Somatotropic axis resistance and ghrelin in critically ill foals.

REASONS FOR PERFORMING STUDY: Resistance to the somatotropic axis and increases in ghrelin concentrations have been documented in critically ill human patients, but limited information exists in healthy or sick foals. OBJECTIVES: To investigate components of the somatotropic axis (ghrelin, growth hormone and insulin-like growth factor-1 [IGF-1]) with regard to energy metabolism (glucose and triglycerides), severity of disease and survival in critically ill equine neonates. It was hypothesised that ghrelin and growth hormone would increase and IGF-1 would decrease in proportion to severity of disease, supporting somatotropic axis resistance, which would be associated with severity of disease and mortality in sick foals. STUDY DESIGN: Prospective multicentre cross-sectional study. METHODS: Blood samples were collected at admission from 44 septic, 62 sick nonseptic (SNS) and 19 healthy foals, all aged <7 days. Foals with positive blood cultures or sepsis scores ≥12 were considered septic, foals with sepsis scores of 5-11 were classified as SNS. Data were analysed by nonparametric methods and multivariate logistic regression. RESULTS: Septic foals had higher ghrelin, growth hormone and triglyceride and lower IGF-1 and glucose concentrations than healthy foals (P<0.01). Sick nonseptic foals had higher growth hormone and triglycerides and lower IGF-1 concentrations than healthy foals (P<0.05). Growth hormone:IGF-1 ratio was higher in septic and SNS foals than healthy foals (P<0.05). Hormone concentrations were not different between septic nonsurvivors (n = 14) and survivors (n = 30), but the growth hormone:IGF-1 ratio was lower in nonsurvivors (P = 0.043). CONCLUSIONS: Somatotropic axis resistance, characterised by a high growth hormone:IGF-1 ratio, was frequent in sick foals, associated with the energy status (hypoglycaemia, hypertriglyceridaemia) and with mortality in septic foals. POTENTIAL RELEVANCE: A functional somatotropic axis appears to be important for foal survival during sepsis. Somatotropic resistance is likely to contribute to severity of disease, a catabolic state and likelihood of recovery.

Renin-Angiotensin-aldosterone system and hypothalamic-pituitary-adrenal axis in hospitalized newborn foals.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals. OBJECTIVES/HYPOTHESIS: To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals. ANIMALS: A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals. METHODS: Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals. RESULTS: ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P < .05). No difference in PRA between groups was found. High serum potassium and low serum chloride concentrations were associated with hyperaldosteronemia in septic foals. CONCLUSIONS AND CLINICAL IMPORTANCE: RAAS activation in critically ill foals is characterized by increased ANG-II and aldosterone concentrations. Inappropriately low cortisol and aldosterone concentrations defined as high ACTH/cortisol and ACTH/aldosterone ratios in septic foals suggest that RAI is not restricted to the zona fasciculata in critically ill newborn foals.

Presumptive nonthyroidal illness syndrome in critically ill foals.

REASONS FOR PERFORMING THE STUDY: Hypothalamic-pituitary-thyroid (HPT) axis dysfunction is associated with morbidity and mortality in critically ill people. To date, investigations of HPT axis in critically ill foals are limited. OBJECTIVES: To document the occurrence of low thyroid hormone concentrations (presumptive nonthyroidal illness syndrome; NTIS) in critically ill newborn foals and investigate whether NTIS is associated with severity of disease and outcome. HYPOTHESIS: NTIS occurs frequently in foals with sepsis and is associated with sepsis score and outcome. Reverse T3 (rT3) concentrations will be increased in septic foals and highest in nonsurvivors. METHODS: Thyroid hormones (total and free thyroxine [TT4 and fT4], total and free tri-iodothyronine [TT3 and fT3], reverse T3 [rT3]) were prospectively measured in healthy, sick nonseptic and septic foals. Clinical and laboratory information was retrieved from the medical records. Hormones were measured by validated radioimmunoassays. RESULTS: Concentrations of all thyroid hormones except rT3 (P = 0.69) were decreased in septic and sick nonseptic foals (P < 0.01). Reductions in hormone concentrations were associated with an increased sepsis score (P < 0.01). Nonsurviving septic foals had lower TT4, fT4, TT3 and fT3 concentrations than surviving septic foals (P < 0.01). rT3 concentrations were higher in nonsurviving septic prematurefoals than surviving septic premature foals (P < 0.05). CONCLUSIONS: NTIS (euthyroid sick syndrome) is frequently observed in critically ill and premature foals, and associated with severity of disease and mortality. POTENTIAL RELEVANCE: More research is needed to better understand the mechanism of this finding and determine whether manipulation of the HPT axis or thyroid replacement therapy could be beneficial.

Insulin, glucagon, and leptin in critically ill foals.

