Treating Cushing’s means deliberately lowering a hormone the body cannot do without. Cortisol in excess causes the disease; cortisol in deficiency causes a different and more acute problem. The therapeutic target sits between the two, and the whole apparatus of dose adjustment and periodic monitoring exists to keep a dog inside that window.
Most dogs on trilostane do well. But every owner giving it should be able to recognize the signs that cortisol has gone too low — because that is the situation where prompt action matters most and where waiting until Monday morning is the wrong call.
What Trilostane Actually Does
Trilostane inhibits an enzyme in the adrenal steroid synthesis pathway, reducing cortisol production. It does not destroy adrenal tissue, and its effect is largely reversible as the drug clears — which is precisely why it is generally preferred over older approaches.
That reversibility is genuinely reassuring. It is not, however, a guarantee. Excessive suppression can occur, and in a subset of cases the adrenal effect is more prolonged than the drug’s presence would suggest.
Several situations raise the risk: the period shortly after starting treatment or after a dose increase; concurrent illness, particularly anything causing vomiting or diarrhea; dehydration; and dosing errors, including the entirely understandable one of two people in a household each giving the dog its tablet.
The Early Signs — Subtle and Easy to Attribute Elsewhere
Cortisol deficiency rarely announces itself dramatically at first. The early signs are vague, and the trap is that they are easy to attribute to something else — a hot day, a change in routine, simple aging.
Reduced appetite is often the first thing owners notice, and it is worth taking seriously in this context. A dog whose defining symptom for months was relentless hunger, now leaving food, has changed in a direction that deserves a phone call. It is easy to read as progress. It may not be.
Lethargy beyond the welcome calming that accompanies successful treatment. There is a difference between a dog who has stopped pacing and panting and a dog who does not want to get up.
Vomiting or diarrhea, particularly if new or persistent.
Weakness or reluctance to exercise.
The pattern that matters more than any single sign is a dog who was improving and has now started going backwards. Improvement followed by decline is the shape to watch for.
Addisonian Crisis: The Emergency
At the severe end, cortisol deficiency can progress to an Addisonian (adrenal) crisis — a genuine medical emergency requiring immediate veterinary attention.
Signs include profound weakness or collapse; persistent vomiting; severe lethargy or unresponsiveness; slow heart rate; and shock. Electrolyte disturbance, classically elevated potassium with low sodium, is a central feature and one reason emergency bloodwork is so informative.
This is uncommon. It is also treatable when addressed promptly, and dangerous when it is not. A dog on trilostane who collapses, cannot stand, or is vomiting repeatedly needs to be seen immediately — not at the next available routine appointment.
What to Do
The guidance most veterinarians give, and which is worth confirming with your own:
Stop the trilostane and call. If your dog shows appetite loss, unusual lethargy, vomiting, or diarrhea, withholding the next dose and speaking to your veterinarian is generally safer than continuing on schedule and waiting to see. Cushing’s is a chronic disease; missing doses while a question is resolved does not undo months of progress. Continuing to suppress cortisol in a dog who is already suppressed does real harm.
Do not adjust the dose yourself beyond stopping. Restarting, and at what dose, is a decision that should follow assessment — often including cortisol measurement and electrolytes.
Have the emergency number to hand. Crises have an inconvenient habit of occurring outside clinic hours.
Keep dosing unambiguous in a multi-person household. A written log or a pill organizer eliminates the double-dose scenario entirely, and it is a two-minute fix.
Why Monitoring Exists
This is the argument for the recheck appointments that can feel excessive, particularly in a dog who seems to be doing well.
Monitoring — whether by ACTH stimulation testing or pre-pill cortisol measurement, depending on your veterinarian’s protocol — is what detects excessive suppression *before* a dog becomes unwell. A dog whose cortisol has drifted too low may look entirely normal at the point where a blood test would show it. The test is the early warning; the clinical signs are the late one.
Rechecks are also how the dose keeps pace with a dog who is changing. Body weight shifts, concurrent illness develops, kidney and liver function change with age. A dose that was correct in March is not automatically correct in September.
The Balance Worth Holding
None of this is an argument against treating Cushing’s. Untreated hyperadrenocorticism carries its own well-documented consequences — hypertension, proteinuria, infection risk, diabetes, thromboembolic disease. Trilostane is an effective drug with a reasonable safety profile, and the great majority of dogs on it live comfortably for years.
The point is narrower: this is a medication that works by suppressing something essential, and it deserves an informed owner. Knowing the four or five signs above, and being willing to skip a dose and make a phone call, is most of what that requires.
For owners exploring adjunct natural support alongside trilostane, this is exactly why anything added to the plan should be discussed with your veterinarian rather than started independently — so that if something changes, everyone knows what changed and when. Background on the research behind lignans and melatonin is available at lignans.com.
The Bottom Line
Trilostane lowers cortisol, and occasionally it lowers it too far. Reduced appetite, lethargy, vomiting, diarrhea, and weakness — especially in a dog who had been improving — are the signs to act on. Withhold the next dose and call your veterinarian. Collapse, repeated vomiting, or profound weakness is an emergency. Regular monitoring exists to catch excessive suppression before a dog ever becomes unwell, which is why the recheck schedule is worth keeping.
Sources
- Merck Veterinary Manual — Cushing Disease (Pituitary-Dependent Hyperadrenocorticism) in Animals. https://www.merckvetmanual.com/endocrine-system/the-pituitary-gland/cushing-disease-pituitary-dependent-hyperadrenocorticism-in-animals
- Merck Veterinary Manual — Addison Disease (Hypoadrenocorticism) in Animals. https://www.merckvetmanual.com/endocrine-system/the-adrenal-glands/addison-disease-hypoadrenocorticism-in-animals
