The adrenal response to critical illness and its role in prognostication is an important issue in human medicine. A positive association between high basal serum cortisol and adverse outcome has been demonstrated in human and canine illness. The association of serum ACTH-stimulated cortisol and delta cortisol concentrations with outcome in critical illness is less clear.
This prospective, case controlled study was conducted on sixty-three puppies with parvoviral diarrhea. The diagnosis was confirmed by detection of viral particles on fecal electron microscopy. Seventeen healthy puppies were used as controls. Blood samples were obtained in each dog at admission prior to treatment and daily thereafter until death or discharge from the hospital. Immediately after the basal samples were drawn, each dog was injected daily with 5 ug/kg of ACTH (tetracosactrin) intravenously. A second sample was taken 1 hour later for serum ACTH-stimulated cortisol measurement and the calculation of delta cortisol. Cortisol concentrations were determined by a commercial canine radioimmunoassay kit (Coat-a-count®, DPC, CA). Dogs were retrospectively assigned to two groups: survivors (n=50) and non-survivors (n=13). Hormone concentrations between the survivors and non-survivors were compared with the Mann Whitney U test for non-parametric data. Significance was set at p< 0.05.
Median day 1 (D1) basal cortisol and ACTH-stimulated cortisol was significantly higher in patients than in controls (259 vs. 77 nmol/L) and (393 vs. 295 nmol/L); P<0.01 for both. Median delta cortisol was lower in patients (68 vs. 203 nmol/L). In nonsurvivors vs. survivors, D1 basal cortisol was significantly higher (539 vs 234 nmol/L), P< 0.05. ACTH-stimulated cortisol did not differ significantly (459 vs. 380 nmol/L); P = 0.2, therefore delta cortisol was significantly lower in nonsurvivors (-60 vs 128 nmol/L); P < 0.05. On day 3 (D3), basal cortisol was still higher in non-survivors, but not significantly so (189 vs. 68 nmol/L); P = 0.18, yet ACTH-stimulated cortisol was significantly higher in nonsurvivors (417 vs. 345 nmol/L); P < 0.05. In contrast to D1, delta cortisol was not significantly lower in nonsurvivors on D3 (179 vs. 256 nmol/L); P = 0.2.
This study confirmed the previously described association between high basal serum cortisol concentrations and mortality in parvoviral diarrhea dogs. Low delta cortisol was also associated with mortality on D1. However, the D3 delta cortisol was not significantly lower in nonsurvivors compared to survivors. This study highlights the important limitation of designating a patient as adrenal insufficient on the basis of a one-off ACTH stimulation test in the early stages of acute illness. During this stage basal cortisol production is close to maximum and delta cortisol would be low, without necessarily indicating adrenal insufficiency. The serial sampling in this study provided novel insights on the adrenal response and re-enforces the need to consider basal-, delta- and ACTH-stimulated cortisol in the evaluation of adrenal reserve in canine critical illness.