Use of the urine cortisol-to-creatinine ratio for monitoring dogs with pituitary-dependent hyperadrenocorticism during induction treatment with mitotane (o,p'-DDD)

Abstract

Objective-To determine whether the urine cortisol-to-creatinine ratio (UCCR) could replace the ACTH stimulation test in monitoring effectiveness of mitotane induction treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH). Animals-15 dogs with PDH. Procedure-All 15 dogs were given an induction dose of mitotane (o,p'-DDD: 35 to 50 mg/kg of body weight/d) for 3 to 14 days. During the induction period, free-catch morning urine samples were collected for determination of UCCR, followed by ACTH stimulation testing, every other day. Treatment response was divided into 3 categories: well-controlled PDH (postACTH serum cortisol concentration ≤ 28 nmol/L but ≤ 138 nmol/L), deficient cortisol secretion (post-ACTH serum cortisol concentration < 28 nmol/L), and excess cortisol secretion (post- ACTH serum cortisol concentration > 138 nmol/L). Results-The linear relation between UCCR and post-ACTH serum cortisol concentration was significant (P < 0.001); however, the prediction intervals surrounding the line were too broad to be clinically useful. The UCCR overlapped among the 3 categories of treatment response. Nevertheless, dogs with PDH receiving mitotane induction treatment and with UCCR > 79 x 10-6 were always classified as having excess cortisol secretion. Conclusion and Clinical Relevance-The UCCR failed to predict post-ACTH cortisol concentration during mitotane induction treatment sufficiently close to be a clinically reliable indicator of treatment control. Seemingly, however, UCCR > 79 x 10-6 obtained from a dog with PDH during mitotane induction would indicate inadequate adrenal cortex destruction and the need for continued mitotane induction; UCCR ≤79 x 10-6 would be inconclusive.