Cushing’s syndrome: What is this disease ?

Écrit par Kevin Calatayud
le 28/10/2024

Cushing's syndrome is a rare but serious condition resulting from an excess of cortisol in the body. This can be due to a variety of causes, including prolonged use of corticosteroids or adrenal gland dysfunction. Let's explore the different aspects of Cushing's syndrome, its symptoms, causes and available treatment options.

Causes of Cushing’s syndrome

Prolonged use of corticosteroids

One of the main causes of Cushing’s syndrome is long-term use of corticosteroid drugs. These drugs are often prescribed to treat chronic inflammatory diseases such as asthma or rheumatoid arthritis. Although these drugs are highly effective, their long-term use can lead to excessive cortisol production by the body.

It is crucial for patients undergoing corticosteroid treatment to follow their doctor’s instructions carefully, and not to alter the dosage without medical advice. Regular monitoring is also recommended to detect any early signs of Cushing’s syndrome.

Pituitary adenoma

Another frequent cause is the presence of a pituitary adenoma, a benign tumor located in the pituitary gland. This tumor stimulates excessive secretion of adrenocorticotropic hormone (ACTH), which in turn increases cortisol production by the adrenal glands.

Detection ofpituitary adenoma usually requires imaging tests such as MRI. A consultation with an endocrinologist is essential to confirm the diagnosis and decide on the appropriate treatment.

Cushing’s syndrome and particularities of simple obesity

Widespread weight gain

In contrast to Cushing’s syndrome, simple obesity is characterized by more generalized and progressive weight gain. The distribution of body fat is generally more uniform, although it may vary according to gender and genetic predisposition. In men, there is often preferential accumulation in the abdominal area(android obesity), while in women, fat tends to be deposited more in the hips and thighs (gynoid obesity).

It’s important to note that some obese patients may present with fat accumulation in the face and neck, reminiscent of Cushing’s syndrome. However, the absence of other signs characteristic of Cushing’s syndrome and the history of weight gain usually differentiate these two conditions.

Impact on cardiovascular and metabolic health

Simple obesity, particularly abdominal obesity, is associated with an increased risk of cardiovascular and metabolic complications. It favors the development of the metabolic syndrome, characterized by a constellation of risk factors including arterial hypertension, dyslipidemia, glucose intolerance and chronic low-grade inflammation.

Unlike Cushing’s syndrome, these metabolic disturbances are generally proportional to the degree of obesity, and respond favorably to weight loss.Insulin resistance plays a central role in the pathophysiology of these complications, but is not as severe or as resistant to intervention as in Cushing’s syndrome.

Behavioral and environmental factors

Simple obesity is mainly the result of an imbalance between energy intake and expenditure, influenced by multiple behavioral and environmental factors. Eating habits, physical activity levels, chronic stress and sleep disorders play a major role in its development.

Unlike Cushing’s syndrome, simple obesity does not present with a primary endocrine disturbance. However, excess adipose tissue can lead to secondary hormonal changes, such as increased estrogen production and altered leptin sensitivity, which contribute to maintaining the obese state.

What are the symptoms of Cushing’s syndrome ?

Weight gain and central obesity

A frequent symptom of Cushing’s syndrome is rapid, disproportionate weight gain. This weight gain is mainly concentrated in the abdominal region, while the limbs may remain relatively thin. This is known ascentral obesity.

Patients may also develop a“buffalo hump“, an accumulation of fat between the shoulders, as well as a rounded, reddish face, often referred to as a “moon face”. These physical signs can be particularly disturbing and detract from a person’s self-image.

Skin problems

People with Cushing’s syndrome often suffer from skin problems. Their skin becomes thinner and more fragile, resulting in easy bruising and large, purple stretch marks on the abdomen, thighs and breasts.

In addition, skin infections may occur more frequently due to the weakening of the immune system caused by excess cortisol. Appropriate dermatological care is therefore necessary to help manage these complications.

Hormonal and endocrine disorders

Hormonal disorders are ubiquitous in patients with Cushing’s syndrome. As a result, many women may experience menstrual irregularities or even amenorrhea, while some men may experience a drop in libido. It’s important to note that certain medical conditions, such as intimate dryness, can also be influenced by these hormonal disorders.

Other hormone-related symptoms include high blood pressure, elevated blood sugar levels that can lead to diabetes, and extreme fatigue. Comprehensive management of these secondary disorders is essential to improve patients’ quality of life.

Diagnosis of Cushing’s syndrome

Biological tests

To diagnose Cushing’s syndrome, various biological tests are required to measure cortisol levels in blood, urine and saliva. One of the commonly used tests is the dexamethasone suppression test, which checks whether cortisol levels fall after administration of dexamethasone.

Blood samples taken at specific times of the day help detect abnormal fluctuations in cortisol levels. In addition, a 24-hour urine analysis can provide further information on cortisol production.

