Orbital manifestations of hypercorticism

Maria O. Korchagina; Alexey A. Trukhin; Natalya Yu. Sviridenko

doi:10.14341/ket12699

Orbital manifestations of hypercorticism

Maria O. Korchagina, Alexey A. Trukhin, Natalya Yu. Sviridenko

https://doi.org/10.14341/ket12699

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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.

Keywords

Cushing's syndrome, hypercortisolism, exophthalmos, adipogenesis

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

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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

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

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	Title	Figure 1. Bilateral exophthalmos according to magnetic resonance imaging in a patient with Cushing's syndrome [5]
	Type	Исследовательские инструменты
	Date	2021-06-16
Digital Object Identifier	https://doi.org/10.14341/ket12699-5888

	Title	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)
	Type	Исследовательские инструменты
	Date	2021-06-16
Digital Object Identifier	https://doi.org/10.14341/ket12699-5889

	Title	Figure 3. The role of cortisol in adipogenesis
	Type	Исследовательские инструменты
Brief description	Location of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the ER and its relationship with H6PDH. In Cushing's syndrome, the cytosolic mineralocorticoid receptor (MR) is activated by cortisol. Most (90%) of circulating cortisol (A) is associated with corticosteroid-binding globulin (CBG), about 4-5% - with albumin, the rest of the hormone freely diffuses into the adipocyte [12]. Cortisone (B) is not so strongly associated with CBG and also diffuses into the cell, where it is reduced by 11β-HSD1 to A, increasing the intracellular concentration of A. Cortisol (A) binds to MR and glucocorticoid receptor (GR). These receptors, after binding to the ligand, are translocated into the nucleus, where they stimulate the transcription of genes responsible for the differentiation of pre-adipocytes into adipocytes and the accumulation of lipid droplets (lipid droplet). Due to the low activity of 11β-HSD2, an enzyme that inactivates endogenous cortisol in cells, most of the observed effect of cortisol is due to its effect on MR, not GR [13]. In this case, the role of GR is not fully known.
	Date	2021-02-01
Digital Object Identifier	https://doi.org/10.14341/ket12699-5864

	Title	Figure 4. Sketch of the transcriptional cascade governing adipocyte differentiation
	Type	Исследовательские инструменты
Brief description	Major adipogenic stimuli include glucocorticoids and insulin. Acting synergistically with insulin, glucocorticosteroids increase the expression of numerous genes involved in fat storage [11]. These hormones activate the first wave of adipogenic transcription factors. Two of them are well studied - C / EBPβ and C / EBPδ. They induce a second wave in which PPARg and C / EBPa play an important role [17, 18].
	Date	2021-02-01
Digital Object Identifier	https://doi.org/10.14341/ket12699-5865

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Clinical and experimental thyroidology

Orbital manifestations of hypercorticism

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Abstract

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About the Authors

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