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

Abstract

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.

Dynamics of androgens in healthy and hospitalized newborn foals

“…The ACTH:cortisol is a practical tool that has been used to assess hypothalamic‐pituitary‐adrenal axis activity and adrenocortical insufficiency (RAI/CIRCI) in hospitalized foals 18,47 . Because ACTH stimulation induces androgen steroidogenesis, 4 it is not surprising that illness alters the ACTH:androgen ratios 15 . ACTH has been evaluated in reference to other steroids (progestogens and androgens) in healthy and sick foals 15 .…”

“…Cortisol, aldosterone, progestogens, and DHEA concentrations are elevated in sick foals and linked to disease severity, 11,[14][15][16][17][18] and their response to exogenous ACTH stimulation is associated with outcome. 4 Most studies of steroid concentrations in foals have been on single time measurements, precluding the assessment of steroid dynamics in relation to illness severity and outcome over time. Information on androgen concentrations in newborn foals is lacking, likely because they are seen as sex hormones rather than active steroids or intermediary to other endocrine factors, further underplaying their clinical measurement and relevance in healthy and sick foals.…”

“…Cortisol is the main steroid released by the adrenal gland and in the developing fetus is essential for tissue maturation and differentiation 2,3 . A number of critically ill foals have an insufficient cortisol response to stress, but adequate to abnormally high ACTH concentrations, a phenomenon known as relative adrenal insufficiency (RAI) or critical illness‐related corticosteroid insufficiency (CIRCI) 4,5 . In addition to stimulating glucocorticoid and mineralocorticoid production, ACTH also promotes the secretion of steroid precursors and androgens from the adrenal cortex and developing gonads 6,7 …”

Nociceptive pain and anxiety in equines: Physiological and behavioral alterations

“…In addition, according to a recent study, it has been observed that the experimental stimulation of this axis with ACTH is associated with the increase of cortisol, aldosterone, androstenedione, pregnenolone, 17a-OH-progesterone, and progesterone in critically ill patients compared to healthy animals. But interestingly, it was observed that in the animals that died, a decrease in cortisol and an endogenous increase in ACTH were observed, which suggested adrenocortical dysfunction [ 109 ]. This corroborates what has been stated above, first that the stimulation of cortisol decreases the response of the immune system, while second, this endocrine response has a limited response that can be depleted, which can serve as a prognostic factor in severe conditions.…”

Glucagon, insulin, adrenocorticotropic hormone, and cortisol in response to carbohydrates and fasting in healthy neonatal foals

“…It can secrete insulin in response to glucose and amino acids, and is believed to be important in regulating fetal nutrient utilization and growth 9 . However, complete maturation of the endocrine system and associated energy metabolism in the neonate is delayed 1,11‐13 . In addition, the neonatal foal has minimal hepatic fat stores, little glycogen, and little adipose tissue at birth 2,3 .…”