Imaging tests

Imaging tests such as MRI and CT scans are often carried out to identify abnormalities in the adrenal or pituitary glands. These images can be used to visualize the possible presence ofadenomas or other lesions responsible forhypercortisolism.

In some cases, an adrenal scintigraphy may also be useful to assess gland function and locate autonomous adenomas. These results enable doctors to formulate an appropriate treatment plan.

Endocrine tests specific to cushing’s syndrome

Dexamethasone braking test

The dexamethasone braking test is a key diagnostic tool for Cushing’s syndrome. It exploits the principle of negative feedback from the hypothalamic-pituitary-adrenal axis, which is disrupted in this pathology. The test involves administering a dose of dexamethasone (a synthetic corticosteroid) and measuring blood cortisol levels the following morning.

In healthy subjects, dexamethasone suppresses cortisol production. In Cushing’s syndrome, this suppression does not occur, and cortisol levels remain high. There are several variants of this test, including the weak braking test (1 mg) and the strong braking test (8 mg), each with its own specific indications depending on the clinical context.

Interprétation du test de freinage à la dexaméthasone (1 mg) :- Cortisol < 50 nmol/L (1,8 µg/dL) : Normal- Cortisol > 140 nmol/L (5 µg/dL) : Fortement évocateur du syndrome de Cushing- Valeurs intermédiaires : Nécessitent des investigations supplémentaires

Comparative biological analyses

A battery of biological analyses is essential to differentiate Cushing’s syndrome from simple obesity and assess their respective impacts on metabolism. These analyses include:

Complete lipid profile (total cholesterol, LDL, HDL, triglycerides)
Fasting blood glucose and glycated hemoglobin (HbA1c)
Blood ionogram (especially potassium)
Plasma ACTH assay
Oral glucose tolerance test (OGTT)

In Cushing’s syndrome, hypokalemia and hyperglycemia are typically more marked and resistant to treatment, and dyslipidemia more severe than in simple obesity. The ACTH assay also helps to determine the etiology of Cushing’s syndrome (pituitary, adrenal or ectopic origin).Nocturnal salivary cortisol assay

The nocturnal salivary cortisol assay is a reliable, non-invasive test for assessing cortisol secretion. Under normal conditions, cortisol follows a circadian rhythm, with higher levels in the morning and lower levels in the evening. In Cushing’s syndrome, this rhythm is disrupted, and cortisol levels remain high even late into the evening.

This test has the advantage of being unaffected by variations in cortisol levels due to the stress of venipuncture. It is particularly useful for the initial screening of Cushing’s syndrome and for monitoring patients after treatment.

Is there a cure for Cushing’s disease?

Surgical procedures

When Cushing’s syndrome is caused by a pituitary adenoma or adrenal tumor, surgery may be required to remove the tumor. Transsphenoidal surgery is commonly used to excise pituitary adenomas, while adenomectomy is preferred to remove adrenal tumors.

These operations require specialized expertise and are generally followed by close monitoring to prevent recurrence. Patients may need to take hormone substitutes after surgery to compensate for post-surgical hormonal changes.

Drugs and radiotherapy

In cases where surgery is not an option or has failed to completely resolve the problem, anti-cortisol drugs are prescribed to reduce cortisol production. Ketoconazole, mitotane and metyrapone are just some of the drugs used to controlhypercortisolism. An essential aspect for some patients may be the use of probiotics for intestinal flora.

Radiotherapy may also be an option for patients with recurrent pituitary adenoma, or when surgery has failed to remove the tumor completely. This treatment must be individually adjusted to minimize potential side effects.

Lifestyle monitoring and adaptation

Regular follow-up by an endocrinologist is crucial to monitor disease progression and adapt treatment accordingly. Periodic hormonal check-ups enable the efficacy of treatment to be verified, and medical dosages adjusted if necessary.

In conjunction with medical treatment, lifestyle modifications such as a balanced diet and appropriate exercise can help manage symptoms and improve quality of life. Psychological support can also be beneficial in coping with the emotional challenges of Cushing’s syndrome.

Preventing complications of Cushing’s syndrome

Proactive treatment management

For patients taking corticosteroids, proactive treatment management is essential to avoid the development of Cushing’s syndrome. This means scrupulously following medical prescriptions and never abruptly stopping treatment without medical advice.

A gradual reduction in dose may be necessary to allow the adrenal glands to gradually return to normal function. Patients should also inform their doctors of any worrying side effects, so that treatment can be adjusted promptly.

Nutritional and physical support

Adopting a diet rich in essential nutrients and low in salt can help counter the negative effects of high cortisol, such as water retention and hypertension. Foods rich in calcium and vitamin D are recommended to boost bone density, often compromised byhypercortisolism.

An adapted exercise program, designed in collaboration with a healthcare professional, can help maintain a healthy body weight and improve cardiovascular fitness. This effort not only helps control symptoms, but also builds physical and mental resilience.