Cushing’s Disease
What is Cushing’s Disease?
Overview
Cushing’s disease is a form of Cushing’s syndrome caused by an ACTH-secreting pituitary adenoma, which is a usually benign (non-cancerous) tumor in the pituitary gland. This excess ACTH stimulates the adrenal glands to produce too much cortisol.
Cushing’s syndrome itself refers to the condition of having elevated cortisol levels, which can result from:
- Pituitary tumors (Cushing’s disease)
- Adrenal gland tumors
- Tumors elsewhere in the body that produce ACTH (ectopic ACTH-producing tumors)
For most patients with Cushing’s disease, transsphenoidal tumor removal—a minimally invasive procedure performed through the nose—is the first treatment of choice.
For those patients who do not achieve remission with surgery, expert endocrinologists may recommend advanced medical therapies. In some cases, patients may also be eligible for clinical trials investigating new treatments.
For persistent disease after surgery and medication, focused radiosurgery can target the tumor and help normalize cortisol levels. In rare, severe cases that remain uncontrolled despite these options, bilateral adrenalectomy (removal of both adrenal glands) may be considered to stop excess cortisol production.
Who is Affected?
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.
Cushing’s Disease Symptoms & Causes
Symptoms
Because excess cortisol has so many effects on different parts of the body and brain, symptoms of Cushing’s disease can present in many different and initially subtle ways.
The major types of changes are in body habitus, blood glucose levels, blood pressure, bone and skin integrity, immune system and ability to fight infection, as well as sexual function and psychological state. Unfortunately, the diagnosis of Cushing’s disease is often long delayed.
- 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).
- Both women and men may develop decreased libido.
Additional serious consequences may include hypertension, diabetes mellitus, osteoporosis 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. An endocrinologist should always supervise the evaluation for Cushing’s disease.
Causes
Cushing’s disease specifically results from a benign pituitary adenoma that overproduces adrenocorticotropic hormone (ACTH). This excess ACTH signals the adrenal glands to produce abnormally high levels of cortisol.
While the exact reason these adenomas develop is not fully understood, most occur sporadically without a known inherited cause. Rarely, Cushing’s disease may be linked to genetic syndromes such as Multiple Endocrine Neoplasia type 1 (MEN1) or Carney complex.
When to See a Doctor
Because symptoms can mimic other common conditions, early recognition and specialist evaluation are essential to prevent long-term complications. Seek medical evaluation promptly if you notice:
- Unexplained weight gain, particularly in the face, neck, and trunk.
- New onset or worsening high blood pressure or diabetes.
- Purple stretch marks, easy bruising, or skin thinning.
- Muscle weakness, especially in the upper arms or thighs.
- Significant mood changes such as depression, anxiety, or irritability.
- Menstrual irregularities or decreased libido.
Cushing’s Disease Diagnosis
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.
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.
Once the diagnosis of Cushing’s disease is confirmed by hormonal testing, 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.
Cushing’s Disease Treatment & Outcomes
Treatment Options
Fortunately, this surgical technique in experienced hands at a Pituitary Center of Excellence has a relatively high rate of success. Notably, there have been major technical advances in endoscopic pituitary surgery that have helped improve surgical success rates, including high-definition endoscopy, surgical navigation techniques and more effective skull base closure methods.
Surgical removal is the primary means to achieve long term remission in Cushing’s disease; at Pituitary Centers of Excellence, remission rates range from 80-90% for microadenomas and 30-70% for invasive adenomas or macroadenomas; for non-visible adenomas, the surgical success rate ranges from 40-60%. Because of improved visualization, the endoscopic endonasal approach is rapidly becoming the preferred method for removal of most pituitary adenomas, including ACTH-secreting 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.
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 which inhibits steroid (cortisol) production in the adrenal glands. These are initially effective but have some side effects, and the overall long-term control of Cushing’s disease with these drugs is rather poor.
For patients with persistent Cushing’s disease after surgery, include Signifor (pasireotide) and Korlym (mifepristone). Both medications have shown moderate success in clinical trials. Pasireotide is an injectable somatostatin receptor ligand with strong affinity for somatostatin receptor 5. In clinical trials, pasireotide reduced urinary free cortisol (UFC) levels in a majority of Cushing’s disease patients. The main side effect is hyperglycemia. Mifepristone is a glucocorticoid receptor blocker that can result in improvements in symptoms of Cushing’s and blood glucose control. The main side effects are adrenal insufficiency, low blood potassium levels and vaginal bleeding in women.
