Table Info

Table 2.

Patient 2: serial biochemistries

Times the URL	7/23/2019 urine	7/23/2019 plasma	9/13/2019 plasma	*Normal values pg/mL [μg/24h]**
Normetanephrine	1.8 [683]	0.2 (25)	0.5 (58)	18–112 [103–390]
Metanephrine	1.1 [204]	0.4 (22)	0.3 (18)	12–61 [35–180]
Norepinephrine	0.7 [56]	0.3 (191)	0.3 (251)	112–750 [15–80]
Dopamine	1.2 [462]	U	U	0–29 [65–400]
Epinephrine	0.1 [1.7]	U	U	0–50 [< 21]
Chromogranin A		1.0 (92)		[< 93]

Elevated values are bolded. * Note fractionated plasma values (e.g., fractionated metanephrines) are provided in picograms per milliliter in parenthesis (pg/mL) while 24-hour urine values are provided in micrograms over 24 hours in brackets [μg/24h]. Blank cells indicate an absence of laboratory data for the respective time point. URL: upper reference limit; U: undetectable/below the lower limit of the reference range

Declarations

Author contributions

KMC and KP: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. MAN: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Supervision. AJ, MP, AL, and TP: Investigation, Data curation. ST: Writing—review & editing. MJMK: Investigation. ASA, AD, AC, JG, and JDR: Investigation, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Prof. Karel Pacak is the Editor-in-Chief of Exploration of Endocrine and Metabolic Diseases, but he was not involved in the decision-making or review process of this manuscript.

Ethical approval

This study was part of a protocol (NCT00004847) approved by the National Institutes of Health Institutional Review Board (Protocol: 00-CH-0093).

Consent to participate

Informed consent to participate in the study was obtained from the parents (and or guardians) of the participants.

Consent to publication

Informed consent to publish this article was obtained from the parents (and or guardians) of the participants.

Availability of data and materials

The datasets that support the findings of this study are available from the corresponding author upon reasonable request.

Funding

This study was funded by the National Institutes of Health [Z1AHD008735]. This work was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Lenders JWM, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet. 2005;366:665–75. [DOI] [PubMed]

Pamporaki C, Hamplova B, Peitzsch M, Prejbisz A, Beuschlein F, Timmers HJLM, et al. Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas. J Clin Endocrinol Metab. 2017;102:1122–32. [DOI] [PubMed] [PMC]

Eisenhofer G, Pamporaki C, Lenders JWM. Biochemical Assessment of Pheochromocytoma and Paraganglioma. Endocr Rev. 2023;44:862–909. [DOI] [PubMed]

Richter S, Qiu B, Ghering M, Kunath C, Constantinescu G, Luths C, et al. Head/neck paragangliomas: focus on tumor location, mutational status and plasma methoxytyramine. Endocr Relat Cancer. 2022;29:213–24. [DOI] [PubMed] [PMC]

Van Duinen N, Corssmit EPM, De Jong WHA, Brookman D, Kema IP, Romijn JA. Plasma levels of free metanephrines and 3-methoxytyramine indicate a higher number of biochemically active HNPGL than 24-h urinary excretion rates of catecholamines and metabolites. Eur J Endocrinol. 2013;169:377–82. [DOI] [PubMed]

Nölting S, Grossman A, Pacak K. Metastatic Phaeochromocytoma: Spinning Towards More Promising Treatment Options. Exp Clin Endocrinol Diabetes. 2019;127:117–28. [DOI] [PubMed] [PMC]

Ilanchezhian M, Jha A, Pacak K, Del Rivero J. Emerging Treatments for Advanced/Metastatic Pheochromocytoma and Paraganglioma. Curr Treat Options Oncol. 2020;21:85. [DOI] [PubMed] [PMC]

Nölting S, Ullrich M, Pietzsch J, Ziegler CG, Eisenhofer G, Grossman A, et al. Current Management of Pheochromocytoma/Paraganglioma: A Guide for the Practicing Clinician in the Era of Precision Medicine. Cancers (Basel). 2019;11:1505. [DOI] [PubMed] [PMC]

Jochmanova I, Abcede AMT, Guerrero RJS, Malong CLP, Wesley R, Huynh T, et al. Clinical characteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents. J Cancer Res Clin Oncol. 2020;146:1051–63. [DOI] [PubMed] [PMC]

10.

