Use of Basal Cortisol to Assess Efficacy of Twice-daily Trilostane Administration

Evaluation of baseline cortisol concentration to monitor efficacy of twice-daily administration of trilostane to dogs with piutuitary dependent hyperadrenocorticism: 22 cases (2008 – 2012) Woolcock, AD, Bugbee AC, Creevy KE. 2016 Journal of the American Veterinary Medical Association Vol 248(7):814 – 821
Summarised : Dr Liesel van der Merwe , BVSc MMedVet(Med)

Why they did it?

Hyperadrenocorticism (HAC)/Cushings syndrome is a common endocrinopathy. Trilostane or mitotane (Lysodren®) can be used to lower circulating corti­sol concentrations. Conventionally control of HAC is monitored by regression of clinical signs and the ACTH stimulation test. According the product insert for trilostane a cortisol concentration of 40 – 250 nmol/L as the ideal target range. Synthacten® is how­ever expensive.

A previous study has attempted to prove baseline cor­tisol as a predictor for post ACTH stimulation cortisol levels but the baseline cortisol did not accurately iden­tify 1.5% of patients with excessive cortisol suppres­sion (< 40nmol/L and at risk of severe side effects. Another study showed a poor correlation between baseline and post ACTH stimulation cortisol levels in dogs treated once a day with trilostane. The purpose of this study was to evaluate the use of baseline corti­sol concentrations to predict the post ACTH stimula­tion cortisol concentrations in dogs with pituitary de­pendent HAC administered trilostane BID.

 

What they did.

Retrospective study using medical records. All ACTH test were performed at the standardised 4-6 hours post pilling time slot. Cortisol assays were determined using a validated solid phase chemiluminescent im­munoassay (Immulite cortisol assay, Siemens).

 

What they found.

Only 22 patients of the 65 dogs undergoing ACTH stimulation tests had complete medical records. 109 ACTH stimulation tests were performed on theses dogs. Of these 22 dogs 15 (68.2%) had multiple co-morbidities and 4 (18.2%) had a single co-morbidity. Only 3 (13.6%) did not have a co-morbidity. For the study the mean trilostane dose was 1.98 ±0.73mg/kg/ day po split into 2 doses administered approximately 12 hours apart.

The median baseline cortisol concentration was 96 nmol/L (range < 5– 315 nmol/L). The median post ACTH stimulation cortisol concentration was 155nmol/L (range 23 – 588 nmol/L).

Of 109 tests performed 6 (5.5%) had a post stimulation concentration identical to the baseline concentration, 18 (16.5%) had a post stimulation concentration less than the base line cortisol concentration and the re­maining 85 (78%) had post stimulation cortisol con­centrations greater than the baseline cortisol.

Twenty of the 109 ACTH tests performed (on 22 pa­tients) has a baseline cortisol of <40nmol/L .Of these cases, 10 tests showed post stimulation cortisol con­centrations with adequate control (>50nmol/L) and 10 showed over suppression (<50nmol/L).

The remaining 89 tests has basal cortisol levels > 36 nmol/L of which 83 showed signs of adequate control in the post stimulation cortisol result and 6 showed excessive suppression of the adrenal gland. Thus the ability of the baseline cortisol to predict that a dog does not have excessive suppression of the adrenal gland from a baseline cortisol concentration (negative predictive value) was 93% (n=83/89).

Forty-five of the 109 adrenal stimulation tests had a baseline cortisol concentration of ≤ 88nmol/L of which 30 showed adequate control of adrenal gland function post stimulation and 15 showed results of ex­cessive suppression of the adrenal gland. The remain­ing 64 tests all had a post stimulation cortisol concen­tration in the adequately controlled range. A baseline cortisol concentration > 88nmol/L predicted that the post ACTH stimulation cortisol would be ≥ 55nmol/L with 100% certainty.

 

Conclusion:

This study showed that the use of baseline cortisol only to monitor the efficacy of twice daily trilostane treatment provided inadequate information about the extent of suppression of cortisol production. The risk of underestimating over-suppression of the adrenal gland was too great.

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