Investigation of the urine cortisol to creatinine ratio for the diagnosis of hypoadrenocorticism in dogs

Melissa V. Moya Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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 DVM
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Kent R. Refsal Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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 DVM, PhD
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Daniel K. Langlois Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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 DVM, DACVIM
DOI:
https://doi.org/10.2460/javma.21.12.0538
Volume/Issue:
Volume 260: Issue 9
Online Publication Date:
13 Apr 2022
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Abstract

OBJECTIVE

To evaluate the urine cortisol-to-creatinine ratio (UCCR) for the diagnosis of hypoadrenocorticism (HA) in dogs and to determine whether the method of urine cortisol measurement affects results. 

ANIMALS

41 dogs with naturally occurring HA and 107 dogs with nonadrenal illness.

PROCEDURES

Urine samples were prospectively collected from dogs undergoing testing for HA. Urine cortisol concentrations were measured at a veterinary diagnostic laboratory using either a radioimmunoassay (RIA) or a chemiluminescent immunoassay (CLIA). Receiver operating characteristic (ROC) curves were constructed to assess UCCR performance by both methods for HA diagnosis. Sensitivities, specificities, accuracies, and predictive values were calculated for various cutpoints.

RESULTS

The areas under the ROC curves for UCCR diagnosis of HA were 0.99 (95% CI, 0.98 to 1.00) and 1.00 (95% CI, 1.00 to 1.00) when urine cortisol was determined by RIA and CLIA, respectively. An RIA UCCR of ≤ 2 was 97.2% sensitive, 93.6% specific, and 94.7% accurate for HA diagnosis, whereas a CLIA UCCR of ≤ 10 was 100% sensitive, specific, and accurate. An RIA UCCR > 4 and a CLIA UCCR of > 10 had negative predictive values of 100%.

CLINICAL RELEVANCE

The UCCR was an accurate diagnostic test for HA in this study population, although equivocal results are possible. Case characteristics, method of cortisol measurement, and laboratory-specific cutpoints must be considered when interpreting results.

Abstract

OBJECTIVE

To evaluate the urine cortisol-to-creatinine ratio (UCCR) for the diagnosis of hypoadrenocorticism (HA) in dogs and to determine whether the method of urine cortisol measurement affects results. 

ANIMALS

41 dogs with naturally occurring HA and 107 dogs with nonadrenal illness.

PROCEDURES

Urine samples were prospectively collected from dogs undergoing testing for HA. Urine cortisol concentrations were measured at a veterinary diagnostic laboratory using either a radioimmunoassay (RIA) or a chemiluminescent immunoassay (CLIA). Receiver operating characteristic (ROC) curves were constructed to assess UCCR performance by both methods for HA diagnosis. Sensitivities, specificities, accuracies, and predictive values were calculated for various cutpoints.

RESULTS

The areas under the ROC curves for UCCR diagnosis of HA were 0.99 (95% CI, 0.98 to 1.00) and 1.00 (95% CI, 1.00 to 1.00) when urine cortisol was determined by RIA and CLIA, respectively. An RIA UCCR of ≤ 2 was 97.2% sensitive, 93.6% specific, and 94.7% accurate for HA diagnosis, whereas a CLIA UCCR of ≤ 10 was 100% sensitive, specific, and accurate. An RIA UCCR > 4 and a CLIA UCCR of > 10 had negative predictive values of 100%.

CLINICAL RELEVANCE

The UCCR was an accurate diagnostic test for HA in this study population, although equivocal results are possible. Case characteristics, method of cortisol measurement, and laboratory-specific cutpoints must be considered when interpreting results.

Supplementary Materials

    • Supplementary Appendix S1 (PDF 157 KB)

Contributor Notes

Corresponding author: Dr. Langlois (langlo21@msu.edu)
Cover Journal of the American Veterinary Medical Association
Journal of the American Veterinary Medical Association
Publication Date:
01 Jun 2022
  • 1.

    Hess RS. Hypoadrenocorticism. In: Ettinger SJ, Feldman EC, Côté E, eds. Textbook of Veterinary Internal Medicine. 8th ed. Elsevier; 2017:1825–1833.

    • Search Google Scholar
    • Export Citation
  • 2.

