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Journal of veterinary internal medicine2026; 40(1); aalag023; doi: 10.1093/jvimsj/aalag023

Associations among beta-endorphin, ACTH, cortisol concentration, age, and clinical signs indicative of pituitary pars intermedia dysfunction in geriatric horses.

Abstract: Limited published data are available regarding the relationships among clinical signs associated with pituitary pars intermedia dysfunction (PPID), age, and concentrations of proopiomelanocortin-derived peptides and cortisol. Objective: Identify clinical signs associated with age, beta-endorphin (β-END), adrenocorticotropic hormone (ACTH), and cortisol concentrations and compare β-END and cortisol concentrations between horses with PPID and geriatric controls. Methods: A total of 113 horses aged 18-32 years. Methods: Cross-sectional study. Clinical signs were scored, plasma β-END, ACTH, and serum cortisol concentrations were measured, and their associations were evaluated. Horses were classified as PPID or controls based on haircoat abnormalities and ACTH concentrations, and group comparisons were performed. Results: Increased β-END and ACTH concentrations were associated with haircoat abnormalities (P < .001), whereas advanced age was associated with muscle atrophy, weight loss, and lethargy (P < .001). Cortisol concentrations were not associated with any of the clinical signs. The β-END concentrations were higher in the PPID group (median, 291 pg/mL; interquartile range [IQR], 122-836 pg/mL; n = 40) compared with the control group (median, 55.0 pg/mL; IQR, 45.0-68.0 pg/mL; n = 53; P < .001). Conclusions: In this geriatric study cohort, haircoat abnormalities were associated with increased β-END and ACTH concentrations, whereas other clinical signs, such as muscle atrophy, weight loss, and lethargy, were primarily linked to age. Because PPID is diagnosed based on clinical signs and ACTH concentrations, it is important to distinguish clinical signs that are age-related from those associated with PPID.
© The Author(s) 2026. Published by Oxford University Press on behalf of the American College of Veterinary Internal Medicine.
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Publication Date: 2026-02-26 PubMed ID: 41742592PubMed Central: PMC12927883DOI: 10.1093/jvimsj/aalag023Google 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.

Overview

  • This study investigates the relationships between clinical signs of pituitary pars intermedia dysfunction (PPID), age, and hormone concentrations (beta-endorphin, ACTH, and cortisol) in older horses.
  • The research aims to differentiate which clinical signs are related to PPID versus those simply related to aging in geriatric horses.

Background

  • PPID is a common endocrine disorder in older horses involving the pituitary gland’s pars intermedia.
  • Clinical signs of PPID often overlap with normal aging signs, making diagnosis challenging.
  • Key hormones related to PPID include proopiomelanocortin (POMC)-derived peptides such as ACTH and beta-endorphin (β-END), as well as cortisol.
  • Previous literature has limited data on how these hormones relate to clinical signs and age in older horses.

Objectives

  • Evaluate associations among clinical signs suggestive of PPID, age, and concentrations of β-END, ACTH, and cortisol.
  • Compare β-END and cortisol levels between horses diagnosed with PPID and geriatric controls.

Methods

  • Study Design: Cross-sectional study involving 113 horses aged 18 to 32 years.
  • Clinical signs were scored and documented for each horse.
  • Blood samples were collected to measure plasma β-END, ACTH, and serum cortisol concentrations.
  • Horses were classified into PPID or control groups based on haircoat condition and ACTH levels.
  • Statistical analyses evaluated associations between hormone concentrations, age, and clinical signs, and compared hormone levels between groups.

Key Results

  • Higher β-END and ACTH concentrations showed a strong association with haircoat abnormalities (P<.001), a classic sign of PPID.
  • Advanced age was significantly associated with muscle atrophy, weight loss, and lethargy (P<.001), which are general aging signs rather than PPID-specific.
  • Cortisol concentrations did not show association with any clinical signs examined.
  • The PPID group exhibited markedly higher median β-END concentrations (291 pg/mL) compared to controls (55 pg/mL), confirming a hormonal difference between disease and normal aging.

