Journal of veterinary internal medicine2019; 33(5); 2272-2279; doi: 10.1111/jvim.15601

Effect of thyrotropin-releasing hormone stimulation testing on the oral sugar test in horses when performed as a combined protocol.

Abstract: The use of parallel dynamic tests to identify insulin dysregulation (ID) and pituitary pars intermedia dysfunction (PPID) in horses could have better diagnostic utility than measuring baseline hormone concentrations, if the tests do not alter diagnostic interpretation of one another. Objective: Performing a thyrotropin-releasing hormone (TRH) stimulation test before an oral sugar test (OST) would not affect results of OST. Methods: Twenty-six healthy university-owned horses. Methods: A prospective randomized placebo-controlled, crossover design was used to evaluate 3 OST protocols: OST alone, TRH followed by OST (TRH + OST), and placebo followed by OST (placebo + OST). Agreement for plasma insulin concentrations and diagnostic interpretation were assessed with Bland-Altman and logistic regression analyses, respectively. Results: Bland-Altman analysis of TRH + OST versus OST alone showed good agreement between testing protocols, with bias ± SD for insulin concentrations at baseline 0.4 ± 4.7 μIU/mL (95% limits of agreement [LOA], -8.8 to 9.7), 60 minute -0.5 ± 22.6 μIU/mL (95% LOA, -44.7 to 43.8), and 90 minute 1.9 ± 20.6 μIU/mL (95% LOA, -38.5 to 42.4) after OST, similar to placebo + OST versus OST alone. Diagnostic interpretation (positive/negative) was not different between protocols (TRH + OST versus OST alone [P = .78], placebo + OST versus OST alone [P = .77], or TRH + OST versus placebo + OST [P = .57]). Conclusions: Concurrent testing for PPID and ID with a TRH stimulation test before an OST is an acceptable diagnostic tool for investigation of endocrinopathies in horses and allows accurate testing to be performed efficiently in 1 visit.
Publication Date: 2019-08-20 PubMed ID: 31432575PubMed Central: PMC6766522DOI: 10.1111/jvim.15601Google Scholar: Lookup
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  • Journal Article

Summary

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The research aimed to assess the impact of performing a thyrotropin-releasing hormone (TRH) stimulation test prior to an oral sugar test (OST) on identifying insulin dysregulation (ID) and pituitary pars intermedia dysfunction (PPID) in horses. Findings suggested that both tests could be conducted effectively together to identify these disorders without interference in the results.

Methodology

  • The research used a prospective randomized placebo-controlled, crossover design.
  • Twenty-six healthy university-owned horses were involved in the study.
  • Three OST protocols were evaluated: OST alone, TRH followed by OST (TRH + OST), and a placebo followed by OST (placebo + OST).
  • The agreement for plasma insulin concentrations and diagnostic interpretation was assessed using Bland-Altman and logistic regression analyses.

Results

  • The Bland-Altman analysis comparing TRH + OST and OST alone showed good agreement, indicating similar insulin concentrations between the two testing procedures.
  • Comparisons of TRH + OST with OST alone were nearly identical to that of placebo + OST with OST alone.
  • The diagnostic interpretations (positive or negative results) didn’t significantly differ across the different protocols.
  • Results demonstrated strong concurrence across all testing protocols, suggesting the co-administration of TRH and OST tests doesn’t affect the reliability of results.

Conclusions

  • The TRH stimulation test can be performed before an OST without altering the test results, demonstrating appropriate diagnostic tools for testing hormone dysregulation in horses.
  • Coupled testing allows accurate and efficient diagnosis of endocrinopathies in horses in a single visit, enhancing practicality and convenience for veterinarians and horse owners.

Cite This Article

APA
Hodge E, Kowalski A, Torcivia C, Lindborg S, Stefanovski D, Hart K, Frank N, van Eps A. (2019). Effect of thyrotropin-releasing hormone stimulation testing on the oral sugar test in horses when performed as a combined protocol. J Vet Intern Med, 33(5), 2272-2279. https://doi.org/10.1111/jvim.15601

Publication

ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 33
Issue: 5
Pages: 2272-2279

Researcher Affiliations

Hodge, Elizabeth
  • School of Veterinary Medicine, University of Pennsylvania, Clinical Studies-New Bolton Center, Kennett Square, Chester, Pennsylvania.
Kowalski, Alycia
  • School of Veterinary Medicine, University of Pennsylvania, Clinical Studies-New Bolton Center, Kennett Square, Chester, Pennsylvania.
Torcivia, Catherine
  • School of Veterinary Medicine, University of Pennsylvania, Clinical Studies-New Bolton Center, Kennett Square, Chester, Pennsylvania.
Lindborg, Sue
  • School of Veterinary Medicine, University of Pennsylvania, Clinical Studies-New Bolton Center, Kennett Square, Chester, Pennsylvania.
Stefanovski, Darko
  • School of Veterinary Medicine, University of Pennsylvania, Clinical Studies-New Bolton Center, Kennett Square, Chester, Pennsylvania.
Hart, Kelsey
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia.
Frank, Nicholas
  • Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts.
van Eps, Andrew
  • School of Veterinary Medicine, University of Pennsylvania, Clinical Studies-New Bolton Center, Kennett Square, Chester, Pennsylvania.

