Cushing’s syndrome is a hormonal disorder caused by prolonged exposure to high levels of cortisol. Cortisol is a glucocorticoid steroid hormone that is produced by your adrenal glands to help your body respond to stressors. 

When you have elevated levels of cortisol over time with Cushing’s syndrome, you can experience hormonal and metabolic issues. This can lead to symptoms such as changes in blood pressure and blood sugar regulation, a fatty lump on the upper back, a rounded "moon” face, purple or pink stretch marks on the skin, bone loss, and mood issues. 

Recognizing the complex symptoms that can occur due to this increase in cortisol is important so that a personalized treatment plan can be enacted. Functional medicine helps to recognize the contributing factors to this hormonal imbalance and implement individualized management for optimal control of hypercortisolism and management of comorbidities. 

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What is Cushing's Syndrome?

Under stress, your body implements a complex neuroendocrine response that helps you deal with the increased demands. This process involves several neurobiological pathways that carry out a stress response. One part of the stress response involves sending signals via the hypothalamus-pituitary-adrenal (HPA) axis that results in the secretion of glucocorticoids such as cortisol. 

Cortisol impacts many functions throughout the body, causing inflammatory, immune, metabolic, hormone, circadian, and gastrointestinal impacts that help your body respond to stress. Cortisol helps you mobilize sugar (glucose) from your liver so that you have fast energy, increases your heart rate and blood pressure to flee from danger, impacts the immune system, and makes you more alert. 

Cushing’s syndrome occurs when the body has elevated cortisol levels over a prolonged period. This can occur due to endogenous causes within the body or due to external factors like medications. Over an extended period, a variety of physical and mental changes can result from having too much cortisol in the blood. 

Endogenous Cushing’s syndrome is rare, impacting around 40 to 70 out of every million people. It most commonly impacts adults between the ages of 30 to 50 but can also sometimes occur in children. Women are impacted three times more frequently than men by too much cortisol produced from within the body. 

Symptoms of Cushing's Syndrome

Elevated levels of cortisol in the body over time result in symptoms associated with Cushing’s syndrome. These include metabolic impacts, such as problems with blood sugar regulation, and resulting characteristic changes in the body including unexplained and rapid weight gain especially in the abdomen and a rounded "moon” face, a fatty lump on the upper back, and purple or pink stretch marks on the skin. 

Chronically elevated cortisol can also cause Cushing’s syndrome symptoms such as elevated blood pressure (hypertension), bone loss, and mood instability. 

The symptoms of Cushing's syndrome can vary significantly among individuals, complicating diagnosis. Early and accurate recognition of this condition is important to prevent potentially life-threatening complications. If untreated, prolonged elevated levels of cortisol can contribute to infections, blood clots, heart attack, metabolic problems like metabolic syndrome and Type 2 diabetes, obesity, depression, memory problems, broken bones, and even death.

Diagnostic Testing for Cushing's Syndrome

The symptoms of Cushing’s syndrome can have various etiologies making the diagnostic process challenging in some cases. Initial screening tests are usually used, measuring cortisol in the saliva, urine, or blood. This cortisol testing can help establish the diagnosis, but it is important to note that elevated cortisol levels can happen in cycles. In healthy people, cortisol levels in saliva are very low between 11:00 p.m. and midnight but are often elevated in Cushing’s syndrome. Measuring cortisol levels in urine collected over 24 hours can also help indicate elevations.

To confirm abnormally high cortisol levels and help pinpoint their cause, a dexamethasone suppression test is used. This test involves measuring cortisol levels in the morning after taking a late-night dose of the laboratory-made steroid drug dexamethasone. In healthy people, a low dose of this drug will suppress the body's production of cortisol since it mimics the body’s normal negative feedback loop where cortisol levels feedback to the pituitary to suppress ACTH secretion, so cortisol levels will drop very low. In people with Cushing disease, where the pituitary is producing too much ACTH, cortisol levels do not drop even after giving a high dose of dexamethasone.

If these tests confirm elevated cortisol levels, ACTH levels are then measured in the blood to differentiate why cortisol levels are high. In both Cushing's syndrome and Cushing disease there is too much cortisol in the body. Cushing disease is one type of Cushing's syndrome where the cause of elevated cortisol is a pituitary tumor or overgrowth that produces too much ACTH which then stimulates the adrenals to make too much cortisol. People with Cushing disease have elevated cortisol levels with levels of ACTH that are also high or sometimes within the normal range. 

To further pinpoint the source of elevated cortisol, imaging of the brain and pituitary gland is carried out with an MRI scan. These imaging studies can identify overgrowth of the pituitary gland or any tumors. Imaging may also be used to look for other tumors throughout the body that can produce ectopic ACTH that leads to Cushing’s syndrome. 

Although more invasive, another technique that can help to confirm a diagnosis of Cushing's Disease is inferior petrosal sinus sampling (IPSS). This test involves taking a sample of blood from each side of the veins that drain the pituitary gland and measuring ACTH levels there compared to levels in the blood from the veins in the chest. This can help pinpoint the location of a tumor that is overproducing ACTH to help with surgical planning.

Causes of Cushing's Syndrome

Around 70% of cases of Cushing’s syndrome are due to too much cortisol being produced inside the body from endogenous Cushing’s syndrome like Cushing's disease. During stress, the hypothalamus in the brain is triggered to produce corticotropin-releasing hormone (CRH) that stimulates the nearby pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH goes into your bloodstream and travels to the adrenal glands where it stimulates them to release cortisol. 

