When the stress hormone takes over – this is how you recognize Cushing's syndrome

Cushing's can sneak up on you. It often starts with things that are easily dismissed: weight gain despite unchanged habits, bruises that appear for no apparent reason, blood pressure that suddenly becomes difficult to lower, or unusual fatigue that doesn't fit in with the rest of your life. When several such changes occur at the same time, the explanation may lie in the body's stress hormone, cortisol.

What is Cushing's syndrome?

Cushing's syndrome means that the body is exposed to excessively high levels of cortisol for a long time. Cortisol is produced in the adrenal glands and normally helps the body regulate blood pressure, blood sugar, metabolism, and immune system. When levels become chronically elevated, almost the entire body is affected, from skin and muscles to bones, brain, and heart.

The condition can be difficult to detect early on because the symptoms are similar to much more common problems, such as stress, obesity, type 2 diabetes, or lack of sleep. That is why the combination of symptoms is more important than a single finding. For example, a person with Cushing's can both experience central weight gain, thinner arms and legs, bruise easily and at the same time develop high blood pressure or elevated blood sugar.

Cushing's syndrome is uncommon, but it is medically significant because untreated hypercortisolism increases the risk of, among other things, blood clot, infections, osteoporosis, depression and cardiovascular disease. This means that the condition needs to be taken seriously, even when the symptoms initially seem to be diffuse.

Cause of Cushing's - medication, pituitary gland, adrenal gland or other tumor

The most common cause of Cushing's syndrome overall is treatment with glucocorticoids, i.e. medications that are similar to cortisol. This can involve tablets, injections and sometimes also other steroid treatment depending on the dose, duration of treatment and how the medication is used. Examples include treatment for asthma, rheumatic diseases, inflammatory bowel disease or after organ transplantation.

When the body itself produces too much cortisol, it is called endogenous Cushing's syndrome. There are several possible mechanisms. The most common endogenous form is that a benign tumor in the pituitary gland produces too much ACTH, a hormone that stimulates the adrenal glands to produce cortisol. This form is often called Cushing's disease, which is therefore a subgroup of Cushing's syndrome.

Another cause is that a tumor outside the pituitary gland produces ACTH, so-called ectopic ACTH production. This is seen in certain lung tumors, for example, but other organs may also be involved. In other cases, the problem lies directly in the adrenal gland, for example in an adenoma or, more rarely, a malignant tumor that produces cortisol independently.

In practice, the investigation often begins with a simple but crucial question: is the person using steroids? If the answer is yes, this in itself can explain the symptom picture and change the entire treatment. This is also the reason why the drug history is central, even when the doses are not perceived as “that high”.

Symptoms of Cushing’s syndrome that arouse suspicion

The symptoms often develop gradually. Many people first notice that the fat distribution changes: more fat on the abdomen, around the face and over the upper back, while the arms and legs become relatively thinner. A round face, fat accumulation between the shoulders and wide reddish-violet stretch marks over the abdomen, hips or breasts are classic findings.

The skin often becomes thinner and more fragile. Wounds may heal more slowly, acne may develop and bruises occur more easily than before. At the same time, muscle tissue breaks down, which can cause weakness in the thighs and shoulders. Someone who previously walked up stairs without problems may start to need to hold onto the railing or have difficulty getting up from a squat.

Excess cortisol also affects hormones and the nervous system. Women may experience increased body hair and irregular or absent periods. Men may experience decreased libido, erectile dysfunction, or decreased fertility. Depression, irritability, anxiety, sleep problems, and difficulty concentrating are also common and can sometimes dominate the picture.

In children, a special combination is often seen: weight gain while height growth is slowed. In adults, suspicion should increase if several of the following occur simultaneously:

• central weight gain with relatively thin extremities

• easy bruising or wide purple striae

• muscle weakness, especially in the thighs and shoulders

• newly onset or difficult-to-treat high blood pressure

• elevated blood sugar or diabetes

• osteoporosis or fractures without obvious trauma

Biomarkers and tests affected in Cushing's

The most important thing in Cushing's is to demonstrate elevated cortisol exposure and disrupted circadian rhythm. Normally, cortisol drops clearly late in the evening and during the night. In Cushing's, this nocturnal drop is often absent, making late-night salivary cortisol testing an important biomarker in the investigation.

Three first-line tests are widely used to detect endogenous cortisol excess:

• late-night salivary cortisol testing

• 24-hour urine for free cortisol

• low-dose dexamethasone inhibition test, where cortisol should normally drop but does not in Cushing's

If screening tests indicate Cushing's, further testing is carried out to find the source. ACTH is then central. A low ACTH indicates that the adrenal gland itself is producing too much cortisol, while normal or high ACTH points to pituitary or ectopic ACTH production. Imaging diagnostics and sometimes specialized sampling are then used to determine where the overproduction is located. In addition to the diagnostic biomarkers, several other laboratory values ​​are indirectly affected. Excess cortisol is linked to elevated glucose, insulin resistance, dyslipidemia and sometimes hypokalemia, especially in cases of pronounced ACTH-driven or ectopic disease. Blood pressure, bone density and sensitivity to inflammation are also affected, although these do not in themselves establish the diagnosis. For those seeking answers to diffuse metabolic symptoms, a broader perspective can therefore be valuable: glucose, HbA1c, blood fats and sometimes potassium can provide clues that something hormonally is not right. At the same time, it is important to know that a single abnormal test is not enough. Cortisol can be affected by depression, high alcohol consumption, severe obesity, poorly controlled diabetes and certain medications. Therefore, at least two pathological tests and an assessment in the right clinical context are often required.

Treatment of Cushing's and what happens afterwards

Treatment is guided by the cause. If the condition is caused by steroid drugs, an attempt is made, when medically possible, to gradually lower the dose or change treatment. This must be done under medical supervision because long-term steroid treatment can also inhibit the body's own cortisol production.

In endogenous Cushing's, surgery is usually the first-line treatment. Pituitary tumors are usually operated on through the nose with transsphenoidal surgery. Adrenal tumors are usually treated with surgery where the diseased adrenal gland is removed. Ectopic ACTH-producing tumors are operated on if possible, and in the case of cancer, oncological treatment may also be needed.

When surgery is not enough, is not possible, or when waiting for the effect of other treatments, drugs that lower cortisol levels are used. Other treatments include drugs that inhibit steroid production, and in some cases pituitary-directed therapy or glucocorticoid receptor blockade, especially when diabetes or glucose intolerance is a major problem. Radiation therapy may be considered for persistent or recurrent Cushing's disease from the pituitary gland.

Recovery often takes longer than many people expect. Cortisol may normalize before the patient feels recovered. Muscle weakness, psychological symptoms, blood pressure, risk of diabetes and osteoporosis may require continued follow-up for a long time, even after successful treatment. Guidelines therefore emphasize lifelong follow-up of comorbidities and risk of relapse in many patients.