FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of veterinary internal medicine2023; 37(1); 292-301; doi: 10.1111/jvim.16604

The hypothalamic-pituitary-adrenal axis response to ovine corticotropin-releasing-hormone stimulation tests in healthy and hospitalized foals.

Abstract: The hypothalamic-pituitary-adrenocortical axis (HPAA) response to sepsis can be impaired in critical illness. Corticotropin-releasing hormone (CRH) stimulation test might assess HPAA function in foals. Objective: To evaluate plasma cortisol, ACTH, arginine vasopressin (AVP), and endogenous CRH (eCRH) response to different doses of ovine CRH (oCRH). Methods: Healthy (n = 14) and hospitalized (n = 15) foals <7 days of age. Methods: In this prospective randomized study, oCRH (0.1, 0.3, and 1 μg/kg) was administered intravenously and blood samples were collected before, 15, 30, 60, and 90 minutes after administration of oCRH to determine plasma hormone concentrations. The hormonal response was evaluated as the difference (Delta; μg/dL or pg/mL) or percent change between baseline hormone concentration and each time point after oCRH stimulation. Results: Cortisol concentrations increased from baseline at 15 minutes with 0.1 and 0.3 μg/kg and at 30 and 60 minutes from baseline with 1 μg/kg oCRH (P < .05) in healthy and hospitalized foals. ACTH concentrations increased from baseline at 15 minutes with 0.1 μg/kg and at 30 minutes with 1 μg/kg oCRH (P < .05) in hospitalized foals. Delta cortisol 0 - 30, ACTH 0 - 30, and eCRH 0 - 30 was higher for the 1 μg/kg compared with 0.1 μg/kg oCRH in healthy foals (P < .05). Delta ACTH 0 - 15 and eCRH 0 - 30 was higher for the 1 μg/kg compared with the lower doses of oCRH in hospitalized foals (P < .05). Conclusions: Cortisol, ACTH, and eCRH concentrations increased in response to administration of all doses of oCRH. One microgram per kilogram of oCRH appears to be optimal for the assessment of HPAA in healthy and hospitalized foals.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Get Full Text
Publication Date: 2023-01-18 PubMed ID: 36651191PubMed Central: PMC9889673DOI: 10.1111/jvim.16604Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Randomized Controlled Trial
  • Veterinary
  • 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.

This research investigates how the hypothalamic-pituitary-adrenocortical (HPAA) axis in healthy and hospitalized foals reacts to injections of different doses of ovine corticotropin-releasing hormone (oCRH). The research found that injecting 1 microgram per kilogram of oCRH seemed to be optimal for investigating the HPAA response in young foals, whether healthy or ill.

Objective and Methodology

  • The researchers aimed to evaluate plasma cortisol, ACTH, arginine vasopressin (AVP), and endogenous CRH (eCRH) response to different doses of ovine CRH (oCRH) in healthy and hospitalized foals.
  • This was a prospective randomized study involving 14 healthy and 15 hospitalized foals less than 7 days old.
  • Different doses of oCRH (0.1, 0.3, and 1 μg/kg) were administered intravenously.
  • Blood samples were collected before administration and 15, 30, 60, and 90 minutes afterward to determine plasma hormone concentrations.
  • The hormonal response was evaluated as the difference (Delta) or percent change between the baseline hormone concentration and each time point after oCRH stimulation.

Results

  • The cortisol concentrations in both healthy and hospitalized foals increased from the baseline at 15 minutes with 0.1 and 0.3 μg/kg and at 30 and 60 minutes from baseline with 1 μg/kg oCRH.
  • ACTH concentrations increased from baseline at 15 minutes with 0.1 μg/kg and at 30 minutes with 1 μg/kg oCRH in hospitalized foals.
  • In healthy foals, Delta cortisol 0 – 30, ACTH 0 – 30, and eCRH 0 – 30 were higher for the 1 μg/kg dose compared to the 0.1 μg/kg oCRH dose.
  • In hospitalized foals, Delta ACTH 0 – 15 and eCRH 0 – 30 were higher for the 1 μg/kg dose compared to the lower doses of oCRH.

Conclusions

  • Cortisol, ACTH, and eCRH concentrations increased in response to the administration of all doses of oCRH.
  • The study concludes that 1 μg/kg of oCRH appears to be the optimal dosage for assessing HPAA function in both healthy and hospitalized foals.

