argentina over recent decades. A multicenter retrospective cross-sectional analysis was carried out using a database comprising both pediatric and adult patients with confirmed PPGL diagnoses based on pathological reports. A cohort of 486 patients with PPGL was recruited. Women represent 58.4% of the patients, with a mean age of 38.3 years old at the time of diagnosis and 15.2% of the patients were under the age of 18. Hypertension, as well as classic signs and symptoms, were present in 80.9% of the patients. The adrenal incidentaloma, as a mode of presentation, increased in the last two decades rising from 3.9% (1953-2000) to 21.8% (2001-2022), p<0.001. Most tumors were located within the adrenal glands, accounting 83.0% of the cases, with bilateral occurrences noted in 20.0%. The median tumor size was 4.8cm. Local recurrence and metastases were observed in 10.9% and 12.2%. Out of 412 patients, 87.0% exhibited urinary excretion elevation of catecholamines and/or their metabolites. Furthermore, 148 patients, representing 30.4% of the study population, displayed a distinct genetic profile indicative of hereditary syndromes. The distribution of hereditary syndromes revealed that MEN2, VHL, and PGL4 constituted the most prevalent syndromes. This population-based study, spanning seven decades, offers valuable insights into the demographic and clinical characteristics of PPGL patients in Argentina.

Jugular Foramen Paragangliomas.

Paragangliomas are the most common tumors at jugular foramen and pose a great surgical challenge. Careful clinical history and physical examination must be performed to adequately evaluate neurological deficits and its chronologic evolution, also to delineate an overview of the patient performance status. Complete imaging evaluation including MRI and CT scans should be performed, and angiography is a must to depict tumor blood supply and sigmoid sinus/internal jugular vein patency. Screening for multifocal paragangliomas is advisable, with a whole-body imaging. Laboratory investigation of endocrine function of the tumor is necessary, and adrenergic tumors may be associated with synchronous lesions. Preoperative prepare with alpha-blockage is advisable in norepinephrine/epinephrine-secreting tumors; however, it is not advisable in exclusively dopamine-secreting neoplasms. Best surgical candidates are young otherwise healthy patients with smaller lesions; however, treatment should be individualized each case. Variations of infratemporal fossa approach are employed depending on extensions of the mass. Regarding facial nerve management, we avoid to expose or reroute it if there is preoperative function preservation and prefer to work around facial canal in way of a fallopian bridge technique. If there is preoperative facial nerve compromise, the mastoid segment of the nerve is exposed, and it may be grafted if invaded or just decompressed. A key point is to preserve the anteromedial wall of internal jugular vein if there is preoperative preservation of lower cranial nerves. Careful multilayer closure is essential to avoid at most cerebrospinal fluid leakage. Residual tumors may be reoperated if growing and presenting mass effect or be candidate for adjuvant stereotactic radiosurgery.

Collet-Sicard syndrome caused by a paraganglioma in the region of the jugular foramen on one side: A case report and review.

Collet-Sicard syndrome is a rare neurological disorder caused by injury to the cranial nerve pairs IX, X, X, and XII. The author reports on a previously fit 27-year-old man who presented with dysphagia, choking on drinking water, hoarseness, weakness when turning the neck and shrugging the shoulders, and unexplained weight loss. Enhanced magnetic resonance imaging indicated a space-occupying lesion at the right jugular foramen. After surgical resection, the pathologic findings suggested a paraganglioma of the right jugular foramen and confirmed the diagnosis of Collet-Sicard syndrome. After postoperative treatment with a combination of acupuncture and modern medicine, the patient's symptoms significantly improved. This article analyzes previous literature regarding Collet-Sicard syndrome etiology and reports the case of a patient with a rare etiology, whose prognosis improved significantly after treatment with a combination of acupuncture and modern medicine.

Radio theranostics in paragangliomas and pheochromocytomas.

This continuing education aims to present in a clear and easy-to-understand manner the biology of paragangliomas and pheochromocytomas (PPGLs), the functional imaging studies available for their diagnosis and therapeutic planning, the requirements necessary to administer radioligand therapy (RLT) and the characteristics of these treatments (inclusion criteria, administration protocols, adverse effects and future perspectives). In this pathology we have two RLT options: [131I]MIBG and [177Lu]Lu-DOTA-TATE. The indication for treatment is determined by the expression of its therapeutic target in functional imaging studies, allowing precision and personalized medicine. Although most of the results we have for both treatments have as origin small retrospective series, RLT is presented as a safe and well-tolerated therapeutic option in PPGLs with slow-moderate progression or with uncontrollable symptoms, obtaining high disease control rates.

