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Equine veterinary journal2020; 53(2); 250-260; doi: 10.1111/evj.13292

Clinically and temporally specific diagnostic thresholds for plasma ACTH in the horse.

Abstract: Pituitary pars intermedia dysfunction (PPID) is commonly investigated using plasma ACTH concentrations but problems exist with currently available diagnostic thresholds. Objective: To derive temporally specific diagnostic thresholds for equine plasma ACTH concentration to be used alongside clinical judgement in each individual week of the year and appropriate for the degree of clinical suspicion in any given case. Furthermore, to apply these thresholds to compare the prevalence of high and low ACTH in two subgroups of animals with high and low clinical suspicion of PPID. Methods: A retrospective population study examining a large laboratory database of equine plasma ACTH concentrations using an indirect approach to calculate diagnostic thresholds. Methods: Logs of plasma ACTH concentrations from 75 892 individual horses were examined using robust L estimation of mixtures of two normal distributions in categories of each week and month of the year. Thresholds dividing the two populations of high-ACTH and low-ACTH horses were then established at different levels of sensitivity and specificity and compared with clinical subgroups of horses divided based on reported clinical signs, as having high (n = 4036) or low (n = 3022) clinical suspicion of PPID. Results: For most of the year there were small interweek differences in diagnostic thresholds. However, from mid-June to early-December diagnostic thresholds showed greater interweek variability, reaching a maximum in late September and early October. Grouping of high- and low-ACTH compared favourably with grouping based on clinical signs. Conclusions: Given the multiple sources of diagnostic samples, pre-analytical data could not be fully verified. Conclusions: Diagnostic thresholds for equine plasma ACTH vary through the year. It is especially important to consider the temporally specific threshold between June and December. Different clinical thresholds can be used depending on the case circumstances and whether a false-positive or false-negative diagnosis is deemed least desirable.
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Publication Date: 2020-06-23 PubMed ID: 32470177DOI: 10.1111/evj.13292Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research establishes time-based diagnostic thresholds for the concentration of Adrenocorticotropic hormone (ACTH) in horse plasma, which assists in the detection of Pituitary pars intermedia dysfunction (PPID). The study also highlights the importance of these temporal thresholds in determining the prevalence of high and low ACTH, particularly relevant when there’s a high or low clinical suspicion of PPID.

Objective and Methodology

  • The objective of the study was to identify specific diagnostic thresholds for equine plasma ACTH concentration for each week of the year. The goal was to have a more accurate and temporally specific way of diagnosing PPID in horses.
  • The research also aimed to compare the prevalence of high and low ACTH in two subgroups of horses, those with high clinical suspicion of PPID and those with low suspicion.
  • The researchers carried out a retrospective population study, where they examined logs of plasma ACTH concentrations from 75,892 individual horses using robust L estimation of mixtures of two normal distributions.
  • The data was categorized by each week and month of the year. Using this data, thresholds that divide the high and low ACTH populations were established.

Key Findings

  • Interweek differences in diagnostic thresholds were minimal for most parts of the year.
  • However, from mid-June to early-December, these thresholds demonstrated increased variability, peaking in late September and early October.
  • The study found that grouping horses based on high and low ACTH concentration aligned favorably with grouping based on reported clinical signs of PPID.

Conclusion and Implications

  • Since the multiple sources of diagnostic samples prevented full verification of pre-analytical data, validation of the findings may be required.
  • The study concludes that diagnostic thresholds for equine plasma ACTH vary throughout the year, highlighting the importance of considering these temporal variations, especially between June and December.
  • The study also recommends that different clinical thresholds should be applied based on the case circumstances and whether a false-positive or false-negative diagnosis would have a more significant impact.

Cite This Article

APA
Durham AE, Clarke BR, Potier JFN, Hammarstrand R, Malone GL. (2020). Clinically and temporally specific diagnostic thresholds for plasma ACTH in the horse. Equine Vet J, 53(2), 250-260. https://doi.org/10.1111/evj.13292

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 53
Issue: 2
Pages: 250-260

Researcher Affiliations

Durham, Andy E
  • The Liphook Equine Hospital, Liphook, UK.
Clarke, Brenton R
  • Mathematics and Statistics, ITMAS, College of Science, Health, Engineering and Education, Murdoch University, Western Australia, Australia.
Potier, Julie F N
  • The Liphook Equine Hospital, Liphook, UK.
Hammarstrand, Robert
  • Mathematics and Statistics, ITMAS, College of Science, Health, Engineering and Education, Murdoch University, Western Australia, Australia.
Malone, George L
  • Mathematics and Statistics, ITMAS, College of Science, Health, Engineering and Education, Murdoch University, Western Australia, Australia.

