Hyperadrenocorticism in Dogs: Medication Options

Hyperadrenocorticism (HAC) is often called Cushing’s in dogs. You may also hear the phrase “Cushing’s disease”. Technically, that term is sometimes used specifically for pituitary-dependent HAC, but in everyday practice many people use it to mean HAC in general. Either way, it can feel overwhelming at first. The good news is that most dogs do very well once the condition is identified and treated thoughtfully. As a veterinary assistant, I have seen how much better dogs feel when their excessive thirst, constant panting, and “bottomless” appetite finally start to calm down.

This article walks you through the most common medication options, what they do, what to watch for at home, and why follow-up testing matters so much. Always partner closely with your veterinarian, because the right plan depends on the type of HAC, your dog’s symptoms, and overall health.

Quick refresher: what Cushing’s is

Cushing’s (HAC) happens when a dog’s body is exposed to too much cortisol over time. Cortisol is a normal, essential hormone, but chronically high levels can affect the skin, muscles, immune system, liver values, and even blood pressure.

Common signs you might notice

• Increased thirst and urination
• Increased appetite
• Panting, restlessness
• Pot-bellied appearance, muscle weakness
• Hair thinning, recurrent skin or ear infections
• Thin skin, slow wound healing

Main types (and why it matters for meds)

• Pituitary-dependent hyperadrenocorticism (PDH): the most common form. The pituitary gland signals the adrenal glands to make too much cortisol. This is the classic condition many clinicians mean when they say “Cushing’s disease.”
• Adrenal-dependent hyperadrenocorticism (ADH): less common. A tumor on one adrenal gland produces excess cortisol.
• Iatrogenic Cushing’s: caused by long-term or high-dose steroid medications (for example, prednisone) or other steroid-like drugs. The treatment approach is different and often involves a careful, veterinarian-guided taper, not trilostane or mitotane.

Medication can be used for PDH and many ADH cases, but the long-term strategy may look different. For some ADH cases, surgery is considered if the dog is a good candidate and the tumor appears removable.

Medication option 1: Trilostane (Vetoryl)

Trilostane is the most commonly prescribed medication for Cushing’s in dogs today. It works by inhibiting an enzyme used to make cortisol (it inhibits 3β-hydroxysteroid dehydrogenase). Think of it as turning down the cortisol “faucet.”

When it is typically used

• First-line treatment for many dogs with PDH
• Often used in ADH if surgery is not possible or is delayed

How it is given

Trilostane is usually given once or twice daily with food. Your veterinarian will decide dosing based on your dog’s response and follow-up testing.

Monitoring and follow-up

Trilostane requires regular rechecks. Many veterinarians use an ACTH stimulation test, but protocols vary. Some clinics lean more on timed cortisol measurements (often tied to when the pill is given) and your dog’s day-to-day clinical signs. The goal is not to chase a perfect number, it is to get your dog feeling better while keeping cortisol in a safe range.

If you like having a general roadmap, ask your veterinarian what their clinic typically does. Many plans include an early recheck after starting or changing the dose, then additional testing and visits as the dose is fine-tuned, and eventually periodic monitoring once things are stable.

Possible side effects and what to watch for

Most dogs tolerate trilostane well. Some dogs have transient gastrointestinal upset (like decreased appetite, vomiting, or diarrhea), especially early on or after a dose change. More rarely, trilostane can lower cortisol too much, leading to hypoadrenocorticism (an Addisonian episode), which is an emergency.

• Call your vet right away if you notice: repeated vomiting or diarrhea, refusal to eat, severe lethargy, collapse, marked weakness, trembling, or signs of dehydration.
• Milder changes like a brief dip in appetite or energy should also be reported, especially soon after starting or adjusting the dose. Your vet may want to pause the medication and check labs.

Medication option 2: Mitotane (Lysodren)

Mitotane (o,p’-DDD) is an older, still-useful medication. It is adrenocorticolytic, meaning it selectively damages parts of the adrenal cortex (especially the zones that produce cortisol) to reduce cortisol production.

When it may be chosen

• Some cases where trilostane is not tolerated or not effective
• Situations where a veterinarian prefers its mechanism or has extensive experience with it
• Sometimes used for PDH, and in select cases of ADH when surgery is not feasible (this depends on the individual case and specialist input)

How it is typically used

Mitotane commonly involves an induction phase (higher or more frequent dosing to bring cortisol down) followed by a maintenance phase (a lower long-term schedule). This is very veterinarian-guided. Do not adjust dosing on your own.

Important cautions

Because mitotane can reduce cortisol more aggressively, monitoring is critical. Owners should be educated on the signs of low cortisol, which can resemble stomach upset at first.