MeSH Terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Cross-Over Studies
  • Female
  • Glucose Tolerance Test / veterinary
  • Horses / blood
  • Horses / metabolism
  • Insulin / blood
  • Male
  • Pituitary Gland, Intermediate / physiology
  • Prospective Studies
  • Random Allocation
  • Thyrotropin-Releasing Hormone / pharmacology

Grant Funding

  • Raymond Firestone Trust Research Grant
  • Tamworth Research Fund

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 45 references
  1. Patterson-Kane JC, Karikoski NP, McGowan CM. Paradigm shifts in understanding equine laminitis.. Vet J 2018 Jan;231:33-40.
    doi: 10.1016/j.tvjl.2017.11.011pubmed: 29429485google scholar: lookup
  2. Morgan R, Keen J, McGowan C. Equine metabolic syndrome.. Vet Rec 2015 Aug 15;177(7):173-9.
    pmc: PMC4552932pubmed: 26273009doi: 10.1136/vr.103226google scholar: lookup
  3. Karikoski NP, Horn I, McGowan TW, McGowan CM. The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital.. Domest Anim Endocrinol 2011 Oct;41(3):111-7.
  4. Donaldson MT, Jorgensen AJ, Beech J. Evaluation of suspected pituitary pars intermedia dysfunction in horses with laminitis.. J Am Vet Med Assoc 2004 Apr 1;224(7):1123-7.
    doi: 10.2460/javma.2004.224.1123pubmed: 15074858google scholar: lookup
  5. Tadros EM, Fowlie JG, Refsal KR, Marteniuk J, Schott HC 2nd. Association between hyperinsulinaemia and laminitis severity at the time of pituitary pars intermedia dysfunction diagnosis.. Equine Vet J 2019 Jan;51(1):52-56.
    doi: 10.1111/evj.12963pubmed: 29761574google scholar: lookup
  6. 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 Nov;34(7):679-85.
    doi: 10.2746/042516402776250333pubmed: 12455838google scholar: lookup
  7. 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 Jan;45(1):74-9.
  8. 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 Jul;44(4):440-3.
  9. Rendle DI, Duz M, Beech J, Parkin T, Durham AE. Investigation of single and paired measurements of adrenocorticotropic hormone for the diagnosis of pituitary pars intermedia dysfunction in horses.. J Vet Intern Med 2015 Jan;29(1):355-61.
    doi: 10.1111/jvim.12489pmc: PMC4858100pubmed: 25312676google scholar: lookup
  10. Mc Gowan TW, Pinchbeck GP, Mc Gowan CM. Evaluation of basal plasma u03b1-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 Jan;45(1):66-73.
  11. 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 Aug 1;231(3):417-26.
    doi: 10.2460/javma.231.3.417pubmed: 17669045google scholar: lookup
  12. Carter RA, Treiber KH, Geor RJ, Douglass L, Harris PA. Prediction of incipient pasture-associated laminitis from hyperinsulinaemia, hyperleptinaemia and generalised and localised obesity in a cohort of ponies.. Equine Vet J 2009 Feb;41(2):171-8.
    doi: 10.2746/042516408X342975pubmed: 19418747google scholar: lookup
  13. Asplin KE, Sillence MN, Pollitt CC, McGowan CM. Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies.. Vet J 2007 Nov;174(3):530-5.
    doi: 10.1016/j.tvjl.2007.07.003pubmed: 17719811google scholar: lookup
  14. de Laat MA, McGowan CM, Sillence MN, Pollitt CC. Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses.. Equine Vet J 2010 Mar;42(2):129-35.
    doi: 10.2746/042516409X475779pubmed: 20156248google scholar: lookup
  15. McGowan CM, Frost R, Pfeiffer DU, Neiger R. Serum insulin concentrations in horses with equine Cushing's syndrome: response to a cortisol inhibitor and prognostic value.. Equine Vet J 2004 Apr;36(3):295-8.
    doi: 10.2746/0425164044877288pubmed: 15147141google scholar: lookup
  16. de Laat MA, McGree JM, Sillence MN. Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation.. Am J Physiol Endocrinol Metab 2016 Jan 1;310(1):E61-72.
    doi: 10.1152/ajpendo.00362.2015pubmed: 26530154google scholar: lookup
