강아지 미토탄·트릴로스탄 치료 증상과 원인, 진단·치료와 관리 포인트 총정리

Is it safe to give my dog Cushing’s medication? — Side effects and monitoring points for mitotane and trilostane

EndocrineDiseasesMeongsiljang Veterinary Advisory Board

Metyrapone and trilostane are medications used to treat Cushing’s disease (hyperadrenocorticism) in dogs. Accurate diagnosis and regular monitoring are essential.

Mitotane and trilostane treatment for dogs is a key method for managing hyperadrenocorticism

A medical illustration explaining the production of adrenal cortex hormones.

Hyperadrenocorticism, commonly known as Cushing’s disease, is an endocrine disorder caused by excessive cortisol production. Mitotane and trilostane are the primary medications used to treat this condition. - Mitotane: Works by destroying adrenal cortex cells, thereby reducing hormone production. - Trilostane: Regulates cortisol levels by inhibiting hormone synthesis. Both medications must be prescribed only after an accurate diagnosis, as overdosing can lead to adrenal insufficiency. During the initial treatment phase, regular check-ups are essential to monitor the pet’s response to the medication. Never stop these drugs abruptly; always consult your veterinarian to adjust the dosage gradually. Consistent, ongoing care is key to preventing recurrence.

Causes and pathogenesis of hyperadrenocorticism

Canine hyperadrenocorticism, commonly known as Cushing’s disease, is an endocrine disorder characterized by excessive cortisol production from the adrenal glands. It is broadly categorized into three main causes: - Pituitary-dependent hyperadrenocorticism (PDH): This occurs when a pituitary tumor, most commonly a microadenoma, secretes excessive amounts of adrenocorticotropic hormone (ACTH), continuously stimulating the adrenal glands. It accounts for approximately 85% of all cases. - Adrenal-dependent hyperadrenocorticism (ADH): This results from an adrenal adenoma or carcinoma autonomously overproducing cortisol, accounting for about 15% of cases. - Iatrogenic (drug-induced) hyperadrenocorticism: This develops following long-term administration of glucocorticoids (steroids). While it is reported more frequently in certain breeds, it can occur regardless of breed. Accurate diagnosis requires a series of tests to identify the underlying cause. Early diagnosis and treatment are crucial, as leaving the condition untreated can lead to serious complications.

An anatomical illustration showing enlarged adrenal cortex

Checklist of main symptoms and signs

The symptoms of hyperadrenocorticism (Cushing’s disease) can vary widely, so it’s important for pet owners to observe their pets closely. Excessive thirst and urination (polydipsia and polyuria): Your pet will drink significantly more water, and both the volume and frequency of urination will noticeably increase. Increased appetite: It’s common for pets to show polyphagia, seeking out and eating more food than usual. Abdominal enlargement: The belly may appear distended due to liver enlargement, muscle weakness, and accumulation of abdominal fat. Hind leg weakness is also common. Skin changes: Hair loss typically occurs symmetrically on both sides of the body. The skin becomes thin, bruises easily, and wounds heal slowly. Muscle weakness and lethargy: Pets may struggle to stand or walk, show reduced energy levels, and exhibit increased panting. If these symptoms persist, consult your veterinarian immediately.

A dog showing symptoms of hyperadrenocorticism (Cushing’s disease)

Emergency signs requiring immediate veterinary visit

If your pet shows signs such as severe lethargy, loss of appetite, vomiting, diarrhea, or collapse that may indicate adrenal insufficiency (an adrenal crisis), seek veterinary care immediately. An overdose of mitotane or trilostane can cause permanent adrenal necrosis and dysfunction, which may be fatal.

Diagnostic tests for accurate diagnosis

Diagnosing hyperadrenocorticism (Cushing’s disease) is challenging with a single test, so a comprehensive evaluation is necessary. - ACTH Stimulation Test: This is a primary screening test that compares cortisol levels before and after administering synthetic ACTH to check for an excessive response. - Low-Dose Dexamethasone Suppression Test (LDDST): This test evaluates whether cortisol is suppressed normally to help determine if the disease is present. - Blood Tests and Urinary Cortisol:Creatinine Ratio (UCCR): These tests help assess overall functional status and hormone levels. - Ultrasound Examination: Ultrasound is not used to confirm the diagnosis but rather to evaluate the size and structure of the adrenal glands to differentiate between pituitary-dependent and adrenal tumor-dependent forms. Starting treatment without an accurate diagnosis can lead to drug side effects or worsening of the condition. Please bring all test results with you when visiting the clinic.