Cite This Article

APA
Johnson K, Peterson J, Kopper J, Dembek K. (2023). The hypothalamic-pituitary-adrenal axis response to ovine corticotropin-releasing-hormone stimulation tests in healthy and hospitalized foals. J Vet Intern Med, 37(1), 292-301. https://doi.org/10.1111/jvim.16604

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 37
Issue: 1
Pages: 292-301

Researcher Affiliations

Johnson, Katheryn
  • Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA.
Peterson, Jackie
  • Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA.
Kopper, Jamie
  • Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA.
Dembek, Katarzyna
  • Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.

MeSH Terms

  • Animals
  • Sheep
  • Horses
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone / pharmacology
  • Hydrocortisone
  • Hypothalamo-Hypophyseal System
  • Prospective Studies
  • Pituitary-Adrenal System

Grant Funding

  • Iowa State University

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 44 references
  1. Giguère S, Weber EJ, Sanchez LC. Factors associated with outcome and gradual improvement in survival over time in 1065 equine neonates admitted to an intensive care unit.. Equine Vet J 2017 Jan;49(1):45-50.
    pubmed: 26538009doi: 10.1111/evj.12536google scholar: lookup
  2. Wong DM, Ruby RE, Dembek KA, Barr BS, Reuss SM, Magdesian KG, Olsen E, Burns T, Slovis NM, Wilkins PA. Evaluation of updated sepsis scoring systems and systemic inflammatory response syndrome criteria and their association with sepsis in equine neonates.. J Vet Intern Med 2018 May;32(3):1185-1193.
    pmc: PMC5980351pubmed: 29582480doi: 10.1111/jvim.15087google scholar: lookup
  3. Dembek KA, Onasch K, Hurcombe SD, MacGillivray KC, Slovis NM, Barr BS, Reed SM, Toribio RE. Renin-Angiotensin-aldosterone system and hypothalamic-pituitary-adrenal axis in hospitalized newborn foals.. J Vet Intern Med 2013 Mar-Apr;27(2):331-8.
    pubmed: 23398197doi: 10.1111/jvim.12043google scholar: lookup
  4. Corley KT, Donaldson LL, Furr MO. Arterial lactate concentration, hospital survival, sepsis and SIRS in critically ill neonatal foals.. Equine Vet J 2005 Jan;37(1):53-9.
    pubmed: 15651735doi: 10.2746/0425164054406856google scholar: lookup
  5. Hart KA, Slovis NM, Barton MH. Hypothalamic-pituitary-adrenal axis dysfunction in hospitalized neonatal foals.. J Vet Intern Med 2009 Jul-Aug;23(4):901-12.
    pubmed: 19496914doi: 10.1111/j.1939-1676.2009.0323.xgoogle scholar: lookup
  6. Hurcombe SD, Toribio RE, Slovis N, Kohn CW, Refsal K, Saville W, Mudge MC. Blood arginine vasopressin, adrenocorticotropin hormone, and cortisol concentrations at admission in septic and critically ill foals and their association with survival.. J Vet Intern Med 2008 May-Jun;22(3):639-47.
    pubmed: 18466247doi: 10.1111/j.1939-1676.2008.0090.xgoogle scholar: lookup
  7. Dembek KA, Johnson LM, Timko KJ, Minuto JS, Hart KA, Barr BS, Toribio RE. Multiple adrenocortical steroid response to administration of exogenous adrenocorticotropic hormone to hospitalized foals.. J Vet Intern Med 2019 Jul;33(4):1766-1774.
    pmc: PMC6639474pubmed: 31111575doi: 10.1111/jvim.15527google scholar: lookup
  8. Chrousos GP. Regulation and dysregulation of the hypothalamic-pituitary-adrenal axis. The corticotropin-releasing hormone perspective.. Endocrinol Metab Clin North Am 1992 Dec;21(4):833-58.
    pubmed: 1486878
  9. Hurcombe SD. Hypothalamic-pituitary gland axis function and dysfunction in horses.. Vet Clin North Am Equine Pract 2011 Apr;27(1):1-17.