Excess growth (hyperplasia) or a benign tumor in the pituitary gland (pituitary adenoma) can cause too much ACTH to be released, signaling the adrenal glands to release more cortisol into the bloodstream and causing Cushing disease. Too much endogenous production of cortisol by tumors in the adrenal cortex can also cause Cushing’s syndrome. 

In other cases, tumors in the lungs (such as small cell lung cancer), pancreas, thyroid, or thymus can abnormally produce ACTH. This ectopic ACTH syndrome triggers the adrenals to overproduce cortisol causing endogenous Cushing’s syndrome.

Exogenous Cushing’s syndrome can occur when levels of glucocorticoids are too high due to factors outside of the body. This occurs in some people who take corticosteroid medications like prednisone that have similar impacts on the body to cortisol. These medications are often used to reduce inflammation in autoimmune diseases like systemic lupus erythematosus, chronic asthma, and rheumatoid arthritis.

Treatment Options for Cushing's Syndrome

Treatment options for Cushing's Syndrome involve undercovering and targeting the source of excess cortisol and controlling the excess levels of this hormone. The treatment approach depends on the cause of the elevated cortisol and other individual factors. 

Conventional treatment of Cushing’s syndrome due to endogenous causes like tumors usually involves surgery to remove the tumor. If the tumor is located on the pituitary gland in Cushing's disease, removal may be able to be done with a less invasive transsphenoidal microsurgery through the nasal sinuses. In other cases, radiation may be used to help shrink excess growth of the pituitary or a tumor. 

Surgical removal of the adrenal gland(s) (adrenalectomy) can lead to the resolution of excess cortisol in cases of ACTH-dependent Cushing’s syndrome. If both glands are removed, patients must undergo lifelong glucocorticoid and mineralocorticoid replacement.

In some cases of Cushing's disease, medications may be used to decrease cortisol levels. This can be used when the source of excess cortisol remains unknown when surgery or radiation is contraindicated, or while awaiting the effects of radiation therapy. Some medications that reduce cortisol levels include steroidogenesis inhibitors like ketoconazole which act to block the activity enzymes required for cortisol production in the adrenal glands. 

Another type of medication that can help reduce the symptoms of Cushing's syndrome is a dopamine agonist, such as cabergoline. This drug reduces ACTH levels and cortisol production. 

Similarly, pasireotide can help to reduce ACTH levels and cortisol production. This medication is a somatostatin agonist that is given by injection under the skin to reduce cortisol production. Another medication option is mifepristone may be used to stop cortisol from working on the receptors throughout the body when given at higher doses. 

When Cushing’s syndrome is exogenous due to glucocorticoid medications, treatment usually requires tapering off exogenous corticosteroids. This should be done under the guidance of a medical provider.

While the definitive treatment of Cushing’s syndrome often requires surgical intervention, lifestyle approaches, and integrative medicine therapies can help with an individualized management plan. This allows for optimal control of cortisol levels and prevention of comorbidities.

For example, nutrition should be optimized to help balance cortisol levels and provide adequate nutrients for bone health and stable blood sugar balance. An anti-inflammatory diet can be helpful in modulating cortisol levels to some degree and in supporting gut health. An anti-inflammatory diet like the Mediterranean provides high-fiber plant-based foods like fruits, vegetables, and whole grains along with healthy types of fats from olive oil and fatty fish that support blood sugar balance. 

Incorporating naturally probiotic-rich foods such as sauerkraut, kefir, and kimchi nourishes a balanced microbiome that contributes to keeping inflammation, blood sugar, and hormones balanced. In addition, avoiding excess sodium consumed in processed foods and balancing out sodium in the diet with natural sources of potassium like leafy greens helps to balance blood pressure and reduce fluid retention.

Long-term Management and Outlook

Elevated cortisol levels can have significant impacts on the body. Therefore, follow-up care and long-term management strategies are important for patients recovering from Cushing's syndrome. This can include regular monitoring of hormone levels and managing the effects of treatment.

The goal of Cushing’s syndrome treatment is to reduce cortisol levels in the body to within normal levels. If not promptly recognized and properly managed, Cushing’s syndrome can result in significant complications. Untreated patients have a very poor prognosis with an estimated 5-year survival of only 50%.

Regular monitoring of cortisol levels and cortisol-dependent complications like blood glucose imbalances is important for preventing complications from developing. These include bone loss that can lead to osteoporosis and fractures, high blood pressure that can contribute to cardiovascular disease, issues with blood sugar regulation that can lead to metabolic syndrome and Type 2 diabetes, frequent infections, and mood issues. 

As part of a comprehensive approach to long-term management for Cushing’s syndrome, patients must be well educated about the condition and potential signs to look for that may signal an increase in cortisol or other complications. 

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Key Takeaways

Cushing’s syndrome occurs when too much cortisol is in the body over a prolonged period. This can occur due to endogenous causes like pituitary or adrenal tumors or due to exogenous factors like taking corticosteroids for long periods.

Early detection and accurate diagnosis of Cushing’s syndrome are crucial for preventing the development of life-threatening complications. If you are experiencing symptoms of Cushing’s syndrome like unexplained weight gain, especially around the abdomen, shoulders, and face, striae on the skin, high blood pressure, blood sugar imbalances, and cognitive or mood issues, it is important to seek evaluation and medical advice promptly.

Early detection can allow for an effective diagnosis of the factors underlying Cushing’s syndrome. This allows for a personalized approach to treatment to bring cortisol levels and the body back into balance.