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Home / Equine Research Bank / Equine Vet J / Association between insulin dysregulation and adrenocorticot...
Equine veterinary journal2023; doi: 10.1111/evj.13925

Association between insulin dysregulation and adrenocorticotropic hormone in aged horses and ponies with no clinical signs of pituitary pars intermedia dysfunction.

Abstract: High concentrations of adrenocorticotropic hormone (ACTH) are used as an indicator of pituitary pars intermedia dysfunction (PPID), but other factors that may influence ACTH need to be understood, if diagnostic reference ranges for ACTH are to be used with confidence. Insulin dysregulation (ID) could be one such factor, as insulin affects pituitary hormones in other species. Objective: To test the hypothesis that a relationship exists between high insulin and high ACTH in aged (>15-year-old) animals with no clinical signs of PPID. Methods: A cohort study. Methods: Thirteen horses and eleven ponies (17-25 years-old; mares and geldings) were clinically examined for signs of PPID in the spring (November 2020) and autumn (April 2021). On the same day, blood samples were taken before and 2 h after an oral glucose test (OGT). Concentrations of insulin, glucose, ACTH and cortisol were measured. Results: There was no association between ACTH and cortisol. However, there was a positive linear correlation between ACTH and post-OGT (insulin in the autumn (r = 0.427, p = 0.04). Two horses and six ponies had ACTH above the cut-off value for PPID diagnosis, and of these eight animals, six also had insulin concentrations above the cut-off value for ID. Conclusions: The cohort was small and thyrotropin-releasing hormone (TRH) stimulation tests were not performed. Conclusions: In autumn, high ACTH was associated with ID, when no clinical signs of PPID were present. Because ACTH is used in PPID diagnosis, further work is required to understand this interaction.
© 2023 Mars Horsecare UK and The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2023-01-15 PubMed ID: 36641787DOI: 10.1111/evj.13925Google Scholar: Lookup
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  • Journal Article

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 investigates a possible link between increased levels of insulin and ACTH (Adrenocorticotropic hormone), which are both significant for diagnosing pituitary pars intermedia dysfunction in horses and ponies over the age of 15.

Objective of Study

  • The primary aim of the study was to test the hypothesis that there’s a correlation between elevated insulin levels and ACTH in older horses with no visible signs of Pituitary Pars Intermedia Dysfunction (PPID).

    • Method

    • The study conducted was a cohort design, comprising of thirteen horses and eleven ponies aged between 17-25 years, which didn’t show any clinical symptoms of PPID.
    • The animals were evaluated for any signs of PPID in two different seasons: November 2020 (spring) and April 2021 (autumn).
    • On the same day of the clinical examination, blood samples were taken before and after an Oral Glucose Test.
    • The blood samples were then analyzed for their insulin, glucose, ACTH, and cortisol levels.

    Results

    • The findings showed no direct association between levels of ACTH and cortisol.
    • A positive correlation, however, was identified between ACTH and post-Oral Glucose Test insulin levels in autumn.
    • Among the studied horses and ponies, two horses and six ponies showed ACTH levels above the diagnostic threshold for PPID. Six of these eight animals also had elevated insulin levels, suggesting a possible presence of Insulin Dysregulation ID.

    Conclusion

    • Despite the limited sample size, and the lack of thyrotropin-releasing hormone stimulation tests, the study found an association between high ACTH and insulin dysregulation in autumn, even in the absence of clinical PPID symptoms.
    • The authors suggest that this correlation needs further investigation since ACTH levels are an integral part of the PPID diagnosis. An understanding of this correlation may interfere with the diagnostic confidence of ACTH reference ranges if insulin dysregulation can influence ACTH levels.

    Cite This Article

    APA
    Li FI, Spence RJ, de Laat MA, Harris PA, Sonntag J, Menzies-Gow NJ, Durham AE, Bailey SR, Sillence MN. (2023). Association between insulin dysregulation and adrenocorticotropic hormone in aged horses and ponies with no clinical signs of pituitary pars intermedia dysfunction. Equine Vet J. https://doi.org/10.1111/evj.13925

    Publication

    Equine veterinary journal
    ISSN: 2042-3306
    NlmUniqueID: 0173320
    Country: United States
    Language: English

    Researcher Affiliations

    Li, Fang I
    • School of Biology & Environmental Science, Science Faculty, Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
    Spence, Robert J
    • School of Biology & Environmental Science, Science Faculty, Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
    de Laat, Melody A
    • School of Biology & Environmental Science, Science Faculty, Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
    Harris, Patricia A
    • Equine Studies Group, Waltham Petcare Science Institute, Leicestershire, UK.
    Sonntag, Johanna
    • Boehringer Ingelheim Vetmedica GmbH, Ingelheim am Rhein, Germany.
    Menzies-Gow, Nicola J
    • The Royal Veterinary College, North Mymms, UK.
    Durham, Andy E
    • Liphook Equine Hospital, Liphook, UK.
    Bailey, Simon R
    • Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
    Sillence, Martin N
    • School of Biology & Environmental Science, Science Faculty, Queensland University of Technology (QUT), Brisbane, Queensland, Australia.

