Cushing’s syndrome

What is Cushing’s syndrome?

Cushing's syndrome refers to symptoms and clinical findings that occur because of persistently elevated cortisol levels in the blood (hypercortisolism).

How exactly does Cushing’s syndrome develop?

Cushing's syndrome is divided into two main types depending on the underlying mechanism.

• Exogenous Cushing’s syndrome:

In most cases, Cushing's syndrome arises as a side effect of long-term medication with glucocorticoids (different types of cortisone), which causes increased cortisol levels. This type is referred to as exogenous or iatrogenic Cushing's syndrome.

• Endogenous Cushing’s syndrome:

Less commonly, Cushing's syndrome can also be caused by the body's own increased production and release of cortisol. This is referred to as endogenous Cushing's syndrome, which in turn is divided into two subtypes:

In primary hypercortisolism, the elevated cortisol level is caused by increased cortisol production from the adrenal cortex. This is usually caused by adrenal cortex tumors that produce cortisol independently. Rarely, the increased production can also be due to a tissue change (dysplasia) or enlargement (hyperplasia) of the adrenal cortex.

In contrast, in secondary hypercortisolism, the increased cortisol level is caused by increased production of the hormone ACTH (adrenocorticotropic hormone). This hormone is normally produced in the pituitary gland (hypophysis) and regulates the release of cortisone from the adrenal cortex. An increased production of ACTH can have two different causes, so that there are two different subtypes:

• Cushing's disease: In this case, there is an increase in ACTH production caused by the pituitary gland. In 80% of cases, small tumors (known as microadenomas) are responsible for the production and release of ACTH.
• ACTHoma (adrenocorticotropic hormone-producing ectopic tumor): In this subtype, another tumor disease (often lung cancer) leads to the production and release of adrenocorticotropic hormone (ACTH). This is referred to as a paraneoplastic syndrome.

How does Cushing’s syndrome manifest itself?  

The increased cortisol level in Cushing's syndrome can lead to a variety of symptoms, which are described in more detail below.

• Changed physical apperance:
  • Moon face: A rounded face shape caused by fat deposits.
  • Buffalo hump: Visible increase of fat tissue in the neck area.
  • Central obesity: Trunk-focused obesity with a significant increase in waist circumference.
  • Muscle wasting: Particularly in the arms and legs, accompanied by weakness.
• Osteoporosis: Decreased bone density.
• Increased risk of developing diabetes mellitus.
• High blood pressure
• Skin changes:
  • Thin skin.
  • Delayed wound healing.
  • Skin bleeding (e.g., bruising).
  • Facial redness.
  • Reddish stretch marks on the skin.
• Psychological changes:
  • Depressive episodes.
  • Elevated mood (euphoria).
  • Anxious, sad, and irritable mood (dysphoria).

In secondary hypercortisolism, additional symptoms may appear. ACTH does not only increase cortisol production, but it also raises the production of male sex hormones (androgens) in the adrenal cortex. The elevated androgen levels can lead to undesirable symptoms, particularly in women, such as:

• Menstrual irregularities.
• Male-pattern hair growth (hirsutism).
• Development of male characteristics, such as a deep voice (virilization).

How does a specialist diagnose Cushing’s syndrome?

If there is a suspicion of Cushing's syndrome, a blood sample is initially taken and examined to see if there are any abnormal findings in the patient's blood sample. Generally, Cushing's syndrome is linked with changes in some blood parameters.

In addition to analyzing various blood values, detailed hormone diagnostics are carried out. This usually takes the form of step-by-step diagnostics, in which several different tests are carried out one after the other to determine whether Cushing's syndrome is present and, if so, what form it is.

In order to confirm the diagnosis of Cushing's syndrome, cortisol excretion is measured in the urine over a 24-hour period. The cortisol level in the blood and saliva is also often determined at midnight, as the cortisol level fluctuates during the course of the day.

Another test is a short-term dexamethasone test which involves administering the drug dexamethasone at night and determining the patient's cortisol level the next morning. If the cortisol level remains high despite the administration of dexamethasone at night, this test is evidence of the presence of Cushing's syndrome.

Additional hormone tests are carried out to find out which form of Cushing's syndrome is present.

In some cases, a catheter examination is also used, in which a blood sample is taken from cerebral veins and then analyzed in the laboratory.

Depending on the results of the hormone diagnostics, various imaging tests are carried out:

• • CT or MRI scan of the abdomen: to visualize tumours in the area of the adrenal cortex
  • CT or MRI scan of the brain: to visualize tumours in the area of the pituitary gland
  • Further imaging: if there is a suspicion of ectopic ACTH production (ACTHoma)

Therapy and treatment methods for Cushing’s syndrome

• Surgical therapy:

If it is possible to operate on the underlying tumor, then surgical removal of the tumor is the standard therapy.

Before this, efforts must be made to normalize the electrolyte balance and blood sugar levels. In some cases, it is necessary to suppress the tumor's own hormone production with medication known as adrenostatic drugs (e.g. ketoconazole). The exact intervention depends on the causative tumor:

• Tumor of the pituitary gland (pituitary adenoma):

• standard procedure: surgical removal of the tumor with access via the nose
• if surgery is not possible: radiation of the pituitary gland

• Tumor of the adrenal cortex: surgical removal of the adrenal gland
• ACTH-producing ectopic tumor (ACTHoma): surgical removal if possible, otherwise drug therapy

Following the operation, glucocorticoids (cortisol types) must be substituted, as otherwise there is a dangerous lack of glucocorticoids in the body.

• Medication therapy:

In the case of an inoperable adrenal cortical tumor or an inoperable ACTHoma (tumor with ectopic ACTH production), drug therapy is used. Drugs such as ketoconazole or mitotane are administered.

What is the life expectancy of Cushing’s syndrome?

The prognosis of Cushing's syndrome is largely dependent on the cause. The prognosis is good if Cushing's syndrome can be completely cured by treatment. Treatment is successful in around 50-80% of all cases.

Exogenous Cushing's: If Cushing's syndrome is caused by long-term use of glucocorticoids (cortisone variants), the disease is usually completely reversible after discontinuation the medication that triggered it.

Endogenous Cushing’s: the prognosis varies depending on the cause:

• Benign tumor (microadenoma) of the pituitary gland: relatively good prognosis with early treatment.
• Benign tumor of the adrenal cortex: relatively curable.
• Malignant tumor in the adrenal cortex (or in another location): comparatively poor prognosis.

If Cushing's syndrome is left untreated, it is generally associated with a reduced life expectancy.

Which specialists and clinics treat Cushing’s syndrome?

Cushing's syndrome falls within the treatment spectrum of endocrinologists (specialists in hormonal disorders).

Depending on the underlying cause of the disease, doctors from the following specialties are often involved in treatment planning and, if necessary, execution:

• Surgeons, neurosurgeons: perform surgeries.
• Nuclear medicine specialists: carry out radiation treatments using radioactive substances.

If noticeable symptoms are present, the general internist can conduct initial examinations and refer the patient to the appropriate specialists.

Anyone in need of a doctor would expect the best possible medical care for themselves. Therefore, patients are looking for the most suitable clinic for their needs. Since this is not an objective decision and a respectable doctor would refrain from claiming to be the best, patients must trust the experience of a doctor.

We can help you find an appropriate expert for your condition. All the doctors and clinics listed have undergone extensive review and have been verified by us for their outstanding expertise in the field of Cushing’s syndrome. They are looking forward to and are ready to address your questions and treatment requests.