Bulletin of Experimental Biology and Medicine

, Volume 167, Issue 5, pp 676–680 | Cite as

Gas Chromatography–Mass Spectrometry Analysis of Urinary Steroid Metabolomics for Detection of Early Signs of Adrenal Neoplasm Malignancy in Patients with Cushing’s Syndrome

  • L. I. VelikanovaEmail author
  • Z. R. Shafigullina
  • N. V. Vorokhobina
  • E. V. Malevanaya

The metabolomics of urinary steroids was studied by gas chromatography-mass spectrometry in 25 patients with Cushing’s syndrome without malignant potential and in 12 patients with malignant potential of adrenal neoplasms (Weiss score 1-3). Patients with adrenocortical adenoma (N=24) constituted the control group. In patients with Cushing’s syndrome and malignant potential, increased urinary excretion of 16-oxo-androstendiol, tetrahydro-11-deoxycortisol, and 16-hydroxypregnendiol, which had 100% specificity and sensitivity >90% for the diagnosis of malignant potential. Additionally, non-classical 5-ene-pregnenes (16-OHpregnenolone, 21-OH-pregnenolone, 3β,16,20-pregnentriol, and 3β,17,20-pregnentriol) were identified. The revealed changes in the metabolomics of steroids can be early signs of malignant potential in patients with Cushing’s syndrome. In patients with malignant potential, three signs of reduced activity of 11β-hydroxysteroid dehydrogenase type 2 were detected and in patients without malignant potential, one sign was found. In patients with and without malignant potential, three signs increased activity of 5β-reductase were found.

Key Words

steroid profile in urine gas chromatography-mass spectrometry Cushing’s syndrome malignant potential 


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  1. 1.
    Velikanova LI, Shafigullina ZR, Vorokhobina NV, Grigoryan K, Lisitsin AA, Obedkova EV. Differential diagnostics of adrenocortical incidentalomaswith different laboratory technologies. Vestn. Severo-Zapad. Gos. med. Univer. im. I. I. Mechnikova. 2015;7(4):52-57. Russian.Google Scholar
  2. 2.
    Shafigullina ZR, Velikanova LI, Vorohobina NV, Lisicyn AA, Kuhianidze EA, Strelnikova EG, Povarov VG, Talor NF. The diagnostical importance of steroid profiles of biological fluids of patients with Cushing’s syndrome. Probl. Endokrinol. 2015;61(4):4-8. Russian.CrossRefGoogle Scholar
  3. 3.
    Arlt W, Biehl M, Taylor AE, Hahner S, Libé R, Hughes BA, Schneider P, Smith DJ, Stiekema H, Krone N, Porfiri E, Opocher G, Bertherat J, Mantero F, Allolio B, Terzolo M, Nightingale P, Shackleton CH, Bertagna X, Fassnacht M, Stewart PM. Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumor. J. Clin. Endocrinol. Metab. 2011;96(12):3775-3784.CrossRefGoogle Scholar
  4. 4.
    Eisenhofer G, Masjkur J, Peitzsch M, Di Dalmazi G, Bidlingmaier M, Grüber M, Fazel J, Osswald A, Beuschlein F, Reincke M. Plasma steroid metabolome for diagnosis and subtyping patients with Cushing syndrome. Clin. Chem. 2018;64(3):586-596.CrossRefGoogle Scholar
  5. 5.
    Kanagarajah P, Ayyathurai R, Manoharan M, Narayanan G, Kava B.R. Current concepts in the management of adrenal incidentalomas. Urol. Ann. 2012;4(3):137-144.CrossRefGoogle Scholar
  6. 6.
    Kerkhofs TM, Kerstens MN, Kema IP, Willems TP, Haak HR. Diagnostic value of urinary steroid profiling in the evaluation of adrenal tumors. Horm. cancer. 2015;6(4):168-175.CrossRefGoogle Scholar
  7. 7.
    Kirschner LS, Stratakis CA. 5th International ACC Symposium: The New Genetics of Benign Adrenocortical Neoplasia: Hyperplasias, Adenomas, and Their Implications for Progression into Cancer. Horm Cancer. 2016;7(1):9-16.CrossRefGoogle Scholar
  8. 8.
    Kotłowska A, Puzyn T, Sworczak K, Stepnowski P, Szefer P. Metabolomic biomarkers in urine of Cushing’s syndrome patients. Int. J. Mol. Sci. 2017;18(2). pii: E294. doi: 10.3390/ijms18020294.CrossRefGoogle Scholar
  9. 9.
    Krone N, Hughes BA, Lavery GG, Stewart PM, Arlt W, Shackleton CH. Gas chromatography/massspectrometry (GC/MS) remains a pre-eminent discovery tool in clinical steroid investigations even in the era of fast liquid chromatography tandem mass spectrometry (LC/MS/MS). J. Steroid Biochem. Mol. Biol. 2010;121(3-5):496-504.CrossRefGoogle Scholar
  10. 10.
    Morelli V, Reimondo G, Giordano R, Della Casa S, Policola C, Palmieri S, Salcuni AS, Dolci A, Mendola M, Arosio M, Ambrosi B, Scillitani A, Ghigo E, Beck-Peccoz P, Terzolo M, Chiodini I. Long-term follow-up in adrenal incidentalomas: an Italian multicenter study. J. Clin. Endocrinol. Metab. 2014;99(3):827-834.CrossRefGoogle Scholar
  11. 11.
    Morin E, Mete O, Wasserman JD, Joshua AM, Asa SL, Ezzat S. Carney complex with adrenal cortical carcinoma. J. Clin. Endocrinol. Metab. 2012;97(2):E202-E206.CrossRefGoogle Scholar
  12. 12.
    Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2008;93(5):1526-1540.CrossRefGoogle Scholar
  13. 13.
    Tiu SC, Chan AO, Taylor NF, Lee CY, Loung PY, Choi CH, Shek CC. Use of urinary steroid profiling for diagnosing and monitoring adrenocortical tumours. Hong Kong Med. J. 2009;15(6):463-470.PubMedGoogle Scholar
  14. 14.
    Velikanova LI, Shafigullina ZR, Lisitsin AA, Vorokhobina NV, Grigoryan K, Kukhianidze EA, Strelnikova EG, Krivokhizhina NS, Krasnov LM, Fedorov EA, Sablin IV, Moskvin AL, Bessonova EA. Different types of urinary steroid profiling obtained by high-performance liquid chromatography and gas chromatography-mass spectrometry in patients with adrenocortical carcinoma. Horm. Cancer. 2016;7(5-6):327-335.CrossRefGoogle Scholar
  15. 15.
    Velikanova LI, Strel’nikova EG, Obedkova EV, Krivokhizhina NS, Shafigullina ZR, Grigoryan K, Povarov VG, Moskvin AL. Generation of urinary steroid profiles in patients with adrenal incidentaloma using gas chromatography-mass spectrometry. J. Anal. Chem. 2016;71(7):748-754.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • L. I. Velikanova
    • 1
    Email author
  • Z. R. Shafigullina
    • 1
  • N. V. Vorokhobina
    • 1
  • E. V. Malevanaya
    • 1
  1. 1.I. I. Mechnikov North-Western State Medical University, Ministry of Health of the Russian FederationSt. PetersburgRussia

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