    Grant Funding

    • LP180101000 / Australian Research Council
    • Boehringer Ingelheim
    • Liphook Equine Hospital
    • Mars Petcare
    • Queensland University of Technology
    • Racing Analytical Services Limited
    • University of Melbourne

    References

    This article includes 40 references
    1. Bertin F-R, De Laat M. The diagnosis of equine insulin dysregulation.. Equine Vet J 2017;49(5):570-6.
    2. Horn R, Bamford N, Afonso T, Sutherland M, Buckerfield J, Tan RHH. Factors associated with survival, laminitis and insulin dysregulation in horses diagnosed with equine pituitary pars intermedia dysfunction.. Equine Vet J 2019;51(4):440-5.
    3. McGowan C, Frost R, Pfeiffer D, Neiger R. Serum insulin concentrations in horses with equine Cushing's syndrome: response to a cortisol inhibitor and prognostic value.. Equine Vet J 2004;36(3):295-8.
    4. McFarlane D. Equine pituitary pars intermedia dysfunction.. Vet Clin North Am Equine Pract 2011;27(1):93-113.
    5. Couëtil 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):1-6.
    6. Jacob S, Geor R, Weber P, Harris P, McCue M. Effect of dietary carbohydrates and time of year on ACTH and cortisol concentrations in adult and aged horses.. Domest Anim Endocrinol 2018;63:15-22.
    7. McGowan T, Pinchbeck G, McGowan C. Evaluation of basal plasma α-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(1):66-73.
    8. Beech J, Boston RC, McFarlane D, Lindborg S. Evaluation of plasma ACTH, α-melanocyte-stimulating hormone, and insulin concentrations during various photoperiods in clinically normal horses and ponies and those with pituitary pars intermedia dysfunction.. J Am Vet Med Assoc 2009;235(6):715-22.
    9. McFarlane D, Paradis M, Zimmel D, Sykes B, Brorsen BW, Sanchez A. The effect of geographic location, breed, and pituitary dysfunction on seasonal adrenocorticotropin and α-melanocyte-stimulating hormone plasma concentrations in horses.. J Vet Intern Med 2011;25(4):872-81.
    10. Horn R, Stewart AJ, Jackson KV, Dryburgh EL, Medina-Torres CE, Bertin FR. Clinical implications of using adrenocorticotropic hormone diagnostic cutoffs or reference intervals to diagnose pituitary pars intermedia dysfunction in mature horses.. J Vet Intern Med 2021;35(1):560-70.
    11. Karikoski N, Patterson-Kane J, Singer E, McFarlane D, McGowan C. Lamellar pathology in horses with pituitary pars intermedia dysfunction.. Equine Vet J 2016;48(4):472-8.
    12. McGowan T, Pinchbeck G, McGowan C. Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses.. Equine Vet J 2013;45(1):74-9.
    13. 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(4):1430-41.
    14. Wilson MG, Nicholso 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(3):941-54.
    15. Obici S, Feng Z, Tan J, Liu L, Karkanias G, Rossetti L. Central melanocortin receptors regulate insulin action.. J Clin Invest 2001;108(7):1079-85.
    16. Marshall J, Kapcala L, Manning L, McCullough A. Effect of corticotropin-like intermediate lobe peptide on pancreatic exocrine function in isolated rat pancreatic lobules.. J Clin Investig 1984;74(5):1886-9.
    17. Nash AI. Crosstalk between insulin and dopamine signaling: a basis for the metabolic effects of antipsychotic drugs.. J Chem Neuroanat 2017;83:59-68.
    18. Wahlqvist ML, Lee M-S, Hsu C-C, Chuang S-Y, Lee J-T, Tsai H-N. Metformin-inclusive sulfonylurea therapy reduces the risk of Parkinson's disease occurring with Type 2 diabetes in a Taiwanese population cohort.. Parkinsonism Relat Disord 2012;18(6):753-8.
    19. 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(6):1431-8.
    20. Henneke D, Potter G, Kreider J, Yeates B. Relationship between condition score, physical measurements and body fat percentage in mares.. Equine Vet J 1983;15(4):371-2.
    21. Carter RA, Geor RJ, Staniar WB, Cubitt TA, Harris PA. Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies.. Vet J 2009;179(2):204-10.
    22. de Laat M, Sillence M. The repeatability of an oral glucose test in ponies.. Equine Vet J 2017;49(2):238-43.
    23. Meier A, De Laat M, Reiche D, Pollitt CC, Walsh DM, McGree JM. The oral glucose test predicts laminitis risk in ponies fed a diet high in nonstructural carbohydrates.. Domest Anim Endocrinol 2018;63:1-9.
    24. Frank N, Bailey S, Bertin F, de Laat M, Durham A, Kritchevsky J. Recommendations for the diagnosis and treatment of equine metabolic syndrome (EMS).. Equine Endocrinology Group 2020.
    25. Secombe C, Tan R, Perara D, Byrne D, Watts S, Wearn J. The effect of geographic location on circannual adrenocorticotropic hormone plasma concentrations in horses in Australia.. J Vet Intern Med 2017;31(5):1533-40.
    26. Cordero M, Brorsen B, McFarlane D. Circadian and circannual rhythms of cortisol, ACTH, and α-melanocyte-stimulating hormone in healthy horses.. Domest Anim Endocrinol 2012;43(4):317-24.
    27. Karikoski NP, Box JR, Mykkänen AK, Kotiranta VV, Raekallio MR. Variation in insulin response to oral sugar test in a cohort of horses throughout the year and evaluation of risk factors for insulin dysregulation.. Equine Vet J 2021;54(5):905-13.
    28. de Laat MA, Sillence MN, Reiche DB. Phenotypic, hormonal, and clinical characteristics of equine endocrinopathic laminitis.. J Vet Intern Med 2019;33(3):1456-63.
    29. Bamford N, Harris P, Bailey S. Circannual variation in plasma adrenocorticotropic hormone concentrations and dexamethasone suppression test results in Standardbred horses, Andalusian horses and mixed-breed ponies.. Aust Vet J 2020;98(12):616-21.
    30. Mebel DM, Wong JC, Dong YJ, Borgland SL. Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake.. Eur J Neurosci 2012;36(3):2336-46.
    31. Thau L, Gandhi J, Sharma S. Physiology, cortisol.. StatPearls [Internet] Treasure Island, FL: StatPearls Publishing; 2021.
    32. Balon-Perin S, Kolanowski J, Berbinschi A, Franchimont P, Ketelslegers J-M. The effects of glucose ingestion and fasting on plasma immunoreactive beta-endorphin, adrenocorticotropic hormone and cortisol in obese subjects.. J Endocrinol Invest 1991;14(11):919-25.
    33. Enriori PJ, Chen W, Garcia-Rudaz MC, Grayson BE, Evans AE, Comstock SM. α-Melanocyte stimulating hormone promotes muscle glucose uptake via melanocortin 5 receptors.. Mol Metab 2016;5(10):807-22.
    34. Haritou S, Zylstra R, Ralli C, Turner S, Tortonese D. Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing's disease under natural photoperiod.. J Neuroendocrinol 2008;20(8):988-96.
    35. Argo C, Cox J, Gray J. Effect of oral melatonin treatment on the seasonal physiology of pony stallions.. J Reprod Fertil Suppl 1991;44:115-25.
    36. Hardeland R. Melatonin in aging and disease-multiple consequences of reduced secretion, options and limits of treatment.. Aging Dis 2012;3(2):194-225.
    37. Mäntele S, Otway DT, Middleton B, Bretschneider S, Wright J, Robertson MD. Daily rhythms of plasma melatonin, but not plasma leptin or leptin mRNA, vary between lean, obese and type 2 diabetic men.. PLoS One 2012;7(5):e37123.
    38. Zisapel N, Egozi Y, Laudon M. Inhibition by melatonin of dopamine release from rat hypothalamus in vitro: variations with sex and the estrous cycle.. Neuroendocrinology 1983;37(1):41-7.
    39. Misztal T, Romanowicz K, Barcikowski B. Natural and melatonin-stimulated changes in the circadian rhythm of prolactin secretion in the ewe during seasonal anestrus.. Neuroendocrinology 1997;66(5):360-7.
    40. Knowles E, Moreton-Clack M, Shaw S, Harris P, Elliott J, Menzies-Gow N. Plasma adrenocorticotropic hormone (ACTH) concentrations in ponies measured by two different assays suggests seasonal cross-reactivity or interference.. Equine Vet J 2018;50(5):672-7.

