Cushing's Syndrome: Signs, Symptoms, and How Cortisol Is Related to It

Cushing's syndrome is a disease caused by prolonged elevation of cortisol in the human body. Although this disease is considered rare, it affects thousands of people around the world and often results in diminished quality of life for those suffering from it. In this article, we will explore Cushing's syndrome, its relation to cortisol, and how it is diagnosed and treated.

What is Cushing's syndrome?

Cushing's syndrome is often called hypercortisolism, closely relating to its characteristic causal trait — the long-term elevation of the hormone cortisol in the human body. Cortisol is responsible for regulating the immune system and stress response, carbohydrate, and protein metabolism. Cortisol fluctuations throughout the day tightly control these processes and also involve many other regulatory factors.

Cushing's syndrome is considered rare, with an estimated yearly incidence of only one in 50,000 to 800,000 individuals. Even though it is not extremely prevalent, Cushing's syndrome poses serious health risks for humans affected by it, such as the development of metabolic syndrome, muscle weakness, and osteoporosis.

Cushing syndrome can be caused by endogenous or exogenous factors:

  • Endogenous factors are changes in your body that result in increased production of cortisol. These could be specific tumors, such as pituitary adenoma, that signal your body to produce more cortisol or abnormal malignant enlargement of the adrenal cortex, part of adrenal glands where cortisol is synthesized, resulting in higher production of this hormone.
  • Exogenous factors are outside interventions, such as medication, that may increase cortisol levels in your body. One example is the prolonged use of corticosteroid prednisone, which mimics the action of cortisol.

Cortisol is well-established as one of the main factors contributing to the development of Cushing's syndrome. When too much cortisol circulates in the human body for a prolonged period of time, it disrupts many physiological processes that cortisol normally controls.

Cortisol normally regulates immune system response by inhibiting immune system cells and inflammation when needed. However, prolonged elevations of cortisol result in a prolonged state of suppression of the immune system. This results in a higher risk of various bacterial, viral, and fungal infections. Higher susceptibility to these infections is one of the observed patterns in people suffering from Cushing's syndrome.

The human body is constantly triggered by various internal and external stressors. Our bodies have developed to be able to respond and react to these stressful situations. Glucocorticoids, such as cortisol, help us prepare to deal with stress by signaling to release the glucose stored in our liver. This release process is called gluconeogenesis. This increased availability of glucose is used for energy production and is useful for dealing with stress in the short term; however, in Cushing's syndrome, this becomes a constant state. Such long-term exposure to increased glucose levels in the body can cause hyperglycemia, which, over time, could develop into type 2 diabetes. High blood glucose level is another characteristic of Cushing's syndrome.

Another process driven by chronic elevation of cortisol in Cushing's syndrome is muscle wasting and loss. Cortisol is believed to increase protein breakdown in muscle cells, resulting in muscle mass loss and weakness, especially in tights and shoulders.

Cortisol also affects fat distribution in our bodies. Prolonged exposure to high levels of cortisol, which is usually observed in Cushing's syndrome, results in characteristic redistribution of body fat. Fat tends to accumulate in specific areas like the face, termed 'moon face,' trunk, and between shoulders, which is named the "buffalo" hump. This redistribution is not fully understood, but it is believed to be related to cortisol-related changes in sex hormone levels, altered fat metabolism, and fat tissues in different parts of the body responding differently to cortisol.

Lastly, elevated levels of cortisol, as seen in Cushing's syndrome, affect the ability of our bone tissue to regenerate. Bone tissue has to regenerate constantly to be strong to support and protect our organs, as well as allow us to move.

However, high levels of cortisol affect this regeneration process by inhibiting osteoblasts, cells that build our bones. Furthermore, it also affects cells that destroy our bones — osteoclasts, by increasing their activity. This slows the normal bone regeneration process and makes bone destruction faster. Over time, this results in osteoporosis — bone loss, making our bones brittle and more fragile.

How Cushing's syndrome is diagnosed?

Cushing's syndrome can be difficult to diagnose at first as the symptoms take time to become apparent. Your family physician or endocrinologist will evaluate your family history and perform a physical examination, looking for signs such as muscle weakness.

In addition, blood or urine tests are usually performed to check your cortisol, ACTH, and glucose levels, as well as imaging studies such as MRI or CT. In some cases, a specific test called the dexamethasone suppression test is done that allows you to evaluate your hormonal response.

The typical diagnostic criteria for Cushing's syndrome are:

  • Significant weight gain, primarily around the face and abdomen
  • Fatty deposits between the shoulder blades
  • High blood pressure
  • Type 2 diabetes
  • Excessive body hair, called hirsutism, in women
  • Muscle weakness
  • Osteoporosis

It is interesting that Cushing's syndrome is usually diagnosed at 40, and the diagnosis is more predominant in women than in men.

What is the treatment of Cushing's syndrome?

After the diagnosis, Cushing's syndrome is often treated, taking into consideration the underlying cause.

If the underlying cause is endogenous, such as a tumor, surgery is usually done to remove the tumor entirely. As the tumor is eliminated from your body, cortisol levels should return to normal, and the syndrome is considered treated. However, surgery is not always an option due to complications, and in such cases, radiation therapy might be used to eliminate the tumor. If both surgical and radiation therapy options are not feasible, the use of specific medicine to reduce cortisol levels in your body is often considered an alternative treatment option.

In cases when Cushing's syndrome is caused by the use of corticosteroid medication, gradual discontinuation of such medication is done. This helps to slowly but surely reduce the levels of cortisol-mimicking compounds in the body and restore the functionality of the endocrine system.

Every case of Cushing's syndrome is unique in its causes, which is why the treatment approach greatly varies between individuals. It involves considering the original cause, evaluating additional health problems, and thoroughly estimating which treatment or combination of treatments would be the most effective in a particular case.

Navigating cortisol's complex role

Cushing's syndrome is a rare and serious disease that greatly impacts the quality of life of those living with it. Even though various testing methods are required for the diagnosis of Cushing's syndrome, and this can take a long time, the disease can be well-managed or even cured entirely.

Specifically, cortisol helped enhance the brain's response to both negative and positive images, suggesting it might help normalize brain functions disrupted by depression. These findings indicate that cortisol, a hormone commonly associated with stress, might have potential therapeutic benefits for treating depressive symptoms by improving emotional processing in the brain.

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