Cushing Syndrome

Cushing's Syndrome

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What is Cushing’s Syndrome?

Cushing’s syndrome is a group of symptoms caused due to high levels of cortisol in the body. It is also called as hypercortisolism. It is an endocrine disorder.

Every year, approximately 2-3 people per million suffer with Cushing’s syndrome. Generally, it affects people of 20-50 years of age and women are affected three times more often than men. Further, a not so severe form of Cushing’s syndrome without all the symptoms is more common. This syndrome has also been found to occur in other animals including dogs, cats and horses.

What Causes Cushing’s Syndrome?

Cushing’s syndrome develops due to high levels of cortisol in the body which can go up due to the following reasons:

1. Exogenous Cushing’s syndrome or Due to Causes outside the body - Treatment with Steroids (corticosteroids):

Intake of oral steroids such as prednisone in high doses over an extended period of time to treat inflammatory diseases, such as rheumatoid arthritis, lupus and asthma, or to prevent the body from rejecting a transplanted organ, can lead to Cushing’s syndrome (also called iatrogenic Cushing’s syndrome. Iatrogenic means illness caused by medical treatment). Further, repeated injections of steroids for treating joint pain, back pain and bursitis can also lead to high levels of cortisol. The use of steroid inhalers (taken for asthma) and steroid skin creams are generally not associated with Cushing’s syndrome but in some individuals, these can cause Cushing’s syndrome if taken in high doses.

2. Endogenous Cushing’s syndrome or Overproduction of cortisol by the body:

This happens due to the overproduction of cortisol by the adrenal glands due to the following reasons:
  • Pituitary adenoma: It is responsible for the most common type of endogenous Cushing’s syndrome and occurs when a benign tumor of the pituitary gland in the brain secretes an excess amount of ACTH (Adrenocorticotropic hormone), which in turn stimulates the adrenal glands to make more cortisol. This condition is more common in women and is called as Cushing disease. Cushing’s syndrome refers to the general state (signs and symptoms) characterized by excessive levels of cortisol in the blood regardless of the cause whereas Cushing disease is one of the cause of Cushing’s syndrome.
  • Ectopic production of ACTH by tumors: Sometimes, benign or malignant cancer in the lungs, pancreas, thyroid and thymus gland starts producing ACTH and this ectopic (outside adrenal gland) production of ACTH leads to high levels of cortisol.
  • A diseased adrenal gland: In some individuals, a noncancerous tumor of the adrenal cortex, called an adrenal adenoma, leads to excessive cortisol secretion. Carcinomas in the adrenal cortex are rare, but they can also cause Cushing’s syndrome.
3. Familial Cushing’s syndrome: Very rarely, the chances to develop tumors of endocrine glands gets inherited, affecting cortisol levels and causing Cushing’s syndrome. Sometimes, association has been observed between Cushing’s syndrome and inherited disorders such as Carney complex and multiple endocrine neoplasia type 1.

Causes of Cushing's syndrome

What are the Symptoms and Signs of Cushing’s Syndrome?

The signs and symptoms of Cushing’s syndrome depends on the levels of cortisol. Some of the common symptoms of Cushing’s syndrome are:
  • Obesity around abdomen but thin legs and arms
  • High blood pressure
  • Fatty tissue deposits between the shoulders (buffalo hump) and on the face (moon face).
  • Thin fragile skin that doesn’t heal properly
  • Acne
  • Reddish stretch marks on the face, breasts, abdomen, thighs and arms.
  • Severe fatigue, muscle weakness, bone loss giving rise to fractures some time.
  • Anxiety, depression, cognitive issues and irritability, psychosis
  • Loss of emotional control, mood swings, headache, fatigue
  • Impaired growth in children
  • Females with Cushing’s syndrome suffer from either no or irregular periods and thicker hairs on the face and the body (hirsutism)
  • Males with Cushing’s syndrome experience erectile dysfunction, decreased fertility and libido.
Symptoms and Signs of Cushing's Syndrome

How do you Diagnose Cushing’s Syndrome?

