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Veterinary journal (London, England : 1997)2017; 225; 42-49; doi: 10.1016/j.tvjl.2017.05.009

Steroids, steroid precursors, and neuroactive steroids in critically ill equine neonates.

Abstract: Hypothalamic-pituitary-adrenal axis (HPAA) dysfunction has been associated with sepsis and mortality in foals. Most studies have focused on cortisol, while other steroids have not been investigated. The objectives of this study were to characterise the adrenal steroid and steroid precursor response to disease and to determine their association with the HPAA response to illness, disease severity, and mortality in hospitalised foals. All foals (n=326) were classified by two scoring systems into three categories: based on the sepsis score (septic, sick non-septic [SNS] and healthy) and the foal survival score (Group 1: 3-18%; Group 2: 38-62%; Group 3: 82-97% likelihood of survival). Blood concentrations of adrenocorticotropic hormone (ACTH) and steroids were determined by immunoassays. ACTH-cortisol imbalance (ACI) was defined as a high ACTH/cortisol ratio. Septic foals had higher ACTH, cortisol, progesterone, 17α-OH-progesterone, pregnenolone, and androstenedione concentrations as well as higher ACTH/cortisol, ACTH/progesterone, ACTH/aldosterone, and ACTH/DHEAS ratios than SNS and healthy foals (P<0.01). Foals with DHEAS of 0.4-5.4ng/mL were more likely to have ACI (OR=2.5). Foals in Group 1 had higher ACTH, aldosterone, progesterone, and cortisol concentrations as well as ACTH/cortisol, ACTH/progesterone, and ACTH/DHEAS ratios than foals in Groups 2 and 3 (P<0.01). High progesterone concentrations were associated with non-survival and the cutoff value below which survival could be predicted was 23.5ng/mL, with 75% sensitivity and 72% specificity. In addition to cortisol, the response to the stress of illness in foals is characterised by the release of multiple adrenal steroids. DHEAS and progesterone were good predictors of HPAA dysfunction and outcome in hospitalised foals.
Publication Date: 2017-05-30 PubMed ID: 28720298DOI: 10.1016/j.tvjl.2017.05.009Google Scholar: Lookup
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  • Journal Article

Summary

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The research study investigates the role of different types of steroids, specifically those produced by the adrenal gland, in foals (young horses) afflicted with severe illness. The study links the imbalance of adrenocorticotropic hormone (ACTH) and cortisol, among other steroids, to the severity of illness and survival rates in foals.

Study Design and Objectives

  • The study centered on the hormonal response of critically ill foals, with emphasis on their Hypothalamic-pituitary-adrenal axis (HPAA), the body’s central stress response system. Particularly, the research focuses on not just cortisol, which has been the focus of many previous studies, but also a range of other adrenal steroids and precursors.
  • The foals were classified into three groups based on the scoring system related to sepsis (an extreme response to infection) and survival likelihood: septic, sick non-septic [SNS], and healthy; and Group 1 with 3-18% survival probability, Group 2 with 38-62% survival probability, and Group 3 with 82-97% survival probability.

Results

  • The research found that septic foals had higher ACTH, cortisol, progesterone, 17α-OH-progesterone, pregnenolone, and androstenedione levels as well as the ratios of ACTH to these hormones, compared to SNS and healthy foals.
  • The study indicated that certain ranges of DHEAS (adrenal steroid) concentration were linked with greater chances of having an ACTH-cortisol imbalance.
  • Foals in the group with the lowest survival likelihood had higher ACTH, aldosterone, progesterone, and cortisol levels, along with higher ratios of ACTH to these hormones, compared to the other two groups.
  • Higher progesterone levels were linked to higher mortality rates, with the study establishing a specific cut-off level for progesterone, below which survival could be predicted with reasonable accuracy.

Conclusion

  • The study concludes that in foals suffering from severe illness, the stress response includes the release of multiple adrenal steroids, not just cortisol.
  • The levels and ratios of certain adrenal steroids like DHEAS and progesterone can be used as good predictors of HPAA dysfunction and the potential outcome in hospitalized foals.

Cite This Article

APA
Dembek KA, Timko KJ, Johnson LM, Hart KA, Barr BS, David B, Burns TA, Toribio RE. (2017). Steroids, steroid precursors, and neuroactive steroids in critically ill equine neonates. Vet J, 225, 42-49. https://doi.org/10.1016/j.tvjl.2017.05.009

Publication

ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 225
Pages: 42-49
PII: S1090-0233(17)30106-5

