Dismissal of the utility of free cortisol measurement is premature

Cohen, Jérémy; Pretorius, Carel J.; Venkatesh, Balasubramanian

doi:10.1007/s00134-012-2505-4

Cited by 2 publications

(3 citation statements)

References 5 publications

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“…Dysregulation of the hypothalamic-pituitary-adrenal axis associated with variable cortisol levels, altered cortisol metabolism, and tissue resistance to glucocorticoids are considered the three major constituents of CIRCI (1,5,27). Altered cellular glucocorticoid metabolism and specifically reduced cortisol metabolism in sepsis have been well described elsewhere (1,4,58,99).…”

Section: Altered Regulation Of Cortisol and Aldosteronementioning

confidence: 99%

“…Thus, a single adrenocorticotropic hormone stimulation test does not reveal adrenal insufficiency in septic shock (109). Additionally, the decline in plasma binding protein that occurs may result in a decrease in total cortisol levels (70,99). Elevated serum cortisol levels in critical illness raise the concern that lack of a total cortisol response to corticotrophin may be an appropriate negative feedback response of a hypercortisolemic state (4,41).…”

Section: Challenges With the Confirmation Of Deficiency Statesmentioning

confidence: 99%

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CIRMI—a new term for a concept worthy of further exploration: a narrative review

Nethathe¹,

Lipman²,

Anderson³

et al. 2022

Ann Transl Med

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Background and Objective: Critical illness-related corticosteroid insufficiency (CIRCI) describes hypothalamic-pituitary-axis impairment during critical illness associated with three major pathophysiological events; dysregulation of the hypothalamic-pituitary-axis, altered cortisol metabolism, and tissue corticosteroid resistance. Similar changes are evident with regard to mineralocorticoid dysfunction in critical illness. Hyperreninemic hypoaldosteronism describes a sub-population of critically ill patients with an impaired adrenal aldosterone response to increased levels of renin. In the light of the recent demonstration of significant mortality improvements associated with adjunctive glucocorticoid treatment in combination with fludrocortisone in septic shock, and the suggestion that angiotensin II is effective in treating vasodilatory shock, the clinical relevance of mineralocorticoid dysfunction in critical illness requires further exploration. This interpretative review considers hyperreninemic hypoaldosteronism, a concept worth re-examining in the light of the potential mortality benefit of mineralocorticoid supplementation in critical illness. We compare the pathophysiological and clinical characteristics of CIRCI and hyperreninemic hypoaldosteronism, two syndromes that represent corticosteroid and mineralocorticoid dysfunction in critical illness. We highlight gaps in the literature and give novel insights into the limitations of assessment, diagnosis and treatment.Methods: English language abstracts and articles published before June 2021 were identified through PubMed and Google Scholar. Randomized trials, observational studies, basic sciences studies, systematic and narrative reviews were considered. Reference lists of articles were searched for further relevant material.Key Content and Findings: Difficulties are encountered in interpreting measures of gluco-and mineralocorticoid activity in critical illness. Aldosterone levels, like cortisol, have been shown to be increased in sepsis and hemorrhagic shock. The finding of hyperreninemia and hyperaldosteronism with an aldosterone/plasma renin activity ratio below 2 should prompt consideration of hyperreninemic hypoaldosteronism, a finding, which likely signifies the loss of negative feedback control of the renin-angiotensin-aldosterone system.Conclusions: As there is evidence to suggest that in acute critical illness, hyperreninemic hypoaldosteronism, is associated with poor outcomes, co-administration of hydrocortisone with fludrocortisone in patients with septic shock should be considered. In keeping with the concept of CIRCI, we suggest the term critical illness-related mineralocorticoid insufficiency as a more appropriate description ^ ORCID: Gladness Dakalo Nethathe,

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Section: Altered Regulation Of Cortisol and Aldosteronementioning

confidence: 99%

Section: Challenges With the Confirmation Of Deficiency Statesmentioning

confidence: 99%

CIRMI—a new term for a concept worthy of further exploration: a narrative review

Nethathe¹,

Lipman²,

Anderson³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…The letter from Cohen and colleagues [ 1 ] referring to our recently published assessment [ 2 ] of adrenal (in)sufficiency of corticosteroid secretion raises the interesting debate of whether we should measure free cortisol levels in critically ill patients with a suspicion of critical illness-related corticosteroid insufficiency (CIRCI).…”

mentioning

confidence: 99%