MeSH Terms

  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Horse Diseases / diagnosis
  • Horses
  • Pituitary Diseases / diagnosis
  • Pituitary Diseases / veterinary
  • Pituitary Gland, Intermediate / metabolism
  • Plasma / metabolism
  • Retrospective Studies

Grant Funding

  • Murdoch University
  • Boehringer Ingelheim

References

This article includes 32 references
  1. Durham AE, McGowan CM, Fey K, Tamzali Y, van der Kolk JH. Pituitary pars intermedia dysfunction: diagnosis and treatment.. Equine Vet Educ 2014;26:216-23.
  2. McFarlane D. Diagnostic testing for equine endocrine diseases: confirmation versus confusion.. Vet Clin North Am Equine Pract 2019;35:327-38.
  3. Donaldson MT, McDonnell SM, Schanbacher BJ, Lamb SV, McFarlane D, Beech J. Variation in plasma adrenocorticotropic hormone concentration and dexamethasone suppression test results with season, age, and sex in healthy ponies and horses.. J Vet Intern Med 2005;19:217-22.
  4. McGowan TW, Pinchbeck GP, McGowan CM. Evaluation of basal plasma alpha-melanocyte-stimulating hormone and adrenocorticotrophic hormone concentrations for the diagnosis of pituitary pars intermedia dysfunction from a population of aged horses.. Equine Vet J 2013;45:66-73.
  5. Copas VE, Durham AE. Circannual variation in plasma adrenocorticotropic hormone concentrations in the UK in normal horses and ponies, and those with pituitary pars intermedia dysfunction.. Equine Vet J 2012;44:440-3.
  6. Secombe CJ, Tan RHH, Perara DI, Byrne DP, Watts SP, Wearn JG. The effect of geographic location on circannual adrenocorticotropic hormone plasma concentrations in horses in Australia.. J Vet Intern Med 2017;31:1533-40.
  7. Secombe CJ, Bailey SR, de Laat MA, Hughes KJ, Stewart AJ, Sonis JM. Equine pituitary pars intermedia dysfunction: current understanding and recommendations from the Australian and New Zealand Equine Endocrine Group.. Aust Vet J 2018;96:233-42.
  8. Ichihara K, Boyd JC. An appraisal of statistical procedures used in derivation of reference intervals.. Clin Chem Lab Med 2010;48:1537-51.
  9. Clarke B, Heathcote C. Robust estimation of k-component univariate normal mixtures.. Ann Inst Stat Math 1994;46:83-93.
  10. Clarke BR, Davidson T, Hammarstrand R. A comparison of the L2 minimum distance estimator and the EM-algorithm when fitting k-component univariate normal mixtures.. Stat Pap 2017;58:1247-66.
  11. Clarke BR. A remark on robustness and weak continuity of M-estimators.. J Aust Math Soc 2000;68:411-8.
  12. Clarke BR. A review of differentiability in relation to robustness with application to seismic data analysis.. Proc Ind Natl Sci Acad 2000;66:467-82.
  13. Greiner M, Sohr D, Gobel P. A modified ROC analysis for the selection of cut-off values and the definition of intermediate results of serodiagnostic tests.. J Immunol Methods 1995;185:123-32.
  14. Landsheer JA. The clinical relevance of methods for handling inconclusive medical test results: quantification of uncertainty in medical decision-making and screening.. Diagn 2018;8:32.
  15. CLSI. Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline-Third Edition.. Clinical and Laboratory Standards Institute CLSI document EP28-A3c. Wayne, PA.
  16. Jones GRD, Haeckel R, Loh TP, Sikaris K, Streichert T, Katayev A. Indirect methods for reference interval determination - review and recommendations.. Clin Chem Lab Med 2018;57:20-9.
  17. Durham A. Is Equine Pars Intermedia Activity Subdued in the Spring?. Equine Endocrinology Summit Miami, FL; 2017. 4-5.
  18. McFarlane D, Beech J, Cribb A. Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants.. Domest Anim Endocrinol 2006;30:276-88.
  19. Beech J, Boston R, Lindborg S, Russell GE. Adrenocorticotropin concentration following administration of thyrotropin-releasing hormone in healthy horses and those with pituitary pars intermedia dysfunction and pituitary gland hyperplasia.. J Am Vet Med Assoc 2007;231:417-26.
  20. Beech J, Boston R, Lindborg S. Comparison of cortisol and ACTH responses after administration of thyrotropin releasing hormone in normal horses and those with pituitary pars intermedia dysfunction.. J Vet Intern Med 2011;25:1431-8.
  21. Durham A, Shreeve H. Horse-Factors Influencing the Seasonal Increase in Plasma ACTH Secretion.. Equine Endocrinology Summit Miami, FL. 36-7.
  22. Heinrichs M, Baumgartner W, Capen CC. Immunocytochemical demonstration of proopiomelanocortin-derived peptides in pituitary adenomas of the pars intermedia in horses.. Vet Pathol 1990;27:419-25.
  23. Couetil L, Paradis MR, Knoll J. Plasma adrenocorticotropin concentration in healthy horses and in horses with clinical signs of hyperadrenocorticism.. J Vet Intern Med 1996;10:1-6.
  24. Orth DN, Holscher MA, Wilson MG, Nicholson WE, Plue RE, Mount CD. Equine Cushing's disease: plasma immunoreactive proopiolipomelanocortin peptide and cortisol levels basally and in response to diagnostic tests.. Endocrinol 1982;110:1430-41.
  25. Beech J, McFarlane D, Lindborg S, Sojka JE, Boston RC. alpha-Melanocyte-stimulating hormone and adrenocorticotropin concentrations in response to thyrotropin-releasing hormone and comparison with adrenocorticotropin concentration after domperidone administration in healthy horses and horses with pituitary pars intermedia dysfunction.. J Am Vet Med Assoc 2011;238:1305-15.
  26. Rademacher N, Gaschen L, Madrigal R, Duplantis D, Andrews F. Neurologic signs, endocrine testing and rapid-slice contrast computed tomography in an 8 year old Arabian.. Equine Endocrine Summit Middleburg, VA. 25.
  27. McFarlane D, Miller LM, Craig LE, Dybdal NO, Habecker PL, Miller MA. Agreement in histologic assessments of the pituitary pars intermedia in aged horses.. Am J Vet Res 2005;66:2055-9.
  28. Miller MA, Pardo ID, Jackson LP, Moore GE, Sojka JE. Correlation of pituitary histomorphometry with adrenocorticotrophic hormone response to domperidone administration in the diagnosis of equine pituitary pars intermedia dysfunction.. Vet Pathol 2008;45:26-38.
  29. Pease AP, Schott HC 2nd, Howey EB, Patterson JS. Computed tomographic findings in the pituitary gland and brain of horses with pituitary pars intermedia dysfunction.. J Vet Intern Med 2011;25:1144-51.
  30. McFarlane D. Advantages and limitations of the equine disease, pituitary pars intermedia dysfunction as a model of spontaneous dopaminergic neurodegenerative disease.. Ageing Res Rev 2007;6:54-63.
  31. Knowles EJ, Moreton-Clack MC, Shaw S, Harris PA, Elliott J, Menzies-Gow NJ. Plasma adrenocorticotropic hormone (ACTH) concentrations in ponies measured by two different assays suggests seasonal cross-reactivity or interference.. Equine Vet J 2018;50:672-7.
  32. Banse HE, Schultz N, McCue M, Geor R, McFarlane D. Comparison of two methods for measurement of equine adrenocorticotropin.. J Vet Diagn Invest 2018;30:233-7.

