FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Vet Intern Med / Multiple adrenocortical steroid response to administration o...
Journal of veterinary internal medicine2019; 33(4); 1766-1774; doi: 10.1111/jvim.15527

Multiple adrenocortical steroid response to administration of exogenous adrenocorticotropic hormone to hospitalized foals.

Abstract: The hypothalamic-pituitary-adrenal axis regulates the response to sepsis-associated stress. Relative adrenal insufficiency or adrenocorticotropic hormone (ACTH):cortisol imbalance, defined as a poor cortisol response to administration of ACTH, is common and associated with death in hospitalized foals. However, information on other adrenal steroid response to ACTH stimulation in sick foals is minimal. Objective: To investigate the response of multiple adrenocortical steroids to administration of ACTH in foals. Methods: Hospitalized (n = 34) and healthy (n = 13) foals. Methods: In this prospective study, hospitalized foals were categorized into 2 groups using cluster analysis based on adrenal steroids response to ACTH stimulation: Cluster 1 (n = 11) and Cluster 2 (n = 23). After baseline blood sample collection, foals received 10 μg of ACTH with additional samples collected at 30 and 90 minutes after ACTH. Steroid and ACTH concentrations were determined by immunoassays. The area under the curve (AUC) and Delta were calculated for each hormone. Results: The AUC for cortisol, aldosterone, androstenedione, pregnenolone, 17α-OH-progesterone, and progesterone were higher in critically ill (Cluster 1) compared to healthy foals (P < .01). Delta for cortisol and 17α-OH-progesterone was lower in Cluster 1 (24%, 26.7%) and Cluster 2 (16%, 11.2%) compared to healthy foals (125%, 71%), respectively (P < .05). Foals that died had increased AUC for endogenous ACTH (269 versus 76.4 pg/mL/h, P < .05) accompanied by a low AUC for cortisol (5.5 versus 15.5 μg/dL/h, P < .05), suggesting adrenocortical dysfunction. Conclusions: The 17α-OH-progesterone response to administration of ACTH was a good predictor of disease severity and death in hospitalized foals.
© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Get Full Text
Publication Date: 2019-05-20 PubMed ID: 31111575PubMed Central: PMC6639474DOI: 10.1111/jvim.15527Google 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
  • 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 study examines how different adrenocortical steroids in foals (young horses) react to the administration of adrenocorticotropic hormone (ACTH), considering that the effectiveness of the cortisol response to ACTH has been associated with foals’ survival chances.

Research Objectives and Methods

  • The primary objective of this study was to assess how various adrenocortical steroids respond to ACTH administration in foals. This study is based on the role the hypothalamic-pituitary-adrenal axis plays in regulating the body’s response to sepsis-related stress.
  • The study was carried out on two groups of foals: a hospitalised group (34 foals) and a healthy group (13 foals). The hospitalised foals were further divided into two clusters based on their adrenal steroids’ response to ACTH stimulation.
  • Baseline blood samples were obtained from the foals before they were given 10 μg of ACTH. Further samples were taken 30 and 90 minutes after ACTH administration.
  • The researchers measured the concentrations of the steroid and ACTH through immunoassays. The area under the curve (AUC) and Delta (a measure of change) were calculated for each hormone.

Findings and Conclusions

  • Foals in critical health (Cluster 1) had higher AUC for cortisol, aldosterone, androstenedione, pregnenolone, 17α-OH-progesterone, and progesterone compared to the healthy group. This finding indicates higher levels of these hormones in response to stress in critically ill foals.
  • Critically ill foals (Cluster 1) and less critically ill foals (Cluster 2) had lower Delta measures for cortisol and 17α-OH-progesterone compared to the healthy group.
  • Foals that died had a high AUC for endogenous ACTH but a low AUC for cortisol, suggesting a dysfunction in the adrenal gland’s reaction to ACTH.
  • The study concludes that the response of 17α-OH-progesterone to ACTH can be a reliable indicator of disease severity, as well as a predictor of death in hospitalized foals.

