Cushing’s Syndrome

Diseases of the Adrenal Cortex

The adrenal gland has a center gland (medulla) that produces adrenaline and an outer gland (the cortex) that produces several hormones, such as cortisol and aldosterone.Cushing’s syndrome is caused byseveral diseases that result in overproduction of cortisol by the adrenal cortex. Please read the overview of the adrenal glands for more details.

In 1932, a physician named Harvey Cushing described eight patients with central body obesity (gut fat), glucose intolerance, hypertension, excess hair growth, osteoporosis, kidney stones, menstrual irregularity, and emotional liability. These symptoms characterize Cushing’s syndrome, which is the result of overproduction of cortisol. This condition is very rare and can be confused with simple obesity.

Since cortisol production by the adrenal glands is normally under the control of the pituitary, overproduction can be caused by a tumor in the pituitary or within the adrenal glands themselves. When a pituitary tumor secretes too much ACTH (adrenocorticotropic hormone), it causes the otherwise normal adrenal glands to produce too much cortisol. This type of Cushing’s syndrome is termed Cushing Disease and it is diagnosed like other endocrine disorders (by measuring hormone production). In this case, serum cortisol and serum ACTH will both be elevated. When the adrenal glands develop a cortisol secreting tumor, excess amounts of cortisol hormone will be produced, the normal pituitary will sense the excess cortisol and will stop making ACTH in an attempt to slow down the adrenal gland. In this manner, physicians can usually distinguish whether excess cortisol is the result of a pituitary tumor or an adrenal tumor.

Even more rare is when excess ACTH is produced somewhere other than the pituitary. This is extremely uncommon, but certain lung cancers can produce ACTH. In this situation, patients develop Cushing’s syndrome in the same way as if the ACTH was coming from the pituitary, but ACTH levels are typically extremely high.

Causes of Cushing’s Syndrome
ACTH Dependent (80%)
• Pituitary tumors (60%)
• Lung cancers (5%)
ACTH Independent (20%)
• Benign adrenal tumors (adenoma) (25%)
• Malignant adrenal tumors (adrenal cell carcinoma) (10%)

Testing for Cushing’s Syndrome

Testing for Cushings may be complex and usually requires repeated testing. Commonly used tests are overnight low dose dexamethasone test (see below), 24 hour urine collections, and 11:00 PM saliva swabs for three consectutive nights. Other testing may be required in difficult to diagnose patients.

The low-dose dexamethasone suppression test, which measures the cortisol secretion following the administration of a synthetic steroid that will shut down steroid production in everyone with a normal adrenal gland. For this test, Dexamethasone (1 mg) is given at 11:00 PM the night before a cortisol blood test is to be drawn at 8:00 AM the next morning. Subsequent tests will distinguish whether the disease is due to an ACTH dependent or independent cause. 24 hour urine for cortisol can reveal how much cortisol is produced. Saliva testing for cortisol also helps to define abnormal night cortisol secretion.

Once the diagnosis is made, patients will undergo a CT scan (or possibly an MRI or ultrasound) of the adrenal glands to look for tumors in the adrenal glands. If the laboratory tests suggest a pituitary origin, a CT or MRI of the brain (and possibly the chest) will be performed.

Treatment of Cushing’s Syndrome

The treatment of this disease depends on the cause. Pituitary tumors are the most common cause and are removed surgically by neurosurgeons along with ENT physicians. Sometimes radiation oncology treats large tumors with radiation therapy. If the cause is determined to be within a single adrenal gland, this is treated by surgical removal by an experienced endocrine surgeon. If a single adrenal gland possesses a small, well-defined tumor, it can usually be removed with laparoscopic adrenalectomy. If the tumor has characteristics of cancer on any of the x-ray tests, then a larger, conventional operation is in order. There are medications which are also available when surgery cannot cure the disease or when the patient does not have an obvious tumor.