Gamma Knife radiosurgery for the management of glomus jugulare tumors: A systematic review and report of the experience of a radioneurosurgery unit in Latin America.

Background: Glomus jugulare tumors (GJTs) are rare and mainly affect women between the 5th and 6th decades of life. Its localization and anatomic relationships make conventional surgical treatment difficult and with a considerable risk of complications. This manuscript aims to describe the results of Gamma Knife radiosurgery (GKR) in patients with GJT treated in a single center in Latin America, as well as to systematically review the literature to determine the clinical and radiological effectiveness of this technique. Methods: A search of information from January 1995 to June 2023 was performed. Twenty-two articles reporting 721 GJT patients treated with GKR were included in the study. Variables such as symptomatic control, control of tumor size, and complications were evaluated. These variables were described using measures of central tendency and proportions. For the institutional experience, 77 patients with GJT tumors were included in the study. Pre-treatment clinical variables and follow-up data were collected from medical charts and phone interviews. The Short Form-36 scale was applied to assess the quality of life. The data were analyzed using the statistical program STATA17.0. Results: A total of 721 patients were considered. The median of patients included in these studies was 18.5. The mean age was 58.4 years. The median of symptom control was 89%, and the median of imaging control was 95.7%. In our institution, 77 patients were included in the study. The mean age was 53.2 years. The median hospital stay was 4.92 hours. For the clinical follow-up, information on 47 patients was obtained. An improvement in pre-treatment symptoms was described in 58%, with general symptomatic control of 97%. The tumor-control rate was 95%, and there were statistically significant differences in six of the nine Short Form-36 scale domains. Conclusion: GKR is an effective, safe, and cost-effective technique that offers a high degree of symptomatic and tumor size control in patients with GJT.

Gastric paraganglioma: a case report and review of literature.

Paragangliomas (PGLs) are rare neuroendocrine tumors which overproduce catecholamines (CAs). They are extra-adrenal, catecholamine-secreting tumors occurring outside the adrenal glands. Gastric PGLs originating from extra-adrenal paraganglia are exceptionally rare, and their presentation in geriatric patients further adds to the complexity of diagnosis and management. A 72-year-old male patient presented with enduring left upper abdominal pain and anemia persisting for over a year, and hypertension for six months. Physical examination revealed epigastric discomfort and pallor. Computed tomography scans revealed enlarged lymph nodes in the lesser curvature of the stomach and thickening of the gastric antrum wall with concavity. The patient underwent three cycles of neoadjuvant therapy before radical gastrectomy for gastric cancer. These imaging findings were confirmed during surgery and intraoperative blood pressure was in fluctuation. After the successful resection of the tumor, postoperative pathology confirmed paraganglioma. During postoperative examination, it was observed that the patient's CAs and their metabolites had returned to within the normal range. Combined with the existing ten literatures, we retrospective report the clinical and pathological characteristics and treatment strategies of the rare gastric paraganglioma.

Safety and efficacy of multiple-dose versus single-dose MIBG therapy in patients with refractory pheochromocytoma and paraganglioma: a single-center retrospective analysis.

OBJECTIVE: To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). METHODS: A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150 mCi (5.55 GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200 days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. RESULTS: The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. CONCLUSION: In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.

Microsurgery in carotid body paraganglioma.

Objectives: In carotid paraganglioma surgery, magnification is crucial to properly evaluate the anatomical relationships between mass, carotid wall, cranial nerves, tumour vascular supply and fascial envelope. The aims of this study are to describe the microsurgical technique, along with the underlying microsurgical anatomy, and to assess outcomes in terms of disease control, complications and functional results. Methods: Twenty-six patients, accounting for 29 carotid paragangliomas, treated with microsurgery by the same senior surgeon over a 35-year period, were included. Results: No carotid injury requiring repair, nor peri- or post-operative stroke occurred in this series. No surgical injury of the main trunk of VII to XII cranial nerves occurred. Complete excision was obtained in all cases and no recurrence was observed during follow-up. Conclusions: The small study size and its retrospective nature suggests caution; however, our results show that microsurgery can allow a safe and precise dissection of the carotids and nerves.

