Study of urine steroid profiles by gas chromatography-mass spectrometry in patients with adrenocortical cancer in the course of treatment

Cover Page

Cite item

Abstract

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive disease. There are only few studies evaluating the diagnostic value of gas chromatography-mass spectrometry (GC-MS) for detection of ACC recurrence after surgery. It is necessary to conduct an in-depth study to search for the most informative markers of the disease relapse.

Aim: To study urine steroid metabolism by GC-MS during treatment to identify early signs of metastatic disease and relapse.

Materials and methods: Thirty nine (39) ACC patients were examined before and after surgery, in the early postoperative period (< 1 year) and late postoperative period (at 2 to 5 years). Ten (10) patients were disease-free at less than 1 year after surgery. Twenty nine (29) patients had metastases in lungs and other organs: 14, within 1 year after surgery, and 15, at 2 to 5 years. The control group included 25 patients with nonfunctioning adrenocortical adenomas (NAA) without malignant characteristics at histological examination. Urine steroid profiles were assessed with a gas chromatograph-mass spectrometer Shimadzu GCMS-QP2020.

Results: As assessed by GC-MS, 16 major ACC biomarkers were found before surgery, including etiocholanolone, dehydroepiandrosterone (DHEA) and its metabolites, pregnanediol, pregnanetriol, 5-ene-pregnenes, and tetrahydro-11-deoxycortisol (THS). Their urine excretion was increased compared to that in the patients with NAA (р < 0.002). A non-classic 5-ene-pregnene, 3β,16,20-pregnenetriol (3β,16,20-dP3), was identified, with its urine excretion of > 500 mcg/day that was typical for ACC patients. After surgery, decreased urinary excretion of THS (р < 0.0001) and 3β,16,20-dP3 (р < 0.0001), increased 3α,16,20-dP3/3β,16,20-dP3 ratio (р = 0.003), compared to those before surgery, were indicative of the absence of any metastases. No difference of urine THS excretion and 3α,16,20-dP3/3e,16,20-dP3 ratio from the corresponding values before surgery (p > 0.05) is a sign of metastatic diseases in the ACC patients at less than 1 year after the surgery, of the disease relapse at 2 to 5 years, and of the disease relapse after chemotherapy. In addition, in the ACC patients with metastatic disease within 1 year after surgery, increased progestogen urine excretion was found. Urine excretion of DHEA and its metabolites in the patients with the disease relapse after chemotherapy was not different from those in the ACC patients before surgery (p > 0.05).

Conclusion: Determination of urine excretion of THS, DHEA and its metabolites, etiocholanolone, 5-ene-pregnenes, 3β,16,20-dP3, and 3α,16,20-dP3/3β,16,20-dP3 ratio by GC-MS is of utmost importance in the monitoring of treatment for ACC and early diagnosis of the disease progression.

About the authors

L. I. Velikanova

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: velikanova46@gmail.com
ORCID iD: 0000-0002-9352-4035

Ludmila I. Velikanova - Doctor of Biol. Sci., Professor, Head of Scientific Laboratory of Chromatography.

41 Kirochnaya ul., Saint Petersburg, 191015.

Tel.: +7 (921) 379 32 95.

Russian Federation

N. V. Vorokhobina

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru
ORCID iD: 0000-0002-9574-105X

Natalia V. Vorokhobina - MD, PhD, Professor, Head of Chair of Endocrinology named after academician V.G. Baranov.

41 Kirochnaya ul., Saint Petersburg, 191015.

Russian Federation

Z. R. Shafigullina

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru
ORCID iD: 0000-0001-8292-8504

Zulfiya R. Shafigullina - MD, PhD, Associate Professor, Chair of Endocrinology named after academician V.G. Baranov.

41 Kirochnaya ul., Saint Petersburg, 191015.

Russian Federation

V. Yu. Bokhian

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-9066-5190

Vagan Yu. Bokhian - MD, PhD, Head of Surgical Department No. 5 (Endocrine Oncology).

24 Kashirskoe shosse, Moscow, 115478.

Russian Federation

I. S. Stilidi

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-0493-1166

Ivan S. Stilidi - MD, PhD, Professor, Member of the Russian Academy of Sciences, Director.

24 Kashirskoe shosse, Moscow, 115478.

Russian Federation

V. V. Kalugina

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru
ORCID iD: 0000-0002-2812-6911

Valentina V. Kalugina - Postgraduate Student, Chair of Endocrinology named after academician V.G. Baranov.

41 Kirochnaya ul., Saint Petersburg, 191015.

Russian Federation

E. V. Malevanaya

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru
ORCID iD: 0000-0003-0880-0814

Ekaterina V. Malevanaya - PhD (in Chem.), Senior Research Fellow, Scientific Laboratory of Chromatography.

