Cushing's disease is caused by an ACTH-secreting pituitary adenoma. This serious endocrinopathy is a subset of Cushing’s syndrome which refers to elevated blood cortisol levels. Cushing's syndrome results from tumors of the pituitary, adrenal glands or from tumors elsewhere in the body (ectopic ACTH producing tumors). The cause of Cushing's syndrome is a pituitary adenoma in over 70% of patients. Most ACTH adenomas are microadenomas. Cushing's disease is relatively uncommon, affecting 10-15 of every million people each year, and most commonly in adults aged 20-50 years old; women account for over 70% of cases. Given that Cushing’s disease causes so many common problems affecting the general population such as obesity, hypertension and diabetes, it is possible that many patients with Cushing’s disease are undiagnosed for years or perhaps never diagnosed. 

Body changes including weight gain in the face (moon face), above the collar bone (supraclavicular) and on the back of the neck (buffalo hump) are commonly seen in patients with Cushing’s disease. Skin changes may include easy bruising, with purplish stretch marks (stria) and red cheeks (plethora) as well as excess hair growth (hirsutism) on the face and body. The high cortisol levels also cause weakness, fatigue and muscle wasting. Women may develop menstrual disorders including amenorrhea (absence of menses) and decreased libido. Additional serious consequences may include hypertension, diabetes mellitus, osteoprosis and depression.

Patients are often diagnosed with Cushing’s disease after several years of symptoms which might include progressive weight gain, new onset hypertension or diabetes and mood changes. Comparison of old and recent photographs will often demonstrate changes in appearance. Unfortunately, the diagnosis of Cushing's disease is often long delayed. An endocrinologist should always supervise the evaluation for Cushing's disease.

Hormonal diagnosis: The first step in diagnosing Cushing's disease is to confirm excessive cortisol secretion which is done by performing a 24-hour urinary free cortisol collection, midnight salivary cortisol test and/or a low-dose dexamethasone suppression test. If blood ACTH levels are elevated or normal, then the source is from either an ACTH-secreting pituitary adenoma or an ectopic (elsewhere in the body) ACTH-producing tumor. A high-dose dexamethasone suppression test and/or petrosal sinus sampling are tests used to distinguish between ectopic ACTH production and pituitary ACTH production (Cushing's disease). Petrosal sinus sampling should never be performed before the diagnosis of ACTH-dependent Cushing's syndrome is established.

Imaging:Once the diagnosis of Cushing's syndrome is confirmed hormonally, a pituitary MRI can detect an adenoma in 70-80% of cases. Dynamic post-gadolinium MRI is a recent technique that helps diagnose small adenomas that may not be seen on a conventional pituitary MRI. CT scans of the adrenal glands are very useful for determining the presence or absence of an adrenal tumor causing Cushing's syndrome.

Transsphenoidal Surgery: Endonasal surgery is considered the first-line treatment for Cushing’s disease and the only way currently, to achieve long term remission of the disease. Surgical remission rates range from 80-90% for microadenomas and from 30-70% for macroadenomas and invasive adenomas. Long-term follow-up with 24 hour urinary free cortisol levels every 6 months is essential to monitor for tumor recurrence which can occur in 5 – 10% of patients.

Medical therapy:In patients who fail to have remission of their Cushing’s disease or syndrome state after surgery, "adrenal-directed" medications can be used such as ketoconazole and aminoglutethimide which inhibit steroid (cortisol) production in the adrenal glands. They are initially effective but have some side effects, and the overall long-term control of Cushing’s disease with these drugs is rather poor.

Radiosurgery (SRT) or Stereotactic Radiotherapy (SRS):For patients whose Cushing's disease is not controlled with surgery, SRT (multiple doses) and SRS (one dose), are effective in controlling cortisol levels and tumor growth in 50 – 70% of patients. However, the lowering of cortisol levels generally takes significantly longer with SRT compared to SRS. Also, SRT and SRS often result in loss of normal pituitary function over 5 to 10 years. Other complications such as visual loss are rare with either SRS or SRT.