What is Cushing’s syndrome?

Cushing’s syndrome is a rare disease which happens when your body has too much of the hormone cortisol over an extended period (chronic exposure). This can be caused by taking oral corticosteroid medication, or your body itself producing too much cortisol (excess production of cortisol by the adrenal glands).1

Cushing’s syndrome is more common in women than men (by a ratio of 4:1) and patients are typically aged over 40 at the time of their diagnosis.2

Cortisol is a steroid hormone produced by the adrenal glands (two small glands on top of your kidneys) and is sometimes called the “stress hormone” because it helps the body cope with stressors like illness or injury. Cortisol increases the body’s metabolism of fat and carbohydrates and breaks proteins. It also helps control blood pressure and reduce inflammation (anti-inflammatory role).1,3

Harvey Cushing

Harvey Cushing first described the disease in 1932, which came to be known as Cushing’s syndrome.4

Harvey Cushing was a famous American Surgeon who developed many foundational techniques and practices in neurosurgery, most notably the use of X-rays to diagnose brain tumours5.

As the world’s leading teacher of neurosurgeons in the early 20th century, Harvey Cushing is often described as the “father of neurosurgery”.4

Fittingly, Cushing’s Awareness Day is celebrated on April 8th, Harvey Cushing’s birthday.4

What are the clinical symptoms of Cushing’s syndrome?

The clinical manifestations of Cushing’s syndrome, including fatigue which is the first complain of patients, are non-specific and can be confused with similar symptoms of other conditions.1,9

Common signs and symptoms of Cushing’s syndrome





Adapted from Newell–Price J et al., 20061 and Nieman, 20088

Some symptoms are gender or age-related

Signs and symptoms women with Cushing’s syndrome may experience.8

  • Thicker or more visible body and facial hair (hirsutism)
  • Irregular or absent menstrual periods which led to decreased fertility

Signs and symptoms men with Cushing’s syndrome may experience.3,10

  • Decreased sex drive
  • Decreased fertility
  • Erectile dysfunction

Signs and symptoms children with Cushing’s syndrome may experience.6

  • Grow more slowly than other children – drop in the height percentile
  • Delay in puberty

Many comorbidities and clinical complications are associated with mortality in patients with Cushing’s syndrome10

Osteoporosis
Infections
Diabetes
Obesity
High blood pressure
Muscle weakness
Hypercoagulability
Infertility and sexual disorders
Cardiovascular problems
Depression, neurocognitive disorders
Simple fatty liver

How is Cushing’s syndrome diagnosed?

Generally, patients experiencing symptoms and signs of Cushing’s syndrome should speak to their General Practitioner.

Taking glucocorticoid medications is the most common cause of Cushing’s syndrome. Your doctor can review all of your medications – pills, injections, creams, and inhalers – to determine if you’re taking anything that may be causing the disorder. If you are, you probably won’t need any other tests.9

Cushing’s syndrome from inner cortisol overproduction can be more challenging to diagnose because other conditions can have similar signs and symptoms.11,12

Once glucocorticoid exposure is excluded, your doctor will conduct a clinical assessment, and a hormonal work-up, including cortisol testing and imaging. You should then be referred to an endocrinologist, or a reference centre for adults or children, to confirm the diagnosis and to treat you if high cortisol levels are detected.7

Your doctor may perform one of the following tests to measure cortisol levels.

24h UFC ( ≥2 Tests)6
  • You may be asked to collect at least 24-hour urine in order to measure UFC
  • It gives an indication of the UFC measure unbound cortisol which is filtered/excreted through the renal system6
Overnight 1mg DST7
  • The healthcare team give you 1mg of dexamethasone
  • The cortisol level is measured before and after taking medication
  • This medication should trigger (Cushing’s patients) or block (healthy people) the cortisol7
Late night Salivary Cortisol ( ≥2 Tests)14
  • A sample salivation is collected at midnight
  • Usually two tests are done for more sensitivity
  • It assesses cortisol level in saliva
  • Cortisol levels are low in healthy people14

UFC: Urinary Free Cortisol
Dexamethasone: A synthetic glucocorticoid
DST: Dexamethasone Suppression Test

What are the treatment options?

Experts agree that the earlier you are treated, the better. This is why an early diagnosis of Cushing’s syndrome is crucial.9,10

The aim of treatment is to reduce mortality by normalizing cortisol levels and treating comorbidities associated with Cushing’s syndrome.10

The International Guidelines typically recommend surgery. Removing the tumour by surgery is always the first line of treatment. When this is not successful or feasible, other treatments can be used, such as medical therapy (adjuvant agents that lower cortisol levels) and radiotherapy.7,13

The use of each treatment option depends on the etiology.7,13

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An informational resource about Cushing’s syndrome fully funded as a service to the community by ESTEVE