Citations

This article has been cited 5 times.
  1. Drozdzewska K, Gehlen H. Markers for internal neoplasia in the horse.. Vet Med Sci 2023 Jan;9(1):132-143.
    doi: 10.1002/vms3.1042pubmed: 36495211google scholar: lookup
  2. Kirkwood NC, Hughes KJ, Stewart AJ. Prospective Case Series of Clinical Signs and Adrenocorticotrophin (ACTH) Concentrations in Seven Horses Transitioning to Pituitary Pars Intermedia Dysfunction (PPID).. Vet Sci 2022 Oct 17;9(10).
    doi: 10.3390/vetsci9100572pubmed: 36288186google scholar: lookup
  3. Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses.. Vet Sci 2022 Oct 10;9(10).
    doi: 10.3390/vetsci9100556pubmed: 36288169google scholar: lookup
  4. Kam YN, McKenzie K, Coyle M, Bertin FR. Repeatability of a thyrotropin-releasing hormone stimulation test for diagnosis of pituitary pars intermedia dysfunction in mature horses.. J Vet Intern Med 2021 Nov;35(6):2885-2890.
    doi: 10.1111/jvim.16281pubmed: 34642962google scholar: lookup
  5. Dunkel B, Knowles EJ, Chang YM, Menzies-Gow NJ. Influence of endocrine disease on l-lactate concentrations in blood of ponies.. J Vet Intern Med 2021 May;35(3):1582-1588.
    doi: 10.1111/jvim.16079pubmed: 34043845google scholar: lookup
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