    pubmed: 21392650doi: 10.1016/j.cveq.2010.12.006google scholar: lookup
  10. Hart KA, Ferguson DC, Heusner GL, Barton MH. Synthetic adrenocorticotropic hormone stimulation tests in healthy neonatal foals.. J Vet Intern Med 2007 Mar-Apr;21(2):314-21.
    pubmed: 17427394doi: 10.1892/0891-6640(2007)21[314:sahsti]2.0.co;2google scholar: lookup
  11. Hart KA, Barton MH. Adrenocortical insufficiency in horses and foals.. Vet Clin North Am Equine Pract 2011 Apr;27(1):19-34.
    pmc: PMC3073730pubmed: 21392651doi: 10.1016/j.cveq.2010.12.005google scholar: lookup
  12. Alexander SL, Irvine CH, Donald RA. Dynamics of the regulation of the hypothalamo-pituitary-adrenal (HPA) axis determined using a nonsurgical method for collecting pituitary venous blood from horses.. Front Neuroendocrinol 1996 Jan;17(1):1-50.
    pubmed: 8788568doi: 10.1006/frne.1996.0001google scholar: lookup
  13. Dembek KA, Timko KJ, Johnson LM, Hart KA, Barr BS, David B, Burns TA, Toribio RE. Steroids, steroid precursors, and neuroactive steroids in critically ill equine neonates.. Vet J 2017 Jul;225:42-49.
    pubmed: 28720298doi: 10.1016/j.tvjl.2017.05.009google scholar: lookup
  14. Couëtil LL, Hoffman AM. Adrenal insufficiency in a neonatal foal.. J Am Vet Med Assoc 1998 May 15;212(10):1594-6.
    pubmed: 9604031
  15. Gold JR, Divers TJ, Barton MH, Lamb SV, Place NJ, Mohammed HO, Bain FT. Plasma adrenocorticotropin, cortisol, and adrenocorticotropin/cortisol ratios in septic and normal-term foals.. J Vet Intern Med 2007 Jul-Aug;21(4):791-6.
    pubmed: 17708401doi: 10.1892/0891-6640(2007)21[791:pacacr]2.0.co;2google scholar: lookup
  16. Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga G, Bokhari F, Vogeser M. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.. Crit Care Med 2008 Jun;36(6):1937-49.
    pubmed: 18496365doi: 10.1097/CCM.0b013e31817603bagoogle scholar: lookup
  17. Marik PE, Zaloga GP. Adrenal insufficiency in the critically ill: a new look at an old problem.. Chest 2002 Nov;122(5):1784-96.
    pubmed: 12426284doi: 10.1378/chest.122.5.1784google scholar: lookup
  18. Weiss SL, Peters MJ, Alhazzani W, Agus MSD, Flori HR, Inwald DP, Nadel S, Schlapbach LJ, Tasker RC, Argent AC, Brierley J, Carcillo J, Carrol ED, Carroll CL, Cheifetz IM, Choong K, Cies JJ, Cruz AT, De Luca D, Deep A, Faust SN, De Oliveira CF, Hall MW, Ishimine P, Javouhey E, Joosten KFM, Joshi P, Karam O, Kneyber MCJ, Lemson J, MacLaren G, Mehta NM, Møller MH, Newth CJL, Nguyen TC, Nishisaki A, Nunnally ME, Parker MM, Paul RM, Randolph AG, Ranjit S, Romer LH, Scott HF, Tume LN, Verger JT, Williams EA, Wolf J, Wong HR, Zimmerman JJ, Kissoon N, Tissieres P. Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children.. Pediatr Crit Care Med 2020 Feb;21(2):e52-e106.
    pubmed: 32032273doi: 10.1097/PCC.0000000000002198google scholar: lookup
  19. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.. Intensive Care Med 2017 Mar;43(3):304-377.
    pubmed: 28101605doi: 10.1007/s00134-017-4683-6google scholar: lookup
  20. Wong DM, Vo DT, Alcott CJ, Peterson AD, Sponseller BA, Hsu WH. Baseline plasma cortisol and ACTH concentrations and response to low-dose ACTH stimulation testing in ill foals.. J Am Vet Med Assoc 2009 Jan 1;234(1):126-32.
    pubmed: 19119977doi: 10.2460/javma.234.1.126google scholar: lookup
  21. Reijerkerk EP, Visser EK, van Reenen CG, van der Kolk JH. Effects of various doses of ovine corticotrophin-releasing hormone on plasma and saliva cortisol concentrations in horses.. Am J Vet Res 2009 Mar;70(3):361-4.
