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

Dembek, Katarzyna; Timko, Kathryn J.; Johnson, Lindsey M.; Hart, Kelsey A.; Barr, Bonnie S.; David, B. P.; Burns, T.A.; Toribio, Ramiro E.

doi:10.1016/j.tvjl.2017.05.009

Cited by 32 publications

(78 citation statements)

References 36 publications

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“…9,11,16 In contradiction to previous studies, the ACTH/cortisol ratio was not different between groups of foals in the current study. 3,11,25 This difference could be because of the size of the foal population included in studies, variable death rate, and severity of disease. The association of AUCs and death in foals from our study might also suggest that AUC is a more accurate indication of adrenal hypofunction than a hormone ratio on admission.…”

Section: Discussioncontrasting

confidence: 99%

“…Our results are in line with other studies, which demonstrated high basal cortisol, aldosterone, progestogens, and androgens concentrations in hospitalized foals. 2,3,11,26 Elevated steroid secretion in response to critical illness was considered appropriate for most of the foals of this study, whereas concentrations in the reference range indicated a poor response. The traditional definition of RAI or ACI has been based on an inadequate cortisol response to exogenous ACTH stimulation in critically ill patients with septic shock and multiple organ dysfunction, and similar criteria have been applied to severely ill foals.…”

Section: Discussionmentioning

confidence: 99%

“…3,13 High baseline 17α-OH-progesterone and progesterone concentrations are associated with severity of disease and death in septic foals. 11 There are increased progesterone and 17α-OH-progesterone responses to T A B L E 2 Area under the curve and Delta 0-30 for adrenocortical steroids, ACTH/cortisol ratio, and laboratory findings in surviving and non-surviving hospitalized foals (median and ranges) ACTH stimulation in dogs with adrenal-and pituitary-dependent hyperadrenocorticism, in children with congenital adrenal hyperplasia, and in healthy intact and ovariohysterectomized cats and cows. [27][28][29][30] In the current study, the progestogen response to ACTH was lower in foals that died.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the concept of RAI was challenged, suggesting that hypercortisolemia from reduced cortisol biodegradation might lead to endogenous ACTH suppression in the absence of adrenocortical dysfunction . Therefore, a new term, ACTH to cortisol dissociation or ACTH:cortisol imbalance (ACI), has been introduced in critically ill human patients and equine neonates . Regardless of the exact pathogenesis, RAI or ACI has been associated with disease severity and death in children and newborn foals, and it is therefore possible that hormonal replacement treatment might decrease hospitalization durations and increase patient survival .…”

Section: Introductionmentioning

confidence: 99%

“…High baseline concentration of multiple adrenal steroids, including progestogens and androgens, is associated with poor outcome and severity of disease in critically ill foals. 11 Neuroactive steroids (neurosteroids) can be synthesized from cholesterol or steroid precursors (progestogens in particular) in the central and peripheral nervous systems. 14,15 Neurosteroids modulate neuronal activity, including hypothalamic neurons via gamma-aminobutyric acid receptors (GABA A ), and therefore influence HPAA function.…”

Section: Introductionmentioning

confidence: 99%

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

Dembek

Johnson

Timko

et al. 2019

Veterinary Internal Medicne

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Background 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. Animals 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 0‐30 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 0‐30 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. Conclusion and Clinical Importance The 17α‐OH‐progesterone response to administration of ACTH was a good predictor of disease severity and death in hospitalized foals.

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