Hypercortisolism Causes, Prevention and Treatment

Hypercortisolism refers to a range of conditions characterised by an excess of circulating corticosteroids. Endogenous hypercortisolism is known as Cushing’s syndrome, and may arise from the adrenal cortex, e.g. because of an adrenal tumour, or may be secondary to overproduction of pituitary adrenocorticotrophic hormone (ACTH).

The most common cause of hypercortisolism is, however, steroid therapy.

Causes, incidence, and risk factors

Cushing’s syndrome is a condition that results from an excess of cortisol, a hormone produced by the adrenal glands. The most common cause of Cushing’s syndrome is Cushing’s disease, caused by excessive production of the hormone ACTH by the pituitary gland. ACTH stimulates the adrenal glands to produce cortisol.

Cushing’s syndrome can be caused by a tumor of the pituitary gland, a tumor of the adrenal gland, a tumor somewhere other than the pituitary or adrenal glands (ectopic Cushing’s syndrome), or by long-term use of corticosteroids (drugs commonly used to treat conditions such as rheumatoid arthritis and asthma).

Clinical features

The natural regulation of cortisol is governed by a negative feedback response system. Output is initiated when pituitary gland secretions of ACTH stimulate the adrenal glands, which is the producer of glucocorticoids hormones in the zona fasciculata.

Cortisol secretion is affected by stress which, if prolonged, can result in chronic hypercortisolaemia.

Cortisol target tissues include liver, bone, blood, vessels, kidney, muscle, brain, and immune system.

Long-term exposure to cortisol may eventually result in changes such as: osteoporosis, muscle weakening and wasting; high blood pressure, increased fat deposition in the abdomen, shoulders and face; immune dysfunction, leading to delayed healing and steroid-induced diabetes.

Classic clinical signs include a ‘moon face’, thinning of the skin accompanied by purple or pink stretch marks on the abdomen, easy bruising, acne, increased facial and body hair and decreased scalp hair in women.

Risk factors for Cushing’s syndrome are adrenal or pituitary tumors, long-term therapy with corticosteroids, and being female.

See also:

  • Cushing’s disease (pituitary Cushing’s)
  • Cushing’s syndrome – exogenous
  • ectopic Cushing’s syndrome
  • Cushing’s syndrome caused by adrenal tumor


  • moon face (round, red, and full)
  • buffalo hump (a collection of fat between the shoulders)
  • central obesity with protruding abdomen and thin extremities
  • weight gain (unintentional)
  • weakness
  • backache
  • headache
  • acne or superficial skin infections
  • thin skin with easy bruising
  • thirst
  • increased urination
  • purple striations on the skin of the abdomen, thighs, and breasts
  • mental changes
  • impotence or cessation of menses
  • facial hair growth

Additional symptoms that may be associated with this disease:

  • skin spots, red
  • skin blushing / flushing
  • muscle atrophy
  • fatigue
  • bone pain or tenderness
  • high blood pressure

Signs and tests

Tests to confirm high cortisol level:

  • cortisol, urine
  • dexamethasone suppression test
  • serial serum cortisol levels

Tests to determine the cause:

  • ACTH
  • cranial MRI or cranial CT scan may show pituitary tumor
  • abdominal CT may show adrenal mass

General findings:

  • glucose test is elevated
  • potassium test may be low
  • white blood cell count may be elevated


Treatment depends upon the cause of the disorder. In Cushing’s syndrome caused by drug therapy with corticosteroids, the drug dose must be slowly decreased under medical supervision.

In Cushing’s disease caused by a pituitary tumor, surgery to remove the tumor is recommended. Radiation is sometimes needed as well. Hydrocortisone (cortisol) replacement therapy is needed after surgery. In some cases, life-long cortisol-replacement therapy becomes necessary.

Cushing’s syndrome caused by an adrenal tumor is usually treated by surgical removal of the tumor. If the tumor cannot be removed, certain medications can suppress the secretion of cortisol.

In Cushing’s syndrome caused by a tumor secreting ACTH, removal of the tumor is the best way to treat the Cushing’s syndrome. Cortisol replacement therapy is needed after surgery until cortisol production resumes. In some cases, life-long therapy with cortisone drugs becomes necessary.

Support Groups

Expectations (prognosis)

Tumor removal may lead to full recovery, but there is a chance of recurrence. Survival for people with ectopic tumors depends upon the overall outcome associated with the particular tumor type. Untreated, Cushing’s syndrome can lead to death.


  • diabetes mellitus
  • high blood pressure
  • serious infections
  • fractures due to osteoporosis
  • kidney stones
  • enlargement of pituitary tumor

Calling your health care provider:

Call your health care provider if symptoms develop that indicate Cushing’s syndrome.


Cushing’s syndrome may be prevented by an awareness of the associated symptoms so that early detection can be made.


The treatment of Cushing’s syndrome depends upon the underlying cause. When Cushing’s syndrome is caused by an ACTH-producing tumour ,the treatment can include:

Surgery. Transsphenoidal surgery allows access to the base of the brain (where the pituitary is located), through the gums above the upper front teeth or the nose.

If the tumour cannot be identified, the surgeon can remove half of the pituitary (hemihypophysectomy) or 85–90% of the gland (subtotal hypophysectomy). These treatments cause a loss of function of the pituitary so that the patient needs lifelong hormone replacement.

Radiation-chemotherapy. This can be used when the surgery cannot completely remove the tumour. The effects of radiation take 3–12 months to become apparent, so that medical treatment is required in the interim.

These medications include ketoconazole, metyrapone and aminoglutethimide, which reduce the adrenal cortisol production.

Adrenalectomy. This consists in surgical removal of the adrenal glands, but is recommended only if other treatments are not successful. The patient must begin lifelong daily glucocorticoid and mineralocorticoid replacement therapy.

When Cushing’s syndrome is caused by an ectopic ACTH-producing tumour, the treatment consists of the surgical removal of the tumour.

This kind of tumour is often in the lung. If the surgery is not successful, medications that reduce adrenal cortisol production (ketoconazole, metyrapone and aminoglutethimide) can be used.

Source & More Info: endocrinesurgery.ucla.edu and diapedia.org



Leave a Comment