Characterising adrenal function using directly measured plasma free cortisol in stable severe liver disease

Tan, Terrence; Chang, Linus; Woodward, Aidan J.; McWhinney, Brett; Galligan, John; Macdonald, Graeme A.; Cohen, Jérémy; Venkatesh, Balasubramanian

doi:10.1016/j.jhep.2010.05.020

Cited by 86 publications

(123 citation statements)

References 38 publications

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“…67,68 Chronic liver disease is strongly associated with adrenal failure, mainly diagnosed by low base line or stimulated total serum cortisol levels, which occur in 58-77% of patients with chronic liver disease. 67,69,70 Low cortisol levels in these patients have been mostly attributed to low levels of cholesterol, the main pre cursor for adrenal steroidogenesis. 67 However, patients with chronic liver disorders might also have reduced protein synthesis and decreased levels of cortisol-binding proteins, 71 which could lead to the misinterpretation of low total hormone levels and an incorrect diagnosis of adrenal insufficiency.…”

Section: Chronic Liver Disease and The Hpa Axismentioning

confidence: 99%

Regulation of cortisol bioavailability—effects on hormone measurement and action

2012

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Routine assessment of the hypothalamic-pituitary-adrenal axis relies on the measurement of total serum cortisol levels. However, most cortisol in serum is bound to corticosteroid-binding globulin (CBG) and albumin, and changes in the structure or circulating levels of binding proteins markedly affect measured total serum cortisol levels. Furthermore, high-affinity binding to CBG is predicted to affect the availability of cortisol for the glucocorticoid receptor. CBG is a substrate for activated neutrophil elastase, which cleaves the binding protein and results in the release of cortisol at sites of inflammation, enhancing its tissue-specific anti-inflammatory effects. Further tissue-specific modulation of cortisol availability is conferred by corticosteroid 11β-dehydrogenase. Direct assessment of tissue levels of bioavailable cortisol is not clinically practicable and measurement of total serum cortisol levels is of limited value in clinical conditions that alter prereceptor glucocorticoid bioavailability. Bioavailable cortisol can, however, be measured indirectly at systemic, extracellular tissue and cell levels, using novel techniques that have provided new insight into the transport, metabolism and biological action of glucocorticoids. A more physiologically informative approach is, therefore, now possible in the assessment of the hypothalamic-pituitary-adrenal axis, which could prove useful in clinical practice.

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Section: Chronic Liver Disease and The Hpa Axismentioning

confidence: 99%

Regulation of cortisol bioavailability—effects on hormone measurement and action

2012

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“…1a and c it is evident that there were samples with an appropriate FC increment and a TC increment below 250 nmol/L, which argues against the authors' conclusion that the increments are interchangeable. Observations from our group have documented significant discordance in diagnosis of adrenal insufficiency using TC and FC criteria in patients with liver disease, and in septic shock [3,4]. The authors' own observations that relative increases of FC were significantly higher than those of TC, as well as the documented stronger association of FC with sickness severity [5], suggest that FC may be a more valid index of adrenal function.…”

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confidence: 77%

Dismissal of the utility of free cortisol measurement is premature

2012

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“…This test is performed to determine whether the adrenal glands can respond normally to ACTH by producing free cortisol [1,2]. This test is particularly helpful in patient with albumin < 2.5 mg/dL or low CBG.…”

Section: Indicationmentioning

confidence: 99%