Systemic absorption of triamcinolone acetonide is increased from intrasynovial versus extrasynovial sites and induces hyperglycemia, hyperinsulinemia, and suppression of the hypothalamic-pituitary-adrenal axis.
Abstract: Steroid-associated laminitis remains a major concern with use of corticosteroids in horses. Individual case factors such as joint pathology, pre-existing endocrinopathies, or corticosteroid type, dose, and timing influencing steroid-induced laminitis risk have not been investigated. This study aimed to determine if systemic absorption of triamcinolone acetonide (TA) varies between intrasynovial (antebrachiocarpal) and extrasynovial (sacroiliac) injection sites, and to determine the effects of TA absorption on glucose, insulin, cortisol, and adrenocorticotropic hormone (ACTH). Twenty adult horses were randomized into antebrachiocarpal or sacroiliac joint injection groups, and each horse received bilateral injections with a total dose of 18 mg triamcinolone. Blood was collected prior to injection and at 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 60, and 72 h post-injection. Peak TA absorption occurred at 8 h in both groups, and was significantly higher in the intrasynovial group compared to the extrasynovial group (1.397 ng/mL, 0.672 ng/mL, p < 0.05). Plasma TA levels were significantly higher in the intrasynovial group from 8 to 36 h post-injection (p < 0.05). There was no difference in glucose, insulin, cortisol, or ACTH between groups at any time point. Insulin and glucose were significantly increased from baseline at all timepoints from 10-72 h and 1-72 h post-injection, respectively. Horses with elevated baseline insulin values (>20 μU/mL) from both groups experienced a more marked hyperinsulinemia, reaching a mean peak insulin of 197.5 μU/mL as compared to 90.06 μU/mL in those with normal baseline insulin. Cortisol and ACTH were significantly decreased from baseline at timepoints from 4-72 h post-injection in both groups. This study is the first to evaluate drug absorption from the sacroiliac site and demonstrates that drug absorption varies between intrasynovial and extrasynovial injection sites. TA absorption causes metabolic derangements, most notably a marked hyperinsulinemia that is more severe in horses with elevated baseline insulin values. The influence of baseline endocrinopathies on response to corticosteroid administration as well as the effect of corticosteroid-induced metabolic derangements warrant further investigation as risk factors for corticosteroid-associated laminitis.
Copyright © 2024 Hallowell, Dembek, Horne, Knych, Messenger and Schnabel.
Publication Date: 2024-05-15 PubMed ID: 38828366PubMed Central: PMC11141165DOI: 10.3389/fvets.2024.1388470Google Scholar: Lookup
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- Journal Article
Summary
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This study explores how the systemic absorption of the corticosteroid drug triamcinolone acetonide (TA) varies when injected into different areas in horses, and how this affects glucose, insulin, cortisol, and adrenocorticotropic hormone (ACTH) levels. The findings show that triamcinolone absorption causes notable disturbances in metabolism, particularly inducing high insulin levels, especially in horses with already elevated baseline insulin values.
Research Design
- The researchers aimed to identify how systemic absorption of TA would differ if injected into intrasynovial (antebrachiocarpal) or extrasynovial (sacroiliac) sites.
- These sites were selected for investigation due to their frequent utilization for corticosteroid administration in horses.
- Twenty adult horses were used in this study and were randomly assigned to either the intrasynovial or extrasynovial group.
- Each horse received bilateral injections with 18mg of TA and blood samples were collected before injection and at several time points after injection, ranging from one to 72 hours.
Findings
- The results showed that peak TA absorption happened at eight hours post-injection in both groups. However, this peak was higher in the intrasynovial group (1.397ng/mL) compared to the extrasynovial group (0.672ng/mL).
- In fact, plasma levels of TA were significantly higher in the intrasynovial group from eight to 36 hours post-injection.
- There was no difference between the two groups at any time point in terms of glucose, insulin, cortisol, or ACTH levels.
Impact on Insulin and Glucose
- Insulin and glucose levels significantly rose from the baseline at all relevant timepoints.
- Horses with high baseline insulin values (>20 μU/mL) experienced a greater hyperinsulinemia, with a mean peak insulin level of 197.5 μU/mL, compared to 90.06 μU/mL in horses with normal baseline insulin levels.
Impact on Cortisol and ACTH
- Levels of cortisol and ACTH significantly fell from the baseline at time points from four to 72 hours post-injection in both groups.
Implications
- This study is the first to evaluate drug absorption from the sacroiliac site, indicating that drug absorption varies between intrasynovial and extrasynovial injection sites.
- Significantly, the research finds that TA absorption leads to metabolic disturbances, most notably causing severe hyperinsulinemia in horses with elevated baseline insulin values.
- This suggests that the effect of corticosteroid-induced metabolic changes and the influence of pre-existing illnesses on the body’s response to corticosteroid administration deserve more research as potential risk factors for corticosteroid-connected laminitis.
Cite This Article
APA
Hallowell KL, Dembek K, Horne CR, Knych HK, Messenger KM, Schnabel LV.
(2024).
Systemic absorption of triamcinolone acetonide is increased from intrasynovial versus extrasynovial sites and induces hyperglycemia, hyperinsulinemia, and suppression of the hypothalamic-pituitary-adrenal axis.
Front Vet Sci, 11, 1388470.
https://doi.org/10.3389/fvets.2024.1388470 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
- K. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.
- Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
- Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
- Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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