Preview

Clinical and experimental thyroidology

Advanced search

Orbital manifestations of hypercorticism

https://doi.org/10.14341/ket12699

Abstract

Nowadays, Cushing's syndrome (hypercortisolism) and its manifestations are well studied. The main symptoms of hyper-cortisolism are obesity, osteoporosis, cardiomyopathy, muscle atrophy, skin thinning and purple stretch marks (striae) on the body. In practice, obesity and osteoporosis are the most frequent symptoms that are found in 90% of cases. However, there are some patients with an implicit clinical picture of hypercorticism. Some cases might concomitant with exophthalmos. This review describes a rare symptom of hypercortisolism — exophthalmos. Exophthalmos is a pathological protruding of eyeballs. This symptom is known in the context of TED that occurs most commonly in patients with Graves' disease. The article compares the mechanisms of development of eye symptoms in Cushing's syndrome and thyroid diseases, especially the Graves' disease. It discusses possible molecular mechanisms leading to exophthalmia in patients with Cushing's syndrome. Factors affecting adipogenesis in vitro and in vivo are studied, in particular factors leading to an increase of orbital fatty tissue against of elevated cortisol levels. Hormonal signaling and transcription cascades responsible for adipocyte differentiation into mature fat cells are presented. Other orbital manifestations of hypercortisolism, which occur relatively rare in practice, are also discussed in the article. These include glaucoma as well as cataract, Lisha nodules and central serous chorioretinopathy. Clinical cases of Cushing's syndrome with different ocular manifestations are considered and appropriate conclusions have been drawn.

About the Authors

Maria O. Korchagina
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

eLibrary SPIN:7834-5652

Nagornaya street 17/3, 117186, Moscow


Competing Interests:

not



Alexey A. Trukhin
Endocrinology Research Centre
Russian Federation

eLibrary SPIN: 4398-9536

Moscow


Competing Interests:

not



Natalya Yu. Sviridenko
Endocrinology Research Centre
Russian Federation

MD, PhD, Professor; eLibrary SPIN: 5889-6484.

Moscow


Competing Interests:

not



References

1. Rossijskaja associadja endokrinologov i nejrohirurgov. Bolezn’ Icenko-Kushinga. Klinicheskie rekomendacii. Moscow: Ministerstvo zdravoohranenija Rossijskoj Federacii; 2016. (In Russ.).

2. Melnichenko GA, Dedov II, Belaya ZE, et al. Cushing's disease: the clinical features, diagnostics, differential diagnostics, and methods of treatment. Problems of Endocrinology. 2015;61(2):55-77. (In Russ.). doi: https://doi.org/10.14341/probl201561255-77

3. Findling JW, Raff H. Screening and diagnosis of Cushing's syndrome. Endocrinol Metab Clin North Am. 2005;34(2):385-x. doi: https://doi.org/10.1016/j.ecl.2005.02.001

4. Clinicaltrials [Internet]: U.S. National Library of Medicine; 2020 — Hypercorticism, Russia. Available from: https://clinicaltrials.gov/ct2/results?cond=Hypercorticism&term=&cntry=RU&state=&city=&dist=&Search=Search

5. Giugni AS, Mani S, Kannan S, Hatipoglu B. Exophthalmos: A Forgotten Clinical Sign of Cushing's Syndrome. Case Rep Endocrinol. 2013;2013(2):1-3. doi: https://doi.org/10.1155/2013/205208

6. Dedov II, Melnichenko GA, Sviridenko NY, et al. Federal clinical recommendations on diagnostics and treatment of endocrine ophthalmopathy associated with autoimmune thyroid pathology. Problems of Endocrinology. 2015;61(1):61-74. (In Russ.). doi: https://doi.org/10.14341/probl201561161-74

7. Durrani O.M, Onyimba CU, Bujalska IJ, et al. Thyroid Associated Ophthalmopathy — Cushing's Disease of the Orbit? Invest. Ophthalmol. Vis. Sci. 2007;48(13):3573.

8. Cushing H. The basophil adenomas of the pituitary body and their clinical manifestation. Bulletin Johns Hopkins Hospital. 1932;50:173-195.

9. Giugni AS, Mani S, Kannan S, et al. Exophthalmos: A Forgotten Clinical Sign of Cushing's Syndrome. Case Rep Endocrinol. 2013;2013:205-208. doi: https://doi.org/10.1155/2013/205208

10. Kelly W. Exophthalmos in Cushing's syndrome. Clin Endocrinol (Oxf). 1996;45(2):167-170. doi: https://doi.org/10.1046/j.1365-2265.1996.d01-1559.x

11. Lee M-J, Pramyothin P, Karastergiou K, Fried SK. Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity. Biochim Biophys Acta - Mol Basis Dis. 2014;1842(3):473-481. doi: https://doi.org/10.1016/j.bbadis.2013.05.029

12. Paredes S, Ribeiro L. Cortisol: the villain in Metabolic Syndrome? Rev Assoc Med Bras. 2014;60(1):84-92. doi: https://doi.org/10.1590/1806-9282.60.01.017

13. Gomez-Sanchez CE. What is the role of the adipocyte mineralocorticoid receptor in the metabolic syndrome? Hypertension. 2015;66(1):17-19. doi: https://doi.org/10.1161/HYPERTENSIONAHA.115.05148

14. Artemova EV. Synthesis, activation and deactivation of glucocorticoids. The biological role of cortisol in metabolic disorders. Obesity and metabolism. 2017;14(2):48-52. (In Russ.). doi: https://doi.org/10.14341/omet2017248-52