Removal of the adrenal glands was at one time a preferred method for treating Cushing’s disease and lowering cortisol levels. Currently however, this treatment is reserved for patients who have failed prior endonasal transsphenoidal surgery. Although bilateral adrenalectomy has a high success rate in reversing hypercortisolism ranging from 90% to 100%, there is significant risk (25%) of developing Nelson’s syndrome with an aggressive ACTH-secreting adenoma. Prior radiosurgery or radiotherapy to the pituitary gland may reduce the risk and delay onset of Nelson’s syndrome. The average interval between bilateral adrenalectomy and development of Nelson’s syndrome is approximately 5 to 10 years but may be as short as 6 months. Given the long-term risk of Nelson’s syndrome after bilateral adrenalectomy this treatment is generally considered a 2nd or 3rd line therapy.
Patient Outcomes
With successful treatment, most patients experience significant improvement in symptoms and a return toward normal cortisol levels. However, recovery from the effects of prolonged cortisol excess may take months to years. Bone strength, metabolic health, and mood may gradually improve, but some patients may have persistent issues such as fatigue, memory changes, or osteoporosis.
Relapse can occur, especially in cases involving invasive or recurrent tumors, which makes long-term follow-up critical. Life expectancy often returns to normal when the disease is successfully treated, but uncontrolled Cushing’s disease significantly increases the risk of cardiovascular disease, infections, and other complications.
Managing Cushing’s Disease
After initial treatment, ongoing care focuses on:
Hormone Monitoring
Regular cortisol and ACTH testing to detect recurrence early.
Medication Adjustments
Temporary or long-term steroid replacement therapy may be needed if the body’s normal cortisol production is suppressed after surgery.
Lifestyle Measures
Weight-bearing exercise, balanced nutrition, and bone health optimization help counteract the effects of long-term cortisol excess.
Psychological Support
Counseling or support groups can help manage anxiety, depression, or body image concerns.
Specialist Follow-Up
Coordination between endocrinologists, neurosurgeons, and primary care providers ensures comprehensive care.
Meet our Expert Specialists & Surgeons
Experience Compassionate, Expert Care
Pituitary tumors and related hormonal disorders are complex in their diagnosis and treatment and warrant a team approach of experienced specialists to achieve optimal outcomes. Our highly experienced experts work closely together on your behalf. From diagnosis to treatment, as well as education and support, we are here for you.
At the Pacific Pituitary Disorders Center at Pacific Neuroscience Institute, we have one of the world’s largest experiences in endoscopic endonasal transsphenoidal surgery for all types of pituitary adenomas including Cushing’s disease, acromegaly, prolactinomas, non-functional adenomas, pituitary apoplexy and residual or recurrent adenomas.
PNI neurosurgeons and ENT surgeons use a fully endoscopic endonasal approach for all patients presenting with pituitary adenomas, with the median hospital length stay of just one day. By incorporating leading-edge technology and instrumentation with proven surgical experience of over 2,000 endonasal surgeries, our pituitary tumor specialists make pituitary surgery safer, less invasive and more effective leading to the best possible outcomes.
Learn More About Cushing’s Disease
Cushing’s disease is a specific form of Cushing’s syndrome caused by a pituitary tumor that produces too much ACTH, leading to high cortisol levels. Cushing’s syndrome is a broader term for the condition of having excess cortisol in the body, which can be caused by Cushing’s disease, adrenal tumors, or long-term use of steroid medications.
Yes, many people can be cured, especially if the pituitary tumor is completely removed through surgery. Cure rates are highest for small tumors and when surgery is performed by an experienced pituitary neurosurgeon. However, some people may need additional treatments, such as radiation therapy or medication, if surgery does not fully remove the tumor or if it returns.
Cushing’s disease is a serious medical condition that can lead to high blood pressure, diabetes, osteoporosis, infections, blood clots, and heart disease if untreated. The good news is that with early diagnosis and effective treatment, many of these risks can be greatly reduced or eliminated.
Yes. Even after successful surgery, Cushing’s disease can return months or years later. This is why regular follow-up with hormone testing and imaging is so important. If the disease does recur, additional treatment options are available.
Some symptoms, like high blood pressure and blood sugar, may improve quickly. Others, such as weight changes, muscle weakness, and mood issues, can take months to a year or more to improve. Many patients notice gradual but steady progress with time, lifestyle changes, and medical support.
Eating a balanced diet, staying active, protecting bone health with calcium and vitamin D, managing stress, and getting enough sleep can all help recovery. Your care team may also recommend physical therapy, counseling, or a support group to help you adjust during recovery.
Resources
Get Expert Care from Leading Specialists
At Pacific Neuroscience Institute, we bring together world-renowned neurosurgeons, endocrinologists, and skull base specialists to treat Cushing’s disease and other pituitary adenomas. We use state-of-the-art imaging, minimally invasive endoscopic surgery, and advanced medical therapies to provide personalized care for every patient.