Laboratory diagnostics of pheochromocytoma: a modern view on the problem

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Abstract

Pheochromocytoma (PhC) is a tumor originating from the chromaffin cells of the adrenal medulla, capable of hyperproduction of catecholamines (adrenaline, noradrenaline and dopamine). The importance of early diagnosis of this pathology is associated with the survival of patients due to the risk of developing catecholamine crises, which in turn can cause the development of cardiovascular and cerebral accidents, up to and including death. In the primary diagnosis of pheochromocytomas, it is important to determine the level of catecholamine metabolites – metanephrines. In modern clinical practice, there are different options for laboratory determination of these metabolites: in blood plasma or urine, total amount or only free form, fractionated or unfractionated analysis. As the results of a survey conducted among primary care physicians showed, the choice of diagnostic method and the scope of examination in case of suspected pheochromocytoma/paraganglioma causes difficulties for the majority of respondents. This study was aimed to discussion of the modern methods of pheochromocytoma diagnostics, processes of catecholamine synthesis and metabolism, and the nuances of various laboratory diagnostic methods, the rules for collecting samples and factors that can potentially affect the test results. This, in our opinion, will bring some clarity to the existing problem and provide primary care physicians with a convenient algorithm for laboratory diagnostics of pheochromocytoma.

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About the authors

D. O. Ladygina

Sechenov First Moscow State Medical University

Author for correspondence.
Email: d8050005@gmail.com
ORCID iD: 0000-0001-6418-7060
SPIN-code: 7958-9435

Cand. Sci. (Med.), Associate Professor at the Endocrinology Department No. 1 of the Sklifosovsky Institute of Clinical Medicine

Russian Federation, Moscow

V. D. Soldatova

Sechenov First Moscow State Medical University

Email: d8050005@gmail.com
ORCID iD: 0000-0003-2764-7237
Russian Federation, Moscow

E. V. Osipova

Sechenov First Moscow State Medical University

Email: d8050005@gmail.com
ORCID iD: 0009-0005-6333-7844
Russian Federation, Moscow

E. O. Antsiferova

Sechenov First Moscow State Medical University

Email: d8050005@gmail.com
ORCID iD: 0000-0001-7734-2525
Russian Federation, Moscow

D. N. Sotnikov

Sechenov First Moscow State Medical University

Email: d8050005@gmail.com
ORCID iD: 0000-0002-5423-6292
Russian Federation, Moscow

N. M. Platonova

National Medical Research Center of Endocrinology

Email: d8050005@gmail.com
ORCID iD: 0000-0001-6388-1544
SPIN-code: 4053-3033
Russian Federation, Moscow

D. G. Beltsevich

National Medical Research Center of Endocrinology

Email: d8050005@gmail.com
ORCID iD: 0000-0001-7098-4584
SPIN-code: 4475-6327
Russian Federation, Moscow

V. V. Fadeev

Sechenov First Moscow State Medical University

Email: d8050005@gmail.com
ORCID iD: 0000-0002-3026-6315
SPIN-code: 6825-8417
Russian Federation, Moscow

