Complications Of Cushing's Syndrome

In the United States each year, it is estimated about ten to fifteen million individuals experience Cushing’s syndro. This disorder occurs when the body has too much cortisol, which is a type of hormone that impacts all organs and tissues in the body. The adrenal glands produce this hormone. Regulation of cortisol is due to the pituitary gland producing adrenocorticotropic hormone (ACTH). When the normal amount is produced, this hormone helps the body properly respond to change and stress. It modifies the inflammation response, controls water in the body, mobilizes nutrients, and helps manage blood sugar. When this syndrome is present, and cortisol in the body is too high, it can cause several complications. Learn about these now.

Bone Fractures And Bone Loss

While the data is limited, it is estimated bone fractures and bone loss occur in about thirty to fifty percent of patients. The fractures appear to be the most common at the vertebral level, which can result in additional complications, such as back pain, height loss, and kyphosis. The risk of fractures increases as bone density decreases. In children, this complication may interfere with normal growth, reducing the total height the child may have achieved if they did not experience this complication of Cushing’s syndrome. Some research shows bone mass deficits might be able to be partially reversed by getting cortisol under control. However, doctors agree this is not guaranteed. Patients might require treatments to enhance their bone density in addition to the treatments used to treat their high cortisol.

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Type 2 Diabetes

Type 2 diabetes is possible in individuals with Cushing’s syndrome due to how the condition impacts glucose in the body. Research shows diabetes may occur in twenty to fifty percent of patients. Approximately thirty to sixty percent of patients might develop impaired glucose tolerance. When cortisol is too high, it can result in the body’s carbohydrate tolerance decreasing. Glucose production and hepatic glycogen can increase while glucose uptake and peripheral tissue usage of glucose decrease. Treatments focused on blood sugar control, including reduced carbohydrate intake and other dietary changes may be beneficial. However, to improve this complication, it is important to get cortisol under control.

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Kidney Stones

Approximately fifty percent of patients who have Cushing’s syndrome experience kidney stones. Why they develop is still not fully understood. However, the theory is as the bones lose some of their density, calcium leaks from them. The calcium eventually makes its way to the kidneys, resulting in kidney stones. Calcium stones are the most common type found in the kidneys, and they can cause excruciating pain. They might also cause urinary issues, vomiting, nausea, and infection. Some of these kidney stones might pass on their own, but others require medical intervention to remove them from the kidneys and urinary tract. Treating Cushing’s syndrome does usually reduce a patient’s risk of future stone development, but the risk is never eliminated.

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High Blood Pressure

About seventy to eighty percent of patients experience high blood pressure in the form of arterial hypertension, and while it can be severe, it is typically mild to moderate. It is not uncommon for this complication to result in another issue referred to as cardiac hypertrophy. This condition is characterized by the heart muscle becoming abnormally thickened or enlarged. This typically occurs because hypertension associated with Cushing’s syndrome can put increased and prolonged stress on the heart. While medications for hypertension may be effective for some patients, lowering cortisol is typically more efficient in bringing blood pressure back to a normal level.

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Pituitary Tumor Enlargement

Pituitary gland enlargement usually occurs as the result of pituitary tumor enlargement. The tumor can be malignant or benign. About seventy percent of spontaneous Cushing’s syndrome cases are the result of a small benign tumor developing on the pituitary gland, which is referred to as a pituitary adenoma. This causes the gland to produce more ACTH, which is a hormone that tells the adrenal glands to produce cortisol. The more ACTH there is in the body, the more cortisol will be in the body. When this gland is enlarged, it may cause patients to experience headaches, and can also result in vision issues since as the gland grows, it often puts pressure on the optic nerve.

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Loss Of Strength And Muscle Mass

Individuals who have Cushing's syndrome can experience loss of strength and muscle mass as a complication of their disease. The mechanism behind this symptom involves the long term effects of elevated cortisol production and its levels in the muscles. The muscle tissues are made out of thousands of muscle fibers that contain elastic tissue. Elastic tissue is composed of elastic fibers, which are made from numerous bundles of proteins. The building blocks of proteins are called amino acids. Extended periods of elevated cortisol in the muscle tissues causes amino acids to break free from some of their protein chains. This mechanism causes the breakdown of the elastic fibers, leading to the disintegration of the muscle fibers. As this process progresses, the muscles begin to waste away or reduce in size and decrease in their function. This appears externally as a loss of muscle mass in the patient, which is often accompanied by muscle weakness. Muscle weakness is defined by the inability to produce a muscle movement with the greatest effort put forth in doing so.

