TABLE 1.
Predictive value of cortisol in patients with IS.
| Patients | Changes in cortisol/HPA axis | Predictive value/Key conclusion | References |
| IS patients | Acute IS patients had higher post-dexamethasone blood cortisol levels associated with proximity of the lesion to the frontal pole of the brain. | SI patients are exposed to hypercortisolism, which may have negative consequences upon organ functions. | Olsson et al., 1989 |
| IS patients | Urinary free cortisol excretion increased in the acute phase of IS. | Acute IS is associated with increased activity in the cortisol axis. Cortisol excretion is a predictor of poorer functional outcome. | Olsson, 1990 |
| IS patients | IS patients who died had significantly higher urinary cortisol secretion values. The first day urinary 17 oxogenic steroid excretion pointed to the greater adrenocortical response in these patients. | Cortisol secretion rate appears to be a good indicator of the severity of SI-induced stress and may be useful in predicting the prognosis of the disease. | Korsić et al., 1990 |
| IS patients, patients with pre-stroke normoglycemia | Serum cortisol in initial and 1-week samples correlated positively with severity of hemiparesis. Acute IS mortality was associated with increasing serum cortisol levels. A correlation existed between initial 7 p.m. serum cortisol and 7 a.m. fasting blood glucose values. | Serum cortisol predicts stroke outcome during 3 month follow-up. Hyperglycemia during the acute phase of IS is a stress response | Murros et al., 1993 |
| IS patients | Hypercortisolemia was associated with older age, greater severity of neurological deficit, larger ischemic lesions on CT, and worse prognoses. No correlation was found between serum cortisol levels and other markers of stress response. A correlation was found between serum cortisol and markers of inflammatory response. | Prognostic significance of hypercortisolemia in acute IS patients is related to the inflammatory response rather than to the stress response. | Slowik et al., 2002 |
| IS patients, patients with transient ischemic attacks (TIA) | Significant increase of cortisol concentration in plasma and cerebrospinal fluid found in acute IS, with maximum during first 2 days. The increase was highest in patients with brain infarction and lowest in TIA patients. | Measurement of cortisol in plasma and cerebrospinal fluid in patients with acute IS is significant for monitoring intensity of response to acute brain damage. | Selaković, 2004 |
| IS patients | Serum interleukin (IL)-6 and cortisol levels increased in acute IS. In IS patients, IL-6 level correlated significantly with cortisol level; morning serum IL-6 level independently predicted evening/night cortisol level. | Brain ischemia stimulates IL-6 release in blood and in this way modulates HPA axis. | Szczudlik et al., 2004 |
| IS patients | Salivary cortisol positively correlated with 24-h systolic blood pressure and night-time blood pressure in acute IS patients. | Stress is a contributing factor for high blood pressure in acute IS. | Ahmed et al., 2004 |
| IS patients | Serum cortisol in acute IS was independently related to death within 7 days of stroke onset, but was not a predictor of death or dependency within 3 months. Serum cortisol correlated with brain lesion volume. | Serum cortisol levels are associated with stroke severity and other markers reflecting stroke severity. | Christensen et al., 2004 |
| IS patients | Higher levels of plasma cortisol and adrenocorticotropic hormone (ACTH) were observed in IS patients who died during the follow-up. Cortisol levels were associated with catecholamine levels and measures of neurologic deficit. | Plasma levels of cortisol are associated with IS severity and short-term functional outcomes. High acute phase cortisol levels predicts long-term mortality after SI. | Anne et al., 2007 |
| IS patients | Cortisol levels at 3rd and 7th days after SI correlated with lesion volumes, but in prediction of IS prognosis, cortisol was not a deterministic factor. | The study failed to substantiate significance of blood cortisol in the prediction of stroke prognosis. | Varoglu et al., 2009 |
| TIA patients | The study assessed prognostic reliability of 2 distinct stress hormones, copeptin and cortisol, for the risk stratification of re-events in patients with TIA. | In patients with TIA plasma cortisol does not provide additional prognostic information beyond the ABCD2 clinical risk score. | Katan et al., 2011 |
| IS patients | Cortisol was an independent prognostic marker of functional outcome and death in patients with IS within 90 days and 1 year. | Though cortisol is an independent prognostic marker for death and functional outcome in SI, it adds no significant additional predictive value to National Institutes of Health Stroke Scale (NIHSS) score. | Neidert et al., 2011 |
| IS patients | Plasma levels of cortisol and copeptin were associated with stroke severity and short-term functional outcomes and remained independent outcome predictors after adjusting for all other significant outcome predictors. | Plasma cortisol predicts long-term mortality after IS. Increase of cortisol level in blood is prognostically unfavorable. | Tu et al., 2013 |
| Chinese patients with acute IS | Positive correlations were found between levels of cortisol and NIHSS score, glucose levels and infarct volume. Cortisol was an independent prognostic marker of functional outcome and death even after correcting confounding factors. | Cortisol is an independent short-term prognostic marker of functional outcome and death. Cortisol can improve the NIHSS score in predicting short-term functional outcome. | Zi and Shuai, 2013 |
| TIA patients | Serum cortisol levels were significantly increased only in females with TIA. | Cortisol response in TIA is sex-dependent. | Klimenko et al., 2016 |
| IS patients | In acute IS patients, increased plasma cortisol negatively correlated with plasma brain-derived neurotrophic factor (BDNF), neurological condition, cognitive function, functional responses, and emotional status. | Declines in clinical, behavioral, and biochemical blood parameters are associated with stress-induced cortisol elevation. | Casas et al., 2017 |
| IS patients | In patients with acute IS, increased cortisol levels inversely correlated with blood lymphocyte count. After IS, increased serum cortisol was independently associated with neutrophilia and lymphopenia. | HPA axis mediates B lymphopoiesis defects after IS. | Zierath et al., 2018 |
| IS patients, TIA patients | Higher hair cortisol concentration were significantly associated with a larger lesion volume and worse cognitive results 6, 12, and 24 months post-stroke. Higher hair cortisol at baseline was significant risk factor for cognitive decline, after adjustment for age, gender, body mass index, and apolipoprotein E4 (APOE E4) carrier status. | Individuals with higher hair cortisol concentration are prone to develop cognitive decline following moderate IS or TIA. | Ben Assayag et al., 2017 |
| Longitudinal IS survivors cohort | Higher bedtime salivary cortisol levels immediately post-stroke are associated with larger neurological deficits, brain atrophy, worse white matter integrity, and worse cognitive results up to 24 months post-stroke. | High bedtime salivary cortisol post-stroke provides information about dysregulation of diurnal HPA axis activity and predicts worse cognitive outcome. | Tene et al., 2018 |
| Mild cognitive impairment (MCI) after IS | Higher salivary cortisol was associated with a higher probability of secondary MCI occurrence after IS. | Salivary cortisol level is an independent risk factor of MCI after IS and can be used as a predictive marker for MCI. | Wang et al., 2021 |
| IS patients | Systematic review of clinical SI studies | Stress response (cortisol levels, HPA axis activation) is among most promising prognostic biomarkers. | Montellano et al., 2021 |