Comprehensive Investigation of Angiogenesis, PASS Score and Immunohistochemical Factors in Risk Assessment of Malignancy for Paraganglioma and Pheochromocytoma.

A challenging task in routine practice is finding the distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is to conduct a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, succinate dehydrogenase B (SDHB) expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS < 4) and 54 potentially malignant (PASS ≥ 4). We found no notable difference between intratumoral MVD and potentially malignant behavior. The group of potentially malignant tumors is significantly larger in size, has lower intratumoral MVD, and a decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1.02 and 1.22, respectively). Most tumors maintain SDHB expression, only 6 cases (5.2%) showed a loss of expression (4 of them in PASS < 4 group and 2 in PASS ≥ 4). PASS score is easily available for assessment and complemented with markers of biological behavior to complete the risk stratification algorithm. Size is directly related to PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

Case report: Rare case of a preoperatively diagnosed spermatic cord paraganglioma and literature review.

Paraganglioma (PGL) is rare, and PGL that arises from the urogenital system is even rarer. Here we report a case of PGL in spermatic cord and review the relevant literatures. We encountered a 15-year-old boy with a history of hypertension for almost 2 years, accompanied with headache and palpitations. His serum and urine catecholamines were elevated, but no adrenal lesions were detected, suggesting the existence of PGL. Upon physical examination, a painless nodule adherent to the spermatic cord in the right scrotum was found. A systemic Ga68 DOTATATE PET-CT was then performed, and it revealed a mass with high DOTATATE uptake in the right scrotum. The CT, MRI, and ultrasound images showed the abundant blood supply to the tumor. Based on the above-mentioned imaging and biochemical information, a diagnosis of PGL was made prior to surgery. After 2 weeks of preparation with Cardura, an open surgery was performed to remove the tumor together with the right testis and right epididymis. The blood pressure increased to 180/100 mmHg when the tumor was touched intraoperatively and decreased to 90/55 mmHg after the tumor was removed. Post-operative pathology confirmed our diagnosis of PGL originating from the spermatic cord. Immunohistochemical (IHC) staining showed SDHB (+), CgA (+), synaptophysin (+), GATA3 (+), CD56 (+), sertoli cells S-100 (+), and Ki67 (5%). Genetic testing revealed a missense mutation in the SDHA gene. Only 16 cases of spermatic cord PGL have been reported to date. Although it is easy to diagnose by histology and IHC examinations, preoperative diagnosis is quite important as it can actually reduce intraoperative complications.

Effects of Peptide Receptor Radiotherapy in Patients with Advanced Paraganglioma and Pheochromocytoma: A Nation-Wide Cohort Study.

INTRODUCTION: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia. Management of disseminated or metastatic pheochromocytomas and paragangliomas continues to pose challenges and relies on limited evidence. METHOD: In this study, we report retrospective data on median overall survival (OS) and median progression-free survival (PFS) for all Danish patients treated with peptide receptor radionuclide therapy (PRRT) with 177Lu-Dotatate or 90Y-Dotatate over the past 15 years. One standard treatment of PRRT consisted of 4 consecutive cycles with 8-14-week intervals. RESULTS: We included 28 patients; 10 were diagnosed with pheochromocytoma and 18 with paraganglioma. Median age at first PRRT was 47 (IQR 15-76) years. The median follow-up time was 31 (IQR 17-37) months. Eight patients died during follow-up. Median OS was 72 months, and 5-year survival was 65% with no difference between pheochromocytoma and paraganglioma. Patients with germline mutations had better survival than patients without mutations (p = 0.041). Median PFS after the first cycle of PRRT was 30 months. For patients who previously received systemic treatment, the median PFS was 19 months, compared with 32 months for patients with no previous systemic treatment (p = 0.083). CONCLUSIONS: The median OS of around 6 years and median PFS of around 2.5 years found in this study are comparable to those reported in previous studies employing PRRT. Based on historical data, the efficacy of PRRT may be superior to 131I-MIBG therapy, and targeted therapy with sunitinib and PRRT might therefore be considered as first-line treatment in this patient group.