What is Cushing's Syndrome?

Cushing's Syndrome is a disease due to excess of the adrenal hormone cortisol. Cushing's syndrome can also be called primary hypercortisolism, and over time cause many harmful signs and symptoms for the patient. When Cushing's Syndrome is due to an adrenal tumor, surgery (often the Mini Back Scope Adrenalectomy; MBSA), leads to cure of the disease.

Overview of Cushing's Syndrome

In 1932, a physician named Harvey Cushing described 8 patients with central body obesity, glucose intolerance (i.e. diabetes), hypertension (high blood pressure), excess hair growth, osteoporosis, kidney stones, menstrual irregularity, and emotional lability. It is now known that these symptoms characterize Cushing's syndrome, which is the result of excess production of cortisol by the adrenal glands.

Cortisol is a powerful steroid hormone, and excess cortisol has detrimental effects on many cells throughout the body. Keep in mind that overt Cushing's syndrome is rare, occurring in only about 10 patients per one million. However, slight overproduction of cortisol, what we call “subclinical hypercortisolism” or “subclinical Cushing’s syndrome” is very common. This may be related to an adrenal tumor producing too much cortisol. Conversely, obesity can be associated with some of these symptoms in the absence of an adrenal tumor; this is related to the slightly different mechanism by which normally produced steroids are metabolized by individuals who are obese.

Since cortisol production by the adrenal glands is normally under the control of the pituitary (a small endocrine gland located in the bran right behind your eye, and the nerves to the eyes. 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's disease, and it is diagnosed just like other endocrine disorders (by measuring hormone production). In this case, serum cortisol will be elevated, and serum ACTH (adrenocorticotropic hormone; the pituitary hormone controlling the cortisol release from the adrenals) will also be elevated.

Dr. Carling, Editorial note: The surgeons of the Carling Adrenal Center are the most world’s expert surgeons of adrenal tumors and disease. That is what we do. We do not perform surgery on the brain, or pituitary gland. However, if you have Cushing’s disease due to an ACTH producing pituitary tumor, you can always contact us, and we will direct you to a high-volume surgeon who does pituitary surgery (usually a neurosurgeon). You want the most expert pituitary surgeon do your operation! Similar as adrenal surgery, pituitary surgery is tricky and requires significant expertise and experience.

When the adrenal glands develop a tumor, like any other endocrine gland, they usually produce excess amounts of the hormone normally produced by these cells. If the adrenal tumor is composed of cortisol-producing cells, excess cortisol will be produced. Under these conditions, the normal pituitary will sense the excess cortisol and will stop making ACTH to slow the adrenal down. In this manner, physicians can readily distinguish whether excess cortisol is the result of a pituitary tumor or an adrenal tumor.

Even rarer is when excess ACTH is produced somewhere other than the pituitary. This is extremely uncommon, but certain lung cancers can produce ACTH (adrenocorticotropic hormone; the pituitary hormone controlling the cortisol release from the adrenals). In this situation, patients develop Cushing's syndrome in the same way as if the ACTH was coming from the pituitary.

What are the causes of Cushing's Syndrome?

Cushing’s syndrome are divided into a) ACTH Dependent Cushing’s syndrome (i.e. is due to overproduction of the pituitary hormone called ACTH (adrenocorticotropic hormone). Only rarely is adrenal surgery necessary in these cases) b) ACTH Independent Cushing’s syndrome. Adrenal surgery is almost always curative in these cases
  • ACTH Dependent (60%)
    • Pituitary tumors (55%)
    • Lung cancers (5%)
  • ACTH Independent 40%
    • Benign adrenal tumors (adenoma) (30%)
    • Malignant adrenal tumors (adrenal cell carcinoma) (10%)

    Dr. Carling, Editorial note: Adrenal subclinical Cushing’s syndrome is not included in these numbers. This is much more common and can be readily cured by a scope adrenalectomy. Read more about Adrenal Surgery here.