    pubmed: 19254148doi: 10.2460/ajvr.70.3.361google scholar: lookup
  22. Orth DN, Jackson RV, DeCherney GS, DeBold CR, Alexander AN, Island DP, Rivier J, Rivier C, Spiess J, Vale W. Effect of synthetic ovine corticotropin-releasing factor. Dose response of plasma adrenocorticotropin and cortisol.. J Clin Invest 1983 Mar;71(3):587-95.
    pmc: PMC436907pubmed: 6298280doi: 10.1172/jci110804google scholar: lookup
  23. Veissier I, van Reenen CG, Andanson S, Leushuis IE. Adrenocorticotropic hormone and cortisol in calves after corticotropin-releasing hormone.. J Anim Sci 1999 Aug;77(8):2047-53.
    pubmed: 10461980doi: 10.2527/1999.7782047xgoogle scholar: lookup
  24. Tanaka T, Hibi I, Shimizu N, Imura H, Tanaka K, Fukata J, Fujieda K, Ichimura T, Kuribayashi T, Ito K. Evaluation of hypothalamo-pituitary-adrenocortical function in children by human corticotropin-releasing hormone (MCI-028) test.. Endocr J 1993 Oct;40(5):581-9.
    pubmed: 7951524doi: 10.1507/endocrj.40.581google scholar: lookup
  25. Brewer BD, Koterba AM. Development of a scoring system for the early diagnosis of equine neonatal sepsis.. Equine Vet J 1988 Jan;20(1):18-22.
    pubmed: 3366100doi: 10.1111/j.2042-3306.1988.tb01445.xgoogle scholar: lookup
  26. Kinsella HM, Hostnik LD, Rings LM, Swink JM, Burns TA, Toribio RE. Glucagon, insulin, adrenocorticotropic hormone, and cortisol in response to carbohydrates and fasting in healthy neonatal foals.. J Vet Intern Med 2021 Jan;35(1):550-559.
    pmc: PMC7848351pubmed: 33415818doi: 10.1111/jvim.16024google scholar: lookup
  27. Müller V, Toribio RE, Dembek K, Moraes BSS, Mousquer MA, Curcio BR, Nogueira CEW. Serum cortisol and thyroid hormone concentrations and survival in foals born from mares with experimentally induced ascending placentitis.. J Vet Intern Med 2020 May;34(3):1332-1338.
    pmc: PMC7255665pubmed: 32339347doi: 10.1111/jvim.15758google scholar: lookup
  28. Zhang SH, Hennessy DP, Cranwell PD. Pituitary and adrenocortical responses to corticotropin-releasing factor in pigs.. Am J Vet Res 1990 Jul;51(7):1021-5.
    pubmed: 2167618
  29. Silver M, Ousey JC, Dudan FE, Fowden AL, Knox J, Cash RS, Rossdale PD. Studies on equine prematurity 2: Post natal adrenocortical activity in relation to plasma adrenocorticotrophic hormone and catecholamine levels in term and premature foals.. Equine Vet J 1984 Jul;16(4):278-86.
    pubmed: 6090119doi: 10.1111/j.2042-3306.1984.tb01927.xgoogle scholar: lookup
  30. Silver M, Fowden AL. Prepartum adrenocortical maturation in the fetal foal: responses to ACTH.. J Endocrinol 1994 Sep;142(3):417-25.
    pubmed: 7964292doi: 10.1677/joe.0.1420417google scholar: lookup
  31. Fowden AL, Forhead AJ, Ousey JC. Endocrine adaptations in the foal over the perinatal period.. Equine Vet J Suppl 2012 Feb;(41):130-9.
    pubmed: 22594041doi: 10.1111/j.2042-3306.2011.00505.xgoogle scholar: lookup
  32. Hart KA, Dirikolu L, Ferguson DC, Norton NA, Barton MH. Daily endogenous cortisol production and hydrocortisone pharmacokinetics in adult horses and neonatal foals.. Am J Vet Res 2012 Jan;73(1):68-75.
    pubmed: 22204290doi: 10.2460/ajvr.73.1.68google scholar: lookup
  33. Pradier P, Davicco MJ, Safwate A, Tournaire C, Dalle M, Barlet JP, Delost P. Plasma adrenocorticotrophin, cortisol and aldosterone responses to ovine corticotrophin-releasing factor and vasopressin in sheep.. Acta Endocrinol (Copenh) 1986 Jan;111(1):93-100.