  17. Schuver A, Frank N, Chameroy KA, Elliott SB. Assessment of insulin and glucose dynamics by using an oral sugar test in horses. J Equine Vet Sci. 2014;34(4):465u2010470. 10.1016/j.jevs.2013.09.006.
  18. Dunbar LK, Mielnicki KA, Dembek KA, Toribio RE, Burns TA. Evaluation of Four Diagnostic Tests for Insulin Dysregulation in Adult Light-Breed Horses.. J Vet Intern Med 2016 May;30(3):885-91.
    doi: 10.1111/jvim.13934pmc: PMC4913564pubmed: 27013065google scholar: lookup
  19. Restifo MM, Frank N, Hermida P, Sanchez-Londou00f1o A. Effects of withholding feed on thyrotropin-releasing hormone stimulation test results and effects of combined testing on oral sugar test and thyrotropin-releasing hormone stimulation test results in horses.. Am J Vet Res 2016 Jul;77(7):738-48.
    doi: 10.2460/ajvr.77.7.738pubmed: 27347827google scholar: lookup
  20. Frank N, Walsh DM. Repeatability of Oral Sugar Test Results, Glucagon-Like Peptide-1 Measurements, and Serum High-Molecular-Weight Adiponectin Concentrations in Horses.. J Vet Intern Med 2017 Jul;31(4):1178-1187.
    doi: 10.1111/jvim.14725pmc: PMC5508339pubmed: 28543933google scholar: lookup
  21. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares.. Equine Vet J 1983 Oct;15(4):371-2.
  22. Carter RA, Geor RJ, Burton Staniar W, Cubitt TA, Harris PA. Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies.. Vet J 2009 Feb;179(2):204-10.
    doi: 10.1016/j.tvjl.2008.02.029pubmed: 18440844google scholar: lookup
  23. Freestone JF, Wolfsheimer KJ, Kamerling SG, Church G, Hamra J, Bagwell C. Exercise induced hormonal and metabolic changes in Thoroughbred horses: effects of conditioning and acepromazine.. Equine Vet J 1991 May;23(3):219-23.
  24. Knowles EJ, Harris PA, Elliott J, Menzies-Gow NJ. Use of the oral sugar test in ponies when performed with or without prior fasting.. Equine Vet J 2017 Jul;49(4):519-524.
    doi: 10.1111/evj.12607pubmed: 27381044google scholar: lookup
  25. Frank N, Geor R. Current best practice in clinical management of equine endocrine patients. Equine Vet Educ. 2014;26:6u20109. 10.1111/eve.12130.
    doi: 10.1111/eve.12130google scholar: lookup
  26. Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K. ECEIM consensus statement on equine metabolic syndrome.. J Vet Intern Med 2019 Mar;33(2):335-349.
    doi: 10.1111/jvim.15423pmc: PMC6430910pubmed: 30724412google scholar: lookup
  27. Smith S, Harris PA, Menzies-Gow NJ. Comparison of the in-feed glucose test and the oral sugar test.. Equine Vet J 2016 Mar;48(2):224-7.
    doi: 10.1111/evj.12413pubmed: 25582152google scholar: lookup
  28. Bertin FR, de Laat MA. The diagnosis of equine insulin dysregulation.. Equine Vet J 2017 Sep;49(5):570-576.
    doi: 10.1111/evj.12703pubmed: 28543410google scholar: lookup
  29. Frank N, Geor RJ, Bailey SR, Durham AE, Johnson PJ. Equine metabolic syndrome.. J Vet Intern Med 2010 May-Jun;24(3):467-75.
  30. Ikegami K, Yoshimura T. The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of TSH's unexpected role using animal models.. Best Pract Res Clin Endocrinol Metab 2017 Oct;31(5):475-485.
    doi: 10.1016/j.beem.2017.09.002pubmed: 29223282google scholar: lookup
  31. Funk RA, Stewart AJ, Wooldridge AA, Kwessi E, Kemppainen RJ, Behrend EN, Zhong Q, Johnson AK. Seasonal changes in plasma adrenocorticotropic hormone and u03b1-melanocyte-stimulating hormone in response to thyrotropin-releasing hormone in normal, aged horses.. J Vet Intern Med 2011 May-Jun;25(3):579-85.
  32. Rendle DI, Litchfield E, Heller J, Hughes KJ. Investigation of rhythms of secretion and repeatability of plasma adrenocorticotropic hormone concentrations in healthy horses and horses with pituitary pars intermedia dysfunction.. Equine Vet J 2014 Jan;46(1):113-7.
    doi: 10.1111/evj.12114pubmed: 23742059google scholar: lookup
