Cushing’s disease

Cushing’s disease: description

Cushing’s disease was named after its author, neurosurgeon Harvey Cushing. Patients suffering from Cushing’s disease have too much cortisol in their body (hypercortisolism). Cortisol is a hormone that is produced in the adrenal cortices. It is considered a stress hormone and mobilizes energy reserves in stressful situations.

For cortisol to be produced in the adrenal cortex, it must be stimulated by another hormone: corticotropin (ACTH). ACTH is formed in the pituitary gland (pituitary gland). In Cushing’s disease, too much ACTH circulates in the bloodstream causing ACTH-dependent hypercortisolism.

In addition to Cushing’s disease, there are other forms of hypercortisolism such as Cushing syndrome, which is not triggered by ACTH from the pituitary gland.

Cushing’s disease: facts and figures

Cushing’s disease is one of the so-called endogenous forms of hypercortisolism. This means that the body on its own (endogenous = from the inside) produces too much ACTH and therefore cortisol.

The endogenous hypercortisolism is very rare in contrast to the exogenous (externally caused). According to literature, one in every 100,000 people suffer from Cushing’s disease each year. Especially women between the ages of 30 and 40 are affected. It is estimated that about three-quarters of them have a tumor in the pituitary gland that produces ACTH.

Cushing’s disease: symptoms

The following symptoms are typical for Cushing’s disease:

• Redistribution of fat deposits: Fat is stored primarily on the trunk and face. Therefore, patients have a full moon face and a so-called bull’s neck, but comparatively thin arms and legs.
• Loss of strength: The muscle mass decreases (myopathy) and the bones become brittle (osteoporosis).
• Susceptibility to infection: Because the immune system of the body is partially suppressed by cortisol, pathogens can easily multiply. Wound healing is also disturbed.
• high blood pressure
• Increased blood sugar levels
• Streaky reddish discoloration of the skin (Striae rubrae) especially on the upper arms and legs as well as on the flanks
• Thin, parchment-paper-like skin on which more open areas (ulcers) can occur.

In addition, women with Cushing’s disease may have symptoms such as the following due to an excess of male hormones:

• menstrual disorders
• Change in hair type: women increasingly grow hair on the face, on the chest and on the abdomen (hirsutism)
• Humanization (virilization): Women get a deeper voice, male body proportions or their clitoris grows.

In addition, patients with Cushing’s disease may be psychologically conspicuous, for example, due to depression. Children with Cushing’s disease often suffer from growth arrest.

Cushing’s disease: causes and risk factors

The main cause of Cushing’s disease is a pituitary microadenoma in 80 percent of cases. A microadenoma is a small, benign tumor in most cases. In the healthy body, there are control circuits that control the amounts of hormones produced. A microadenoma that produces hormones itself is not subject to this regulatory cycle. Therefore, the amount of hormones in the body increases beyond the required levels.

If Cushing’s disease is present, more corticotropin (ACTH) is produced. ACTH stimulates the adrenal cortex to form cortisol. Therefore, one speaks of an ACTH-dependent hypercortisolism. Apart from the production of cortisol, ACTH also causes a production of male hormones (androgens) in the adrenal cortex. Therefore, women with Cushing’s disease have symptoms that are attributable to increased androgen levels in the blood.

Not just a microadenoma can be the cause of Cushing’s disease. In some cases there is a dysfunction of the hypothalamus. Corticoliberin (CRH) is produced in this brain area. This hormone stimulates the production of ACTH in the pituitary gland. If too much corticcoliberine is formed in the hypothalamus, increased cortisol in the adrenal cortex is accordingly produced by an increased formation of ACTH.

Cushing’s disease: examinations and diagnosis

If you suspect Cushing’s disease, your GP will refer you to a specialist in endocrinology. First, he asks you in detail about your medical history (anamnesis). He will ask you the following questions:

• Did you gain weight?
• Have your body proportions changed?
• Do you have bone pain?
• Are you more likely to catch a cold?

Subsequently, your doctor will examine you physically. He also pays attention to your skin color and possible skin changes. He taps your spine and asks if you are in pain. Your doctor will ask you to squat up to test your muscle power. He also takes blood from you.

Cushing’s disease: laboratory tests

Your blood will be tested in the laboratory for different levels of Cushing’s disease. These include the amount of cortisol in your blood, the blood sugar levels, the concentration of cholesterol, the number of immune cells and the concentration of electrolytes (especially the blood salts sodium and potassium). In Cushing’s disease, the amount of cortisol in the blood is elevated and does not show different levels throughout the day as it would normally be. The blood sugar level is elevated because of increased liver glucose. The cholesterol level is increased. Different blood cells are increased (leucocytes, platelets and erythrocytes), while others are reduced (eosinophils and lymphocytes).

Morbus-Cushing: Specific Tests

Furthermore, a so-called dexamethasone inhibition test is performed. The patient is given dexamethasone (a glucocorticoid such as cortisol) at bedtime before bedtime. The next morning, the body’s cortisol levels should be in the blood. Thus it can be proven that no hypercortisolism is present.

If the value of cortisol is increased the next morning, tests are performed to confirm hypercortisolism. This includes, among other things, the determination of cortisol in urine over a period of 24 hours. In Cushing’s disease the value is increased.

To differentiate between the different forms of hypercortisolism, the amount of ACTH in the blood is now determined. If it is high, ACTH-dependent hypercortisolism is present, as is the case with Cushing’s disease.

Cushing’s disease: Imaging diagnostics

The radiologist performs a magnetic resonance imaging (MRI) of the head. On the MRI image, tumors of the anterior pituitary can be recognized. This is not always possible because the tumors can be very small.

In an ultrasound examination (ultrasound) or computed tomography (CT), the adrenals can be displayed. It is enlarged in Cushing’s disease.

Cushing’s disease: other diseases with similar symptoms

Your doctor must differentiate Cushing’s disease from other diseases and triggers that can cause similar symptoms and findings. These include:

• Taking contraceptives (“pill”)
• Taking steroids like cortisone or sex hormones (without a doctor’s order)
• Metabolic syndrome (= obesity, hypertension and elevated blood lipid levels)
• Tumors of the adrenal cortex
• Diabetes mellitus
• Osteoporosis (bone loss)

Cushing’s disease: treatment

If a microadenoma in the pituitary gland is the cause of Cushing’s disease, it is removed surgically. The neurosurgeons gain access to the pituitary through the nose or through the sphenoid bone (a bone of the skull base). Following surgery, cortisol must be artificially administered for a short time.

If surgery is out of the question as therapy, for example because of severe illnesses that make surgery impossible or because no causative tumor has been found, there are other treatment options. This includes the intake of medication. Cushing’s disease is treated with ketoconazole. It was originally developed as a drug against fungal attack. One side effect is that ketoconazole effectively suppresses the formation of cortisol.

In addition, an irradiation of the pituitary gland is a way to treat Cushing’s disease. In this way, the microadenoma can be destroyed. Rarely, both adrenals are surgically removed in an adrenalectomy. This option is not a causal therapy and is seldom chosen because patients will then have to artificially deliver cortisol and mineral corticosteroids, which are also produced in the adrenal cortex, for life.

Cushing’s disease: disease course and prognosis

Due to the many different effects of cortisol on the body, various complications may occur in the course of Cushing’s disease. These include fractures, heart attacks and strokes.

With an operation succeeds in approximately 80 per cent of the cases a cure of the Cushing’s disease, Shortly after the operation, the level of ACTH in the blood has returned to normal. If all other treatment options do not help and both adrenal glands are removed, patients will need to replace their entire life with cortisol and mineral corticosteroids with medications.