Diagnosis of Cushing’s syndrome is a multi -step process and involves following different procedures:

History and Physical examination: If you have a history of longterm steroid intake, then the doctor will do a detailed physical examination to look for the effects such as rounding of the face (moon face), a pad of fatty tissue between the shoulders and neck (buffalo hump), and thin skin with bruises and stretch marks.

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Urine and blood tests: These tests measure the cortisol hormone levels in the urine and blood samples. Also, the cortisol levels are measured before and after by stimulation and suppression tests with some hormone medications to accurately determine the cause of these symptoms.

Urine and Blood Test Can Helps to Diagnose Cushing's Syndrome

Saliva test: Analysis of cortisol levels in a saliva sample collected late at night is used to diagnose Cushing’s syndrome. Generally, cortisol levels rise and fall throughout the day and then drop significantly in the evening whereas in people suffering with Cushing’s syndrome, cortisol levels are high in the night as well.

Imaging tests: Scans such as CT or MRI can provide images of pituitary and adrenal glands to detect any abnormality such as tumors.

Petrosal sinus sampling: This test is used to determine the cause of endogenous Cushing’s syndrome. In this method, a thin tube is inserted into upper thigh or groin area under the sedative effect, and threaded to the petrosal sinuses. Petrosal sinuses are the veins that drain the pituitary glands. Then, levels of ACTH hormone is measured from the blood samples collected from the petrosal sinuses, and from a blood sample collected from the forearm.

If levels of ACTH is higher in the petrosal sinus sample as compared to the sample collected from the forearm, it suggests the abnormality in pituitary as a cause of Cushing’s syndrome. However, if the ACTH levels are similar in the samples collected from the sinus and forearm, it rules out the involvement of pituitary gland in causing Cushing’s syndrome.

How do you Treat Cushing’s Syndrome?

The main aim for treating the Cushing’s syndrome is to reduce the high levels of cortisol in the body and the type of the treatment depends on the underlying cause.  Some of the common treatment methods are:
  • Reduction in corticosteroids dose: If the Cushing’s syndrome is caused due to the long term use of corticosteroids, then by reducing the dose, the signs and symptoms can be controlled. Sometimes, doctors prescribe non-corticosteroid drugs for treating the ailments so that the dosage of corticosteroids can be reduced or completely eliminated.
  • Surgery: If the Cushing’s syndrome is caused due to a tumor, then the complete surgical removal of the tumor is preferred. Following surgery, it is recommended to use cortisol replacement medications to provide the correct amount of cortisol in the body.

    In some cases, however, none of the treatment options work, and in those cases, doctors may perform bilateral adrenalectomy which involves surgical removal of adrenal glands, to stop the production of cortisol, but it requires lifelong replacement therapy.
  • Radiation therapy: This therapy is generally used in conjunction with the surgery or if the tumor is not fully removed or in cases where surgery cannot be performed. Radiation is either given in small doses or by a technique called as Gamma knife surgery or stereotactic radiosurgery. In this technique, a large dose of radiation is given specifically to the tumor minimizing the exposure to the surrounding tissues.
  • Chemotherapy: Drugs are recommended in cases where surgery and radiation therapy are not possible. Also, drugs are given before surgery to improve the signs and symptoms and to minimize surgical risks.

    Drugs which are given to control cortisol production by adrenal glands are mitotane (Lysodren), ketoconazole (Nizoral) and metyrapone (Metopirone). For individuals who are type 2 diabetics and suffering from Cushing’s syndrome, mifepristone (Korlym) is recommended which does not affect cortisol production, but it interferes with the effect of cortisol on tissues.

    In some cases of Cushing’s syndrome, where pituitary surgery cannot be performed or is unsuccessful, a drug called pasireotide or Signifor (twice daily injections) is given which works by decreasing ACTH production from a pituitary tumor.

What are the Complications of Cushing’s Syndrome?

If not treated properly, Cushing’s syndrome will lead to complications such as:
  • Osteoporosis which can result in unusual bone fractures, such as rib fractures and fractures of the bones in the feet
  • Hypertension
  • Type 2 diabetes
  • Frequent or unusual infections
  • Loss of muscle mass and strength
Complications of Cushing's Syndrome

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