Jha A, De Luna K, Balili CA, Millo C, Paraiso CA, Ling A, et al. Clinical, Diagnostic, and Treatment Characteristics of SDHA-Related Metastatic Pheochromocytoma and Paraganglioma. Front Oncol. 2019;9:53. [DOI] [PubMed] [PMC]

11.

Kuo MJM, Nazari MA, Jha A, Pacak K. Pediatric Metastatic Pheochromocytoma and Paraganglioma: Clinical Presentation and Diagnosis, Genetics, and Therapeutic Approaches. Front Endocrinol (Lausanne). 2022;13:936178. [DOI] [PubMed] [PMC]

12.

Fliedner SMJ, Lehnert H, Pacak K. Metastatic paraganglioma. Semin Oncol. 2010;37:627–37. Erratum in: Semin Oncol. 2011;38:467. [DOI] [PubMed] [PMC]

13.

Pacak K. New Biology of Pheochromocytoma and Paraganglioma. Endocr Pract. 2022;28:1253–69. [DOI] [PubMed] [PMC]

14.

Ayala-Ramirez M, Feng L, Johnson MM, Ejaz S, Habra MA, Rich T, et al. Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab. 2011;96:717–25. [DOI] [PubMed]

15.

Ayala-Ramirez M, Palmer JL, Hofmann M, De la Cruz M, Moon BS, Waguespack SG, et al. Bone metastases and skeletal-related events in patients with malignant pheochromocytoma and sympathetic paraganglioma. J Clin Endocrinol Metab. 2013;98:1492–7. [DOI] [PubMed] [PMC]

16.

Hamidi O, Young WF Jr, Iñiguez-Ariza NM, Kittah NE, Gruber L, Bancos C, et al. Malignant Pheochromocytoma and Paraganglioma: 272 Patients Over 55 Years. J Clin Endocrinol Metab. 2017;102:3296–305. [DOI] [PubMed] [PMC]

17.

Jha A, Patel M, Ling A, Shah R, Chen CC, Millo C, et al. Diagnostic performance of [⁶⁸Ga]DOTATATE PET/CT, [¹⁸F]FDG PET/CT, MRI of the spine, and whole-body diagnostic CT and MRI in the detection of spinal bone metastases associated with pheochromocytoma and paraganglioma. Eur Radiol. 2024;34:6488–98. [DOI] [PubMed] [PMC]

18.

Kluckova K, Tennant DA. Metabolic implications of hypoxia and pseudohypoxia in pheochromocytoma and paraganglioma. Cell Tissue Res. 2018;372:367–78. [DOI] [PubMed] [PMC]

19.

Jochmanová I, Yang C, Zhuang Z, Pacak K. Hypoxia-inducible factor signaling in pheochromocytoma: turning the rudder in the right direction. J Natl Cancer Inst. 2013;105:1270–83. [DOI] [PubMed] [PMC]

20.

Nazari MA, Rosenblum JS, Haigney MC, Rosing DR, Pacak K. Pathophysiology and Acute Management of Tachyarrhythmias in Pheochromocytoma: JACC Review Topic of the Week. J Am Coll Cardiol. 2020;76:451–64. [DOI] [PubMed] [PMC]

21.

Jimenez C, Xu G, Varghese J, Graham PH, Campbell MT, Lu Y. New Directions in Treatment of Metastatic or Advanced Pheochromocytomas and Sympathetic Paragangliomas: an American, Contemporary, Pragmatic Approach. Curr Oncol Rep. 2022;24:89–98. [DOI] [PubMed]

22.

Fishbein L, Del Rivero J, Else T, Howe JR, Asa SL, Cohen DL, et al. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Management of Metastatic and/or Unresectable Pheochromocytoma and Paraganglioma. Pancreas. 2021;50:469–93. [DOI] [PubMed]

23.

