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

John F. Randolph From the Department of Clinical Sciences (Randolph, Toomey, Center, Scarlett) and the Diagnostic Laboratory (Reimers), College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, and the Endocrinology Section of the Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824 (Graham, Nachreiner).

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Jane Toomey From the Department of Clinical Sciences (Randolph, Toomey, Center, Scarlett) and the Diagnostic Laboratory (Reimers), College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, and the Endocrinology Section of the Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824 (Graham, Nachreiner).

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Sharon A. Center From the Department of Clinical Sciences (Randolph, Toomey, Center, Scarlett) and the Diagnostic Laboratory (Reimers), College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, and the Endocrinology Section of the Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824 (Graham, Nachreiner).

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Janet M. Scarlett From the Department of Clinical Sciences (Randolph, Toomey, Center, Scarlett) and the Diagnostic Laboratory (Reimers), College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, and the Endocrinology Section of the Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824 (Graham, Nachreiner).

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Thomas Reimers From the Department of Clinical Sciences (Randolph, Toomey, Center, Scarlett) and the Diagnostic Laboratory (Reimers), College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, and the Endocrinology Section of the Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824 (Graham, Nachreiner).

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Peter Graham From the Department of Clinical Sciences (Randolph, Toomey, Center, Scarlett) and the Diagnostic Laboratory (Reimers), College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, and the Endocrinology Section of the Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824 (Graham, Nachreiner).

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Raymond F. Nachreiner From the Department of Clinical Sciences (Randolph, Toomey, Center, Scarlett) and the Diagnostic Laboratory (Reimers), College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, and the Endocrinology Section of the Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824 (Graham, Nachreiner).

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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 (post-ACTH 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 × 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 × 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 × 10−6 would be inconclusive. (Am J Vet Res 1998;59:258–261)

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 (post-ACTH 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 × 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 × 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 × 10−6 would be inconclusive. (Am J Vet Res 1998;59:258–261)

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