    pubmed: 3004095doi: 10.1530/acta.0.1110093google scholar: lookup
  34. Wood CE, Cudd TA. Development of the hypothalamus-pituitary-adrenal axis of the equine fetus: a comparative review.. Equine Vet J Suppl 1997 Jun;(24):74-82.
    pubmed: 9355806doi: 10.1111/j.2042-3306.1997.tb05082.xgoogle scholar: lookup
  35. Wong DM, Vo DT, Alcott CJ, Stewart AJ, Peterson AD, Sponseller BA, Hsu WH. Adrenocorticotropic hormone stimulation tests in healthy foals from birth to 12 weeks of age.. Can J Vet Res 2009 Jan;73(1):65-72.
    pmc: PMC2613599pubmed: 19337398
  36. Hackett ES, Lunn DP, Ferris RA, Horohov DW, Lappin MR, McCue PM. Detection of bacteraemia and host response in healthy neonatal foals.. Equine Vet J 2015 Jul;47(4):405-9.
    pubmed: 24917427doi: 10.1111/evj.12307google scholar: lookup
  37. Livesey JH, Donald RA, Irvine CH, Redekopp C, Alexander SL. The effects of cortisol, vasopressin (AVP), and corticotropin-releasing factor administration on pulsatile adrenocorticotropin, alpha-melanocyte-stimulating hormone, and AVP secretion in the pituitary venous effluent of the horse.. Endocrinology 1988 Aug;123(2):713-20.
    pubmed: 2840266doi: 10.1210/endo-123-2-713google scholar: lookup
  38. Ross JL, Schulte HM, Gallucci WT, Cutler GB Jr, Loriaux DL, Chrousos GP. Ovine corticotropin-releasing hormone stimulation test in normal children.. J Clin Endocrinol Metab 1986 Feb;62(2):390-2.
    pubmed: 3001126doi: 10.1210/jcem-62-2-390google scholar: lookup
  39. Ng PC, Wong GW, Lam CW, Lee CH, Wong MY, Fok TF, Wong W, Chan DC. The pituitary-adrenal responses to exogenous human corticotropin-releasing hormone in preterm, very low birth weight infants.. J Clin Endocrinol Metab 1997 Mar;82(3):797-9.
    pubmed: 9062485doi: 10.1210/jcem.82.3.3832google scholar: lookup
  40. Conaglen JV, Donald RA, Espiner EA, Livesey JH, Nicholls MG. The effect of ovine corticotropin-releasing factor on catecholamine, vasopressin, and aldosterone secretion in normal man.. J Clin Endocrinol Metab 1984 Mar;58(3):463-6.
    pubmed: 6319453doi: 10.1210/jcem-58-3-463google scholar: lookup
  41. Tsigos C, Chrousos GP. Physiology of the hypothalamic-pituitary-adrenal axis in health and dysregulation in psychiatric and autoimmune disorders.. Endocrinol Metab Clin North Am 1994 Sep;23(3):451-66.
    pubmed: 7805648
  42. Watts AG. Glucocorticoid regulation of peptide genes in neuroendocrine CRH neurons: a complexity beyond negative feedback.. Front Neuroendocrinol 2005 Oct-Dec;26(3-4):109-30.
    pubmed: 16289311doi: 10.1016/j.yfrne.2005.09.001google scholar: lookup
  43. Keenan DM, Alexander S, Irvine C, Veldhuis JD. Quantifying nonlinear interactions within the hypothalamo-pituitary-adrenal axis in the conscious horse.. Endocrinology 2009 Apr;150(4):1941-51.
    pmc: PMC2659283pubmed: 19022882doi: 10.1210/en.2008-1249google scholar: lookup
  44. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress.. J Psychosom Res 2002 Oct;53(4):865-71.
    pubmed: 12377295doi: 10.1016/s0022-3999(02)00429-4google scholar: lookup

Citations

This article has been cited 1 times.
  1. Elder E, Wong D, Johnson K, Robertson H, Marner M, Dembek K. Assessment of the hypothalamic-pituitary-adrenocortical axis function using a vasopressin stimulation test in neonatal foals. J Vet Intern Med 2023 Sep-Oct;37(5):1881-1888.
    doi: 10.1111/jvim.16808pubmed: 37432047google scholar: lookup
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.