Pacak K, Taieb D, Lin FI, Jha A. Approach to the Patient: Concept and Application of Targeted Radiotherapy in the Paraganglioma Patient. J Clin Endocrinol Metab. 2024;109:2366–88. [DOI] [PubMed] [PMC]

24.

Nazari MA, Hasan R, Haigney M, Maghsoudi A, Lenders JWM, Carey RM, et al. Catecholamine-induced hypertensive crises: current insights and management. Lancet Diabetes Endocrinol. 2023;11:942–54. Erratum in: Lancet Diabetes Endocrinol. 2024;12:e1. [DOI] [PubMed]

25.

NOT-OD-16-010: Inclusion of Children in Clinical Research: Change in NIH Definition [Internet]. National Institutes of Health Office of Extramural Research; [cited 2024 Sep 22]. Available from: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-010.html

26.

Definition of adolescent—NCI Dictionary of Cancer Terms—NCI [Internet]. National Cancer Institute at the National Institutes of Health; [cited 2024 Sep 20]. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/adolescent

27.

Reiterer M, Colaço R, Emrouznejad P, Jensen A, Rundqvist H, Johnson RS, et al. Acute and chronic hypoxia differentially predispose lungs for metastases. Sci Rep. 2019;9:10246. Erratum in: Sci Rep. 2020;10:1627. [DOI] [PubMed] [PMC]

28.

Takabatake N, Arao T, Sata M, Abe S, Inoue S, Shibata Y, et al. Involvement of pulmonary endothelial cell injury in the pathogenesis of pulmonary fibrosis: clinical assessment by ¹²³I-MIBG lung scintigraphy. Eur J Nucl Med Mol Imaging. 2005;32:221–8. [DOI] [PubMed]

29.

Giordano A, Calcagni ML, Rossi B, Rufini V, Fuso L, Valente S, et al. Use of metaiodobenzylguanidine (MIBG) in pneumology. Q J Nucl Med. 1995;39:49–54. [PubMed]

30.

Phelps TE, Del Rivero J, Chertow DS, Rosing D, Pacak K, Lin FI. Managing Catecholamine Release Syndrome During and Following Lu-177-DOTATATE in High-Risk Pheochromocytoma Patients. JCEM Case Rep. 2024;2:luae049. [DOI] [PubMed] [PMC]

31.

Lenders JWM, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SKG, Murad MH, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:1915–42. Erratum in: J Clin Endocrinol Metab. 2023;108:e200. [DOI] [PubMed]

32.

Casey RT, Hendriks E, Deal C, Waguespack SG, Wiegering V, Redlich A, et al. International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents. Nat Rev Endocrinol. 2024; [Epub ahead of print]:Erratum in: Nat Rev Endocrinol. 2024. [DOI] [PubMed]

33.

Taïeb D, Nölting S, Perrier ND, Fassnacht M, Carrasquillo JA, Grossman AB, et al. Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement. Nat Rev Endocrinol. 2024;20:168–84. [DOI] [PubMed]

34.

Taïeb D, Wanna GB, Ahmad M, Lussey-Lepoutre C, Perrier ND, Nölting S, et al. Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants. Lancet Diabetes Endocrinol. 2023;11:345–61. [DOI] [PubMed]

35.

Nazari MA, Jha A, Kuo MJM, Patel M, Prodanov T, Rosenblum JS, et al. Paediatric phaeochromocytoma and paraganglioma: A clinical update. Clin Endocrinol (Oxf). 2024;101:446–54. [DOI] [PubMed]

36.

Turkova H, Prodanov T, Maly M, Martucci V, Adams K, Widimsky J Jr, et al. Characteristics and Outcomes of Metastatic SDHB and Sporadic Pheochromocytoma/Paraganglioma: An National Institutes of Health Study. Endocr Pract. 2016;22:302–14. [DOI] [PubMed] [PMC]

37.

