Features of steroid metabolomics in patients with Cushing’s syndrome with unilateral and bilateral adrenocortical pathology


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Abstract

Background. The possibility of using chromatographic methods to determine a wide range of steroid hormones of the adrenal cortex in the blood and urine made it possible to reveal the features of steroid metabolomics in patients with Cushing’s syndrome (CS) with unilateral and bilateral adrenocortical pathology and to compare the data obtained with the features of the course of the disease. Objective. Evaluation of the steroid metabolomics in patients with CS with unilateral and bilateral adrenocortical pathology to optimize diagnosis and management tactics. Methods. The state of the pituitary-adrenal cortex and renin-aldosterone systems was assessed by the immunochemical methods using functional tests. The steroid metabolomics in biological fluids was studied using the methods of high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Statistical analysis was carried out using the Statistica software package for Windows (version 10). Results. 36 patients with CS were examined: 8 - with bilateral macronodular adrenal hyperplasia (BMAH), 9 - with bilateral adrenocortical adenoma (BAA), and 19 - with solitary (unilateral) adrenocortical adenoma (SAA). According to ELISA and GC-MS, 21-hydroxylase deficiency was revealed in patients with CS and BMAH; furthermore, an increase in androgenic, mineralocorticoid and a decrease in glucocorticoid functions of the adrenal cortex (CA) were detected compared with those of patients with SAA. In CS patients with BAA, urinary excretion of the main androgens, progestogens, tetrahydrometabolites of cortisol, cortisone, and corticosterone did not differ from those of patients with CS and SAH, and urinary excretion of tetrahydro-11-deoxycortisol (THS) was reduced., According to HPLC and GC-MS data, pronounced signs of type 2 11β-hydroxysteroid dehydrogenase (11β-HSDH) deficiency were revealed in patients with CS and SAA, which indicates the production of active glucocorticosteroids to a greater extent than in patients with BMAH. The clinical picture of CS develops faster and is more pronounced in patients with CS and SAA compared with those of other CS groups. A significant increase in urinary THS excretion (more than 485 pg/day), the signs of 11ß-HSDH deficiency suggest the presence of a malignant potential in a number of CS patients with BMAH. Conclusion. Chromatographic methods revealed significant differences in the metabolism of androstenedione, tetrahydrometabolites of cortisol and corticosterone in patients with SC and unilateral and bilateral adrenocortical pathology. In CS patients with BMAH, signs of 21-hydroxylase deficiency, as well as an increase in the mineralocorticoid function of the adrenal cortex, and the highest urinary androgen excretion were revealed in comparison with SAA. An increase in urinary THS excretion more than 485 pg/day indicates the presence of a malignant potential in a number of patients with CS and BMAH.

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About the authors

Zh. V Paltsman

North-Western State Medical University n.a. I.I. Mechnikov

St. Petersburg, Russia

Lyudmila I. Velikanova

North-Western State Medical University n.a. I.I. Mechnikov

Email: velikanova46@gmail.com
Dr. Sci. (Biol.), Professor, Head of the Research Chromatography Laboratory 41 Kirochnaya St., St. Petersburg 191015, Russian Federation