    Citations

    This article has been cited 4 times.
    1. Yao Z, Xu D, Xie Y, Jing H, Chen H. Nomogram prediction model for postoperative anterior pituitary dysfunction in patients with nonfunctioning pituitary adenomas: A multidimensional analysis and validation of Short-Term and Mid-to-Long-Term outcomes. Endocrine 2025 Dec 29;91(1):7.
      doi: 10.1007/s12020-025-04533-zpubmed: 41460549google scholar: lookup
    2. Davis EL, Wood AD, Potier JFN. Prevalence and Progression of Resting ACTH, Insulin and Adiponectin Values as Indicators of Suspected Endocrine Diseases in Sport Horses and Ponies Compared to Non-Sport Horses, Ponies and Donkeys. Animals (Basel) 2025 May 1;15(9).
      doi: 10.3390/ani15091316pubmed: 40362130google scholar: lookup
    3. Fouché N, Doras C, Schüpbach-Regula G, Scherer A, Freudenschuss B, Gerber V. Association Between Adrenocorticotropic Hormone Concentration and Clinical Signs of Pituitary Pars Intermedia Dysfunction in Swiss and Austrian Equids. J Vet Intern Med 2025 Mar-Apr;39(2):e70008.
      doi: 10.1111/jvim.70008pubmed: 40095750google scholar: lookup
    4. Menzies-Gow NJ, Knowles EJ. Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses. J Vet Pharmacol Ther 2025 Jan;48 Suppl 1(Suppl 1):31-40.
      doi: 10.1111/jvp.13470pubmed: 38984777google scholar: lookup
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