Seabrook A, Vasudevan A, Neville K, Gerstl B, Benn D, Smith J, et al. Genotype-phenotype correlations in paediatric and adolescent phaeochromocytoma and paraganglioma: a cross-sectional study. Arch Dis Child. 2024;109:201–8. [DOI] [PubMed]

38.

Barontini M, Levin G, Sanso G. Characteristics of pheochromocytoma in a 4- to 20-year-old population. Ann N Y Acad Sci. 2006;1073:30–7. [DOI] [PubMed]

39.

Waguespack SG, Rich T, Grubbs E, Ying AK, Perrier ND, Ayala-Ramirez M, et al. A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2010;95:2023–37. [DOI] [PubMed]

40.

Bausch B, Wellner U, Bausch D, Schiavi F, Barontini M, Sanso G, et al. Long-term prognosis of patients with pediatric pheochromocytoma. Endocr Relat Cancer. 2013;21:17–25. [DOI] [PubMed]

41.

Eisenhofer G, Lenders JWM, Goldstein DS, Mannelli M, Csako G, Walther MM, et al. Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines. Clin Chem. 2005;51:735–44. [DOI] [PubMed]

42.

Mei L, Khurana A, Al-Juhaishi T, Faber A, Celi F, Smith S, et al. Prognostic Factors of Malignant Pheochromocytoma and Paraganglioma: A Combined SEER and TCGA Databases Review. Horm Metab Res. 2019;51:451–7. Erratum in: Horm Metab Res. 2019;51:e2. [DOI] [PubMed]

43.

Eisenhofer G, Lenders JWM, Siegert G, Bornstein SR, Friberg P, Milosevic D, et al. Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status. Eur J Cancer. 2012;48:1739–49. [DOI] [PubMed] [PMC]

44.

Eisenhofer G, Lenders JWM, Timmers H, Mannelli M, Grebe SK, Hofbauer LC, et al. Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma. Clin Chem. 2011;57:411–20. [DOI] [PubMed] [PMC]

45.

Eisenhofer G, Huynh T, Elkahloun A, Morris JC, Bratslavsky G, Linehan WM, et al. Differential expression of the regulated catecholamine secretory pathway in different hereditary forms of pheochromocytoma. Am J Physiol Endocrinol Metab. 2008;295:E1223–33. [DOI] [PubMed] [PMC]

46.

Timmers HJLM, Pacak K, Huynh TT, Abu-Asab M, Tsokos M, Merino MJ, et al. Biochemically Silent Abdominal Paragangliomas in Patients with Mutations in the Succinate Dehydrogenase Subunit B gene. J Clin Endocrinol Metab. 2008;93:4826–32. [DOI] [PubMed] [PMC]

47.

Timmers HJLM, Taïeb D, Pacak K, Lenders JWM. Imaging of Pheochromocytomas and Paragangliomas. Endocr Rev. 2024;45:414–34. [DOI] [PubMed] [PMC]

48.

Carrasquillo JA, Chen CC, Jha A, Ling A, Lin FI, Pryma DA, et al. Imaging of Pheochromocytoma and Paraganglioma. J Nucl Med. 2021;62:1033–42. [DOI] [PubMed] [PMC]

49.

Taïeb D, Hicks RJ, Hindié E, Guillet BA, Avram A, Ghedini P, et al. European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2019;46:2112–37. [DOI] [PubMed] [PMC]

50.

Taïeb D, Jha A, Treglia G, Pacak K. Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups. Endocr Relat Cancer. 2019;26:R627–52. [DOI] [PubMed] [PMC]

51.

Fargette C, Shulkin B, Jha A, Pacak K, Taïeb D. Clinical utility of nuclear imaging in the evaluation of pediatric adrenal neoplasms. Front Oncol. 2023;12:1081783. [DOI] [PubMed] [PMC]

52.

Carrasquillo JA, Chen CC, Jha A, Pacak K, Pryma DA, Lin FI. Systemic Radiopharmaceutical Therapy of Pheochromocytoma and Paraganglioma. J Nucl Med. 2021;62:1192–9. [DOI] [PubMed] [PMC]

53.

