Steroid profiling characteristics in pediatrc adrenal diseases
https://doi.org/10.14341/probl13166
Abstract
BACKGROUND: Adrenocortical adenomas are often followed with steroid hormones hyperproduction, and therefore determination of their concentration plays an important role in the differential diagnosis of adrenal diseases. Steroid profiling by tandem mass spectrometry is one of the main diagnostic methods in steroidogenesis characterization. Currently plasma and urinary steroid profiling is of particular interest in differential diagnosis and subtyping patients with adrenocortical adenomas.
AIM: Steroid profiling of pediatric patients with adrenal diseases (incidentalomas, ACTH-secreting pituitary adenoma, ACTH-independent Cushing syndrome, premature adrenarche).
MATERIALS AND METHODS: We conducted a retrospective analysis of steroid profile of 41 pediatric patients with adrenal diseases who were observed between 2005 and 2020 at the Endocrinology Research Centre.
RESULTS: All patients were divided into groups due to diagnosis: with ACTH-secreting pituitary adenoma [n=7], ACTH-independent Cushing syndrome (autonomous cortisol secretion by an adrenal adenoma) [n=4], with incidentaloma [n=7] and premature adrenarche [n=23]. In group of patients with ACTH-independent Cushing syndrome identified statistically significant higher levels of 11-deoxycortisol (р=0, 0035) and significant lower levels of 17-hydroxypregnenolone (р=0, 0026) and DHEA (р=0, 0047) compared to other groups. Statistically significant differences in steroid profiles between other groups were not identified.
CONCLUSION: Results of our study steroid profiling can be used as additional differential diagnosis method in patients with adrenocortical adenomas with or without hormonal hyperproduction (ACTH-independent Cushing syndrome and incidentaloma). Further studies are needed to identify steroid markers for subtyping pediatric adrenal diseases.
About the Authors
E. A. YanarRussian Federation
Eda A. Yanar
11 Dm. Ulyanova street, 117036 Moscow
SPIN-код: 3104-6767
Competing Interests:
None
N. V. Makazan
Russian Federation
Nadezhda V. Makazan - MD, PhD
11 Dm. Ulyanova street, 117036 Moscow
SPIN-код: 7156-6517
Competing Interests:
None
V. A. Ioutsi
Russian Federation
Vitaliy A. Ioutsi - PhD
11 Dm. Ulyanova street, 117036 Moscow
SPIN-код: 9734-0997
Competing Interests:
None
M. A. Kareva
Russian Federation
Maria A. Kareva - PhD
11 Dm. Ulyanova street, 117036 Moscow
SPIN-код: 5089-0310
Competing Interests:
None
O. B. Bezlepkina
Russian Federation
Olga B. Bezlepkina - MD, PhD, Professor
11 Dm. Ulyanova street, 117036 Moscow
SPIN-код: 3884-0945
Competing Interests:
None
V. A. Peterkova
Russian Federation
Valentina A. Peterkova - MD, PhD
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
None
References
1. Choi MH, Chung BC. Bringing GC-MS profiling of steroids into clinical applications. Mass Spectrom Rev. 2015; 34(2):219-236. doi: https://doi.org/10.1002/mas.21436
2. Wooding KM, Auchus RJ. Mass spectrometry theory and application to adrenal diseases. Mol Cell Endocrinol. 2013; 371(1-2):201-207. doi: https://doi.org/10.1016/j.mce.2012.12.026
3. Wheeler MJ. Immunoassay techniques. Methods Mol Biol. 2013; (1065):7-25. doi: https://doi.org/10.1007/978-1-62703-616-0_2
4. Hawley JM, Keevil BG. Endogenous glucocorticoid analysis by liquid chromatography–tandem mass spectrometry in routine clinical laboratories. J Steroid Biochem Mol Biol. 2016; 162:27-40. doi: https://doi.org/10.1016/j.jsbmb.2016.05.014
5. Baydakova GV, Ivanova TA, Zakharova EYu, Kokorina OS. The role of tandem mass spectrometry in the diagnosis of inherited metabolic diseases. Russian Journal of Pediatric Hematology and Oncology. 2018; 5(3):96-105. (In Russ.). doi: https://doi.org/10.17650/2311-1267-2018-5-3-96-105
6. Eneroth P, Hellström K, Ryhage R. Identification and quantification of neutral fecal steroids by gas–liquid chromatography and mass spectrometry: studies of human excretion during two dietary regimens. J Lipid Res. 1964; 5(2):245-262. doi: https://doi.org/10.1016/S0022-2275(20)40246-9
7. Schoenheimer R, Rittenberg D. Deuterium as an indicator in the study of intermediary metabolism. Science. 1935; 82(2120):156-157. doi: https://doi.org/10.1126/science.82.2120.156
8. Taylor AE, Keevil B, Huhtaniemi IT. Mass spectrometry and immunoassay: how to measure steroid hormones today and tomorrow. Eur J Endocrinol. 2015; 173(2):D1-D12. doi: https://doi.org/10.1530/EJE-15-0338
9. Ghulam A, Kouach M, Racadot A, et al. Quantitative analysis of human serum corticosterone by high-performance liquid chromatography coupled to electrospray ionization mass spectrometry. J Chromatogr B Biomed Sci Appl. 1999; 727(1-2):227-233. doi: https://doi.org/10.1016/s0378-4347(99)00048-1
10. Shackleton C. Clinical steroid mass spectrometry: a 45-year history culminating in HPLC-MS/MS becoming an essential tool for patient diagnosis. J Steroid Biochem Mol Biol. 2010; 121(3-5):481-490. doi: https://doi.org/10.1016/j.jsbmb.2010.02.017
11. Lin CL, Wu TJ, Machacek DA, et al. Urinary free cortisol and cortisone determined by high performance liquid chromatography in the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 1997; 82(1):151-155. doi: https://doi.org/10.1210/jcem.82.1.3687
12. Eisenhofer G, Masjkur J, Peitzsch M, et al. Plasma steroid metabolome profiling for diagnosis and subtyping patients with Cushing syndrome. Clin Chem. 2018; 64(3):586-596. doi: https://doi.org/10.1373/clinchem.2017.282582
13. Di Dalmazi G, Fanelli F, Zavatta G, et al. The steroid profile of adrenal incidentalomas: subtyping subjects with high cardiovascular risk. J Clin Endocrinol Metab. 2019; 104(11):5519-5528. doi: https://doi.org/10.1210/jc.2019-00365
14. Taylor DR, Ghataore L, Couchman L, et al. A 13-steroid serum panel based on LC-MS/MS: Use in detection of adrenocortical carcinoma. Clin Chem. 2017; 63(12):1836-1846. doi: https://doi.org/10.1373/clinchem.2017.277624
15. Schweitzer S, Kunz M, Kurlbaum M, et al. Plasma steroid metabolome profiling for the diagnosis of adrenocortical carcinoma. Eur J Endocrinol. 2019; 180(2):117-125. doi: https://doi.org/10.1530/EJE-18-0782
16. Doerr HG, Sippell WG, Drop SL, et al. Evidence of 11 betahydroxylase deficiency in childhood adrenocortical tumors. The plasma corticosterone/11-deoxycorticosterone ratio as a possible marker for malignancy. Cancer. 1987; 60(7):1625-1629. doi: https://doi.org/10.1002/1097-0142(19871001)60:7<1625::aidcncr2820600734> 3.0.co; 2-m
17. Hanukoglu I. Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis. J Steroid Biochem Mol Biol. 1992; 43(8):779-804. doi: https://doi.org/10.1016/0960-0760(92)90307-5
18. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders [published correction appears in Endocr Rev. 2011; 32(4):579]. Endocr Rev. 2011; 32(1):81-151. doi: https://doi.org/10.1210/er.2010-0013
Supplementary files
|
1. Figure 1. Scheme of steroidogenesis | |
Subject | ||
Type | Исследовательские инструменты | |
View
(455KB)
|
Indexing metadata ▾ |
|
2. Figure 2. Distribution of 11-deoxycortisol levels by group: group 1 — patients with ACTH-dependent hypercorticism (corticotropinomas; n=7), group 2 — patients with ACTH-independent hypercorticism (corticosteroma; n=4), group 3 — patients with adrenal incidentaloma (n=7), group 4 — patients with premature adrenarche (n=23) | |
Subject | ||
Type | Исследовательские инструменты | |
View
(138KB)
|