Cite This Article

APA
Dembek KA, Johnson LM, Timko KJ, Minuto JS, Hart KA, Barr BS, Toribio RE. (2019). Multiple adrenocortical steroid response to administration of exogenous adrenocorticotropic hormone to hospitalized foals. J Vet Intern Med, 33(4), 1766-1774. https://doi.org/10.1111/jvim.15527

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 33
Issue: 4
Pages: 1766-1774

Researcher Affiliations

Dembek, Katarzyna A
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa.
Johnson, Lindsey M
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.
Timko, Kathryn J
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.
Minuto, Jillian S
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.
Hart, Kelsey A
  • Department of Large Animal Medicine, University of Georgia College of Veterinary Medicine, Athens, Georgia.
Barr, Bonnie S
  • Internal Medicine, Rood and Riddle Equine Hospital, Lexington, Kentucky.
Toribio, Ramiro E
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.

MeSH Terms

  • 17-alpha-Hydroxyprogesterone / blood
  • Adrenal Cortex Hormones / blood
  • Adrenocorticotropic Hormone / administration & dosage
  • Adrenocorticotropic Hormone / pharmacology
  • Animals
  • Animals, Newborn
  • Area Under Curve
  • Cluster Analysis
  • Critical Illness
  • Female
  • Horse Diseases / blood
  • Horse Diseases / drug therapy
  • Horse Diseases / mortality
  • Horses
  • Male
  • Prognosis
  • Prospective Studies
  • Sepsis / drug therapy
  • Sepsis / veterinary

Grant Funding

  • T35 OD010977 / NIH HHS
  • Grayson-Jockey Club Research Foundation
  • Fellowship Training Grant / Morris Animal Foundation