References

  1. Lenders J.W.M., Kerstens M.N., Amar L., et al. Genetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens. 2020 Aug;38(8):1443-1456. doi: 10.1097/HJH.0000000000002438.
  2. Pacak K., Tella S.H. Pheochromocytoma and Paraganglioma. [Updated 2018 Jan 4]. In: Feingold K.R., Anawalt B., Blackman M.R., et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK481899/
  3. Lenders J.W., Duh Q.Y., Eisenhofer G., et al; Endocrine Society. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42. doi: 10.1210/jc.2014-1498. Erratum in: J Clin Endocrinol Metab. 2023 Apr 13;108(5):e200. doi: 10.1210/clinem/dgad064. PMID: 24893135.
  4. Клинические рекомендации «Феохромо-цитома/параганглиома». Министерство здравоохранения Российской Федерации. [Clinical guidelines «Pheochromocytoma/paraganglioma». Ministry of Health of the Russian Federation. (In Russ.)]. URL: https://rae-org.ru/system/files/documents/pdf/kr272_feohromocitoma-paraganglioma.pdf
  5. Dajani R., Cleasby A., Neu M., et al. X-ray crystal structure of human dopamine sulfotransferase, SULT1A3. Molecular modeling and quantitative structure-activity relationship analysis demonstrate a molecular basis for sulfotransferase substrate specificity. J Biol Chem. 1999 Dec 31;274(53):37862–8. doi: 10.1074/jbc.274.53.37862.
  6. Eisenhofer G., Aneman A., Hooper D., et al. Mesenteric organ production, hepatic metabolism, and renal elimination of norepinephrine and its metabolites in humans. J Neurochem. 1996 Apr;66(4):1565–73. doi: 10.1046/j.1471-4159.1996.66041565.x.
  7. Eisenhofer G., Coughtrie M.W., Goldstein D.S. Dopamine sulphate: an enigma resolved. Clin Exp Pharmacol Physiol Suppl. 1999 Apr; 26:S41-53.
  8. Jain A., Baracco R., Kapur G. Pheochromocytoma and paraganglioma – an update on diagnosis, evaluation, and management. Pediatr Nephrol. 2020;35(4):581–594. doi: 10.1007/s00467-018-4181-26.
  9. Lenders J.W., Keiser H.R., Goldstein D.S., et al. Plasma metanephrines in the diagnosis of pheochromocytoma. Ann Intern Med. 1995 Jul 15;123(2):101–9. doi: 10.7326/0003-4819-123-2-199507150-00004.
  10. Eisenhofer G., Kopin I.J., Goldstein D.S. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004 Sep;56(3):331–49. doi: 10.1124/pr.56.3.1.
  11. Шихмагомедов Ш.Ш., Реброва Д.В., Краснов Л.М. и др. Сравнение эффективности различных методов определения уровня метанефринов в диагностике феохромоцитом. Проблемы эндокринологии. 2024;70(2):46–52. [Shikhmagomedov Sh.Sh., Rebrova D.V., Krasnov L.M., et al. Comparison of the effectiveness of various methods for determining the level of metanephrines in the diagnosis of pheochromocytomas. Problems of Endocrinology. 2024;70(2):46–52. (In Russ.)]. doi: 10.14341/probl13309.
  12. Lenders J.W., Eisenhofer G., Mannelli M., Pacak K. Phaeochromocytoma. Lancet. 2005 Aug 20-26;366(9486):665–75. doi: 10.1016/S0140-6736(05)67139-5.
  13. Mornex R., Peyrin L., Pagliari R., Cottet-Emard J.M. Measurement of plasma methoxyamines for the diagnosis of pheochromocytoma. Horm Res. 1991;36(5-6):220–6. doi: 10.1159/000182167. PMID: 1688051.
  14. Marini M., Fathi M., Vallotton M. Dosage des metanephrines seriques pour le diagnostic du pheochromocytome [Determination of serum metanephrines in the diagnosis of pheochromocytoma]. Ann Endocrinol (Paris). 1994;54(5):337–42. French.
  15. Pallant A, Mathian B, Prost L, Theodore C, Patricot MC. Determination of plasma methoxyamines. Clin Chem Lab Med. 2000 Jun;38(6):513–7. doi: 10.1515/CCLM.2000.075.
  16. Grouzmann E., Fathi M., Gillet M., et al. Disappearance rate of catecholamines, total metanephrines, and neuropeptide Y from the plasma of patients after resection of pheochromocytoma. Clin Chem. 2001 Jun;47(6):1075–82. Erratum in: Clin Chem 2001 Sep;47(9):1748. PMID: 11375294.
  17. Eisenhofer G. Free or Total Metanephrines for Diagnosis of Pheochromocytoma: What Is the Difference? Clin Chem. 2001;47(6):988–989. doi: 10.1093/clinchem/47.6.988.
  18. Eisenhofer G. Impact of LC-MS/MS on the laboratory diagnosis of catecholamine-producing tumors. Trends in Analytical Chemistry. 2016.
  19. de Jong W.H., Graham K.S., van der Molen J.C., et al. Plasma free metanephrine measurement using automated online solid-phase extraction HPLC tandem mass spectrometry. Clin Chem. 2007 Sep;53(9):1684–93. doi: 10.1373/clinchem.2007.087114.
  20. de Jong W.H., Eisenhofer G., Post W.J., et al. Dietary influences on plasma and urinary metanephrines: implications for diagnosis of catecholamine-producing tumors. J Clin Endocrinol Metab. 2009 Aug;94(8):2841–9. doi: 10.1210/jc.2009-0303.
  21. Lenders J.W., Pacak K., Walther M.M., et al. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002 Mar 20;287(11):1427–34. doi: 10.1001/jama.287.11.1427.

Supplementary files

Supplementary Files
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1. JATS XML
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2. Fig. 1. Distribution of respondents by speciality

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3. Fig. 2. Distribution of answers to the question about necessary investigations in case of detection of adrenal gland volumetric mass with CT native density less than 10 HU

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4. Fig. 3. Distribution of answers to the question about necessary investigations in case of detection of adrenal mass with native CT density more than 10 HU without phenotypic signs of hypercorticism and increased blood pressure

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5. Fig. 4. Distribution of answers to the question about necessary investigations in case of detection of an adrenal mass with native CT density more than 10 HU without phenotypic signs of hypercorticism, but with increased blood pressure

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6. Fig. 5. Distribution of answers to the question about laboratory tests used in personal clinical practice of respondents to rule out paraganglioma/pheochromocytoma

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7. Fig. 6. Process of catecholamine synthesis

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8. Fig. 7. Processes of catecholamine metabolism

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9. Fig. 8. Conjugation processes of catecholamine metabolites

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