Longitudinal assessment of adrenocortical steroid and steroid precursor response to illness in hospitalized foals

Abstract

Sepsis is a major cause of morbidity and mortality in neonatal foals. Relative adrenal insufficiency (RAI), defined as an inadequate cortisol response to stress, has been associated with sepsis, prematurity, and poor outcome in newborn foals. In addition to cortisol, the adrenal gland synthesizes several biologically important steroids and steroid precursors, including aldosterone, androgens, and progestogens. However, concentration of these hormones during hospitalization and their association with the severity of disease and mortality in critically ill foals have not been completely evaluated. We hypothesized, that in addition to cortisol and aldosterone, concentration of steroid precursors (progestogens and androgens) will be altered in critically ill foals. We also proposed that septic foals will have higher concentrations of steroid precursors than healthy foals, and steroid concentrations will be persistently increased during hospitalization in non-surviving septic and premature foals. Foals <4 days of age were categorized as healthy, septic, sick non-septic, and premature based on physical exam, medical history, and laboratory data. Blood samples were collected on admission (0 h), 24 h, and 72 h after admission. Concentrations of steroids and ACTH were measured by immunoassays. The area under the curve over 72 h (AUC0-72h) of hospitalization was calculated for each hormone. Serum cortisol, aldosterone, progesterone, pregnenolone, dehydroepiandrosterone sulfate (DHEAS), and 17 α-hydroxyprogesterone concentrations were higher in septic and premature foals compared to healthy foals at 0 h and throughout 72 h of hospitalization (P < 0.05). Plasma ACTH concentrations were higher in septic and premature foals on admission compared to healthy controls (P < 0.05). The progesterone (AUC0-72h) cut-off value above which non-survival could be reliably predicted in hospitalized foals was 1,085 ng/mL/h, with 82% sensitivity and 77% specificity. Critically ill neonatal foals had an appropriate response to stress characterized by increased concentrations of cortisol and steroid precursors on admission. A rapid decline in steroid concentration was observed in healthy foals. However, persistently elevated progestogen and androgen concentrations were associated with a lack of improvement in the course of disease and poor outcome.