BACKGROUND: Endocrine dysregulation of hormones of energy metabolism is well documented in critically ill humans, but limited information exists in septic foals. The purpose of this study was to provide information on the hormonal response to energy metabolism in critically ill foals, focusing on insulin, glucagon, and leptin. HYPOTHESIS: Concentrations of insulin, glucagon, leptin, and triglycerides will be higher, whereas glucose concentration will be lower in septic foals than in healthy and sick nonseptic foals. The magnitude of these differences will be associated with severity of disease and nonsurvival. ANIMALS: Forty-four septic, 62 sick nonseptic, and 19 healthy foals <7 days of age. METHODS: In this prospective multicenter cross-sectional study, blood samples were collected at admission. Foals with positive blood culture or sepsis score ≥12 were considered septic. RESULTS: Septic foals had lower glucose and insulin and higher triglyceride and glucagon concentrations than did healthy foals. Glucagon concentrations were not different between septic foals that died (n = 14) or survived (n = 30). Higher insulin and lower leptin concentrations were associated with mortality. Quantitative insulin-sensitivity check index was higher in septic foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Energy metabolism and the endocrine response of related hormones in septic foals are characterized by hypoglycemia, hypertriglyceridemia, low insulin concentration, and high glucagon concentration. Leptin and insulin may have prognostic value for nonsurvival in septic foals. The hormonal response related to energy metabolism in critical illness differs between foals and humans.

Calcium regulating hormones and serum calcium and magnesium concentrations in septic and critically ill foals and their association with survival.

BACKGROUND: Disorders of calcium regulation are frequently found in humans with critical illness, yet limited information exists in foals with similar conditions including septicemia. The purpose of this study was to determine whether disorders of calcium exist in septic foals, and to determine any association with survival. HYPOTHESIS: Blood concentrations of ionized calcium (Ca(2+)) and magnesium (Mg(2+)) will be lower in septic foals with concomitant increases in parathyroid hormone (PTH), calcitonin (CT), and parathyroid-related peptide (PTHrP) compared with healthy foals. The magnitude of these differences will be negatively associated with survival. ANIMALS: Eighty-two septic, 40 sick nonseptic, and 24 healthy foals of or=14 were considered septic. Foals with disease other than sepsis and healthy foals were used as controls. Hormone concentrations were measured with validated immunoassays. RESULTS: Septic foals had decreased Ca(2+) (5.6 versus 6.1 mg/dL, P < .01) and increased serum PTH (16.2 versus 3.2 pmol/L, P < .05), and phosphorus concentrations (7.1 versus 6.3 mg/dL, P < .01). No differences in serum Mg(2+), PTHrP, and CT concentrations were found. Nonsurviving septic foals (n = 42/82) had higher PTH concentrations (41.1 versus 10.7 pmol/L, P < .01) than survivors (n = 40/82). CONCLUSIONS AND CLINICAL IMPORTANCE: Septic foals were more likely to have disorders of calcium regulation compared with healthy foals, where hyperparathyroidemia was associated with nonsurvival.

Blood arginine vasopressin, adrenocorticotropin hormone, and cortisol concentrations at admission in septic and critically ill foals and their association with survival.

BACKGROUND: Sepsis is an important cause for neonatal foal mortality. The hypothalamic-pituitary-adrenal axis (HPAA) responses to sepsis are well documented in critically ill humans, but limited data exist in foals. The purpose of this study was to evaluate the HPAA response to sepsis in foals, and to associate these endocrine changes with survival. HYPOTHESIS: Blood concentrations of arginine vasopressin (AVP), adrenocorticotropin hormone (ACTH), and cortisol will be higher in septic foals as compared with sick nonseptic and healthy foals. The magnitude of increase in hormone concentration will be negatively associated with survival. ANIMALS: Fifty-one septic, 29 sick nonseptic, and 31 healthy foals of < or =7 days of age were included. METHODS: Blood was collected at admission for analysis. Foals with positive blood culture or sepsis score > or =14 were considered septic. Foals admitted with disease other than sepsis and healthy foals were used as controls. AVP, ACTH, and cortisol concentrations were measured using validated immunoassays. RESULTS: AVP, ACTH, and cortisol concentrations were increased in septic foals. Septic nonsurvivor foals (n = 26/51) had higher plasma ACTH and AVP concentrations than did survivors (n = 25/51). Some septic foals had normal or low cortisol concentrations despite increased ACTH, suggesting relative adrenal insufficiency. AVP, ACTH, and cortisol concentrations were higher in sick nonseptic foals compared with healthy foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased plasma AVP and ACTH concentrations in septic foals were associated with mortality. Several septic foals had increased AVP : ACTH and ACTH : cortisol ratios, which indicates relative adenohypophyseal and adrenal insufficiency.