Interpretation

  • Haircoat abnormalities in older horses likely indicate increased β-END and ACTH, consistent with PPID pathology.
  • Other signs like muscle wasting, weight loss, and lethargy tend to reflect the natural aging process rather than the disease.
  • Cortisol does not appear to be a useful marker for distinguishing PPID-related clinical signs in geriatric horses.
  • Elevated β-END might be a supportive diagnostic biomarker for PPID when combined with ACTH levels and clinical evaluation.

Conclusions and Clinical Implications

  • Veterinarians should carefully differentiate clinical signs caused by PPID from those resulting from normal aging to avoid misdiagnosis.
  • Testing ACTH and β-END concentrations alongside clinical assessment of haircoat can improve PPID diagnosis accuracy in older horses.
  • This study emphasizes the importance of recognizing specific hormone patterns linked to PPID versus aging symptoms in geriatric equine patients.

Cite This Article

APA
Billmann P, Durham A, Christen G, Savioli G, Gross JJ, Gerber V, Fouché NE. (2026). Associations among beta-endorphin, ACTH, cortisol concentration, age, and clinical signs indicative of pituitary pars intermedia dysfunction in geriatric horses. J Vet Intern Med, 40(1), aalag023. https://doi.org/10.1093/jvimsj/aalag023

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 40
Issue: 1
PII: aalag023

Researcher Affiliations

Billmann, Paula
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Durham, Andy
  • Liphook Equine Hospital, Liphook, Hampshire, United Kingdom.
Christen, Garance
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Savioli, Giulia
  • Veterinary Public Health Institute, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Federal Food Safety and Veterinary Office, Bern, Switzerland.
Gross, Josef Johann
  • Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Gerber, Vinzenz
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Fouché, Nathalie Elisa
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

Grant Funding

  • Vontobel Foundation
  • Vetsuisse Faculty, University of Bern
  • Internal Research Funds
  • ISMEquine Research No. 33-890 / Swiss Institute of Equine Medicine, Bern, Switzerland

Conflict of Interest Statement

A.D. is employed by Liphook Equine Hospital which offers commercial laboratory services for horses.

