Hyperadrenocorticism, also known as Cushing’s syndrome or Cushing’s disease, is a condition where the body is exposed to too much cortisol over time. The main goal of treatment is to bring cortisol levels back to a healthier range, reduce symptoms like weight gain and muscle weakness, and improve overall quality of life. Treatment options include surgery, radiation therapy, and medications that control hormone production.

Understanding Treatment Goals for High Cortisol

When a person or animal is diagnosed with hyperadrenocorticism, the focus of care shifts toward managing the excessive production of cortisol, a hormone made by the adrenal glands. Cortisol plays essential roles in the body, such as helping regulate blood pressure, blood sugar, and the body’s response to stress. However, when cortisol levels remain too high for too long, serious health problems can emerge. These include weight gain concentrated around the midsection and face, weakened muscles, thinning skin that bruises easily, high blood pressure, and increased vulnerability to infections. Left untreated, the condition can also lead to complications such as diabetes, bone loss, blood clots, and heart problems.^[1][3][6]

The approach to treatment depends on what is causing the excess cortisol, the severity of symptoms, and whether the patient is a human or an animal (as hyperadrenocorticism is also common in dogs). In humans, treatment can involve stopping medications that mimic cortisol, surgically removing tumors in the pituitary or adrenal glands, or using medications to reduce cortisol production. In dogs, medical therapy is the most common and practical approach, as surgical and radiation options are available only at specialty centers. The ultimate aim is not just to lower cortisol, but to restore vitality, reduce discomfort, and help patients return to a more normal and comfortable daily life.^[8][12]

Once treatment begins, patients and their doctors must work together to monitor progress. This involves regular blood tests, physical exams, and careful tracking of symptoms like appetite, thirst, urination, energy levels, and mood. Adjustments to medication doses or treatment plans are often necessary as the body responds. The sooner treatment begins, the better the chances for recovery and prevention of long-term complications.^[1][7]

Standard Medical and Surgical Treatments

The most commonly used treatments for hyperadrenocorticism depend on whether the condition is caused by medication use or by a tumor in the pituitary or adrenal glands. When hyperadrenocorticism is caused by long-term use of glucocorticoid medications such as prednisone or hydrocortisone, the primary treatment involves gradually tapering the dose of these drugs under close medical supervision. This is done carefully to avoid adrenal insufficiency, a dangerous condition that can occur when the body suddenly lacks the cortisol it needs to function.^[6][7]

When the cause is a tumor in the pituitary gland—a condition specifically called Cushing’s disease—one standard approach is surgery to remove the tumor. This procedure, called transsphenoidal hypophysectomy, involves accessing the pituitary gland through the nose or upper lip. In some cases, radiation therapy is used instead of or in addition to surgery, especially if the tumor is difficult to remove completely or if it returns. Radiation can help shrink or control pituitary tumors over time, although it may take months to see full effects.^[8][11]

When the source of excess cortisol is a tumor in one of the adrenal glands, surgical removal of the affected gland, called adrenalectomy, is often recommended. This may be done through traditional open surgery or, in some cases, minimally invasive techniques. After adrenal surgery, patients may need to take replacement hormones temporarily or permanently, depending on whether both glands are affected.^[8]

Medical therapy is widely used, especially in cases where surgery is not an option or when the patient is not a good candidate for invasive procedures. In dogs, the most commonly prescribed medication is trilostane, sold under the brand name Vetoryl. Trilostane works by blocking an enzyme called 3-beta-hydroxysteroid dehydrogenase, which is involved in the production of cortisol. By inhibiting this enzyme, trilostane reduces the amount of cortisol the adrenal glands produce. The medication is given orally once daily with food, and the dose is adjusted based on regular monitoring with blood tests, particularly the ACTH stimulation test. Some dogs may need the medication twice daily for better control. Side effects can include loss of appetite, vomiting, diarrhea, and, in rare cases, a dangerous drop in cortisol levels that requires immediate veterinary attention.^[11][12][20]

