CUSHING'S DISEASE: Diagnosis and Treatments

Cushing's Disease

Cushing's disease is a disorder that occurs when a pituitary tumor produces too much of a certain hormone (ACTH), which causes the body to produce extra cortisol. Symptoms can include excessive weight gain, fatigue, and purplish stretch marks on the abdomen, thighs, and breasts. There are several treatment options for this condition, including surgery, radiation therapy, and medications.

What Is Cushing's Disease?

Cushing's disease is a hormonal disorder caused by a benign (non-cancerous) pituitary tumor which produces large amounts of ACTH (adrenocorticotropin). This excess ACTH causes the body to produce extra cortisol, resulting in Cushing's disease.

Cushing's disease affects women five times more frequently than men.

Understanding Cortisol and the Pituitary Gland

Normally, the production of cortisol follows a precise chain of events. First, the hypothalamus, a part of the brain that is about the size of a small sugar cube, sends corticotropin-releasing hormone (CRH) to the pituitary gland. CRH causes the pituitary gland to secrete ACTH, a hormone that stimulates the adrenal glands. When the adrenals, which are located just above the kidneys, receive the ACTH, they respond by releasing cortisol into the bloodstream.

Cortisol performs vital tasks in the body. Cortisol helps:

Maintain blood pressure and cardiovascular function

Reduce the immune system's inflammatory response

Balance the effects of insulin in breaking down sugar for energy

Regulate the metabolism of proteins, carbohydrates, and fats

Assist the body as it responds to stress.

When the amount of cortisol in the blood is adequate, the hypothalamus and pituitary release less CRH and ACTH. This ensures that the amount of cortisol released by the adrenal glands is precisely balanced to meet the body's daily needs. However, if something goes wrong with the adrenals (or with their regulating switches in the pituitary gland or the hypothalamus) the level of cortisol produced may be more or less than what the body needs.

The pituitary gland sits in the middle of the head in a bony box called the sella turcica. The eye nerves sit directly above the pituitary gland. Enlargement of the pituitary gland can cause localized symptoms, such as headaches or visual disturbances.

Understanding Pituitary Adenomas

Most pituitary tumors are not cancerous. These non-cancerous pituitary tumors are called adenomas. A pituitary adenoma is classified based on its size:

Microadenomas are smaller than 10 millimeters

Macroadenomas are 10 millimeters or larger.

Most pituitary adenomas are microadenomas.

A pituitary adenoma is also classified based on whether it produces hormones or not. A pituitary tumor that makes one or more of the pituitary hormones is called a functioning pituitary tumor. A pituitary adenoma that does not make hormones is called a nonfunctioning pituitary tumor. Each type of functioning pituitary tumor causes different symptoms, depending on the type of hormone that is produced by the tumor. 


Examples of functioning pituitary tumors include:

Prolactin-producing tumors (which account for about 43 percent of all pituitary adenomas)

ACTH-producing tumors (which represent approximately 7 percent of all pituitary adenomas)

Growth hormone-producing tumors (which account for about 17 percent of all pituitary adenomas)

Thyroid hormone-producing tumors (which make up about 3 percent of all pituitary adenomas).

Nonfunctioning adenomas make up the remaining 30 percent of all pituitary adenomas.

Causes of Cushing's Disease

Cushing's disease occurs when the body's tissues are exposed to excessive levels of cortisol for long periods of time. The cause of Cushing's disease is an ACTH-secreting pituitary adenoma.

ACTH-producing pituitary tumors produce a hormone called adrenocorticotropin (ACTH), which stimulates the adrenal glands to make glucocorticoids. When the body makes too much ACTH, it causes Cushing's disease.

Symptoms

Too much cortisol in the body for long periods of time is responsible for the classic Cushing's disease symptoms. Cushing's disease symptoms will vary among patients. Symptoms of Cushing's disease also vary based on the person's age.

Cushing's disease symptoms can include:

Extreme weight gain, especially around the midsection and upper back

Excess hair growth

Purplish-pink stretch marks on the abdomen, thighs, buttocks, arms, and breasts

Acne

High blood pressure

Skin problems

Growth retardation

Either very early or late puberty

Sleep disturbances

Muscle weakness

Menstrual disorders in women

Osteoporosis

Moodiness, irritability, or depression

Diabetes

Decreased fertility in men

Diminished or absent desire for sex.

Making a Diagnosis

In order to make a diagnosis, the doctor will typically ask a number of questions about things such as:

The patient's medical history

His or her current symptoms

Whether there is a family history of any medical problems

Any medicines the patient is taking.

The doctor will also usually perform a physical exam, looking for any signs of Cushing's disease. If these suggest Cushing's disease, more tests are done.

Testing for Cushing's disease generally involves a two-step process. First, doctors order tests to see if there is too much cortisol in the body. If so, then they call for tests to see if a pituitary adenoma is causing the excess cortisol. If a pituitary adenoma is causing the excess cortisol, the condition is diagnosed as Cushing's disease; if the excess cortisol is being caused by another condition, it is known as Cushing's syndrome.

Tests used for diagnosing Cushing's disease can include:

A 24-hour urinary free cortisol level test

Dexamethasone suppression test

CRH stimulation test

Imaging tests

Petrosal sinus sampling.

Treating Cushing's Disease

There are several treatment options for cases of Cushing's disease. Treatment options vary based on:

The symptoms present

How far the tumor has spread into the brain

The patient's age and overall health.

Treating Cushing's disease may involve:

Surgery to remove the tumor (usually transsphenoidal surgery), with or without radiation therapy

Radiation therapy alone

Drug therapy to stop the tumor from making ACTH

A clinical trial of stereotactic radiation surgery.

Your doctor can describe your treatment choices and the expected results of each. You and the doctor can work together to develop a treatment plan that best meets your medical needs and personal values. Choosing the most appropriate treatment method is a decision that ideally involves the patient, family, and healthcare team.