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 38 references
  1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.. Intensive Care Med 2013 Feb;39(2):165-228.
    pmc: PMC7095153pubmed: 23361625doi: 10.1007/s00134-012-2769-8google scholar: lookup
  2. 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
  3. 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
  4. 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
  5. 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
  6. Toribio RE. Endocrine dysregulation in critically ill foals and horses.. Vet Clin North Am Equine Pract 2011 Apr;27(1):35-47.
    pubmed: 21392652doi: 10.1016/j.cveq.2010.12.011google scholar: lookup
  7. Annane D. Adrenal insufficiency in sepsis.. Curr Pharm Des 2008;14(19):1882-6.
    pubmed: 18691099doi: 10.2174/138161208784980626google scholar: lookup
  8. 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
  9. Boonen E, Vervenne H, Meersseman P, Andrew R, Mortier L, Declercq PE, Vanwijngaerden YM, Spriet I, Wouters PJ, Vander Perre S, Langouche L, Vanhorebeek I, Walker BR, Van den Berghe G. Reduced cortisol metabolism during critical illness.. N Engl J Med 2013 Apr 18;368(16):1477-88.
    pmc: PMC4413428pubmed: 23506003doi: 10.1056/nejmoa1214969google scholar: lookup
  10. Boonen E, Bornstein SR, Van den Berghe G. New insights into the controversy of adrenal function during critical illness.. Lancet Diabetes Endocrinol 2015 Oct;3(10):805-15.
    pubmed: 26071883doi: 10.1016/s2213-8587(15)00224-7google scholar: lookup
  11. 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
  12. Peeters B, Boonen E, Langouche L, Van den Berghe G. The HPA axis response to critical illness: New study results with diagnostic and therapeutic implications.. Mol Cell Endocrinol 2015 Jun 15;408:235-40.
    pubmed: 25462585doi: 10.1016/j.mce.2014.11.012google scholar: lookup
  13. 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
  14. Crowley SK, Girdler SS. Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?. Psychopharmacology (Berl) 2014 Sep;231(17):3619-34.
    pmc: PMC4135030pubmed: 24756763doi: 10.1007/s00213-014-3572-8google scholar: lookup
  15. Gunn BG, Cunningham L, Mitchell SG, Swinny JD, Lambert JJ, Belelli D. GABAA receptor-acting neurosteroids: a role in the development and regulation of the stress response.. Front Neuroendocrinol 2015 Jan;36:28-48.
    pmc: PMC4349499pubmed: 24929099doi: 10.1016/j.yfrne.2014.06.001google scholar: lookup
  16. Jellyman JK, Valenzuela OA, Allen VL, Forhead AJ, Holdstock NB, Fowden AL. Neonatal glucocorticoid overexposure programs pituitary-adrenal function in ponies.. Domest Anim Endocrinol 2015 Jan;50:45-9.
    pubmed: 25240233doi: 10.1016/j.domaniend.2014.06.006google scholar: lookup
  17. Beishuizen A, Thijs LG, Vermes I. Decreased levels of dehydroepiandrosterone sulphate in severe critical illness: a sign of exhausted adrenal reserve?. Crit Care 2002 Oct;6(5):434-8.
    pmc: PMC130144pubmed: 12398784doi: 10.1186/cc1530google scholar: lookup
  18. Oberbeck R, Kobbe P. Dehydroepiandrosterone (DHEA): a steroid with multiple effects. Is there any possible option in the treatment of critical illness?. Curr Med Chem 2010;17(11):1039-47.
    pubmed: 20156161doi: 10.2174/092986710790820570google scholar: lookup
  19. Sayyed Kassem L, El Sibai K, Chaiban J, Abdelmannan D, Arafah BM. Measurements of serum DHEA and DHEA sulphate levels improve the accuracy of the low-dose cosyntropin test in the diagnosis of central adrenal insufficiency.. J Clin Endocrinol Metab 2012 Oct;97(10):3655-62.
    pmc: PMC3462936pubmed: 22851486doi: 10.1210/jc.2012-1806google scholar: lookup
  20. Wishart D. Efficient hierarchical cluster analysis for data mining and knowledge discovery. Comput Sci Stat 1998;30:257‐263.
  21. Fekedulegn DB, Andrew ME, Burchfiel CM, Violanti JM, Hartley TA, Charles LE, Miller DB. Area under the curve and other summary indicators of repeated waking cortisol measurements.. Psychosom Med 2007 Sep-Oct;69(7):651-9.
    pubmed: 17766693doi: 10.1097/psy.0b013e31814c405cgoogle scholar: lookup
  22. Pruessner JC, Gaab J, Hellhammer DH, Lintz D, Schommer N, Kirschbaum C. Increasing correlations between personality traits and cortisol stress responses obtained by data aggregation.. Psychoneuroendocrinology 1997 Nov;22(8):615-25.
    pubmed: 9483706doi: 10.1016/s0306-4530(97)00072-3google scholar: lookup
  23. 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
  24. Dembek KA, Hurcombe SD, Frazer ML, Morresey PR, Toribio RE. Development of a likelihood of survival scoring system for hospitalized equine neonates using generalized boosted regression modeling.. PLoS One 2014;9(10):e109212.
    pmc: PMC4189956pubmed: 25295600doi: 10.1371/journal.pone.0109212google scholar: lookup
  25. 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
  26. Aleman M, Pickles KJ, Conley AJ, Stanley S, Haggett E, Toth B, Madigan JE. Abnormal plasma neuroactive progestagen derivatives in ill, neonatal foals presented to the neonatal intensive care unit.. Equine Vet J 2013 Nov;45(6):661-5.
    pubmed: 23600660doi: 10.1111/evj.12065google scholar: lookup
  27. Chatdarong K, Ponglowhapan S, Karlsson A, Linde-Forsberg C. The effect of ACTH stimulation on cortisol and progesterone concentrations in intact and ovariohysterectomized domestic cats.. Theriogenology 2006 Oct;66(6-7):1482-7.
    pubmed: 16527341doi: 10.1016/j.theriogenology.2006.01.005google scholar: lookup
  28. Honour JW. 17-Hydroxyprogesterone in children, adolescents and adults.. Ann Clin Biochem 2014 Jul;51(Pt 4):424-40.
    pubmed: 24711560doi: 10.1177/0004563214529748google scholar: lookup
  29. Monroe WE, Panciera DL, Zimmerman KL. Concentrations of noncortisol adrenal steroids in response to ACTH in dogs with adrenal-dependent hyperadrenocorticism, pituitary-dependent hyperadrenocorticism, and nonadrenal illness.. J Vet Intern Med 2012 Jul-Aug;26(4):945-52.
    pubmed: 22708651doi: 10.1111/j.1939-1676.2012.00959.xgoogle scholar: lookup
  30. Yoshida C, Nakao T. Plasma cortisol and progesterone responses to low doses of adrenocorticotropic hormone in ovariectmized lactating cows.. J Reprod Dev 2006 Dec;52(6):797-803.
    pubmed: 16988492doi: 10.1262/jrd.17051google scholar: lookup
  31. Khashana A, Ojaniemi M, Leskinen M, Saarela T, Hallman M. Term neonates with infection and shock display high cortisol precursors despite low levels of normal cortisol.. Acta Paediatr 2016 Feb;105(2):154-8.
    pubmed: 26537554doi: 10.1111/apa.13257google scholar: lookup
  32. McManus F, Fraser R, Davies E, Connell JM, Freel EM. Plasma steroid profiling and response to trophins to illustrate intra-adrenal dynamics.. J Endocrinol 2015 Feb;224(2):149-57.
    pubmed: 25413366doi: 10.1530/joe-14-0561google scholar: lookup
  33. Perrin A, Pascal O, Defaye G, Feige JJ, Chambaz EM. Transforming growth factor beta 1 is a negative regulator of steroid 17 alpha-hydroxylase expression in bovine adrenocortical cells.. Endocrinology 1991 Jan;128(1):357-62.
    pubmed: 1986928doi: 10.1210/endo-128-1-357google scholar: lookup
  34. Rainey WE, Naville D, Saez JM, Carr BR, Byrd W, Magness RR, Mason JI. Transforming growth factor-beta inhibits steroid 17 alpha-hydroxylase cytochrome P-450 expression in ovine adrenocortical cells.. Endocrinology 1990 Oct;127(4):1910-5.
    pubmed: 2169408doi: 10.1210/endo-127-4-1910google scholar: lookup
  35. Straub RH, Glück T, Cutolo M, Georgi J, Helmke K, Schölmerich J, Vaith P, Lang B. The adrenal steroid status in relation to inflammatory cytokines (interleukin-6 and tumour necrosis factor) in polymyalgia rheumatica.. Rheumatology (Oxford) 2000 Jun;39(6):624-31.
    pubmed: 10888707doi: 10.1093/rheumatology/39.6.624google scholar: lookup
  36. 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
  37. Ousey JC, Rossdale PD, Fowden AL, Palmer L, Turnbull C, Allen WR. Effects of manipulating intrauterine growth on post natal adrenocortical development and other parameters of maturity in neonatal foals.. Equine Vet J 2004 Nov;36(7):616-21.
    pubmed: 15581327doi: 10.2746/0425164044864598google scholar: lookup
  38. 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