Researcher Affiliations

Dembek, K A
  • College of Veterinary Medicine, The Ohio State University, 601 Vernon Tharp St., Columbus, OH 43210, USA.
Timko, K J
  • College of Veterinary Medicine, The Ohio State University, 601 Vernon Tharp St., Columbus, OH 43210, USA.
Johnson, L M
  • College of Veterinary Medicine, The Ohio State University, 601 Vernon Tharp St., Columbus, OH 43210, USA.
Hart, K A
  • College of Veterinary Medicine, University of Georgia, 501 D.W. Brooks Drive, Athens, GA 30602, USA.
Barr, B S
  • Rood and Riddle Equine Hospital, 2150 Georgetown Rd, Lexington, KY 40511, USA.
David, B
  • Hagyard Equine Medical Institute, 4250 Iron Works Pike, Lexington, KY 40511, USA.
Burns, T A
  • College of Veterinary Medicine, The Ohio State University, 601 Vernon Tharp St., Columbus, OH 43210, USA.
Toribio, R E
  • College of Veterinary Medicine, The Ohio State University, 601 Vernon Tharp St., Columbus, OH 43210, USA. Electronic address: toribio.1@osu.edu.

MeSH Terms

  • Adrenocorticotropic Hormone / blood
  • Androstenedione / blood
  • Animals
  • Animals, Newborn / blood
  • Critical Illness
  • Horse Diseases / blood
  • Horse Diseases / mortality
  • Horses
  • Hydrocortisone / blood
  • Hypothalamic Diseases / blood
  • Hypothalamic Diseases / veterinary
  • Hypothalamo-Hypophyseal System / physiopathology
  • Pituitary-Adrenal System / physiopathology
  • Pregnenolone / blood
  • Progesterone / blood
  • Prognosis
  • Sepsis / veterinary
  • Steroids / blood

Citations

This article has been cited 13 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. Peric T, Ellero L, Comin A, Pividori I, Prandi A. Validation of an ELISA kit to measure allopregnanolone in human and equine hair.. J Vet Diagn Invest 2023 Jul;35(4):354-358.
    doi: 10.1177/10406387231171045pubmed: 37114774google scholar: lookup
  3. 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
  4. Lauteri E, Mariella J, Beccati F, Roelfsema E, Castagnetti C, Pepe M, Peric T, Barbato O, Montillo M, Rouge S, Freccero F. Adrenal Gland Ultrasonographic Measurements and Plasma Hormone Concentrations in Clinically Healthy Newborn Thoroughbred and Standardbred Foals.. Animals (Basel) 2021 Jun 19;11(6).
    doi: 10.3390/ani11061832pubmed: 34205258google scholar: lookup
  5. Wong DM, Young L, Dembek KA. Blood thiamine (vitamin B(1) ), ascorbic acid (vitamin C), and cortisol concentrations in healthy and ill neonatal foals.. J Vet Intern Med 2021 Jul;35(4):1988-1994.
    doi: 10.1111/jvim.16188pubmed: 34056771google scholar: lookup
  6. 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
  7. Aleman M, Chigerwe M, Varga A, Madigan JE. Steroid precursors, steroids, neuroactive steroids, and neurosteroids concentrations in serum and saliva of healthy neonatal heifer Holstein calves.. J Vet Intern Med 2020 Nov;34(6):2767-2775.
    doi: 10.1111/jvim.15957pubmed: 33201530google scholar: lookup
  8. Falomo ME, Del Re B, Rossi M, Giaretta E, Da Dalt L, Gabai G. Relationship between postpartum uterine involution and biomarkers of inflammation and oxidative stress in clinically healthy mares (Equus caballus).. Heliyon 2020 Apr;6(4):e03691.
    doi: 10.1016/j.heliyon.2020.e03691pubmed: 32258514google scholar: lookup
  9. Stewart AJ, Hackett E, Bertin FR, Towns TJ. Cortisol and adrenocorticotropic hormone concentrations in horses with systemic inflammatory response syndrome.. J Vet Intern Med 2019 Sep;33(5):2257-2266.
    doi: 10.1111/jvim.15620pubmed: 31512777google scholar: lookup
  10. Aleman M, McCue PM, Chigerwe M, Madigan JE. Plasma concentrations of steroid precursors, steroids, neuroactive steroids, and neurosteroids in healthy neonatal foals from birth to 7 days of age.. J Vet Intern Med 2019 Sep;33(5):2286-2293.
    doi: 10.1111/jvim.15618pubmed: 31489708google scholar: lookup
  11. Corder-Ramos NLB, Flatland B, Fry MM, Sun X, Fecteau K, Giori L. Cortisol, progesterone, 17α-hydroxyprogesterone, and TSH responses in dogs injected with low-dose lipopolysaccharide.. PeerJ 2019;7:e7468.
    doi: 10.7717/peerj.7468pubmed: 31410314google scholar: lookup
  12. 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.
    doi: 10.1111/jvim.15527pubmed: 31111575google scholar: lookup
  13. Aleman M, Costa LRR, Crowe C, Kass PH. Presumed Neuroglycopenia Caused by Severe Hypoglycemia in Horses.. J Vet Intern Med 2018 Sep;32(5):1731-1739.
    doi: 10.1111/jvim.15245pubmed: 30084236google scholar: lookup