Janssen I, Blanchet EM, Adams K, Chen CC, Millo CM, Herscovitch P, et al. Superiority of [⁶⁸Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma. Clin Cancer Res. 2015;21:3888–95. [DOI] [PubMed] [PMC]

54.

Jha A, Ling A, Millo C, Gupta G, Viana B, Lin FI, et al. Superiority of ⁶⁸Ga-DOTATATE over ¹⁸F-FDG and anatomic imaging in the detection of succinate dehydrogenase mutation (SDHx)-related pheochromocytoma and paraganglioma in the pediatric population. Eur J Nucl Med Mol Imaging. 2018;45:787–97. [DOI] [PubMed] [PMC]

55.

Patel M, Jha A, Ling A, Chen CC, Millo C, Kuo MJM, et al. Performances of Functional and Anatomic Imaging Modalities in Succinate Dehydrogenase A-Related Metastatic Pheochromocytoma and Paraganglioma. Cancers (Basel). 2022;14:3886. [DOI] [PubMed] [PMC]

56.

Janssen I, Chen CC, Millo CM, Ling A, Taieb D, Lin FI, et al. PET/CT comparing ⁶⁸Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2016;43:1784–91. [DOI] [PubMed] [PMC]

57.

Janssen I, Chen CC, Taieb D, Patronas NJ, Millo CM, Adams KT, et al. 68Ga-DOTATATE PET/CT in the Localization of Head and Neck Paragangliomas Compared with Other Functional Imaging Modalities and CT/MRI. J Nucl Med. 2016;57:186–91. [DOI] [PubMed] [PMC]

58.

Jha A, Patel M, Carrasquillo JA, Chen CC, Millo C, Maass-Moreno R, et al. Choice Is Good at Times: The Emergence of [⁶⁴Cu]Cu-DOTATATE-Based Somatostatin Receptor Imaging in the Era of [⁶⁸Ga]Ga-DOTATATE. J Nucl Med. 2022;63:1300–1. [DOI] [PubMed] [PMC]

59.

Imperiale A, Pepponi M, Poterszman N, Jha A, Collen C, Brumaru D, et al. Molecular imaging phenotyping of germline fumarate hydratase (FH) pathogenic variant-positive metastatic pheochromocytoma. Eur J Nucl Med Mol Imaging. 2023;50:3155–6. [DOI] [PubMed]

60.

Jha A, Ling A, Millo C, Chen C, Gupta G, Viana B, et al. Superiority of ⁶⁸Ga-DOTATATE PET/CT to other functional and anatomic imaging modalities in the detection of SDHD-related pheochromocytoma and paraganglioma—A comparative prospective study. J Nucl Med. 2018;59:46.

61.

Janssen I, Chen CC, Zhuang Z, Millo CM, Wolf KI, Ling A, et al. Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes. J Nucl Med. 2017;58:1236–42. [DOI] [PubMed] [PMC]

62.

Pang Y, Gupta G, Jha A, Yue X, Wang H, Huynh TT, et al. Nonmosaic somatic HIF2A mutations associated with late onset polycythemia-paraganglioma syndrome: Newly recognized subclass of polycythemia-paraganglioma syndrome. Cancer. 2019;125:1258–66. [DOI] [PubMed] [PMC]

63.

Taïeb D, Jha A, Guerin C, Pang Y, Adams KT, Chen CC, et al. ¹⁸F-FDOPA PET/CT Imaging of MAX-Related Pheochromocytoma. J Clin Endocrinol Metab. 2018;103:1574–82. [DOI] [PubMed] [PMC]

64.

Jha A, Patel M, Ling A, Chen C, Millo C, Charles K, et al. Diagnostic performance of PET or PET/CT utilizing ¹⁸F-FDOPA, ⁶⁸Ga-DOTATATE, 1⁸F-FDG, ¹⁸F-FDA, and CT and MRI in the detection of MEN2A-related pheochromocytoma—A comparative prospective study. J Nucl Med. 2022;63:3014.