Citations

This article has been cited 5 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
  2. Johnson K, Peterson J, Kopper J, Dembek K. The hypothalamic-pituitary-adrenal axis response to ovine corticotropin-releasing-hormone stimulation tests in healthy and hospitalized foals. J Vet Intern Med 2023 Jan;37(1):292-301.
    doi: 10.1111/jvim.16604pubmed: 36651191google scholar: lookup
  3. Hernández-Avalos I, Mota-Rojas D, Mendoza-Flores JE, Casas-Alvarado A, Flores-Padilla K, Miranda-Cortes AE, Torres-Bernal F, Gómez-Prado J, Mora-Medina P. Nociceptive pain and anxiety in equines: Physiological and behavioral alterations. Vet World 2021 Nov;14(11):2984-2995.
    doi: 10.14202/vetworld.2021.2984-2995pubmed: 35017848google scholar: lookup
  4. 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.
    doi: 10.1111/jvim.16024pubmed: 33415818google scholar: lookup
  5. Swink JM, Rings LM, Snyder HA, McAuley RC, Burns TA, Dembek KA, Gilsenan WF, Browne N, Toribio RE. Dynamics of androgens in healthy and hospitalized newborn foals. J Vet Intern Med 2021 Jan;35(1):538-549.
    doi: 10.1111/jvim.15974pubmed: 33277956google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.