• Loss of appetite
• Vomiting or diarrhea
• Weakness or collapse

If any of these occur, your vet may advise stopping the medication and coming in for testing.

Other medications your vet may discuss

Not every dog follows the textbook, and sometimes veterinarians use additional options depending on the type of HAC, other diseases, or response to treatment. These tend to be less common choices today compared with trilostane or mitotane.

Selegiline (Anipryl)

Selegiline is sometimes used in select, often milder cases, but overall it is less consistently effective for typical PDH compared with trilostane or mitotane. It is not a common go-to medication now, but your veterinarian will tell you if your dog is a reasonable candidate.

Ketoconazole

Ketoconazole is an antifungal medication that can reduce steroid hormone production as a side effect. It is not usually a first choice for Cushing’s and is used less often today due to variable efficacy and the potential for gastrointestinal upset and liver effects. Liver monitoring is important if it is used.

Melatonin and lignans

You may see these discussed online, often in the context of coat and skin support, especially for “atypical Cushing’s” presentations. This area is controversial and not well standardized. Diagnosis and treatment approaches vary, and this is best handled with a veterinarian (and sometimes an internal medicine specialist). Supplements should not replace proven therapy in dogs with clear clinical Cushing’s. If you want to use supplements, ask your veterinarian first to avoid interactions and to keep expectations realistic.

Surgery and radiation

Adrenal tumor surgery

For adrenal-dependent Cushing’s caused by a removable adrenal tumor, an adrenalectomy may be curative. This is a specialized procedure with meaningful risks, and it typically requires advanced imaging and referral-level care.

Radiation therapy

Some pituitary tumors may be treated with radiation in certain cases, particularly if there are neurologic signs or the tumor is large. Many dogs are still managed medically even if radiation is an option.

Life at home: how you can help

Medication is a big piece of treatment, but your day-to-day observations are just as valuable. You are the one who knows what “normal” looks like for your dog.

Track the signs that matter most

• Water intake: if you can, measure how much you pour each morning (in ounces or milliliters) and subtract what is left 24 hours later. Bring that number to rechecks.
• Urination frequency and accidents
• Appetite changes
• Panting and restlessness
• Energy and willingness to exercise
• Skin issues and recurrent infections

Why follow-ups matter (beyond cortisol)

Rechecks are not only about medication dosing. Dogs with Cushing’s can be more prone to issues your veterinarian may screen for or discuss, such as urinary tract infections, high blood pressure, diabetes, pancreatitis, and changes in clotting risk. Catching these early can make a big difference in comfort and safety.

Nutrition and weight support

Many dogs with Cushing’s gain weight easily and lose muscle. Work with your veterinarian on a plan that supports lean body mass and avoids unnecessary calories. If your dog has other issues like pancreatitis, kidney disease, diabetes, or high blood pressure, diet choices should be individualized.

Cushing’s is very treatable, but it is also very monitoring-dependent. The best outcomes come from steady follow-ups plus a caregiver who speaks up early when something changes.

When to call your vet urgently

Please call your veterinarian or an emergency clinic right away if your dog is being treated for Cushing’s and you notice:

• Collapse, extreme weakness, or unresponsiveness
• Repeated vomiting or diarrhea
• Refusing food for a full day, especially with lethargy
• Shaking, severe listlessness, or signs of dehydration

These signs can indicate cortisol has dropped too low, or another serious complication is developing. It is always better to check early.

Bottom line

Most dogs with hyperadrenocorticism can enjoy a great quality of life with the right medication and monitoring. For many, trilostane is the go-to option. Mitotane is another effective choice when used carefully. Your veterinarian will tailor the plan based on your dog’s type of HAC and how they respond.

If you are feeling anxious about starting treatment, you are not alone. Take it one step at a time, keep a simple symptom journal (including daily water intake if you can), and lean on your veterinary team. Small improvements add up fast when cortisol gets back under control.

References

• Behrend EN, Kooistra HS, Nelson R, et al. Diagnosis of hyperadrenocorticism in dogs: an American College of Veterinary Internal Medicine (ACVIM) consensus statement (ACVIM Consensus Statement).
• Behrend EN, Kooistra HS, Nelson R, et al. Treatment of hyperadrenocorticism in dogs: an American College of Veterinary Internal Medicine (ACVIM) consensus statement (ACVIM Consensus Statement).
• Vetoryl (trilostane) prescribing information and monitoring guidance.
• Plumb’s Veterinary Drug Handbook: trilostane, mitotane, ketoconazole, selegiline.
• Merck Veterinary Manual: Hyperadrenocorticism in Small Animals.