    Frank CB, Valentin SY, Scott-Moncrieff JC, Miller MA. Correlation of inflammation with adrenocortical atrophy in canine adrenalitis. J Comp Pathol. 2013;149(2-3):268–279.

    • Search Google Scholar
    • Export Citation
  • 3.

    Schaer M, Riley WJ, Buergelt CD, et al. Autoimmunity and Addison’s disease in the dog. J Am Anim Hosp Assoc. 1986;22:789–794.

  • 4.

    Hauck C, Schmitz SS, Burgener IA, et al. Prevalence and characterization of hypoadrenocorticism in dogs with signs of chronic gastrointestinal disease: a multicenter study. J Vet Intern Med. 2020;34(4):1399–1405.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Peterson ME, Kintzer PP, Kass PH. Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism: 225 cases (1979–1993). J Am Vet Med Assoc. 1996;208(1):85–91.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Vincent AM, Okonkowski LK, Brudvig JM, et al. Low-dose desoxycorticosterone pivalate treatment of hypoadrenocorticism in dogs: a randomized controlled clinical trial. J Vet Intern Med. 2021;35(4):1720–1728.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Klein SC, Peterson ME. Canine hypoadrenocorticism: part I. Can Vet J. 2010;51(1):63–69.

  • 8.

    DiBartola SP, Johnson SE, Davenport DJ, Prueter JC, Chew DJ, Sherding RG. Clinicopathologic findings resembling hypoadrenocorticism in dogs with primary gastrointestinal disease. J Am Vet Med Assoc. 1985;187(1):60–63.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Gold AJ, Langlois DK, Refsal KR. Evaluation of basal serum or plasma cortisol concentrations for the diagnosis of hypoadrenocorticism in dogs. J Vet Intern Med. 2016;30(6):1798–1805.

    • Search Google Scholar
    • Export Citation
  • 10.

    Lathan P, Scott-Moncrieff JC, Wills RW. Use of the cortisol-to-ACTH ratio for diagnosis of primary hypoadrenocorticism in dogs. J Vet Intern Med. 2014;28(5):1546–1550.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Baumstark ME, Sieber-Ruckstuhl NS, Müller C, Wenger M, Boretti FS, Reusch CE. Evaluation of aldosterone concentrations in dogs with hypoadrenocorticism. J Vet Intern Med. 2014;28(1):154–159.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Borin-Crivellenti S, Garabed RB, Moreno-Torres KI, Wellman ML, Gilor C. Use of a combination of routine hematologic and biochemical test results in a logistic regression model as a diagnostic aid for the diagnosis of hypoadrenocorticism in dogs. Am J Vet Res. 2017;78(10):1171–1181.

    • Search Google Scholar
    • Export Citation
  • 13.

    Bovens C, Tennant K, Reeve J, Murphy KF. Basal serum cortisol concentration as a screening test for hypoadrenocorticism in dogs. J Vet Intern Med. 2014;28(5):1541–1545.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Dropkin CA, Kruger JM, Langlois DK. Evaluation of urine electrolytes for the diagnosis of hypoadrenocorticism in dogs. Vet Clin Pathol. 2021;50(4):507–514.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Javadi S, Galac S, Boer P, Robben JH, Teske E, Kooistra HS. Aldosterone-to-renin and cortisol-to-adrenocorticotropic hormone ratios in healthy dogs and dogs with primary hypoadrenocorticism. J Vet Intern Med. 2006;20(3):556–561.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Lennon EM, Boyle TE, Hutchins RG, et al. Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000–2005). J Am Vet Med Assoc. 2007;231(3):413–416.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Lennon EM, Hummel JB, Vaden SL. Urine sodium concentrations are predictive of hypoadrenocorticism in hyponatraemic dogs: a retrospective pilot study. J Small Anim Pract. 2018;59(4):228–231.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Reagan KL, Reagan BA, Gilor C. Machine learning algorithm as a diagnostic tool for hypoadrenocorticism in dogs. Domest Anim Endocrinol. 2020;72:106396. doi:10.1016/j.domaniend.2019.106396

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Zeugswetter FK, Schwendenwein I. Diagnostic efficacy of the leukogram and the chemiluminometric ACTH measurement to diagnose canine hypoadrenocorticism. Tierarztl Prax Ausg K Kleintiere Heimtiere. 2014;42(4):223–230.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Kemppainen RJ, Sartin JL. Evidence for episodic but not circadian activity in plasma concentrations of adrenocorticotrophin, cortisol and thyroxine in dogs. J Endocrinol. 1984;103(2):219–226.