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Increased Infections

Increased infections occur in Cushing's syndrome patients as a complication of the disease. Cortisol in the body is immunosuppressive in nature. Cortisol produces these immunosuppressive effects on an individual through several mechanisms. Cortisol is known to decrease the quality of certain transcription factors in the process of inflammation called NF-kB and AP-1. Cortisol is also known to increase the quality of the suppressor of pro-inflammatory cytokines or SOCS. These mechanisms cause the inhibition of the activation of signal transducer and activator of transcription proteins important in the transcription of pro-inflammatory genes. The combined result of these actions is a collaborative weakening of the pro-inflammatory response by the patient's immune system. Fewer antibodies and white blood cells are produced, leaving the body more vulnerable to invasion by foreign pathogens. The immune system in individuals affected by Cushing's syndrome is unable to respond to the introduction of bacteria and viruses properly, allowing them to fester, colonize, and produce an infection. While this effect of cortisol has been utilized in the treatment of autoimmune problems, it is not helpful for those who have Cushing's syndrome.

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Unhealthy Levels Of Cholesterol

Individuals affected by Cushing's syndrome may have unhealthy levels of cholesterol in their blood. Elevated cortisol levels in the body over an extended period can cause the total cholesterol and triglyceride levels to become elevated. Several factors contribute to the occurrence of this complication, including indirect cortisol action on lipid breakdown, free fatty acid turnover, fatty accumulation in the liver, indirect cortisol action on lipid breakdown, free fatty acid production, and synthesis of very-low-density lipoproteins. Cortisol is known to increase the lipase actions on the lipoproteins responsible for the transportation of fats and other lipids in an individual's blood. This process is increased in the adipose and visceral fat tissues where it activates the breakdown of this stored fat, releasing free fatty acids into the patient's blood circulation. It is this increase in free fatty acids in the blood that results in the unhealthy levels of cholesterol in individuals affected by Cushing's syndrome.

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Issues With Memory And Concentration

Issues with memory and concentration have been reported in a large number of Cushing's syndrome patients. The mechanism behind this complication has to do with the effects of high cortisol levels on certain parts of the brain over an extended durations. Cortisol can cause the individual to overproduce the cells that make myelin and underproduce the actual neurons in the brain. While myelin around the nerves is important, an excess of it is essentially non-beneficial. The reason behind such myelin buildup is the effect cortisol has on the stem cells meant to mature into neurons. Cortisol reduces the number of these cells that actually reach maturity by causing them to mature into a different type of cell that produces myelin sheathing. The result is a reduction in neurons in the patient's hippocampus. The hippocampus is the part of the brain that regulates an individual's emotions, learning, memory, and part of their concentration. Decreased numbers of neurons cause the function of the hippocampus to become compromised.

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Blood Clots In Lungs And Legs

Individuals affected by Cushing's syndrome can develop blood clots in the lungs and legs. Long term elevated levels of cortisol in the blood causes it to go into a hypercoagulable and hypofibrinolytic state. This occurs because cortisol is a hormone produced by the body for the purpose of increasing performance when an individual is placed in a stressful situation. A temporary spike in cortisol levels induces a temporary spike in platelet production and clotting factors to prepare the body for possible injury. While this is an effective mechanism in a healthy individual, someone with Cushing's syndrome consistently exhibits this cortisol spike. This causes their body to produce too many platelets on a consistent basis and stimulates elevated levels of clotting factor VIII, von Willebrand factor, and others. All of these changes in the blood cause the platelets to have an increased inclination to stick to the arterial walls and one another inappropriately. When this occurs, it forms a blood clot that can become lodged in the arteries of the legs, lungs, and other parts of the body. The mechanism the body uses to prevent clots called fibrinolysis is disabled by elevated cortisol.