References

This article includes 53 references
  1. Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary pars intermedia dysfunction (PPID) in horses. Vet Sci 2022;9:556.
    doi: 10.3390/vetsci9100556pmc: PMC9611634pubmed: 36288169google scholar: lookup
  2. Fortin JS, Benskey MJ, Lookingland KJ. Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction. BMC Vet Res 2020;16:356.
    doi: 10.1186/s12917-020-02565-3pmc: PMC7517620pubmed: 32977825google scholar: lookup
  3. Durham AE. Endocrine disease in aged horses. Vet Clin North Am Equine Pract 2016;32:301-315.
    doi: 10.1016/j.cveq.2016.04.007pubmed: 27449391google scholar: lookup
  4. 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.
    doi: 10.1016/j.arr.2007.02.001pubmed: 17374512google scholar: lookup
  5. Ireland JL, McGowan CM. Epidemiology of pituitary pars intermedia dysfunction: a systematic literature review of clinical presentation, disease prevalence and risk factors. Vet J 2018;235:22-33.
    doi: 10.1016/j.tvjl.2018.03.002pubmed: 29704935google scholar: lookup
  6. Durham AE, McGowan CM, Fey K. Pituitary dysfunction: diagnosis and treatment. Equine Vet Educ 2014;26:216-223.
    doi: 10.1111/eve.12160google scholar: lookup
  7. Heinrichs M, Baumgartner W, Capen CC. Immunocytochemical demonstration of proopiomelanocortin-derived peptides in pituitary adenomas of the pars intermedia in horses. Vet Pathol 1990;27:419-425.
    doi: 10.1177/030098589902700606pubmed: 2177580google scholar: lookup
  8. McFarlane D. Pathophysiology and clinical features of pituitary dysfunction. Equine Vet Educ 2014;26:592-598.
    doi: 10.1111/eve.12237google scholar: lookup
  9. McGowan TW, Pinchbeck GP, McGowan CM. Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses. Equine Vet J 2013;45:74-79.
    doi: 10.1111/j.2042-3306.2012.00578.xpubmed: 22594955google scholar: lookup
  10. Menzies-Gow NJ, Banse HE, Duff A. BEVA primary care clinical guidelines: diagnosis and management of equine pituitary pars intermedia dysfunction. Equine Vet J 2024;56:220-242.
    doi: 10.1111/evj.14009pubmed: 37795557google scholar: lookup
  11. 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;9:572.
    doi: 10.3390/vetsci9100572pmc: PMC9607114pubmed: 36288186google scholar: lookup
  12. Horn R, Bamford NJ, Afonso T. Factors associated with survival, laminitis and insulin dysregulation in horses diagnosed with equine pituitary pars intermedia dysfunction. Equine Vet J 2019;51:440-445.
    doi: 10.1111/evj.13041pubmed: 30417404google scholar: lookup
  13. Fouché N, Doras C, Schupbach-Regula G. Association between adrenocorticotropic hormone concentration and clinical signs of pituitary pars intermedia dysfunction in Swiss and Austrian equids. J Vet Intern Med 2025;39:e70008.
    doi: 10.1111/jvim.70008pmc: PMC11912427pubmed: 40095750google scholar: lookup
  14. Millington WR, Dybdal NO, Dawson RJ Jr. Equine Cushing’s disease: differential regulation of beta-endorphin processing in tumors of the intermediate pituitary. Endocrinology 1988;123:1598-1604.
    doi: 10.1210/endo-123-3-1598pubmed: 2456916google scholar: lookup
  15. Schott HC 2nd. Pituitary pars intermedia dysfunction: equine Cushing’s disease. Vet Clin North Am Equine Pract 2002;18:237-270.
    doi: 10.1016/S0749-0739(02)00018-4pubmed: 15635907google scholar: lookup
  16. McFarlane D. Equine pituitary pars intermedia dysfunction. Vet Clin North Am Equine Pract 2011;27:93-113.
    doi: 10.1016/j.cveq.2010.12.007pubmed: 21392656google scholar: lookup
  17. Hart KA, Kitchings KM, Kimura S. Measurement of cortisol concentration in the tears of horses and ponies with pituitary pars intermedia dysfunction. Am J Vet Res 2016;77:1236-1244.
    doi: 10.2460/ajvr.77.11.1236pubmed: 27805438google scholar: lookup
  18. Hart KA, Wochele DM, Norton NA, McFarlane D, Wooldridge AA, Frank N. Effect of age, season, body condition, and endocrine status on serum free cortisol fraction and insulin concentration in horses. J Vet Intern Med 2016;30:653-663.
    doi: 10.1111/jvim.13839pmc: PMC4913614pubmed: 26860336google scholar: lookup