15. Morgan S, McCabe E, Gathercole L, et al. 11-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess. Proceedings of the National Academy of Sciences. 2014;111(24):E2482-E2491. doi: https://doi.org/10.1073/pnas.1323681111

16. Lee J-E, Schmidt H, Lai B, Ge K. Transcriptional and Epigenomic Regulation of Adipogenesis. Mol Cell Biol. 2019;39(11). doi: https://doi.org/10.1128/MCB.00601-18

17. Rosen E, MacDougald O. Adipocyte differentiation from the inside out. Nature Reviews Molecular Cell Biology. 2006;7(12):885-896. doi: https://doi.org/10.1038/nrm2066

18. Lowe C, O'Rahilly S, Rochford J. Adipogenesis at a glance. J Cell Sci. 2011;124(21):3726-3726. doi: https://doi.org/10.1242/jcs.101741

19. Moseti D, Regassa A, Kim W-K. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules. Int J Mol Sci. 2016;17(1):124. doi: https://doi.org/10.3390/ijms17010124

20. Egorov AD, Penkov DN, Tkachuk VA. Molecular and cellular mechanisms of adipogenesis. Diabetesmellitus. 2015;18(2):12-19. (In Russ.). doi: https://doi.org/10.14341/DM2015212-19

21. Galitzky J, Bouloumie A. Human Visceral-Fat-Specific Glucocorticoid Tuning of Adipogenesis. Cell Metab. 2013;18(1):3-5. doi: https://doi.org/10.1016/j.cmet.2013.06.008

22. Luong Q, Huang J, Lee KY. Deciphering White Adipose Tissue Heterogeneity. Biology (Basel). 2019;8(2):23. doi: https://doi.org/10.3390/biology8020023

23. Chen J, Yang Y, Li S, et al. E2F1 Regulates Adipocyte Differentiation and Adipogenesis by Activating ICAT. Cells. 2020;9(4):1024. doi: https://doi.org/10.3390/cells9041024

24. Christodoulides C, Lagathu C, Sethi J, et al. Adipogenesis and WNT signalling. Trends in Endocrinology & Metabolism. 2009;20(1):16-24. doi: https://doi.org/10.1016/j.tem.2008.09.002

25. Peyster R, Ginsberg F, Silber J, et al, Exophthalmos caused by excessive fat: CT volumetric analysis and differential diagnosis. American Journal of Roentgenology. 1986;146(3):459-464.

26. Borzenok SA, Gushchina MB, Afanasyeva DS, et al. Orbital adipose tissue is a new resource for transplantology. Russian Journal of Transplantology and Artificial Organs. 2015;17(4):118-123. (In Russ.). doi: https://doi.org/10.15825/1995-1191-2015-4-118-123

27. Onyimba C, Bujalska I, Durrani O, et al. Glucocorticoid metabolic pathways in human orbital adipose tissue: a comparison with subcutaneous and omental depots. Endocrine Abstracts. 2007;13:115.

28. Habib SN, Lin Z, Puvanachandra N. Ocular hypertension secondary to high endogenous steroid load in Cushing's disease. BMJ Case Rep. 2019;12(1):bcr-2018-226738. doi: https://doi.org/10.1136/bcr-2018-226738

29. Bouzas EA, Mastorakos G, Friedman TC et al. Posterior subcapsular cataract in endogenous Cushing syndrome: an uncommon manifestation. Invest Ophthalmol Vis Sci. 1993;34(13):3497-3500.

30. Ibrahim IM, Al-Bermani A, James RA. Ophthalmic presentations of Cushing's syndrome. Presented at Society for Endocrinology BES, Glasgow, UK. Endocrine Abstracts 2006;11:79.

31. Appa S. Subclinical hypercortisolism in central serous chorioretinopathy. Retin Cases Brief Rep. 2014;8(4):310-313. doi: https://doi.org/10.1097/icb.0000000000000036

32. Clarke C, Smith SV, Lee AG. A rare association: Cushing disease and central serous chorioretinopathy. Can J Ophthalmol. 2017;52(2):e77-e79. doi: https://doi.org/10.1016/jjcjo.2016.09.002

33. Jacob J, Chopra R, Chander A. The eye as a window to rare endocrine disorders. Indian J Endocrinol Metab. 2012;16(3):331. doi: https://doi.org/10.4103/2230-8210.95659


Supplementary files

1. Figure 1. Bilateral exophthalmos according to magnetic resonance imaging in a patient with Cushing's syndrome [5]
Subject
Type Исследовательские инструменты
View (132KB)    
Indexing metadata ▾
2. Figure 2. "Lipogenic" variant of endocrine orbitopathy: (B) multispiral computed tomography of the orbits, axial projection (the posterior pole of the eyeball is located on the inter-zygomatic line - white line)
Subject
Type Исследовательские инструменты
View (159KB)    
Indexing metadata ▾
3. Figure 3. The role of cortisol in adipogenesis
Subject
Type Исследовательские инструменты
View (115KB)    
Indexing metadata ▾
4. Figure 4. Sketch of the transcriptional cascade governing adipocyte differentiation
Subject
Type Исследовательские инструменты
View (110KB)    
Indexing metadata ▾

Review

For citations:


Korchagina M.O., Trukhin A.A., Sviridenko N.Yu. Orbital manifestations of hypercorticism. Clinical and experimental thyroidology. 2020;16(4):4-13. (In Russ.) https://doi.org/10.14341/ket12699

Views: 968


ISSN 1995-5472 (Print)
ISSN 2310-3787 (Online)