ArticleAmerican journal of physiology. Endocrinology and metabolism2014
Reduced nocturnal ACTH-driven cortisol secretion during critical illness.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Corticosteroids in septic shock: a systematic review and network meta-analysis.Critical care (London, England) · 2017Pooled it
- Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study.Critical care (London, England) · 2022Trial
- Persisting neuroendocrine abnormalities and their association with physical impairment 5 years after critical illness.Critical care (London, England) · 2021Trial
- ACTH and cortisol responses to CRH in acute, subacute, and prolonged critical illness: a randomized, double-blind, placebo-controlled, crossover cohort study.Intensive care medicine · 2018Trial
- Endocrine and metabolic alterations in response to systemic inflammation and sepsis: a review article.Molecular medicine (Cambridge, Mass.) · 2025Review
- Altered association between cortisol and adrenocorticotropic hormone levels in the early stage of type 2 diabetic ketoacidosis.Frontiers in endocrinology · 2025Article
- Critical illness-related corticosteroid insufficiency: latest pathophysiology and management guidelines.Acute and critical care · 2024Article
- SEMIPARAMETRIC BIVARIATE HIERARCHICAL STATE SPACE MODEL WITH APPLICATION TO HORMONE CIRCADIAN RELATIONSHIP.The annals of applied statistics · 2024Article
- Critical illness-related corticosteroid insufficiency (CIRCI) - an overview of pathogenesis, clinical presentation and management.Frontiers in endocrinology · 2024Review
- The Hypothalamus-pituitary-adrenocortical Response to Critical Illness: A Concept in Need of Revision.Endocrine reviews · 2023Article
- Article
- Glucocorticoid dysfunction in children with severe malaria.Frontiers in immunology · 2023Article
- Four-Compartment Diffusion Model of Cortisol Disposition: Comparison With 3 Alternative Models in Current Clinical Use.Journal of the Endocrine Society · 2022Article
- Adrenal Insufficiency in Cirrhosis.Journal of the Endocrine Society · 2022Review
- Critical Illness-induced Corticosteroid Insufficiency: What It Is Not and What It Could Be.The Journal of clinical endocrinology and metabolism · 2022Review
- Septic Shock: A Disruptor of the Hypothalamic-Adrenal Axis as We Know It.Endocrinology · 2022Article
- Adrenal function/dysfunction in critically ill patients: a concise narrative review of recent novel insights.Journal of anesthesia · 2021Review
- Decreased maximal cortisol secretion rate in patients with cirrhosis: Relation to disease severity.JHEP reports : innovation in hepatology · 2021Article
- Sepsis as a Pan-Endocrine Illness-Endocrine Disorders in Septic Patients.Journal of clinical medicine · 2021Review
- Dynamic Pituitary-Adrenal Interactions in the Critically Ill after Cardiac Surgery.The Journal of clinical endocrinology and metabolism · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P < 0.04). Pulsatile cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ≤ 0.03), as was ACTH-cortisol cross-approximate entropy (P ≤ 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.