Cortisol: ACTH ratio to test for primary hypoadrenalism: a pilot study

Lee, Mark K V; Vasikaran, Samuel; Doery, James C.G.; Wijeratne, Nilika; Prentice, David

doi:10.1136/postgradmedj-2012-131723

Cited by 18 publications

(15 citation statements)

References 19 publications

(12 reference statements)

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“…Particularly during the chronic or prolonged phase of critical illness (rather than in the acute phase, as in the Boonen et al study [ 20 ]), low ACTH and elevated cortisol levels can be seen, suggestive of increased sensitivity to ACTH or ACTH-independent cortisol production [ 2 , 21 - 23 ]. The latter may be caused by non-ACTH pituitary stimulants or feedback suppression of ACTH after impaired cortisol metabolism and persistent hypercortisolemia [ 2 , 21 - 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with etomidate-inhibiting adrenal cortisol synthesis, indeed, reduces the cortisol/ACTH ratio and diminishes the cortisol response to exogenous ACTH [ 16 , 19 ]. The ratio is used to diagnose primary absolute adrenal insufficiency [ 20 ]. However, Boonen et al [ 21 ] recently suggested that, during critical illness, impaired cortisol metabolism (measured in relatively few patients) contributes to elevated (free) cortisol levels and low endogenous ACTH levels via feedback inhibition, and thereby to a diminished response to exogenous ACTH in the absence of adrenal dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study

et al. 2015

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IntroductionAdrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recovery from the acute phase.MethodsWe prospectively included 59 consecutive septic and nonseptic patients in the intensive care unit with treatment-insensitive hypotension in whom CIRCI was suspected; patients having received etomidate and prolonged corticosteroids were excluded. An ACTH test (250 μg) was performed, followed by a second test after ≥7 days in acute-phase survivors. Serum total and free cortisol, ACTH, and clinical variables were assessed. Patients were divided according to responses (delta, Δ) of cortisol to ACTH at the first and second tests.ResultsPatients with low (<250 nM) Δ cortisol (n = 14 to 17) had higher baseline cortisol and ACTH but lower cortisol/ACTH ratios than patients with a normal Δ cortisol (≥250 nM) in the course of time. A low Δ cortisol in time was associated with more-severe disease, culture-positive sepsis, and prolonged activated prothrombin time. Results for free cortisol were similar.ConclusionsEven though the pituitary-adrenal axis is activated after stress during critical illness, diminished adrenal sensitivity to endogenous ACTH predicts a low increase of cortisol to exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of disease. The data further suggest a role of disease severity and culture-positive sepsis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study

et al. 2015

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“…In particular, no patient had a ratio <3.0 suggestive of primary hypoadrenalism. 14 We found no correlation between the change in LDL-C from baseline to week 52 and the corresponding change in cortisol (Online Figure I). Cortisol, ACTH, and the cortisol:ACTH ratio also showed no significant changes in placebo-treated patients.…”

Section: Steroid Hormonesmentioning

confidence: 79%

“…We calculated cortisol:ACTH for all patients, because a ratio of <3.0 (nmol/pmol) may suggest a diagnosis of primary hypoadrenalism. 14 The primary end point of the study (percent change from baseline in ultracentrifugation LDL-C at week 52 with evolocumab when …”

Section: Discussionmentioning

confidence: 99%

“…The fact that the cortisol:ACTH ratio was >3.0 in all patients is reassuring because a cortisol:ACTH ratio of <3.0 was recently shown to be 100% sensitive for the diagnosis of primary hypoadrenalism in 349 patients undergoing testing because of suspected adrenal or pituitary disease. 14 In conclusion, we show that adding evolocumab to lipidlowering therapies ranging from diet alone to the combination of maximal dose of atorvastatin with ezetimibe does not affect vitamin E or steroid hormone metabolism in a clinically significant fashion, despite LDL-C being lowered to previously unprecedented levels. What Is Known?…”

Section: 22mentioning

confidence: 99%

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Effects of Evolocumab on Vitamin E and Steroid Hormone Levels

Blom

Djedjos

Monsalvo

et al. 2015

Circulation Research

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Rationale : Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels. Objective: To determine the effects of evolocumab on vitamin E and steroid hormone levels. Methods and Results: After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C ≥2.0 mmol/L were randomized to 52 weeks of monthly, subcutaneous evolocumab, or placebo. Vitamin E, cortisol, adrenocorticotropic hormone, and gonadal hormones were analyzed at baseline and week 52. In a substudy (n=100), vitamin E levels were also measured in serum, LDL, high-density lipoprotein, and red blood cell membranes at baseline and week 52. Absolute vitamin E decreased in evolocumab-treated patients from baseline to week 52 by 16% but increased by 19% when normalized for cholesterol. In the substudy, vitamin E level changes from baseline to week 52 mirrored the changes in the lipid fraction, and red blood cell membrane vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but adrenocorticotropic hormone and the cortisol:adrenocorticotropic hormone ratio did not change. No patient had a cortisol:adrenocorticotropic hormone ratio <3.0 (nmol/pmol). Among evolocumab-treated patients, gonadal hormones did not change from baseline to week 52. Vitamin E and steroid changes were consistent across subgroups by minimum postbaseline LDL-C <0.4 and <0.6 mmol/L. Conclusions: As expected, vitamin E levels changed similarly to lipids among patients treated for 52 weeks with evolocumab. No adverse effects were observed in steroid or gonadal hormones, even at very low LDL-C levels. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01516879.

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