N. V Vorokhobina

North-Western State Medical University n.a. I.I. Mechnikov

St. Petersburg, Russia

S. B Shustov

North-Western State Medical University n.a. I.I. Mechnikov

St. Petersburg, Russia

Z. R Shafigullina

North-Western State Medical University n.a. I.I. Mechnikov

St. Petersburg, Russia

A. A Lisitsyn

North-Western State Medical University n.a. I.I. Mechnikov

St. Petersburg, Russia

E. V Malevanaya

North-Western State Medical University n.a. I.I. Mechnikov

St. Petersburg, Russia

E. G Strelnikova

North-Western State Medical University n.a. I.I. Mechnikov

St. Petersburg, Russia

References

  1. Arnaldi G., Angeli A., Atkinson A.B., et al. Diagnosis and Complications of Cushing's syndrome: A Consensus Statement. J Clin Endocrinol Metab. 2003;88(12):5593-602. doi: 10.1210/jc.2003-030871.
  2. Eisenhofer G., Masjkur J., Peitsch M., et al. Plasma steroid metabolome profiling for diagnosis and subtyping patients with Cushing syndrome. Clin Chem. 2018;64(3):586-96. doi: 10.1373/clinchem.2017.282582.
  3. Velikanova L.I. Strelnikova E.G. Obedkova E.V., et al. Generation of urinary steroid profiles in patients with adrenal incidentaloma using gas chromatography-mass spectrometry. J Anal Chem. 2016;71(7):748-54. doi: 10.1134/S1061934816070169.
  4. Шафигуллина З.Р., Великанова Л.И., Ворохобина Н.В. Диагностическое значение стероидных профилей биологических жидкостей у больных синдромом Иценко-Кушинга. Проблемы эндокринологии. 2015;61(4):4-8. doi: 10.14341/probl20156144-8.
  5. Agrons M.M., Corey J.T., Habra M.A., et al. Adrenal cortical hyperplasia: Diagnostic workup, subtypes, imaging features and mimics. Br J Radiol. 2017;1079(90):20170330. doi: 10.1259/bjr.20170330.
  6. Lacroix A., Bourdeau I. Bilateral adrenal Cushing's syndrome: macronodular adrenal hyperplasia and primary pigmented nodular adrenocortical disease. Endocrinol Metab Clin N Am. 2005;34(2):441-58. doi: 10.1016/j.ecl.2005.01.004.
  7. Bourdeau I., Parisien-La Salle S., Lacroix A. Adrenal hyperplasia: A multifaceted disease. Best Pract Res Clin Endocrinol Metab. 2020;34(3):101386. doi: 10.1016/j.beem.2020.101386.
  8. Rockall A.G., Babar S.A., Sohaib S.A.A., et al. CT and MR Imaging of the Adrenal Glands in ACTH-independent Cushing Syndrome. Radio Graphics. 2004;24(2):435-42. doi: 10.1148/rg.242035092.
  9. Jea W., Li S., Liu Q., et al. ACTH-independent Cushing's syndrome with bilateral cortisol-secreting adrenal adenomas: a case report and review of literatures. BMC. Endocr Disord. 2018;18(1):22. doi: 10.1186/s12902-018-0250-6.
  10. Hannah-Shmouni F., Berton A., Fauch F., et al. Mass spectrometry-based steroid profiling in primary bilateral macronodular adrenocortical hyperplasia. Endocrine-Related Cancer. 2020;(27):403-13. doi: 10.1530/ERC-20-0102.
  11. Delivanis D.A., Vassiliadi D.A., Tsagarakis S. Adrenal Imaging in Patients with Endocrine Hypertension. Endocrinol Metab Clin North Am. 2019;48(4):667-80. doi: 10.1016/j.ecl.2019.08.001.
  12. Weiss L.M., Medeiros L.J., Vickery A.L. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol. 1989;13:5147-85. doi: 10.1097/00000478-198903000-00004.
  13. Мельниченко Г.А., Дедов И.И., Белая Ж.Е. и др. Болезнь Иценко-Кушинга: клиника, диагностика, дифференциальная диагностика, методы лечения. Проблемы эндокринологии. 2015;61(2):55-78. doi: 10.14341/probl201561255-77.
  14. Kerkhofs T.M.A., Kerstens M.N., Kema I.P., et al. Diagnostic value of urinary steroid profiling in the evaluathion of adrenal tumors. Horm Cancer. 2015;6(4):168- 75. doi: 10.1007/s12672-015-02224-3.
  15. Bancos I., Arlt W. Diagnosis of a malignant adrenal mass: the role of urinary steroid metabolite profiling. Curr Opin Endocrinol Diab Obes. 2017;24(3):200-7. doi: 10.1097/MED.0000000000000333.
  16. Hui-Pin H., Kirschner S.L., Bourdeau I., et al. Clinical and Genetic Heterogeneity, Overlap with Other Tumor Syndromes, and Atypical Glucocorticoid Hormone Secretion in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Compared with Other Adrenocortical Tumors. Clin Endocrinol Matab. 2009;94(48):2930-7. doi: 10.1210/jc.2009-0516.
  17. Berthon A., Faucz F.R., Stratakis K.A., et al. Age-dependent effects of Armc5 haploinsufficiency on adrenocortical function. Human Mol Genet. 201 7;26( 18):3495-507. doi: 10.1093/hmg/ddx235.
  18. Albiger N.M., Regazzo D., Rubin B., et al. A multicenter experience on the prevalence of ARMC5 mutations in patients with primary bilateral macronodular adrenal hyperplasia: from genetic characterization to clinical phenotype. Endocrine. 2017;3(55):959-68. doi: 10.1007/s12020-016-0956-z.

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