Cushing syndrome: Symptoms, Treatment and Prognosis.

Definition

Cushing’s syndrome is a debilitating endocrine disorder characterized by excessive cortisol levels in the blood which may be the result of a tumor of the pituitary gland, adrenal glands (located above the kidneys) or from tumors or cancer arising elsewhere in the body (ectopic ACTH producing tumors). Cushings disease also refers to excessive ACTH secretion by a pituitary tumor (also called pituitary adenoma). Below figure describes the feedback system of cortisol.

The HPA (hypothalamic-pituitary-adrenal axis)

Background of Cushing syndrome

In 1932 American neurosurgeon Harvey Cushing described the clinical findings that provided the link between specific physical characteristics (e.g., abnormal obesity of the face and trunk) and a specific type of pituitary tumour. This pituitary disorder became known as Cushing syndrome. However, it later became clear that many patients with similar symptoms and signs did not have a pituitary tumour.

Thus, the term Cushing syndrome has been modified to refer to all patients with the classic symptoms and signs of the condition, regardless of the cause, while the term Cushing disease is restricted to patients in whom the symptoms and signs are caused by an adrenocorticotropic hormone- (ACTH-) secreting pituitary tumour. Among patients with spontaneously occurring Cushing syndrome, about 70 percent have Cushing disease.

Epidemiology in worldwide

Cushing’s syndrome is relatively uncommon. Older European literature reports an incidence of 2-3 cases per million per year. However, newer studies of high-risk groups report a significantly greater prevalence. Hypercortisolism has been reported in 0.5% to 1% of patients with hypertension, 2% to 3% of patients with uncontrolled diabetes, 6% to 9% of patients with adrenal masses, and 11% of patients with osteoporosis and vertebral fractures. It is unclear if this increase in prevalence is due to higher-sensitivity testing, a greater recognition of disease in high-risk groups, or variability in the diagnostic criteria between historical and more-recent studies.

Cushing’s syndrome due to adrenal disease occurs 4 times more commonly in women than in men, and Cushing’s disease (ACTH-secreting pituitary tumour) has a 3.5 to 1 female-to-male predominance. No ethnic disparities in prevalence have been identified. The majority of adults are diagnosed between the ages of 20 and 50, although it can occur at any age.

Causes

Adrenal glands produce cortisol, which helps in number of body’s functions, including:

  • Regulating blood pressure and the cardiovascular system
  • Reducing the immune system’s inflammatory response
  • Converting carbohydrates, fats, and proteins into energy
  • Balancing the effects of insulin
  • Responding to stress

High levels of cortisol is produced due to the following reasons:

  • High stress levels, including stress related to an acute illness, surgery, injury, or pregnancy, especially in the final trimester
  • Athletic training
  • Malnutrition
  • Alcoholism
  • Depression, panic disorders, or high levels of emotional stress

The most common cause of Cushing’s syndrome is the use of corticosteroid medications, such as prednisone, in high doses for a long period. Familial Cushing’s syndrome is another possible cause.

Other causes include:

  • a pituitary gland tumor in which the pituitary gland releases too much adrenocorticotropic hormone, which is also known as Cushing’s disease
  • ectopic ACTH syndrome, which causes tumors that usually occur in the lung, pancreas, thyroid, or thymus gland
  • an adrenal gland abnormality or tumor

Symptoms

Common signs and symptoms involve progressive obesity and skin changes, such as:

  • Weight gain and fatty tissue deposits, particularly around the midsection and upper back, in the face (moon face), and between the shoulders (buffalo hump)
  • Pink or purple stretch marks (striae) on the skin of the abdomen, thighs, breasts and arms
  • Thinning, fragile skin that bruises easily
  • Slow healing of cuts, insect bites and infections
  • Acne

Symptoms of Cushing syndrome

Women with Cushing syndrome may experience:

  • Thicker or more visible body and facial hair (hirsutism)
  • Irregular or absent menstrual periods

Men with Cushing syndrome may experience:

  • Decreased libido
  • Decreased fertility
  • Erectile dysfunction

Other signs and symptoms include:

  • Severe fatigue
  • Muscle weakness
  • Depression, anxiety and irritability
  • Loss of emotional control
  • Cognitive difficulties
  • New or worsened high blood pressure
  • Headache
  • Bone loss, leading to fractures over time
  • In children, impaired growth

Complications

Without treatment, complications of Cushing syndrome may include:

  • Bone loss (osteoporosis), which can result in unusual bone fractures, such as rib fractures and fractures of the bones in the feet
  • High blood pressure (hypertension)
  • Type 2 diabetes
  • Frequent or unusual infections
  • Loss of muscle mass and strength

Diagnosis

  • Urine and blood tests. These tests measure hormone levels in your urine and blood and show whether your body is producing excessive cortisol. For the urine test, you may be asked to collect your urine over a 24-hour period.
  • Saliva test. Cortisol levels normally rise and fall throughout the day. In people without Cushing syndrome, levels of cortisol drop significantly in the evening. By analyzing cortisol levels from a small sample of saliva collected late at night, doctors can see if cortisol levels are too high, suggesting a diagnosis of Cushing syndrome.
  • Imaging tests. CT-Scan and MRI scans can provide images of your pituitary and adrenal glands to detect abnormalities, such as tumors.
  • Petrosal sinus sampling. This test can help determine whether the cause of endogenous Cushing syndrome is rooted in the pituitary or somewhere else. For the test, blood samples are taken from the petrosal sinuses – veins that drain the pituitary glands.

Treating Cushing’s syndrome

  • The main treatment for iatrogenic Cushing’s syndrome is to decrease or withdraw the use of corticosteroids. However, this must be done gradually to avoid any unpleasant side effects.
  • Surgery to remove the tumour is usually recommended. If surgery is unsuccessful or it’s not possible to remove the tumour safely, medication can be used to counter the effects of the high cortisol levels.
  • Radio-therapy. For patients whose Cushing’s disease is not controlled with surgery, both conventional (external beam) and stereotactic radiosurgery are effective in controlling cortisol levels and tumor growth in many patients. However, the lowering of cortisol levels generally takes significantly longer with external beam radiotherapy compared to stereotactic radiotherapy. Neurologic complications such as visual loss, weakness, and memory impairment have rarely been reported with both external beam and stereotactic radiotherapy.
  • Medications which can be used to help control cortisol levels. Most typically, these include “adrenal-directed” medications: ketoconazole, aminoglutethemide, and metyrapone. These agents all inhibit steroid (cortisol) production in the adrenal glands. All are relatively effective but all have some side effects.

Prevention

  • Eating a balanced diet
  • Getting regular check-ups
  • Monitoring mental health
  • Soothe aches and pains
  • Exercise your brain

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