41 Kirochnaya ul., Saint Petersburg, 191015.

Russian Federation

E. G. Strelnikova

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru
ORCID iD: 0000-0002-1208-8092

Elena G. Strelnikova - PhD (in Chem.), Senior Research Fellow, Scientific Laboratory of Chromatography.

41 Kirochnaya ul., Saint Petersburg, 191015.

Russian Federation

N. E. Kushlinskii

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-3898-4127

Nikolay E. Kushlinskii - MD, PhD, Professor, Member of Russian Academy of Sciences, Head of Laboratory of Clinical Biochemistry.

24 Kashirskoe shosse, Moscow, 115478.

Russian Federation

References

  1. Мельниченко ГА, Стилиди ИС, Алексеев БЯ, Горбунова ВА, Бельцевич ДГ, Райхман АО, Кузнецов НС, Жуков НВ, Бохян ВЮ. Федеральные клинические рекомендации по диагностике и лечению адренокортикального рака. Проблемы Эндокринологии. 2014;60(2): 51-67. doi: 10.14341/probl201460251-67.
  2. Pommier RF, Brennan MF. An eleven-year experience with adrenocortical carcinoma. Surgery. 1992;112(6):963-970; discussion 970-971.
  3. Stojadinovic A, Ghossein RA, Hoos A, Nissan A, Marshall D, Dudas M, Cordon-Cardo C, Jaques DP, Brennan MF. Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol. 2002;20(4):941-950. doi: 10.1200/JCO.2002.20.4.941.
  4. Fassnacht M, Dekkers OM, Else T, Baudin E, Berruti A, de Krijger R, Haak HR, Mihai R, Assie G, Terzolo M. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2018;179(4):G1-G46. doi: 10.1530/EJE-18-0608.
  5. Cawood TJ, Hunt PJ, O'Shea D, Cole D, Soule S. Recommended evaluation of adrenal incidentalomas is costly, has high false-positive rates and confers a risk of fatal cancer that is similar to the risk of the adrenal lesion becoming malignant; time for a rethink? Eur J Endocrinol. 2009;161(4):513-527. doi: 10.1530/EJE-09-0234.
  6. Arlt W, Biehl M, Taylor AE, Hahner S, Libe R, Hughes BA, Schneider P, Smith DJ, Stiekema H, Study of urine steroid profiles by gas chromatography-mass spectrometry in patients with adrenocortical cancer in the course of treatment 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 tumors. J Clin Endocrinol Metab. 2011;96(12): 3775-3784. doi: 10.1210/jc.2011-1565.
  7. 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. doi: 10.1007/s12672-015-0224-3.
  8. 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. doi: 10.1007/s12672-016-0267-0.
  9. Grondal S, Eriksson B, Hagenas L, Werner S, Curstedt T. Steroid profile in urine: a useful tool in the diagnosis and follow up of adrenocortical carcinoma. Acta Endocrinol (Copenh). 1990;122(5):656-663. doi: 10.1530/acta.0.1220656.
  10. Wangberg B, Khorram-Manesh A, Jansson S, Nilsson B, Nilsson O, Jakobsson CE, Lindstedt S, Oden A, Ahlman H. The long-term survival in adrenocortical carcinoma with active surgical management and use of monitored mitotane. Endocr Relat Cancer. 2010;17(1):265-272. doi: 10.1677/ERC-09-0190.
  11. Chortis V, Bancos I, Nijman T, Gilligan LC, Taylor AE, Ronchi CL, O'Reilly MW, Schreiner J, Asia M, Riester A, Perotti P, Libe R, Quinkler M, Canu L, Paiva I, Bugalho MJ, Kastelan D, Dennedy MC, Sherlock M, Ambroziak U, Vassiliadi D, Bertherat J, Beuschlein F, Fassnacht M, Deeks JJ, Biehl M, Arlt W. Urine Steroid Metabolomics as a Novel Tool for Detection of Recurrent Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2020;105(3):e307-e318. doi: 10.1210/clinem/dgz141.
  12. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol. 1989;13(3):202-206. doi: 10.1097/00000478198903000-00004.
  13. Velikanova LI, Strelnikova EG, Obedkova EV, Krivokhizhina NS, Shafigullina Z, 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. doi: 10.1134/S1061934816070169.

Supplementary files

There are no supplementary files to display.


Copyright (c) 2021 Velikanova L.I., Vorokhobina N.V., Shafigullina Z.R., Bokhian V.Y., Stilidi I.S., Kalugina V.V., Malevanaya E.V., Strelnikova E.G., Kushlinskii N.E.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies