Preview

Problems of Endocrinology

Advanced search

Assessment of autoantibodies against 21-hydroxylase in the diagnosis of primary autoimmune adrenal insufficiency

https://doi.org/10.14341/probl12106

Abstract

Primary adrenal insufficiency is manifested by a deficiency of adrenal cortex hormones and can lead to a life-threatening condition. Early diagnosis is key to patient survival. Auto-antibodies to one of the adrenal steroidogenesis enzymes, 21-hydroxylase, are an immunological marker of autoimmune adrenal insufficiency. On the one hand, the study of antibodies to 21-hydroxylase is a method that helps establish the etiology of the disease – the autoimmune genesis of adrenal gland damage. On the other hand, the determination of autoantibodies to 21-hydroxylase is the only prognostic factor of the risk of adrenal insufficiency, which makes it possible to prevent the development of acute adrenal crisis. The article provides a brief literature review on autoantibodies to 21-hydroxylase and the pathogenesis of autoimmune adrenal insufficiency, and a series of clinical cases that illustrates the significant role of autoantibodies to 21-hydroxylase in diagnosis of adrenal insufficiency.

About the Authors

Leila S. Sozaeva
Endocrinology Research centre
Russian Federation

MD, PhD, senior researcher



Nadezhda V. Makazan
Endocrinology research centre
Russian Federation

MD, PhD, senior researcher



Larisa V. Nikankina
Endocrinology Research centre
Russian Federation

MD, PhD



Natalya M. Malysheva
Endocrinology Research centre
Russian Federation

MD, PhD, leading researcher



Ekaterina V. Kuvaldina
The Russian National Research Medical University named after N.I. Pirogov
Russian Federation

MD



Maria A. Kareva
Endocrinology research centre
Russian Federation

MD, PhD



Elizaveta M. Orlova
Endocrinology research centre
Russian Federation

MD



Valentina A. Peterkova
Endocrinology Research centre
Russian Federation

MD, PhD, professor, academician of RAS



References

1. Федеральные клинические рекомендации (протоколы) по ведению детей с эндокринными заболеваниями. Под ред. Дедова И.И. и Петерковой В.А. М.: Практика; 2014. Federal’nye klinicheskie rekomendatsii (protokoly) po vedeniyu detei s endokrinnymi zabolevaniyami. Ed by Dedov I.I., Peterkova V.A. M.: Praktika; 2014. (In Russ.).

2. Dunlop D. Eighty-six cases of Addison’s disease. Br Med J. 1963; 2(5362):887-891. doi: https://doi.org/10.1136/bmj.2.5362.887

3. Betterle C, Scarpa R, Garelli S, et al. Addison’s disease: a survey on 633 patients in Padova. Eur J Endocrinol. 2013;169(6):773-784. doi: https://doi.org/10.1530/EJE-13-0528

4. Erichsen MM, Løvås K, Skinningsrud B, et al. Clinical, immunological, and genetic features of autoimmune primary adrenal insufficiency: observations from a Norwegian registry. J Clin Endocrinol Metab. 2009;94(12):4882-4890. doi: https://doi.org/10.1210/jc.2009-1368

5. Laureti S, Vecchi L, Santeusanio F, Falorni A. Is the prevalence of Addison’s disease underestimated? J Clin Endocrinol Metab. 1999;84(5):1762. doi: https://doi.org/10.1210/jcem.84.5.5677-7

6. Willis AC, Vince FP. The prevalence of Addison’s disease in Coventry, UK. Postgrad Med J. 1997;73(859):286-288. doi: https://doi.org/10.1136/pgmj.73.859.286

7. Betterle C, Morlin L. Autoimmune Addison’s disease. Endocr Dev. 2011;20:161-172. doi: https://doi.org/10.1159/000321239

8. Orlova EM, Sozaeva LS, Kareva MA, et al. Expanding the phenotypic and genotypic landscape of autoimmune polyendocrine syndrome type 1. J Clin Endocrinol Metab. 2017;102(9):3546-3556. doi: https://doi.org/10.1210/jc.2017-00139

9. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. doi: https://doi.org/10.1210/jc.2015-1710

10. Extract of Suprarenal Cortex in the Treatment of Addison’s Disease. Edinb Med J. 1932;39(4):268-270.

11. Anderson JR, Goudie RB, Gray K, Timbury GC. Auto-antibodies in Addison’s disease. Lancet. 1957;269(6979):1123-1124. doi: https://doi.org/10.1016/s0140-6736(57)91687-2

12. Winqvist O, Karlsson FA, Kämpe O. 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet. 1992;339(8809): 1559-1562. doi: https://doi.org/10.1016/0140-6736(92)91829-w

13. Boscaro M, Betterle C, Volpato M, et al. Hormonal responses during various phases of autoimmune adrenal failure: no evidence for 21-hydroxylase enzyme activity inhibition in vivo. J Clin Endocrinol Metab. 1996;81(8):2801-2804. doi: https://doi.org/10.1210/jcem.81.8.8768833

14. Rottembourg D, Deal C, Lambert M, et al. 21-Hydroxylase epitopes are targeted by CD8 T cells in autoimmune Addison’s disease. J Autoimmun. 2010;35(4):309-315. doi: https://doi.org/10.1016/j.jaut.2010.07.001

15. Wolff AS, Mitchell AL, Cordell HJ, et al. CTLA-4 as a genetic determinant in autoimmune Addison’s disease. Genes Immun. 2015;16(6):430-436. doi: https://doi.org/10.1038/gene.2015.27

16. Blomhoff A, Lie BA, Myhre AG, et al. Polymorphisms in the cytotoxic T lymphocyte antigen-4 gene region confer susceptibility to Addison’s disease. J Clin Endocrinol Metab. 2004;89(7):3474-3476. doi: https://doi.org/10.1210/jc.2003-031854

17. Salmond RJ, Brownlie RJ, Morrison VL, Zamoyska R. The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals. Nat Immunol. 2014;15(9):875-883. doi: https://doi.org/10.1038/ni.2958

18. Skinningsrud B, Husebye ES, Gervin K, et al. Mutation screening of PTPN22: association of the 1858T-allele with Addison’s disease. Eur J Hum Genet. 2008;16(8):977-982. doi: https://doi.org/10.1038/ejhg.2008.33

19. Mitchell AL, Cordell HJ, Soemedi R, et al. Programmed death ligand 1 (PD-L1) gene variants contribute to autoimmune Addison’s disease and Graves’ disease susceptibility. J Clin Endocrinol Metab. 2009;94(12):5139-5145. doi: https://doi.org/10.1210/jc.2009-1404

20. de Filette J, Andreescu C, Cools F, et al. A systematic review and meta-analysis of endocrine-related adverse events associated with immune checkpoint inhibitors. Horm Metab Res. 2019;51(3):145-156. doi: https://doi.org/10.1055/a-0843-3366

21. Hellesen A, Bratland E, Husebye ES. Autoimmune Addison’s disease – an update on pathogenesis. Ann Endocrinol (Paris). 2018; 79(3):157-163. doi: https://doi.org/10.1016/j.ando.2018.03.008

22. Eriksson D, Bianchi M, Landegren N, et al. Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison’s disease in Sweden. Sci Rep. 2018;8(1):8395. doi: https://doi.org/10.1038/s41598-018-26842-2

23. Betterle C, Garelli S, Presotto F, Furmaniak J. From appearance of adrenal autoantibodies to clinical symptoms of Addison’s disease: natural history. Front Horm Res. 2016;46:133-145. doi: https://doi.org/10.1159/000443872


Supplementary files

Review

For citations:


Sozaeva L.S., Makazan N.V., Nikankina L.V., Malysheva N.M., Kuvaldina E.V., Kareva M.A., Orlova E.M., Peterkova V.A. Assessment of autoantibodies against 21-hydroxylase in the diagnosis of primary autoimmune adrenal insufficiency. Problems of Endocrinology. 2019;65(6):466-473. https://doi.org/10.14341/probl12106

Views: 3658


ISSN 0375-9660 (Print)
ISSN 2308-1430 (Online)