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      Comparison of 2 Doses for ACTH Stimulation Testing in Dogs Suspected of or Treated for Hyperadrenocorticism

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          Abstract

          Background

          Lowering the cosyntropin dose needed for ACTH stimulation would make the test more economical.

          Objectives

          To compare the cortisol response to 1 and 5 μg/kg cosyntropin IV in dogs being screened for hyperadrenocorticism ( HAC) and in dogs receiving trilostane or mitotane for pituitary‐dependent HAC.

          Animals

          Healthy dogs (n = 10); client‐owned dogs suspected of having HAC (n = 39) or being treated for pituitary‐dependent HAC with mitotane (n = 12) or trilostane (n = 15).

          Procedures

          In this prospective study, healthy dogs had consecutive ACTH stimulation tests to ensure 2 tests could be performed in sequence. For the first test, cosyntropin (1 μg/kg IV) was administered; the second test was initiated 4 hours after the start of the first (5 μg/kg cosyntropin IV). Dogs suspected of having HAC or being treated with mitotane were tested as the healthy dogs. Dogs receiving trilostane treatment were tested on consecutive days at the same time post pill using the low dose on day 1.

          Results

          In dogs being treated with mitotane or trilostane, the 2 doses were pharmacodynamically equivalent (90% confidence interval, 85.1–108.2%; P = 0.014). However, in dogs suspected of having HAC, the doses were not pharmacodynamically equivalent (90% confidence interval, 73.2–92.8%; P = 0.37); furthermore, in 23% of the dogs, clinical interpretation of test results was different between the doses.

          Conclusions and Clinical Relevance

          For dogs suspected of having HAC, 5 μg/kg cosyntropin IV is still recommended for ACTH stimulation testing. For dogs receiving mitotane or trilostane treatment, a dose of 1 μg/kg cosyntropin IV can be used.

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          Most cited references15

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          Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM consensus statement (small animal).

          This report offers a consensus opinion on the diagnosis of spontaneous canine hyperadrenocorticism. The possibility that a patient has hyperadrenocorticism is based on the history and physical examination. Endocrine tests should be performed only when clinical signs consistent with HAC are present. None of the biochemical screening or differentiating tests for hyperadrenocorticism are perfect. Imaging can also play a role. Awareness of hyperadrenocorticism has heightened over time. Thus, case presentation is more subtle. Due to the changes in manifestations as well as test technology the Panel believes that references ranges should be reestablished. The role of cortisol precursors and sex hormones in causing a syndrome of occult hyperadrenocorticism remains unclear.
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            Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test.

            Adrenal response to iv administration of 1-24 ACTH (250 micrograms) was examined in normal volunteers under various conditions. The effect of basal cortisol levels was examined by performing the tests at 0800 h with and without pretreatment with dexamethasone. The effect of time of day was evaluated by performing the tests at 0800 h and at 1600 h, eliminating possible basal cortisol influence by pretreatment with dexamethasone. In the first set of tests, despite significantly different baseline levels, 30-min cortisol levels were not different (618 +/- 50 vs. 590 +/- 52 nmol/L). Afternoon cortisol levels in response to ACTH were found to be significantly higher than morning levels at 5 min (254 +/- 50 vs. 144 +/- 36 nmol/L, p less than 0.01) and at 15 min (541 +/- 61 vs. 433 +/- 52 nmol/L, p less than 0.02). This difference in response was no longer notable at 30 min (629 +/- 52 and 591 +/- 52 nmol/L). We tried also to determine the lowest ACTH dose which will elicit a maximal cortisol response. No difference was found in cortisol levels at 30 and 60 min in response to 250 and 5 micrograms 1-24 ACTH. Using 1 micrograms ACTH, the 30-min response did not differ from that to 250 micrograms (704 +/- 72 vs. 718 +/- 55 nmol/L, respectively). However, the 60-min response to 1 microgram was significantly lower (549 +/- 61 vs. 842 +/- 110 nmol/L, p less than 0.01). Using this low dose ACTH test (1 microgram, measuring 30-min cortisol level), we were able to develop a much more sensitive ACTH test, which enabled us to differentiate a subgroup of patients on long-term steroid treatment who responded normally to the regular 250 micrograms test, but had a reduced response to 1 microgram. The stability of 1-24 ACTH in saline solution, kept at 4 C, was checked. ACTH was found to be fully stable after 2 hs in a concentration of 5 micrograms/ml in glass tube and 0.5 micrograms/ml in plastic tube. It was also found to be fully stable, both immunologically and biologically, for 4 months, under these conditions. We conclude that the 30-min cortisol response to ACTH is constant, unrelated to basal cortisol level or time of day. It is therefore the best criterion for measuring adrenal response in the short ACTH test. The higher afternoon responses at 5 and 15 min suggest greater adrenal sensitivity in the afternoon, but further studies are needed to clarify this issue.(ABSTRACT TRUNCATED AT 400 WORDS)
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              Trilostane treatment in dogs with pituitary-dependent hyperadrenocorticism.

              To evaluate the efficacy of trilostane in treating dogs with pituitary-dependent hyperadrenocorticism.
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                Author and article information

                Contributors
                behreen@auburn.edu
                Journal
                J Vet Intern Med
                J. Vet. Intern. Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley and Sons Inc. (Hoboken )
                0891-6640
                1939-1676
                18 July 2016
                Sep-Oct 2016
                : 30
                : 5 ( doiID: 10.1111/jvim.2016.30.issue-5 )
                : 1637-1641
                Affiliations
                [ 1 ] Department of Clinical SciencesAuburn University Auburn AL
                [ 2 ] Department of Anatomy, Physiology, and PharmacologyAuburn University Auburn AL
                [ 3 ] Department of Veterinary Clinical SciencesWashington State University Pullman WA
                [ 4 ] Department of Small Animal Medicine and SurgeryUniversity of Georgia Athens GA
                [ 5 ]VCA West Los Angeles Animal Hospital Los Angeles CA
                [ 6 ] Department of Mathematics and StatisticsAuburn University Auburn AL
                [ 7 ]Present address: ACCESS Specialty Hospital Culver City CA
                Author notes
                [*] [* ]Corresponding author: E. Behrend, Department of Clinical Sciences, Auburn University, Auburn, AL 36849; e‐mail: behreen@ 123456auburn.edu .
                Article
                JVIM14528
                10.1111/jvim.14528
                5032869
                27425787
                bf442e9e-6087-4bbc-aa5a-cbf08ddc3906
                Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine .

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 01 February 2016
                : 10 May 2016
                : 28 June 2016
                Page count
                Figures: 1, Tables: 1, Pages: 5, Words: 4205
                Funding
                Funded by: Interdepartmental Research Grants Program
                Funded by: Scott‐Ritchey Research Center
                Funded by: College of Veterinary Medicine
                Funded by: Auburn University
                Categories
                Standard Article
                SMALL ANIMAL
                Standard Articles
                Endocrinology
                Custom metadata
                2.0
                jvim14528
                September/October 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.4 mode:remove_FC converted:26.09.2016

                Veterinary medicine
                adrenal,cosyntropin,mitotane,trilostane
                Veterinary medicine
                adrenal, cosyntropin, mitotane, trilostane

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