65.

Tepede AA, Welch J, Lee M, Mandl A, Agarwal SK, Nilubol N, et al. ¹⁸F-FDOPA PET/CT accurately identifies MEN1-associated pheochromocytoma. Endocrinol Diabetes Metab Case Rep. 2020;2020:19-0156. [DOI] [PubMed] [PMC]

66.

Nambuba J, Därr R, Janssen I, Bullova P, Adams KT, Millo C, et al. Functional Imaging Experience in a Germline Fumarate Hydratase Mutation—Positive Patient With Pheochromocytoma and Paraganglioma. AACE Clin Case Rep. 2016;2:e176–81. [DOI]

67.

Jha A, Patel M, Carrasquillo JA, Ling A, Millo C, Saboury B, et al. Sporadic Primary Pheochromocytoma: A Prospective Intraindividual Comparison of Six Imaging Tests (CT, MRI, and PET/CT Using ⁶⁸Ga-DOTATATE, FDG, ¹⁸F-FDOPA, and ¹⁸F-FDA). AJR Am J Roentgenol. 2022;218:342–50. [DOI] [PubMed] [PMC]

68.

Jha A, Taïeb D, Carrasquillo JA, Pryma DA, Patel M, Millo C, et al. High-Specific-Activity-¹³¹I-MIBG versus ¹⁷⁷Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma. Clin Cancer Res. 2021;27:2989–95. [DOI] [PubMed] [PMC]

69.

Nölting S, Bechmann N, Taieb D, Beuschlein F, Fassnacht M, Kroiss M, et al. Personalized Management of Pheochromocytoma and Paraganglioma. Endocr Rev. 2022;43:199–239. [DOI] [PubMed] [PMC]

70.

Wang K, Crona J, Beuschlein F, Grossman AB, Pacak K, Nölting S. Targeted Therapies in Pheochromocytoma and Paraganglioma. J Clin Endocrinol Metab. 2022;107:2963–72. [DOI] [PubMed] [PMC]

71.

Jimenez C, Subbiah V, Stephen B, Ma J, Milton D, Xu M, et al. Phase II Clinical Trial of Pembrolizumab in Patients with Progressive Metastatic Pheochromocytomas and Paragangliomas. Cancers (Basel). 2020;12:2307. [DOI] [PubMed] [PMC]

72.

Angelousi A, Tzoulis P, Tsoli M, Chatzellis E, Koumarianou A, Kaltsas G. Immunotherapy for endocrine tumours: a clinician’s perspective. Endocr Relat Cancer. 2024;31:e230296. [DOI] [PubMed]

73.

Jimenez C, Armaiz-Pena G, Dahia PLM, Lu Y, Toledo RA, Varghese J, et al. Endocrine and Neuroendocrine Tumors Special Issue-Checkpoint Inhibitors for Adrenocortical Carcinoma and Metastatic Pheochromocytoma and Paraganglioma: Do They Work? Cancers (Basel). 2022;14:467. [DOI] [PubMed] [PMC]

74.

Ramirez RA, Beyer DT, Chauhan A, Boudreaux JP, Wang Y, Woltering EA. The Role of Capecitabine/Temozolomide in Metastatic Neuroendocrine Tumors. Oncologist. 2016;21:671–5. [DOI] [PubMed] [PMC]

75.

Baudin E, Goichot B, Berruti A, Hadoux J, Moalla S, Laboureau S, et al.; ENDOCAN-COMETE, ENSAT Networks. Sunitinib for metastatic progressive phaeochromocytomas and paragangliomas: results from FIRSTMAPPP, an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial. Lancet. 2024;403:1061–70. [DOI] [PubMed]

76.

Tian R, Yao X, Song J, Wang J, Fu J, Shi L, et al. Anlotinib for Metastatic Progressed Pheochromocytoma and Paraganglioma: A Retrospective Study of Real-World Data. J Endocr Soc. 2024;8:bvae061. [DOI] [PubMed] [PMC]

77.

