The hypothalamic-pituitary-adrenal axis in critical illness: response to dexamethasone and corticotropin-releasing hormone.

Reincke, Martín; Allolio, Bruno; Würth, G; Winkelmann, W.

doi:10.1210/jcem.77.1.8392081

Cited by 83 publications

(83 citation statements)

References 42 publications

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“…These observations are in line with the studies reporting up to 5 to 15-fold increased blood cortisol levels of critically ill-patients, such as patients with septic shock or massive bleeding (Uete et al, 1970;Sandberg et al, 1956;Jurney et al, 1987;Schroeder et al, 2001;Lamberts et al, 1997;Aygen et al, 1997). Since a positive correlation was observed between the degree of elevation of endogenous cortisol levels and the survival rate in critical disease conditions, the strong increase in endogenous cortisol is presumed to be a protective reflex of the organism against a fatal threat (Schroeder et al, 2001;Lamberts et al, 1997;Aygen et al, 1997;Reincke et al, 1993;Garcia Garcia et al, 2001;Shimada et al, 2000;Bollaert et al, 1998). High-dose glucocorticoids are, therefore, often used as supportive medication for critically ill patients in intensive care units (Shimada et al, 2000;Bollaert et al, 1998).…”

Section: Introductionsupporting

confidence: 87%

“…The high levels of cortisol during the moribund stage were also observed by clinical researchers in different kinds of fatal conditions (Sandberg et al, 1956;Reincke et al, 1993;Schroeder et al, 2001). Since patients who cannot achieve a cortisol rise during critical health conditions due to adrenal insufficiency have significantly lower survival rates (Schroeder et al, 2001), the rise in endogenous cortisol in fatal conditions is thought to help the patient to survive this critical stage.…”

Section: Discussionmentioning

confidence: 79%

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Stress of Dying is not Suppressed by High-dose Morphine or by Dementia

Erkut

Klooker

Endert

et al. 2003

Neuropsychopharmacol

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Hypothalamo-pituitary-adrenal (HPA)-axis activation is a response of the organism to psychological and physical stress, resulting in elevated levels of glucocorticoids, mainly cortisol in humans. In our previous studies we found post-mortem blood and cerebrospinal fluid (CSF) cortisol levels to be up to 20-fold higher than in vivo levels. Since clinical observations point to similar strong elevations of cortisol in fatally ill patients, we suggested that the high post-mortem cortisol levels might be due to the stress during the process of dying. We hypothesized that if the cortisol rise during dying is due to the psychological stress of the impending death, then the rise in cortisol should be inversely proportional to the degree of dementia, and that high-dose morphine giving analgesia, sedation, and sleep would suppress this response. Therefore, we measured the cortisol levels by radioimmunoassay (RIA) in the post-mortem CSF of 85 Alzheimer patients and 52 controls. In addition, post-mortem serum cortisol of 17 subjects from the Alzheimer group and nine from the control group were measured. The Alzheimer patients were subdivided according to their degree of dementia, as scored on the Reisberg Scale, before their death. All groups were further analyzed for the effect of morphine treatment, as well as for the effects of the confounding factors like age, gender, time, and season of death. Alzheimer patients had significantly higher cortisol levels than controls, both in CSF (mean (nmol/ l) 7 SEM: 482 7 32 vs 285 7 30, respectively, po0.001) and in serum (2854 7 279 vs 1533 7 395, p ¼ 0.011). Mean CSF cortisol level of the severely demented Alzheimer group was even significantly higher than that of mildly demented group (508 7 35 vs 225 7 65, p ¼ 0.024) and controls (po0.001). Cortisol levels correlated positively with the degree of dementia in the Alzheimer group (r ¼ 0.236, p ¼ 0.035). High-dose morphine did not cause a suppression of cortisol rise, neither in controls nor in Alzheimer patients. Our results indicate that the extreme elevations of cortisol levels during dying are rather due to the organic stress of the organism than to psychological stress of the patient, and is not suppressed by high-dose morphine.

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Section: Introductionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 79%

Stress of Dying is not Suppressed by High-dose Morphine or by Dementia

Erkut

Klooker

Endert

et al. 2003

Neuropsychopharmacol

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“…57 We also measured ACTH concentrations in a subset of these critically ill infants (n ¼ 10), and found that they were 12 pg ml À1 (5.5 to 19.2), similar to what Soliman et al 57 found in their ill infant population (n ¼ 10, median 11.9 pg ml À1 (4.3 to 19)), far lower than the concentrations found in critically ill adults and children. 60,61 Thus, the majority of these critically ill newborns had very low cortisol and ACTH values, without the expected increase in response to critical illness; however, their response to exogenous ACTH was normal, showing that the inadequate response to critical illness in these newborns does not result from adrenal dysfunction, and therefore must arise from another component of the HPA axis. 59 Data regarding the association of treatment of adrenal insufficiency with outcomes in the term newborn are limited, 56,58 with no studies on outcomes beyond the immediate neonatal period.…”

Section: Clinical Evidencementioning

confidence: 97%

Relative adrenal insufficiency in the preterm and term infant

2009

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Cortisol release in the face of illness or stress is vital for survival. Relative adrenal insufficiency occurs when a patient's cortisol response is inadequate for the degree of illness or stress. Numerous studies have documented the existence of relative adrenal insufficiency in critically ill adults, and its association with increased morbidity and mortality. There is increasing evidence that relative adrenal insufficiency may be an etiology for hemodynamic instability and hypotension in the critically ill newborn, but compared with the adult population, there is still a paucity of data in this population. Randomized controlled trials are needed to evaluate the efficacy and safety of glucocorticoids for the treatment of cardiovascular insufficiency due to relative adrenal insufficiency in ill preterm and term newborn infants. Keywords: adrenocorticotropin; ACTH; adrenal insufficiency; corticotrophin-releasing hormone; cortisol; critically ill infants hypothalamic-pituitary-adrenal axis; newborns-full term Introduction Activation of the hypothalamic-pituitary-adrenal (HPA) axis and ultimate release of cortisol are critical in maintaining homeostasis in response to stress. Relative adrenal insufficiency occurs when the HPA axis produces insufficient cortisol for the degree of illness or stress. In some critically ill adult populations, relative adrenal insufficiency is prevalent, 1-4 and is associated with increased morbidity and mortality. 2,3,5 Some studies of glucocorticoid treatment in critically ill adults have shown benefit, with faster reversal of shock and reduction in mortality. 3,[5][6][7][8] Recently, increasing evidence supports the existence of relative adrenal insufficiency in ill newborns, but, similar to other ill populations, there remains no general consensus on which patients should be tested, which tests to use and how to interpret them, which patients should be treated or how they should be treated. 9 The following discussion is an overview of corticosteroid physiology, relative adrenal insufficiency in critically ill populations and evidence of its existence in newborn infants, with proposed underlying

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“…[1][2][3][4][5][6][7] This activation is an essential component of the general adaptation to stress and contributes to the maintenance of homeostasis. 8 The efficacy of replacement doses or high doses of corticosteroids in patients with severe illness, especially those with multiorgan-system diseases, is uncertain.…”

mentioning

confidence: 99%