    • Search Google Scholar
    • Export Citation
  • 21.

    Rijnberk A, van Wees A, Mol JA. Assessment of two tests for the diagnosis of canine hyperadrenocorticism. Vet Rec. 1988;122(8):178–180.

  • 22.

    Peterson ME. Diagnosis of hyperadrenocorticism in dogs. Clin Tech Small Anim Pract. 2007;22(1):2–11.

  • 23.

    Rowland AJ, Birkenheuer AJ, Mamo L, Lunn KF. Comparison of urine cortisol:creatinine ratio and basal cortisol for the diagnosis of canine hypoadrenocorticism. Abstract in: Proceedings of the American College of Veterinary Internal Medicine Forum Research Abstract Program. American College of Veterinary Internal Medicine; 2018:2228–2229.

    • Search Google Scholar
    • Export Citation
  • 24.

    Smiley LE, Peterson ME. Evaluation of a urine cortisol:creatinine ratio as a screening test for hyperadrenocorticism in dogs. J Vet Intern Med. 1993;7(3):163–168.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Diagnostics test directory. Antech. Accessed January 22, 2021. https://www.antechdiagnostics.com/laboratorydiagnostics/test-guide

  • 26.

    Reference laboratories directory of services. Idexx. Accessed January 22, 2021. https://www.idexx.com/en/veterinary/reference-laboratories/tests-and-services/#directory

    • Search Google Scholar
    • Export Citation
  • 27.

    Hernandez-Bures A, White AG, Riordan L. Presumptive iatrogenic hypoadrenocorticism induced by high-dose ketoconazole administration in a dog. J Vet Intern Med. 2019;33(5):2235–2238.

    • Search Google Scholar
    • Export Citation
  • 28.

    Moore GE, Hoenig M. Duration of pituitary and adrenocortical suppression after long-term administration of anti-inflammatory doses of prednisone in dogs. Am J Vet Res. 1992;53(5):716–720.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Sullivant AM, Lathan P. Ketoconazole-induced transient hypoadrenocorticism in a dog. Can Vet J. 2020;61(4):407–410.

  • 30.

    Korchia J, Freeman KP. Validation study of canine urine cortisol measurement with the Immulite 2000 Xpi cortisol immunoassay. J Vet Diagn Invest. 2021;33(6):1052–1068.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Boretti FS, Meyer F, Burkhardt WA, et al. Evaluation of the cortisol-to-ACTH ratio in dogs with hypoadrenocorticism, dogs with diseases mimicking hypoadrenocorticism and in healthy dogs. J Vet Intern Med. 2015;29(5):1335–1341.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Golinelli S, de Marco V, Leal RO, et al. Comparison of methods to monitor dogs with hypercortisolism treated with trilostane. J Vet Intern Med. 2021;35(6)2616–2627.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Galeandro L, Sieber-Ruckstuhl NS, Riond B, et al. Urinary corticoid concentrations measured by 5 different immunoassays and gas chromatography-mass spectrometry in healthy dogs and dogs with hypercortisolism at home and in the hospital. J Vet Intern Med. 2014;28(5):1433–1441.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Zeugswetter FK, Neffe F, Schwendenwein I, Tichy A, Möstl E. Configuration of antibodies for assay of urinary cortisol in dogs influences analytic specificity. Domest Anim Endocrinol. 2013;45(2):98–104.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    European Veterinary Endocrine Quality Assurance Scheme (EVE-QAS). European Society of Veterinary Endocrinology. Accessed December 13, 2021. https://www.esve.org/esve/eve-qas/default.aspx

    • Search Google Scholar
    • Export Citation
  • 36.

    Citron LE, Weinstein NM, Littman MP, Foster JD. Urine cortisol-creatinine and protein-creatinine ratios in urine samples from healthy dogs collected at home and in hospital. J Vet Intern Med. 2020;34(2):777–782.

    • PubMed
    • Search Google Scholar
    • Export Citation

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