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BACKGROUND & AIMS: Hepatic enzymes play a major role in the metabolic elimination of cortisol, and reduced rates of cortisol clearance have been consistently observed in patients with chronic liver disease. It is less clear whether there are concomitant abnormalities of adrenocortical function in patients with cirrhosis. In the present study, we sought to assess adrenocortical function in patients with cirrhosis using measures of free cortisol appearance and elimination rates that are independent of serum concentrations of cortisol binding proteins. METHODS: Post hoc analysis used computer-assisted numerical and modelling methods with serial total and free cortisol concentration data to obtain rates of free cortisol appearance and elimination. Rate parameters were obtained in 114 patients with chronic liver disease, including Child-Pugh (CP) ≤8 (n = 53) and CP >8 (n = 61). RESULTS: Maximal cortisol secretion rate (CSRmax) was significantly decreased (p = 0.01) in patients with cirrhosis with CP >8 (0.28 nM/s; 95% CI 0.24-0.34) compared with those with CP ≤8 (0.39 nM/s; 95% CI 0.33-0.46), and CSRmax was negatively correlated with CP score (r = -0.19, p = 0.01). Free cortisol elimination rate was significantly (p = 0.04) decreased in the CP >8 group (0.16 ± 0.20 min-1) compared with that in the CP ≤8 group (0.21 ± 0.21 min-1), and free cortisol elimination rates were negatively correlated with CP score (r = -0.23, p = 0.01). A significant correlation between CSRmax and free cortisol elimination rate (r = 0.88, p <0.001) was observed. CONCLUSIONS: CSRmax and free cortisol elimination rates were significantly reduced according to severity of cirrhosis. In contrast to stimulated total cortisol concentrations, CSRmax estimates were independent of cortisol-binding protein concentrations. Results provide additional evidence of subnormal adrenocortical function in patients with cirrhosis. LAY SUMMARY: We applied numerical analytic methods to characterise adrenocortical function in patients with varying stages of chronic liver disease. We found that patients with more severe cirrhosis have decreased rate of free cortisol elimination and decreased maximal cortisol secretion rate, which is a measure of adrenocortical function. In contrast to conventional measures of adrenocortical function, those obtained using numerical methods were not affected by variation in corticosteroid binding globulin and albumin concentrations. We conclude that patients with cirrhosis demonstrate measurable abnormalities of adrenocortical function, evidence of which supports aspects of the hepatoadrenal syndrome hypothesis.
RESUMEN
BACKGROUND/AIMS: Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with high morbidity and mortality. Treatment with steroids is known to decrease short-term mortality in severe AH patients. Hence, we hypothesize that adrenal insufficiency can be associated with severe AH and affects prognosis. The aim of this study was (1) to evaluate relative adrenal insufficiency (RAI) in patients with AH and (2) to Compare RAI with the severity of AH. METHODS: Newly diagnosed cases of AH hospitalized in SMS Medical College and Hospital, Department of Gastroenterology were, enrolled. All patients of AH were classified as mild and severe AH on the basis of Maddrey discriminant function (DF). After baseline serum cortisol, 25 IU ACTH (Adreno Corticotrophic Hormone) was injected intramuscularly and blood sample was collected after 1 h and assessed for serum cortisol. RAI was defined as <7 µg increase in the cortisol level from baseline. RAI was compared with severity of AH. RESULTS: Of 120 patients of AH, 58 patients fulfilled the inclusion criteria, in which 48 patients were diagnosed as severe AH and 10 patients were diagnosed as mild AH. In patients with severe AH, the baseline mean serum cortisol level was significantly high as compared with mild AH; 26 patients (54.16 %) of 48 patients with severe AH showed RAI (P ≤ 0.001).Whereas in patients with mild AH, none of patients showed RAI. RAI also showed negative correlation with DF. There was no difference in RAI with respect to acute kidney injury (AKI). CONCLUSION: RAI is a common entity in patients with severe AH, and it is related with the severity of disease.
RESUMEN
In the last two decades there was important evolution on the knowledge of the function of the hypothalamic-pituitary-adrenal axis. In the last decade, the expression "relative adrenal insufficiency" (RAI) was created, and more recently "critical illness-related corticosteroid insufficiency" (CIRCI) was used to designate those patients in which cortisol production was not sufficiently increased in stress situations. Patients with CIRCI have elevated hospital morbidity and mortality. Currently, there is a wide discussion about diagnostic criteria for this dysfunction. Besides basal cortisol, some publications now study the role of other tests, such as cortrosyn test - either in low (1 μg) or high doses (250 μg); free cortisol, salivary cortisol, metyrapone test and others. With this review, we aimed at summarizing the results of the most influent papers that intended to define diagnostic criteria for CIRCI. We also suggest an approach for CIRCI diagnosis and make it clear that the decision about steroid therapy in septic shock patients is matter apart from RAI.
Nas últimas décadas, houve uma importante evolução no conhecimento sobre a função do eixo hipotálamo-pituitária-adrenal. Na última década, foi cunhada a expressão "insuficiência adrenal relativa" (IAR) e, mais recentemente, a expressão "insuficiência adrenal relacionada à doença grave" (CIRCI) foi utilizada para designar aqueles pacientes nos quais a produção de cortisol não era suficientemente elevada em situações de estresse. Pacientes com CIRCI apresentam elevada morbidade e mortalidade em hospitais. Atualmente, há uma ampla discussão sobre os critérios de diagnóstico para essa desordem. Além do cortisol basal, algumas publicações analisaram o papel de outros testes, tais como o teste de estímulo com ACTH (cortrosina), com doses baixas (1 mg) ou altas (250 mg), cortisol livre, cortisol salivar, teste da metirapona e outros. O objetivo desta revisão foi resumir os resultados dos artigos mais importantes que buscaram definir os critérios de diagnóstico para a CIRCI. Também sugerimos uma abordagem para o diagnóstico da CIRCI e deixamos claro que a decisão sobre a terapia com esteroides em pacientes em choque séptico é uma questão separada da IAR.