Cushing's Disease Is Subtler and More Common Than Most Owners Realise
A pot-bellied dog that drinks excessively, urinates through the night, eats as though starving, and has developed a thin coat and prominent skin veins — this is the clinical portrait of hyperadrenocorticism, more commonly called Cushing's disease or syndrome. It is among the most frequently diagnosed endocrine disorders in dogs over six years of age, yet it often goes undetected for months or years because its signs are easily attributed to normal ageing.
The condition results from chronic excess of cortisol — the body's primary stress hormone. In approximately 85 per cent of cases, the cause is a tumour of the pituitary gland (PDH — pituitary-dependent hyperadrenocorticism) stimulating the adrenal glands to overproduce cortisol. In the remaining 15 per cent, the source is a tumour of the adrenal gland itself (ADH — adrenal-dependent hyperadrenocorticism). This distinction directly determines which treatment is most appropriate.
Trilostane: The Current First-Line Medical Treatment
Trilostane has become the preferred medical option in most countries where it is licensed for veterinary use. It works by inhibiting an enzyme essential to cortisol synthesis, reducing production without destroying adrenal tissue. This means that if the drug is stopped or the dose becomes too high, the situation is reversible — a significant safety advantage.
Dosing and Monitoring
Trilostane is given orally, typically once daily with food, though twice-daily dosing is sometimes used to achieve more consistent cortisol suppression. Monitoring is demanding in the first few months — ACTH stimulation tests are performed at ten days, four weeks, twelve weeks, and then every three to six months thereafter. The aim is adequate cortisol suppression without triggering hypoadrenocorticism (an Addisonian crisis), which can be life-threatening.
Efficacy and Side Effects
Clinical improvement — reduced thirst, appetite normalisation, improved coat — is typically seen within four to eight weeks. Efficacy is good in pituitary-dependent disease. Side effects include lethargy, vomiting, and diarrhoea, often indicating over-suppression. Rarely, trilostane can cause acute adrenal necrosis — a serious complication requiring emergency management. Any dog on trilostane that becomes acutely unwell should be assessed by a vet immediately.
Mitotane: The Older Alternative
Mitotane (o,p'-DDD) predates trilostane and works differently — it progressively destroys the cortisol-producing layers of the adrenal gland. This makes it potent and effective, but also less forgiving. It is used in two phases: an induction phase to bring cortisol under control, followed by lifelong maintenance dosing.
Monitoring during induction requires close attention — owners must watch for signs of over-suppression (weakness, vomiting, collapse) and be equipped with emergency hydrocortisone. Water intake is used as a practical daily monitoring tool during induction.
Mitotane can also be used at high, sustained doses to deliberately ablate both adrenal layers — a medical alternative to surgery in dogs with adrenal tumours, though this protocol carries substantial risk and requires intensive monitoring. In some countries, trilostane's superior safety profile has led to mitotane being reserved for cases where trilostane fails or is unavailable, though it remains a valid and effective choice in experienced hands.
Adrenalectomy: Surgical Removal of the Adrenal Gland
For adrenal-dependent hyperadrenocorticism — where a tumour on one adrenal gland is the cause — surgical removal of the affected gland (adrenalectomy) offers the possibility of cure rather than lifelong management.
Surgical Considerations
Adrenalectomy is technically demanding surgery. The adrenal glands are located deep in the retroperitoneum with close proximity to major blood vessels. Perioperative mortality in specialist centres ranges from roughly 5 to 20 per cent depending on tumour size, invasiveness, and the dog's overall condition. Pre-operative stabilisation with trilostane or mitotane for several weeks reduces surgical risk.
Dogs surviving surgery typically require temporary cortisol supplementation post-operatively while the remaining adrenal gland — suppressed by the long-standing excess cortisol — recovers function. This recovery may take weeks to months.
When Surgery Is the Right Choice
Surgery is most appropriate for unilateral adrenal tumours that have not invaded major vessels or metastasised. Imaging — including CT scanning — is essential for pre-surgical planning. Where the tumour is confined and the dog is otherwise a reasonable surgical candidate, adrenalectomy delivers outcomes that medical management cannot match: resolution of clinical signs without lifelong daily medication.
Pituitary-Dependent Disease: Is Radiation an Option?
For the minority of dogs with large pituitary tumours causing neurological signs alongside Cushing's disease, radiation therapy targeting the pituitary tumour is available at specialist referral centres. This is not a mainstream approach for uncomplicated PDH but is worth discussing with a veterinary neurologist where a macroadenoma is identified.
Comparing the Three Main Approaches
- Trilostane: best first-line medical option for PDH and many adrenal tumours where surgery is declined; reversible; requires consistent monitoring; lifelong treatment
- Mitotane: effective alternative or second-line option; greater risk of over-suppression; valuable where trilostane is unavailable or ineffective; lifelong treatment
- Adrenalectomy: potentially curative for adrenal-dependent disease; higher short-term risk; specialist referral required; not appropriate for pituitary-dependent cases
- All approaches require ongoing veterinary monitoring — this is not a set-and-forget condition
- Any dog on adrenal-suppressing medication that becomes acutely unwell needs emergency veterinary assessment the same day
Hyperadrenocorticism is manageable in the vast majority of dogs, and many live comfortably for years post-diagnosis. The choice between treatment approaches should be made with a vet familiar with endocrine disease, taking into account tumour type, your dog's overall health, and your capacity to commit to the monitoring these treatments demand.