Cushing's syndrome presents undeniable signs such as: significant weight gain that can go as far as visceral obesity, diabetes, hypertension, osteoporosis (a decrease in bone density), the appearance of cardiovascular disease, thromboembolic diseases (formation of blood clot in vessels) and an alteration of the reproductive system.
We can find symptoms such as: muscle atrophy (decrease in muscle mass) muscle weakness and back pain, purple/pink stretch marks on the arms, abdomen and thighs, psychiatric and cognitive deficits and infections. Symptoms can also be found in the skin, which is thin with hyperpigmentation, acne and reddening of the face.
At the cardiovascular level, damage is due to hypertension caused by excessively secreted glucocorticoids. Cortisol has mineralocorticoid activity when its level is very high. The renal regulatory enzyme
From: https://www.ohsu.edu/media/127156 (11-hydroxysteroid dehydrogenase type 2) is unable to inactivate this hormone, resulting in hypertension.
There is also a hemostatic disturbance (the process of preventing or stopping the flow of blood), which is caused by impaired hypercoagulation and fibrinolysis (process of dissolution of blood clot). High cortisol levels stimulate the synthesis of clotting factors, such as fibrinogen.
The functional alterations in vascular smooth muscle cells causes impaired vasoreactivity which can lead to atherosclerosis (plaque formation in arterial walls). This is due to hormonal factors of endothelial dysfunction: in addition, cortisol inhibits vasodilator systems such as nitric oxide and inhibition of peripheral catecholamine catabolism, particularly norepinephrine, which can affect endothelial function.
Another physiological alteration is found at the metabolic level. Cushing's syndrome affects glucose and lipid homeostasis by affecting the genes responsible for lipid storage and concentration. Patients present an increase of lipogenesis in the liver and an increase in circulating fatty acids. On the other hand, glucocorticoids alter insulin signalling in the liver and skeletal muscle, including insulin secretion by decreasing the expression of the glucose transporter GLUT2, glucokinase and the insulin receptor post-receptor.
This endocrine disease also influences bone metabolism including: alteration of calcium homeostasis, an imbalance in bone formation by inhibiting osteoblast differentiation and function, aiding in osteoblast apoptosis and osteolysis (responsible for bone formation) and allows for a longer lifespan responsible for the elimination of old bone cells. These hormones decrease the absorption of calcium (via the intestine) through a mechanism linked to vitamin D (important for reabsorbing calcium). This contributes to the decrease in bone mineral density and increase the risk of osteoporosis.
Finally, patients with this disease have a lean body mass, reduced creatine kinase, plasma myoglobin and muscle fibre conduction velocity. This is due to the excess of glucocorticoids leading to muscle atrophy.
In conclusion, this endocrine disease has a large number of deleterious effects, affecting different systems and leading to numerous complications.
Different parts of the organism that Cushing Syndrome afffects
References :
- Barbot M, Zilio M, Scaroni C. Cushing’s syndrome: Overview of clinical presentaOon, diagnostic tools and complications. Best Pract Res Clin Endocrinol Metab. 2020 Mar;34(2):101380. DOI: 10.1016/j.beem.2020.101380
- Ferraù F, Korbonits M. Metabolic Syndrome in Cushing’s Syndrome Patients. Front Horm Res. 2018;49:85–103. DOI: 10.1159/000486002
- Lupoli R, Ambrosino P, Tortora A, Barba L, & Dario Di Minno MN. Markers of atherosclerosis in patients with Cushing’s syndrome: a meta-analysis of literature studies . [Internet]. [cited 2021 Mar 12]. Available from: hpps:// www.tandfonline.com/doi/full/10.1080/07853890.2016.1252055
- Debono M, Newell-Price JD. Cushing’s Syndrome: Where and How to Find It. Front Horm Res. 2016;46:15–27. DOI: 10.1159/000443861
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