16 Feb 2015
Your first case of the afternoon is Poppy – a nine-year-old female, neutered, miniature poodle presented to you for a second opinion.
Poppy was diagnosed with Cushing’s disease 12 months ago and has been treated with trilostane 30mg once a day in the morning (bodyweight 8kg).
Her owner reports that despite treatment Poppy has remained polyuric, polydipsic and polyphagic.
On examination she is pot bellied with generalised thinning of her coat. An adrenocorticotropic hormone (ACTH) stimulation test, performed two weeks ago four hours post-pill, revealed a pre-ACTH cortisol of 58nmol/L and a post-ACTH cortisol of 70nmol/L.
Haematology was unremarkable. Biochemistry revealed a normal alkaline phosphatase and mildly increased alanine aminotransferase of 63IU/L (reference range 5IU/L to 60IU/L). Urinalysis revealed specific gravity 1.006 and pH8.
There were no other abnormalities on dipstick or sediment exam and culture was negative.
How would you investigate Poppy further?
Although the ACTH stimulation test (traditionally recommended to be carried out three to five hours post-dosing) reveals a post-ACTH cortisol within the ideal range for good control of Cushing’s disease (50nmol/L to 200nmol/L), the clinical signs are not improved. In this case, an ACTH stimulation test should be performed at 24 hours after dosing with trilostane.
If post-ACTH cortisol values are greater than 250nmol/L this would suggest trilostane is not lasting for 24 hours and twice daily dosing is required. The total daily dose should be increased by between 30 per cent and 50 per cent and divided daily. If the post- ACTH cortisol at 24 hours is less than 250nmol/L the case should be re-evaluated and other causes of the clinical signs should be considered.
Poppy’s results at 24 hours after dosing showed pre-ACTH cortisol was 262nmol/L and post-ACTH cortisol was 419nmol/L, indicating the need for twice daily dosing. The trilostane dose was increased to 20mg twice a day, which resulted in improvement in her clinical signs over the following month.
Studies comparing once daily dosing versus twice daily dosing following the initial diagnosis of hyperadrenocorticism have revealed lower total daily doses of trilostane are required with twice daily dosing. However, whether the benefit of an overall lower total daily dose is outweighed by the convenience of dosing once a day is dependent on owner preference.
There is no consensus about whether dosing should be started once or twice a day following the diagnosis of hyperadrenocorticism. If starting twice daily, the total daily starting dose should be the same or slightly lower than that recommended for once daily treatment.