  19. Morgan RA, Keen JA, Homer N. Dysregulation of cortisol metabolism in equine pituitary pars intermedia dysfunction. Endocrinology 2018;159:3791-3800.
    doi: 10.1210/en.2018-00726pmc: PMC6202856pubmed: 30289445google scholar: lookup
  20. Grubbs ST, Kirschner KA, Baus MR. Clinical signs associated with PPID in the equine athlete. In: 2017 Equine Endocrinology Summit with the Dorothy Havemeyer Foundation. The Equine Endocrinology Group; 2017 [abstract].
  21. Hofberger S, Gauff F, Licka T. Suspensory ligament degeneration associated with pituitary pars intermedia dysfunction in horses. Vet J 2015;203:348-350.
    doi: 10.1016/j.tvjl.2014.12.037pubmed: 25641552google scholar: lookup
  22. Hofberger SC, Gauff F, Thaller D. Assessment of tissue-specific cortisol activity with regard to degeneration of the suspensory ligaments in horses with pituitary pars intermedia dysfunction. Am J Vet Res 2018;79:199-210.
    doi: 10.2460/ajvr.79.2.199pubmed: 29359976google scholar: lookup
  23. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet J 1983;15:371-372.
    doi: 10.1111/j.2042-3306.1983.tb01826.xpubmed: 6641685google scholar: lookup
  24. Carter RA, Geor RJ, Burton Staniar W. Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies. Vet J 2009;179:204-210.
    doi: 10.1016/j.tvjl.2008.02.029pubmed: 18440844google scholar: lookup
  25. Meier A, de Laat M, Pollitt C. A “modified Obel” method for the severity scoring of (endocrinopathic) equine laminitis. PeerJ 2019;7:e7084.
    doi: 10.7717/peerj.7084pmc: PMC6557244pubmed: 31211020google scholar: lookup
  26. Fouché N, Howard J, Gerber V. Pilot study of β-endorphin concentrations in horses with pituitary pars intermedia dysfunction using a newly validated enzyme-linked immunosorbent assay. Domest Anim Endocrinol 2025;95:106982.
    doi: 10.1016/j.domaniend.2025.106982pubmed: 41317409google scholar: lookup
  27. Perkins GA, Lamb S, Erb HN, Schanbacher B, Nydam DV, Divers TJ. Plasma adrenocorticotropin (ACTH) concentrations and clinical response in horses treated for equine Cushing's disease with cyproheptadine or pergolide. Equine Vet J 2002;34:679-685.
    doi: 10.2746/042516402776250333pubmed: 12455838google scholar: lookup
  28. Irvine KL, Burt K, Hill AJ, Shaw S, Papasouliotis K. Initial analytic quality assessment and method comparison of an immunoassay for adrenocorticotropic hormone measurement in equine samples. Vet Clin Pathol 2016;45:154-163.
    doi: 10.1111/vcp.12326pubmed: 26756538google scholar: lookup
  29. Singh AK, Jiang Y, White T, Spassova D. Validation of nonradioactive chemiluminescent immunoassay methods for the analysis of thyroxine and cortisol in blood samples obtained from dogs, cats, and horses. J Vet Diagn Invest 1997;9:261-268.
    doi: 10.1177/104063879700900307pubmed: 9249165google scholar: lookup
  30. Hart KA, Bertin FR, Durham AE. Recommendations for the Diagnosis and Management of Pituitary Pars Intermedia Dysfunction (PPID). The Equine Endocrinology Group; 2023.
  31. Donaldson MT, McDonnell SM, Schanbacher BJ. 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;19:217-222.
    doi: 10.1111/j.1939-1676.2005.tb02685.xpubmed: 15822567google scholar: lookup
  32. Bamford NJ, Stewart AJ, El-Hage CM. Investigation of breed differences in plasma adrenocorticotropic hormone concentrations among healthy horses and ponies.. Vet J 2023;296-297:105995.
    doi: 10.1016/j.tvjl.2023.105995pubmed: 37207985google scholar: lookup
  33. Durham AE, Potier JF, Huber L. The effect of month and breed on plasma adrenocorticotropic hormone concentrations in equids.. Vet J 2022;286:105857.
    doi: 10.1016/j.tvjl.2022.105857pubmed: 35798232google scholar: lookup
  34. Bamford NJ, Stewart AJ, El-Hage CM. Influence of breed, season and pituitary pars intermedia dysfunction on plasma β-endorphin concentrations in horses and ponies.. In: Proceedings of the Global Equine Endocrine Symposium 2025:40.
  35. Gehlen H, Schwarz B, Bartmann C, Gernhardt J, Stöckle SD. Pituitary pars intermedia dysfunction and metabolic syndrome in donkeys.. Animals (Basel) 2020;10:2335.
    doi: 10.3390/ani10122335pmc: PMC7763272pubmed: 33302557google scholar: lookup