Al-Ward R, Brondani VB, Sawani S, Potter CL, Xu G, Waguespack SG, et al. High-Specific-Activity ¹³¹I-MIBG for the Treatment of Advanced Pheochromocytoma and Paraganglioma. Clin Nucl Med. 2024;49:610–20. [DOI] [PubMed]

78.

Gubbi S, Al-Jundi M, Auh S, Jha A, Zou J, Shamis I, et al. Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [¹⁷⁷Lu]Lu-DOTA-TATE therapy. Front Endocrinol (Lausanne). 2023;14:1275813. [DOI] [PubMed] [PMC]

79.

Gubbi S, Al-Jundi M, Del Rivero J, Jha A, Knue M, Zou J, et al. Case Report: Primary Hypothyroidism Associated with Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma. Front Endocrinol (Lausanne). 2021;11:587065. [DOI] [PubMed] [PMC]

80.

Patel M, Tena I, Jha A, Taieb D, Pacak K. Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World. Front Endocrinol (Lausanne). 2021;12:625312. [DOI] [PubMed] [PMC]

81.

Jha A, Patel M, Baker E, Gonzales MK, Ling A, Millo C, et al. Role of ⁶⁸Ga-DOTATATE PET/CT in a Case of SDHB-Related Pterygopalatine Fossa Paraganglioma Successfully Controlled with Octreotide. Nucl Med Mol Imaging. 2020;54:48–52. [DOI] [PubMed] [PMC]

82.

Jha A, Nilubol N, Pacak K. Some Considerations in Treating Malignant Head and Neck Paragangliomas. JAMA Otolaryngol Head Neck Surg. 2020;146:209–10. [DOI] [PubMed] [PMC]

83.

Lastoria S, Maurea S, Vergara E, Acampa W, Varrella P, Klain M, et al. Comparison of labeled MIBG and somatostatin analogs in imaging neuroendocrine tumors. Q J Nucl Med. 1995;39:145–9. [PubMed]

84.

Maurea S, Lastoria S, Caracò C, Klain M, Varrella P, Acampa W, et al. The role of radiolabeled somatostatin analogs in adrenal imaging. Nucl Med Biol. 1996;23:677–80. [DOI] [PubMed]

85.

Lin FI, Del Rivero J, Carrasquillo J, Shamis I, Zou J, Turkbey B, et al. Phase 2 trial of lu-177-DOTATATE in metastatic or inoperable pheochromocytoma/paraganglioma: interim analysis results. J Nucl Med. 2023;64:1296. [DOI]

86.

Kamihara J, Hamilton KV, Pollard JA, Clinton CM, Madden JA, Lin J, et al. Belzutifan, a Potent HIF2α Inhibitor, in the Pacak-Zhuang Syndrome. N Engl J Med. 2021;385:2059–65. [DOI] [PubMed] [PMC]

87.

Curry L, Soleimani M. Belzutifan: a novel therapeutic for the management of von Hippel-Lindau disease and beyond. Future Oncol. 2024;20:1251–66. [DOI] [PubMed]

88.

Else T, Jonasch E, Iliopoulos O, Beckermann KE, Narayan V, Maughan BL, et al. Belzutifan for von Hippel-Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study. Clin Cancer Res. 2024;30:1750–7. [DOI] [PubMed] [PMC]

89.

Yadav MP, Ballal S, Sahoo RK, Bal C. Efficacy and safety of ²²⁵Ac-DOTATATE targeted alpha therapy in metastatic paragangliomas: a pilot study. Eur J Nucl Med Mol Imaging. 2022;49:1595–606. [DOI] [PubMed] [PMC]

90.

Toledo RA, Jimenez C, Armaiz-Pena G, Arenillas C, Capdevila J, Dahia PLM. Hypoxia-Inducible Factor 2 Alpha (HIF2α) Inhibitors: Targeting Genetically Driven Tumor Hypoxia. Endocr Rev. 2023;44:312–22. [DOI] [PubMed] [PMC]

91.

Harrison L, Blackwell K. Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy? Oncologist. 2004;9:31–40. [DOI] [PubMed]