Indexing metadata ▾ |
|
3. Figure 3. Distribution of 17-hydroxypregnenolone levels by groups: group 1 — patients with ACTH-dependent hypercorticism (corticotropinomas; n=7), group 2 — patients with ACTH-independent hypercorticism (corticosteroma; n=4), 3 group — patients with adrenal incidentaloma (n=7), group 4 — patients with premature adrenarche (n=19). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(153KB)
|
Indexing metadata ▾ |
|
4. Figure 4. Distribution of dehydroepiandrosterone levels by groups: group 1 — patients with ACTH-dependent hypercorticism (corticotropinomas; n=7), group 2 — patients with ACTH-independent hypercorticism (corticosteroma; n=4), group 3 group — patients with adrenal incidentaloma (n=7), group 4 — patients with premature adrenarche (n=23). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(145KB)
|
Indexing metadata ▾ |
|
5. Figure 5. Cortisol/11-deoxycortisol ratio by groups: group 1 — patients with ACTH-dependent hypercorticism (corticotropinomas; n=7), group 2 — patients with ACTH-independent hypercorticism (corticosteroma; n=4), group 3 — patients with adrenal incidentaloma (n=7), group 4 — patients with premature adrenarche (n=23). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(137KB)
|
Indexing metadata ▾ |
|
6. Figure 6. Corticosterone / deoxycorticosterone ratio by groups: group 1 — patients with ACTH-dependent hypercorticism (corticotropinomas; n=7), group 2 — patients with ACTH-independent hypercorticism (corticosteroma; n=4), 3- group 1 — patients with adrenal incidentaloma (n=6), group 4 — patients with premature adrenarche (n=17). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(157KB)
|
Indexing metadata ▾ |
|
7. Figure 7. 11-deoxycortisol/17-hydroxyprogesterone ratio by groups: group 1 — patients with ACTH-dependent hypercorticism (corticotropinomas; n=7), group 2 — patients with ACTH-independent hypercorticism (corticosteroma; n=4 ), group 3 — patients with adrenal incidentaloma (n=7), group 4 — patients with premature adrenarche (n=23). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(158KB)
|
Indexing metadata ▾ |
|
8. Figure 8. The ratio of deoxycorticosterone/progesterone by groups: group 1 — patients with ACTH-dependent hypercorticism (corticotropinomas; n=7), group 2 — patients with ACTH-independent hypercorticism (corticosteroma; n=4), 3- group 1 — patients with adrenal incidentaloma (n=7), group 4 — patients with premature adrenarche (n=21). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(149KB)
|
Indexing metadata ▾ |
|
9. Figure 9. The ratio of 17-hydroxypregnenolone/pregnenolone by groups: group 1 — patients with ACTH-dependent hypercorticism (corticotropinomas; n=6), group 2 — patients with ACTH-independent hypercorticism (corticosteroma; n=3), group 3 — patients with adrenal incidentaloma (n=5), group 4 — patients with premature adrenarche (n=10). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(156KB)
|
Indexing metadata ▾ |
|
10. Figure 10. 17-hydroxyprogesterone/17-hydroxypregnenolone ratio by groups: group 1 — patients with ACTH-dependent hypercorticism (corticotropinomas; n=7), group 2 — patients with ACTH-independent hypercorticism (corticosteroma; n=4 ), group 3 — patients with adrenal incidentaloma (n=7), group 4 — patients with premature adrenarche (n=19). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(177KB)
|
Indexing metadata ▾ |
Review
For citations:
Yanar E.A., Makazan N.V., Ioutsi V.A., Kareva M.A., Bezlepkina O.B., Peterkova V.A. Steroid profiling characteristics in pediatrc adrenal diseases. Problems of Endocrinology. 2022;68(6):110-120. (In Russ.) https://doi.org/10.14341/probl13166

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).