The hypothalamic–pituitary–adrenal axis in critical illness

Abstract

Hypothalamic-pituitary-adrenal (HPA) axis function is crucial to maintain and restore homeostasis. The HPA axis does not function in isolation. Rather, the HPA axis modulates and reacts to signals from endocrine, neural, and immune systems. Cortisol is the major glucocorticoid secreted by the human adrenal cortex. Its actions are largely mediated by the glucocorticoid receptor. The potent anti-inflammatory actions of glucocorticoids led to their use in critically ill patients. Metaanalyses of these early studies (before 1985) concluded that large glucocorticoid doses had no effect and were potentially detrimental. More recently, the pendulum has swung in the opposite direction based on the concept that critically ill patients may have relative adrenal insufficiency and/or acquired glucocorticoid resistance. However, inconsistent diagnostic criteria, heterogeneity of subjects, variable nutritional status, and pre-existing conditions preclude formulating definitive conclusions regarding glucocorticoid use among critically patients. Diagnosing adrenal insufficiency in the critically ill patient remains challenging. To resolve the issue, our challenge is to develop physiologically relevant tools to assess glucocorticoid action and GR function at the cellular level.

No Significance of the Free Cortisol Index Compared to Total Cortisol in Critically Ill Patients

“…Thus, this results made clinicians reluctant to prescribe corticosteroids, though Corticus study was criticized for selection bias (patients least likely to benefit from corticosteroids were enrolled in the study) [14]. Potential benefits of glucocorticoid therapy in critically ill patients include anti-inflammatory effects, inhibition of cytokine production, decreased arachidonic acid synthesis, increased antiinflammatory cytokine expression, and effects on the cardiovascular system to promote both improved vascular tone and catecholamine responsiveness [1]. Adverse sequelae include hyperglycemia, insulin resistance, bone loss, muscle wasting, hypokalemia, and changes in mental status [1].…”

“…Cortisol must be adequately secreted under stressful conditions because it is one of the essential hormones for maintaining and restoring homeostasis following stressful events [1]. Acute physiologic stress, e.g., septic shock, increases adrenocorticotropic hormone (ACTH) and cortisol secretion through activation of the hypothalamus-pituitary-adrenal (HPA) axis.…”

“…Thus, investigations are limited to measurements of basal cortisol levels or the short Synacthen test (SST). Many criteria have been suggested for defining CIRCI, yet this issue is still being debated [1,3,4]. However, the SST has been criticized that sepsis itself may evoke maximum cortisol secretion in individuals, thus SST may not be needed in maximally stimulated situation such as sepsis.…”

“…To overcome these limitations, the free cortisol index (FCI, serum cortisol divided by serum CBG concentration) was suggested to reflect the free cortisol. Forth, the benefit of glucocorticoids in sepsis is still unclear [1,5]. If there were a more confirmative diagnosis, the benefit would be greater.…”

Fungsi Adrenal pada Sepsis di Unit Perawatan Intensif Pediatrik

“…1 Akhir-akhir ini insufisiensi adrenal dilaporkan cukup sering pada pasien kritis seperti sepsis berat dan syok septik dengan insidens 15%-61%. [4][5][6][7][8][9][10][11][12][13][14][15][16] Kondisi tersebut bersifat sementara dan akan kembali normal dengan membaiknya sepsis sehingga diduga mediator inflamasi yang dilepaskan selama syok septik menyebabkan disfungsi jaras HHA dan insufisiensi adrenal.…”