Another medication used in veterinary medicine, particularly in the past, is mitotane. This drug works by selectively destroying cells in the adrenal cortex that produce cortisol. It requires careful dosing and close monitoring, as it can cause adrenal insufficiency if too much of the gland is damaged. Trilostane has largely replaced mitotane in many practices due to a more favorable side effect profile and ease of use.^[11]

Treatment duration varies. In dogs, trilostane is typically given for life, as it manages symptoms but does not cure the disease. Survival times for dogs on trilostane range from approximately 660 to 900 days, with many dogs experiencing significant improvement in their quality of life. Regular veterinary visits every few months are essential to monitor response to treatment, adjust doses, and check for side effects or complications.^[11][20]

In humans, medications that reduce cortisol production include ketoconazole, metyrapone, and mifepristone. These drugs work through different mechanisms to either block cortisol synthesis or block its effects on the body. They are used when surgery is not possible, while waiting for surgery, or when surgery has not been fully successful. Side effects vary by drug and can include liver problems, low blood pressure, nausea, and hormonal imbalances. Close monitoring with blood tests and clinical exams is necessary to ensure safety and effectiveness.^[8]

Emerging Therapies and Clinical Trial Research

While standard treatments for hyperadrenocorticism are well established, researchers continue to explore new medications and approaches that may offer better outcomes, fewer side effects, or more targeted action. Clinical trials are the main way these new therapies are tested before they become available for general use. A clinical trial typically goes through several phases: Phase I focuses on safety and determining the correct dose, Phase II examines whether the treatment works and continues to assess safety, and Phase III compares the new treatment to current standard therapies in larger groups of patients.^[8]

One promising area of research involves more selective drugs that target the production of cortisol without affecting other important hormones. For example, newer steroidogenesis inhibitors are being studied to see if they can reduce cortisol with fewer impacts on aldosterone, a hormone that helps regulate salt and water balance in the body. By preserving aldosterone function, these drugs might reduce the risk of dangerous drops in blood pressure or imbalances in electrolytes like sodium and potassium, which can occur with older medications.^[11]

Research is also exploring the use of drugs that block cortisol receptors in tissues throughout the body. These medications do not lower cortisol levels in the blood, but they prevent cortisol from binding to its receptors and causing harmful effects. This approach may be helpful in patients who cannot tolerate drugs that reduce cortisol production or in cases where cortisol levels are difficult to control.^[8]

In veterinary medicine, studies are ongoing to refine dosing schedules for trilostane and to identify biomarkers that can predict which animals will respond best to treatment. Researchers are also investigating the potential use of other enzyme inhibitors and combination therapies that might offer improved control of symptoms with less frequent dosing or fewer side effects. Some trials are testing the use of pasireotide, a medication that targets receptors in the pituitary gland to reduce the production of ACTH, the hormone that stimulates the adrenal glands to make cortisol. While pasireotide has shown promise in some human studies, its use in animals is still experimental.^[11]

Clinical trials for hyperadrenocorticism are conducted at universities, veterinary specialty hospitals, and medical centers around the world, including in the United States, Europe, and other regions. Participation in a clinical trial may provide access to cutting-edge treatments that are not yet widely available. Patients and pet owners interested in clinical trials should discuss eligibility, potential risks, and benefits with their healthcare provider or veterinarian. Trials may have specific criteria, such as age, disease stage, prior treatment history, and overall health status.^[8]

Monitoring and Follow-Up Care

Successful management of hyperadrenocorticism requires ongoing monitoring even after treatment begins. This is true whether the patient is a human or an animal. Blood tests, physical examinations, and careful observation of symptoms are all essential parts of follow-up care. For dogs receiving trilostane, veterinarians typically perform an ACTH stimulation test a few weeks after starting treatment and then every three to six months thereafter. This test measures how much cortisol the adrenal glands produce in response to a dose of synthetic ACTH. The goal is to achieve a post-stimulation cortisol level that is lower than before treatment but not so low that it causes adrenal insufficiency.^[12][20]