  36. Mendoza FJ, Toribio RE, Perez-Ecija A. Donkey internal medicine-part I: metabolic, endocrine, and alimentary tract disturbances.. J Equine Vet Sci 2018;65:66-74.
    doi: 10.1016/j.jevs.2018.02.001google scholar: lookup
  37. 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.
    doi: 10.1111/j.2042-3306.2012.00575.xpubmed: 22563728google scholar: lookup
  38. Herbst AC, Johnson MG, Gammons H. Development and evaluation of a muscle atrophy scoring system (MASS) for horses.. J Equine Vet Sci 2022;110:103771.
    doi: 10.1016/j.jevs.2021.103771pubmed: 34973594google scholar: lookup
  39. Ireland JL, McGowan CM, Clegg PD, Chandler KJ, Pinchbeck GL. A survey of health care and disease in geriatric horses aged 30 years or older.. Vet J 2012;192:57-64.
    doi: 10.1016/j.tvjl.2011.03.021pubmed: 21550271google scholar: lookup
  40. de Laat MA, Sillence MN, Reiche DB. Phenotypic, hormonal, and clinical characteristics of equine endocrinopathic laminitis.. J Vet Intern Med 2019;33:1456-1463.
    doi: 10.1111/jvim.15419pmc: PMC6524085pubmed: 30697823google scholar: lookup
  41. Frank N, Geor RJ, Bailey SR. Equine metabolic syndrome.. J Vet Intern Med 2010;24:467-475.
    doi: 10.1111/j.1939-1676.2010.0503.xpubmed: 20384947google scholar: lookup
  42. Li FI, Spence RJ, de Laat MA. Association between insulin dysregulation and adrenocorticotropic hormone in aged horses and ponies with no clinical signs of pituitary pars intermedia dysfunction.. Equine Vet J 2023;55:1003-1011.
    doi: 10.1111/evj.13925pubmed: 36641787google scholar: lookup
  43. Tadros EM, Frank N. Endocrine disorders and laminitis.. Equine Vet Educ 2013;25:152-162.
    doi: 10.1111/j.2042-3292.2011.00327.xgoogle scholar: lookup
  44. van der Kolk JH, Nachreiner RF, Schott HC, Refsal KR, Zanella AJ. Salivary and plasma concentration of cortisol in normal horses and horses with Cushing’s disease.. Equine Vet J 2001;33:211-213.
    doi: 10.1111/j.2042-3306.2001.tb00604.xpubmed: 11266074google scholar: lookup
  45. Durham AE, Clarke BR, Potier JFN, Hammarstrand R, Malone GL. Clinically and temporally specific diagnostic thresholds for plasma ACTH in the horse.. Equine Vet J 2021;53:250-260.
    doi: 10.1111/evj.13292pubmed: 32470177google scholar: lookup
  46. 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.. Endocrinology 1982;110:1430-1441.
    doi: 10.1210/endo-110-4-1430pubmed: 6277607google scholar: lookup
  47. Wilson MG, Nicholson WE, Holscher MA, Sherrell BJ, Mount CD, Orth DN. Proopiolipomelanocortin peptides in normal pituitary, pituitary tumor, and plasma of normal and Cushing’s horses.. Endocrinology 1982;110:941-954.
    doi: 10.1210/endo-110-3-941pubmed: 6276164google scholar: lookup
  48. Horowitz ML, Neal L, Watson JL. Characteristics of plasma adrenocorticotropin, β-endorphin and α-melanocyte stimulating hormone as diagnostic tests for pituitary pars intermedia dysfunction in the horse.. J Vet Intern Med 2003;17:386.
    doi: 10.1111/j.1939-1676.2003.tb02465.xgoogle scholar: lookup
  49. Bamford NJ, Galinelli N, Erdody M. Effect of thyrotropin releasing hormone and pergolide on plasma β-endorphin concentrations in horses and ponies.. J Vet Intern Med 2023;37:2643.
    doi: 10.1111/jvim.16902google scholar: lookup
  50. 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;25:1431-1438.
    doi: 10.1111/j.1939-1676.2011.00810.xpubmed: 22092639google scholar: lookup
  51. Orth DN, Nicholson WE. Bioactive and immunoreactive adrenocorticotropin in normal equine pituitary and in pituitary tumors of horses with Cushing’s disease.. Endocrinology 1982;111:559-563.
    doi: 10.1210/endo-111-2-559pubmed: 6284484google scholar: lookup
  52. Desjardins I, Mosca M, Pin D. Comparison of haircoat characteristics in equids affected with pituitary pars intermedia dysfunction and aged controls.. J Vet Intern Med 2023;38:572.
    doi: 10.1111/jvim.16913google scholar: lookup
  53. Thane K, Uricchio C, Frank N. Effect of early or late blood sampling on thyrotropin releasing hormone stimulation test results in horses.. J Vet Intern Med 2022;36:770-777.
    doi: 10.1111/jvim.16362pmc: PMC8965261pubmed: 35049089google scholar: lookup

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