A veterinarian performing an ACTH stimulation test on a puppy

Step-by-step management of mitotane and trilostane treatment

Treatment is administered in stages, tailored to the patient’s condition. - Initial phase: We start with a low dose to monitor for any side effects. - Adjustment phase: The dosage is gradually adjusted based on changes in body weight and the response of symptoms. - Maintenance phase: Once stable, a consistent dose is maintained. Hormone levels are periodically checked using ACTH stimulation tests. Do not stop medication abruptly; always consult your veterinarian before making any adjustments. Regular health check-ups are essential to monitor for recurrence.

A puppy taking medication prescribed by a veterinarian.

Home care and daily care points

While your pet is on medication, maintain a consistent routine of regular meals and exercise. Avoid excessive stress and do not skip scheduled veterinary check-ups. - Weight changes: Record your pet’s weight once a week to monitor for any abnormalities. - Appetite changes: Report any sudden increase or decrease in appetite to your veterinarian immediately. - Vomiting or diarrhea: These may be side effects of the medication, so keep a record and report them. - Drug interactions: Caution is required when combining this medication with others. Keeping a medication log will make consultations with your veterinarian much easier.

Breed-specific precautions and tips for preventing recurrence

While hyperadrenocorticism is more commonly reported in certain breeds, it can occur in any breed, so it’s especially important to keep a close eye on older dogs. Even after treatment, regular check-ups, such as ACTH stimulation tests, are necessary to monitor for recurrence, and medications should never be stopped abruptly without consulting your veterinarian.

Reviewed by a veterinarian

Dr. Tony — Punnawat Phongkittirak

Veterinarian

A veterinarian who majored in veterinary medicine at Khon Kaen University, Thailand, and completed the IVSA program at North Carolina State University in the United States. Drawing on clinical experience at animal hospitals, he works in the pet healthcare field and is dedicated to building a digital care environment that connects pet parents with veterinarians.

Frequently asked questions

What are the differences between Mitotan and Trilostane?

Mitotane destroys adrenal cortex cells, while trilostane inhibits hormone synthesis. Trilostane tends to have fewer side effects.

Can I stop giving my pet medication during treatment?

Absolutely not. Stopping suddenly can worsen hormonal imbalances and become dangerous. You should gradually reduce the dosage under your veterinarian's guidance.

What are the possible side effects after taking the medication?

Symptoms such as vomiting, diarrhea, loss of appetite, and fatigue may occur. If severe side effects develop, consult your veterinarian immediately.

How long does the treatment take?

Typically, treatment lasts from six months to over a year and is adjusted based on your veterinarian’s assessment. In some cases, lifelong management is necessary.

How should regular check-ups be conducted after Mitotan treatment?

Repeat ACTH stimulation tests and blood work every 3 to 6 months to monitor hormone levels and overall health.

Comparison table of mitotane vs. trilostane treatment

Item	Mitotane	Trilostane
Mechanism of action	Destruction of adrenal cortex cells (zona fasciculata and zona reticularis)	Inhibition of adrenal steroid synthesis (cortisol and aldosterone)
Frequency of side effects	High (risk of permanent adrenal necrosis and hypofunction with overdose)	Low (relatively safe, generally well tolerated)
Monitoring method	ACTH stimulation test, ALP, clinical signs	ACTH stimulation test, pre-pill cortisol, clinical signs
Need for regular testing	Every 3–6 months (for dose adjustment in the first year)	Regularly, based on clinical signs and ACTH stimulation test results
When appropriate	Can be used for both pituitary-dependent and adrenal-dependent cases	Preoperative preparation for adrenal tumors, inoperable adrenal tumors, long-term management

The veterinarian selects the most appropriate drug based on the patient's condition.

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References

[1] BSAVA. (2023). BSAVA Manual of Canine and Feline Dermatology, 4th Ed.

[2] Ettinger, S.J., Feldman, E.C., Côté, E. (2017). Textbook of Veterinary Internal Medicine, 8th ed. Elsevier.

[3] Feldman, E.C., Nelson, R.W., Reusch, C. (2015). Canine and Feline Endocrinology and Reproduction, 4th ed. Elsevier.