Back to Endocrine Diseases
Cushing's syndrome, also known as hypercortisolism, occurs when a
person's tissues are exposed to an excess of the hormone cortisol.
When the appropriate amount of cortisol is released by the adrenal
glands, it helps regulate blood pressure, energy production, the ability
to fight disease, and how the body maintains itself and responds to
stress. But too much cortisol can alter the normal function of these
processes, resulting in the symptoms of Cushing's syndrome.
The body produces too much cortisol. Too much cortisol is produced when
the pituitary and adrenal glands are not working properly. This can be
Growths on the adrenal glands, that may or may not be cancerous, can
cause the adrenal glands to release extra cortisol.
Use of exogenous steroids: Steroid hormone
therapy for a long time as treatment for another
disorder or disease, for example, taking a steroidal anti-inflammatory
- A noncancerous tumor of the pituitary gland that produces increased
amounts of the hormone adrenocorticotropin (ACTH). This, in turn,
prompts the adrenal glands to produce too much cortisol. This form of
Cushing's syndrome is known as "Cushing's disease."
- Adrenocortical cancer
- Certain types of cancerous tumors in other parts of the body can produce
ACTH, causing the adrenal glands to produce extra cortisol.
- ACTH secreting pituitary adenomas
- Ectopic ACTH production by nonpituitary tumors.
Hypertension (especially young individuals) and
diabetes and overweight (centripetal) particularly in the presence of :
Proximal muscle weakness.
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Symptoms and signs
Cushing's syndrome is fairly rare. For every one million people, 2-5 new
cases are diagnosed each year, with about 10 percent of these being
children and teenagers.
- weight gain, particularly of the trunk and face with
sparing of the limbs, 'moon' face,
- excess sweating,
- thin and easily
bruised skin, purple striae on the trunk and legs,
- proximal muscle weakness (hips, shoulders),
- The excess cortisol may also affect other endocrine axes and
cause, for example, reduced libido, impotence, and infertility.
- Patients frequently suffer various psychological disturbances.
- persistent hypertension and
- impaired ability to regulate
glucose (typically hyperglycaemic and often with frank diabetes)
Most children and teenagers with Cushing's syndrome will show several of
- extreme weight gain
- growth retardation
- missed periods in teenage girls
- excess hair growth
- reddish-blue streaks on the skin
- high blood pressure
- tiredness and weakness
- either very early or late puberty
Adults with the disease may also have symptoms of extreme weight gain,
excess hair growth, high blood pressure, and skin problems. In addition,
they may show:
- muscle and bone weakness
- moodiness, irritability, or depression
- sleep disturbances
- high blood sugar
- menstrual disorders in women and decreased fertility in men
Doctors review the patient's medical records and do a physical exam. If
these suggest Cushing's syndrome, more tests are done. A definite
- Seeing if there is too much cortisol in the body, and
- Discovering the cause of extra cortisol. A urine test measures how much
cortisol is being produced. If the level indicates Cushing's syndrome,
the doctor will order other tests to discover the cause. These may
- Biochemistry tests. The dexamethasone suppression test involves taking a
man-made cortisol by mouth for several days during which time cortisol
levels in the blood and urine are measured. The CRH stimulation test
involves receiving an injection of the corticotropin-releasing hormone (CRH)
followed by a blood test to see if there is a rise in the levels of ACTH
- Scans. This may include computerized tomography (CT) and magnetic
resonance imaging (MRI) scans of the pituitary and adrenal glands,
chest, and abdomen; ultrasound imaging of the adrenal glands; chest
x-rays; and perhaps a radioisotope procedure called an iodocholesterol
- Catheterization procedures. Samples of the blood leaving the pituitary
gland are tested to see if the pituitary is causing the high level of
Confirm the diagnosis by any of the following
- 24hr urinary cortisol
- Overnight dexamethazone suppression test.
- Other screening tests include cortisol circadian
rhythm & low dose dexamethasone suppresion test but require the patient
to be admitted.
After establishing the diagnosis with one of the tests
above a high dose dexamethasone suppression test suppresses pituitary Cushing's
but not other causes. A plasma ACTH level will then determine if ACTH plays
a role in the pathogenesis. CT or MRI of the pituitary or adrenal gland
to search for an adenoma. A chest x-ray is essential to exclude bronchial
carcinoma or carcinoid.
N.B. Cushing's disease refers to hypercorticism secondary
to ACTH secreting pituitary adenoma.
Whatever the underlying cause, cortisol hypersecretion should be controlled
prior to surgery or radiotherapy to decrease the morbidity and mortality
associated with operating on unprepared patients.
If an adrenal adenoma is identified it may be removed by surgery.
Post-operatively most patients will require steroid replacement at least
in the interim as long-term suppression of pituitary ACTH and normal
adrenal tissue does not recover immediately. Clearly, if both adrenals
are removed replacement with hydrocortisone or prednisolone is
In those patients not suitable for or unwilling to undergo surgery,
several drugs have been found to inhibit cortisol sythesis (e.g.
ketoconazole, metyrapone) but they are of limited efficacy.
In iatrogenic Cushing's, dose adjustment may be sufficient or it may be
necessary to change to another type of immunosuppresive medication.
The drug of choice is metyrapone. The mean level of plasma cortisol during the day should be reduced
to 11-15 ug/dL. Alternatively ketokonazole or aminoglutethamide may be used.
The definitive treatment is surgical removal of the source of hypersecretion,
whether it be pituitary, adrenal or of ectopic origin.