  33. Beech J, Boston RC, McFarlane D, Lindborg S. Evaluation of plasma ACTH, alpha-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 Sep 15;235(6):715-22.
    doi: 10.2460/javma.235.6.715pubmed: 19751169google scholar: lookup
  34. Diez de Castro E, Lopez I, Cortes B, Pineda C, Garfia B, Aguilera-Tejero E. Influence of feeding status, time of the day, and season on baseline adrenocorticotropic hormone and the response to thyrotropin releasing hormone-stimulation test in healthy horses.. Domest Anim Endocrinol 2014 Jul;48:77-83.
  35. 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 Sep;31(5):1533-1540.
    doi: 10.1111/jvim.14782pmc: PMC5598888pubmed: 28661009google scholar: lookup
  36. Horn R, Bamford NJ, Afonso T, Sutherland M, Buckerfield J, Tan RHH, Secombe CJ, Stewart AJ, Bertin FR. Factors associated with survival, laminitis and insulin dysregulation in horses diagnosed with equine pituitary pars intermedia dysfunction.. Equine Vet J 2019 Jul;51(4):440-445.
    doi: 10.1111/evj.13041pubmed: 30417404google scholar: lookup
  37. Bamford NJ, Potter SJ, Baskerville CL, Harris PA, Bailey SR. Effect of increased adiposity on insulin sensitivity and adipokine concentrations in different equine breeds adapted to cereal-rich or fat-rich meals.. Vet J 2016 Aug;214:14-20.
    doi: 10.1016/j.tvjl.2016.02.002pubmed: 27387720google scholar: lookup
  38. Eiler H, Frank N, Andrews FM, Oliver JW, Fecteau KA. Physiologic assessment of blood glucose homeostasis via combined intravenous glucose and insulin testing in horses.. Am J Vet Res 2005 Sep;66(9):1598-604.
    doi: 10.2460/ajvr.2005.66.1598pubmed: 16261835google scholar: lookup
  39. Funk RA, Wooldridge AA, Stewart AJ, Behrend EN, Kemppainen RJ, Zhong Q, Johnson AK. Seasonal changes in the combined glucose-insulin tolerance test in normal aged horses.. J Vet Intern Med 2012 Jul-Aug;26(4):1035-41.
  40. Treiber KH, Kronfeld DS, Geor RJ. Insulin resistance in equids: possible role in laminitis.. J Nutr 2006 Jul;136(7 Suppl):2094S-2098S.
    doi: 10.1093/jn/136.7.2094Spubmed: 16772509google scholar: lookup
  41. Tiley HA, Geor RJ, McCutcheon LJ. Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses.. Am J Vet Res 2007 Jul;68(7):753-9.
    doi: 10.2460/ajvr.68.7.753pubmed: 17605611google scholar: lookup
  42. Geor RJ, Hinchcliff KW, McCutcheon LJ, Sams RA. Epinephrine inhibits exogenous glucose utilization in exercising horses.. J Appl Physiol (1985) 2000 May;88(5):1777-90.
    doi: 10.1152/jappl.2000.88.5.1777pubmed: 10797142google scholar: lookup
  43. Forhead AJ, Smart D, Smith RF, Dobson H. Transport-induced stress responses in fed and fasted donkeys.. Res Vet Sci 1995 Mar;58(2):144-51.
    doi: 10.1016/0034-5288(95)90068-3pubmed: 7761693google scholar: lookup
  44. Bertin FR, Taylor SD, Bianco AW, Sojka-Kritchevsky JE. The Effect of Fasting Duration on Baseline Blood Glucose Concentration, Blood Insulin Concentration, Glucose/Insulin Ratio, Oral Sugar Test, and Insulin Response Test Results in Horses.. J Vet Intern Med 2016 Sep;30(5):1726-1731.
    doi: 10.1111/jvim.14529pmc: PMC5032872pubmed: 27481572google scholar: lookup
  45. Unsal H, Cotelioglu U. The effects of food restriction on some biochemical parameters and certain bacterial groups in the cecum in Sprague Dawley rats. Microb Ecol Heal Dis. 2007;19:17u201024.

Citations

This article has been cited 2 times.
  1. Stefanovski D, Robinson MA, Van Eps A. Effect of a GLP-1 mimetic on the insulin response to oral sugar testing in horses.. BMC Vet Res 2022 Jul 29;18(1):294.
    doi: 10.1186/s12917-022-03394-2pubmed: 35906619google scholar: lookup
  2. 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 Mar;36(2):770-777.
    doi: 10.1111/jvim.16362pubmed: 35049089google scholar: lookup