Cortisol is one of my favorite topics. When I was completing my specialty training in endocrinology, I chose to study high cortisol as the focus of my research. I was lucky to have brilliant women as my mentors, and I learned as much as I could about how cortisol is made and regulated. (I also learned a lot about the adrenal glands in ferrets, but that is a story for another day.)
Many years later, I still perk up when patients have questions or concerns about cortisol. I enjoy helping them to understand all the fantastic things cortisol does for them and, most often, reassure them that their cortisol levels are just fine. Recently, several of you have had those same types of questions. When should you be worried if your cortisol levels are too high — or too low? And what is cortisol, anyway?
What is cortisol?
Cortisol is a steroid hormone — a hormone synthesized from cholesterol — made in the adrenal glands. It is responsible for regulating our circadian rhythms and helps our body respond to stress. Under normal circumstances, cortisol levels are high in the morning, helping to wake our body from sleep. They dip after lunch — when so many cultures go looking for coffee, tea, or a siesta — and rise again around dinnertime. Around bedtime they will fall again, and cortisol levels are at their lowest overnight.
Cortisol levels rise in response to both physical and emotional stress. Some types of infection, such as COVID-19, send cortisol levels soaring. But so can other stressful situations, including dealing with a sick parent or child, or weathering a breakup or divorce. In times of stress, cortisol triggers blood sugars to rise so our brain and muscles have glucose to think and run. It decreases inflammation and dampens down the immune system.
When cortisol causes problems
Our body needs cortisol in just the right amounts. Both too much and too little can lead to big problems.
Issues with too much cortisol
Too much cortisol is called Cushing’s syndrome. It is most often caused by a benign tumor in the pituitary gland or by a tumor in the adrenal glands that makes too much cortisol. In rare cases, a tumor growing in another part of the body, usually the lungs, causes Cushing’s. Patients taking high doses of steroid medications such as prednisone, hydrocortisone, or methylprednisolone can develop signs and symptoms of Cushing’s syndrome. This is called iatrogenic Cushing’s.
Patients with typical Cushing’s syndrome gain weight uncontrollably and lose muscle mass rapidly. Their skin thins, they develop dark purple stretch marks, and their faces become round. They develop diabetes, insomnia, and depression. Luckily, Cushing’s syndrome is quite rare, affecting just two to eight people per million each year worldwide.
In the past 20 years, endocrinologists have become interested in a milder form of Cushing’s syndrome called subclinical hypercortisolism. These patients often have benign growths in their adrenal glands as well as unexplained weight gain and prediabetes, but they lack the dramatic symptoms of classic Cushing’s syndrome and their cortisol levels are not so significantly elevated.
Issues with too little cortisol
Having too little cortisol is equally problematic. The most common cause of too little cortisol is taking steroid medications like prednisone — a synthetic form of cortisol — chronically over weeks or months. Doing so suppresses the hypothalamus and pituitary and stops them from sending signals to the adrenal glands to make cortisol. When the steroid medication is stopped abruptly, a patient can develop low cortisol levels.
Less frequently, benign growths in the pituitary can compress the normal pituitary gland, causing low cortisol. In rare cases, the immune system attacks and destroys the cortisol, producing cells of the adrenal glands — a life-threatening condition called Addison’s disease.
Patients with too little cortisol have poor appetite, fatigue, weight loss, low blood pressure, and low blood sugar. Their bodies are unable to respond to stress, and in severe cases they can develop adrenal crisis, which is characterized by fever, weakness, abdominal pain, low blood sugar, nausea, and vomiting.
In the past two decades, some health-care providers have diagnosed patients with a condition called adrenal fatigue. They argue that chronic stress leads to overuse of the adrenal glands and that this compromises adrenal function. However, in tests comparing cortisol levels under chronic stress with levels from subjects who are not stressed, there is no evidence in the literature that the described compromise occurs.
The challenge of measuring cortisol
More than 95% of the cortisol in our blood is bound to proteins. Cortisol bound to proteins cannot have an effect on our body function. Only the 5% of cortisol that is unbound can act on our cells. Some medications, such as birth control pills, and some conditions, like pregnancy, can increase binding proteins, but unbound levels of cortisol remain roughly the same. This is incredibly important as we think about measuring cortisol. Many of my patients taking birth control pills have elevated total cortisol levels, but their unbound cortisol levels are normal.
We can measure cortisol in the blood, urine, and saliva. In the blood, most often we measure total cortisol — that is, both bound and unbound cortisol. We have tests that can measure unbound cortisol in the blood, but they are unreliable, and normal ranges are not well established. To measure unbound cortisol levels (the only levels that matter when it comes to diagnosis), we would have to do a urine or saliva test.
Equally important as the type of test is the fact that cortisol levels rise and fall over the course of the day. The evidence supports using different tests depending on whether the concern is cortisol that is too high or too low. We diagnose low cortisol by checking cortisol levels in the blood in the morning. We diagnose Cushing’s syndrome by checking cortisol in the saliva late at night, or by measuring the concentration of cortisol in a sample of urine collected over a full 24-hour period.
Some practitioners will recommend testing saliva cortisol levels throughout the day rather than just at night. However, this schedule of testing has not been validated by research. Choosing the right type of test based on what type of problem is suspected and the time of day the testing will be performed is critical to getting useful results.
For those of us in the business of diagnosing Cushing’s syndrome and Addison’s disease, the lesson is never to rely on a single test or even a single type of test. My patients will often ultimately have blood tests, saliva tests, and urine tests performed over weeks before we settle on a diagnosis.
Should you be worried about your cortisol levels?
The subtleties and challenges in testing cortisol levels mean that you should not be concerned if you have a single abnormal cortisol test result. Abnormal cortisol results are common, but both Cushing’s syndrome and Addison’s disease are quite rare. The vast majority of patients with abnormal cortisol results do not have Cushing’s syndrome or Addison’s disease. Patients with Cushing’s syndrome typically have significantly elevated cortisol levels, and those with Addison’s disease typically have very low cortisol levels.
Remember that cortisol serves a purpose in our body. Levels that are a little bit too high or a little bit too low are likely just your body’s response to the time of day or stressors in your life. Even the anticipation of having blood drawn can raise cortisol levels.
If you get abnormal results after a test, your doctor will likely retest to confirm, and if they don’t, you should request it.
The bottom line
- The hormone cortisol plays a critical role in our body’s response to stress. Having too much or too little cortisol has serious consequences for our health. Luckily, these conditions are quite rare.
- Measuring cortisol levels is challenging because cortisol levels vary throughout the day and most cortisol circulates bound to proteins, making it invisible to our cells. We measure cortisol in blood, urine, and saliva, depending on what we are looking for.
- A single blood test is not reliable for making a diagnosis. Most patients need multiple tests of different types to determine a diagnosis.
Log in