OF TRILOSTANE IN THE MANAGEMENT OF EQUINE CUSHING'S DISEASE.
and R. Neiger.
The Royal Veterinary College, London, United Kingdom
(Stegram Pharmaceuticals, UK), a 3beta-hydroxysteroid dehydrogenase inhibitor,
acts to block adrenal steroidogenesis. The aim of this study was to assess the
efficacy of trilostane in twenty horses (mean age 21, SD 5.7 years) diagnosed
with equine Cushing's disease using the combined dexamethasone suppression thyrotropin
releasing hormone (TRH) stimulation test (17 horses) or TRH stimulation test (3
horses). Serum samples for cortisol analysis were collected via indwelling catheter
at baseline, at 210 minutes (30 min after 1 mg i.v. TRH) and 22 hours after 40
mcg/kg dexamethasone i.m. Affected horses were treated with 0.4 to 1 mg/kg (mean
0.5 mg/kg) trilostane administered once daily in feed for a period of 30 days.
After 30 days endocrine testing was repeated. Serum cortisol before and after
treatment was compared by paired t-test.
Polyuria and/or polydipsia,
present in 11 horses, was reduced in all after treatment. Lethargy was present
to some degree in 19 horses, but improvement in demeanour was evident in all horses
after therapy. Recurrent, chronic or persistent laminitis, present in 17 horses,
improved or showed no recurrence in 14 cases. Six horses had phenylbutazone therapy
discontinued during the trial due to improvement in lameness attributed to laminitis
and 1 horse had phenylbutazone therapy reduced from 2 g to 1 g daily. Three horses
showed severe, acute laminitis on presentation, with rotation and sinking evident
on radiographs, which did not respond to trilostane. One of these horses was euthanised
14 days into the trial. One horse developed a mild bout of laminitis during the
trial (Obel grade 1), but was sound by the time he was re-presented at 30 days.
While baseline cortisol
(mean: 141, SD 54 nmol/l) and 22 hours post dexamethasone cortisol (mean: 109,
SD 34 nmol/l) in horses before treatment were not significantly different to post
treatment [baseline (mean: 159, SD 64 nmol/l), post dexamethasone (mean: 104,
SD 48 nmol/l)], there was a significant reduction (p =0.023) of cortisol following
TRH administration before (mean: 176, SD 52 nmol/l) and after (mean: 147, SD 61
In conclusion, trilostane
caused an improvement in clinical signs in all horses, the most consistent being
an improvement in demeanour and a corresponding decrease in cortisol response
to TRH administration. Thus trilostane is a useful therapy for the treatment of
equine Cushing's disease, particularly with respect to improving the quality of
life of affected animals. Safety and long term effect is being investigated for
a further period of 12 months.
McGowan, C & Neiger,
Efficacy of trilostane for the treatment of equine Cushing's syndrome.
Equine vet. J. 35. 414-418.