In addition to laboratory tests, monitoring symptoms at home is crucial. Pet owners are often advised to keep track of their dog’s appetite, water intake, urination frequency, energy level, and any changes in behavior or appearance. If a dog becomes lethargic, stops eating, vomits, or seems weak, the medication should be stopped and veterinary care should be sought immediately, as these may be signs of low cortisol or other complications.^[12]

In humans, follow-up care may include urine tests to measure 24-hour cortisol levels, saliva tests to check nighttime cortisol, and imaging studies such as CT or MRI scans to monitor tumor size if surgery was performed. Blood tests for electrolytes, blood sugar, blood pressure, and bone density may also be part of routine monitoring, as hyperadrenocorticism can affect many systems in the body. Patients are encouraged to report any new or worsening symptoms to their healthcare provider, as adjustments to medication doses or treatment plans may be needed.^[8][15]

Even after successful treatment, some patients continue to experience lingering effects such as fatigue, mood changes, muscle weakness, or difficulty losing weight. These symptoms may improve slowly over time, and supportive therapies such as physical therapy, nutritional counseling, and mental health support can be helpful. It is important for patients to understand that recovery from hyperadrenocorticism can take months or even years, and that patience and persistence are key.^[14][17]

Living with Hyperadrenocorticism

Adapting daily life to manage hyperadrenocorticism can be challenging, but small adjustments can make a big difference. For people, maintaining a balanced diet, staying as active as possible within physical limits, and managing stress are all important. Some individuals find it helpful to work with a dietitian to manage weight gain and blood sugar, or with a physical therapist to rebuild muscle strength. Mental health support, such as counseling or support groups, can also be valuable, as the condition often affects mood, self-esteem, and emotional well-being.^[14][17]

For pet owners, providing a stable routine, ensuring regular veterinary visits, and being attentive to changes in behavior or symptoms are key. Pets with hyperadrenocorticism may benefit from a controlled diet, regular but gentle exercise, and protection from extreme temperatures, as they may be more heat intolerant. Keeping a journal of symptoms and medication schedules can help both owners and veterinarians track progress and make informed decisions about care.^[5]

Most Common Treatment Methods

• Medical Therapy with Trilostane
  • Trilostane is an oral medication that inhibits cortisol production by blocking the enzyme 3-beta-hydroxysteroid dehydrogenase.
  • It is the only FDA-approved treatment for hyperadrenocorticism in dogs and is commonly used in veterinary practice.
  • Typical starting dose is 1 to 3 mg per pound of body weight once daily with food, adjusted based on response and laboratory tests.
  • Requires lifelong administration and regular monitoring with ACTH stimulation tests.
• Surgical Removal of Tumors
  • Transsphenoidal hypophysectomy is surgery to remove a pituitary tumor through the nose or upper lip, used in both humans and sometimes dogs.
  • Adrenalectomy is the surgical removal of one or both adrenal glands when a tumor is present.
  • Surgery can potentially cure the disease but requires specialized expertise and carries risks such as infection, bleeding, and hormonal imbalances.
  • Postoperative care includes hormone replacement therapy and close monitoring for complications.
• Radiation Therapy
  • Used to shrink or control pituitary tumors, especially when surgery is not possible or the tumor has returned.
  • Effects develop gradually over months and may require repeated sessions.
  • Side effects can include fatigue, hair loss, and skin changes in the treatment area.
• Medications to Reduce Cortisol
  • Ketoconazole, metyrapone, and mifepristone are used in humans to lower cortisol production or block its effects.
  • These drugs require careful monitoring for side effects such as liver problems, nausea, and hormonal imbalances.
  • Dosing is individualized based on response and tolerability.
• Gradual Tapering of Steroid Medications
  • For patients whose hyperadrenocorticism is caused by long-term use of glucocorticoid drugs, the treatment is to slowly reduce the dose.
  • Tapering must be done under medical supervision to avoid adrenal crisis, a life-threatening condition.
  • The process can take weeks to months depending on the dose and duration of steroid use.