Paper Chromatography prior to Cortisol RIA Allows for Accurate Use of the Dexamethasone Suppression Test in Chronic Renal Failure

Herle, André J. Van; Birnbaum, Jack; Slomowitz, Larry A.; Mayes, D.; Chandler, D.W.; Rosenblit, Paul D.; Nissenson, Allen R.

doi:10.1159/000045132

Cited by 9 publications

(6 citation statements)

References 13 publications

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“…Evidence is robust that the standard dose of 1mg Dexamethasone given orally at midnight is less effective at supressing morning cortisol in CKD ( Supplementary Table S7 ). Consistent findings are reported by numerous studies ( 29 , 41 , 49 , 58 , 59 , 76 ), while only one study indicated no significant difference to the healthy control group ( 35 ). The pharmacokinetics of oral Dexamethasone appear unaltered in CKD, meaning the data reflect a genuine difference in endogenous cortisol physiology rather than an artefact related to effective Dexamethasone dose ( 59 ).…”

Section: Hpa Axis Regulation Of Cortisol Secretion In Ckdsupporting

confidence: 87%

“…There is however considerable variability between studies in the literature (Table 1 and Supplementary Table S1). No statistically significant change of morning blood cortisol levels in CKD is reported by the majority of studies published since 1995 (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). Still, a substantial number of studies describe significant elevation of morning blood cortisol levels with renal impairment (46-50, 52, 55), while a few isolated studies also report a significant reduction (53, 54).…”

Section: Morning Cortisol In Bloodmentioning

confidence: 99%

“…Evaluation of endogenous ACTH levels entails similar challenges as for cortisol levels, in that levels are highly dynamic over 24 hours, with many studies relying on relatively small sample sizes and significant heterogeneity in study populations. Acknowledging these limitations, comparisons of early morning ACTH level between dialysis-treated patients and control groups have found significant increases ( 35 , 40 , 41 ), trends for non-significant increases ( 39 , 44 ) or no differences ( 32 , 34 , 43 ) ( Table 4 and Supplementary Table S6 ). Studies involving patients with pre-dialysis CKD tended to be larger but give a similarly mixed picture.…”

Section: Hpa Axis Regulation Of Cortisol Secretion In Ckdmentioning

confidence: 99%

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Cortisol excess in chronic kidney disease – A review of changes and impact on mortality

2023

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Chronic kidney disease (CKD) describes the long-term condition of impaired kidney function from any cause. CKD is common and associated with a wide array of complications including higher mortality, cardiovascular disease, hypertension, insulin resistance, dyslipidemia, sarcopenia, osteoporosis, aberrant immune function, cognitive impairment, mood disturbances and poor sleep quality. Glucocorticoids are endogenous pleiotropic steroid hormones and their excess produces a pattern of morbidity that possesses considerable overlap with CKD. Circulating levels of cortisol, the major active glucocorticoid in humans, are determined by a complex interplay between several processes. The hypothalamic-pituitary-adrenal axis (HPA) regulates cortisol synthesis and release, 11β-hydroxysteroid dehydrogenase enzymes mediate metabolic interconversion between active and inactive forms, and clearance from the circulation depends on irreversible metabolic inactivation in the liver followed by urinary excretion. Chronic stress, inflammatory states and other aspects of CKD can disturb these processes, enhancing cortisol secretion via the HPA axis and inducing tissue-resident amplification of glucocorticoid signals. Progressive renal impairment can further impact on cortisol metabolism and urinary clearance of cortisol metabolites. Consequently, significant interest exists to precisely understand the dysregulation of cortisol in CKD and its significance for adverse clinical outcomes. In this review, we summarize the latest literature on alterations in endogenous glucocorticoid regulation in adults with CKD and evaluate the available evidence on cortisol as a mechanistic driver of excess mortality and morbidity. The emerging picture is one of subclinical hypercortisolism with blunted diurnal decline of cortisol levels, impaired negative feedback regulation and reduced cortisol clearance. An association between cortisol and adjusted all-cause mortality has been reported in observational studies for patients with end-stage renal failure, but further research is required to assess links between cortisol and clinical outcomes in CKD. We propose recommendations for future research, including therapeutic strategies that aim to reduce complications of CKD by correcting or reversing dysregulation of cortisol.

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Section: Hpa Axis Regulation Of Cortisol Secretion In Ckdsupporting

confidence: 87%

Section: Morning Cortisol In Bloodmentioning

confidence: 99%

Section: Hpa Axis Regulation Of Cortisol Secretion In Ckdmentioning

confidence: 99%

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Cortisol excess in chronic kidney disease – A review of changes and impact on mortality

2023

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“…24-h UFC, assayed by HPLC Tandem Mass Spectrometry, was measured by Esoterix Endocrinology [25, 26]. The 95 % tolerance interval (normal range) for women was determined by measurement in 20 healthy adult females and found to be 10–34 µg/d (28–94 nmol/d) in females and 11–84 µg/d (28–94 nmol/d) in males [25].…”

Section: Methodsmentioning

confidence: 99%

High Prevalence of Normal Tests Assessing Hypercortisolism in Subjects with Mild and Episodic Cushing's Syndrome Suggests that the Paradigm for Diagnosis and Exclusion of Cushing's Syndrome Requires Multiple Testing

et al. 2010

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Many Endocrinologists believe that a single determination of eucortisolism or a single demonstration of appropriate suppression to dexamethasone excluded Cushing's syndrome, except in what was previously thought to be the rare patient with episodic or periodic Cushing's syndrome. We hypothesize that episodic Cushing's syndrome is relatively common and a single test assessing hypercortisolism may not be sufficient to accurately rule out or diagnose Cushing's syndrome and retrospectively examined the number of normal and abnormal tests assessing hypercortisolism performed on multiple occasions in 66 patients found to have mild and/or episodic Cushing's syndrome compared to a similar group of 54 patients evaluated for, but determined not to have Cushing's syndrome. We found that 65 of the 66 patients with Cushing's syndrome had at least one normal test of cortisol status and most patients had several normal tests. The probability of having Cushing's syndrome when one test was negative was 92 % for 23:00 h salivary cortisol, 88 % for 24-h UFC, 86 % for 24-h 17OHS, and 54 % for nighttime plasma cortisol. These results demonstrated that episodic hypercortisolism is highly prevalent in subjects with mild Cushing's syndrome and no single test was effective in conclusively diagnosing or excluding the condition. Rather, the paradigm for the diagnosis should be a careful history and physical examination and in those patients in whom mild Cushing's syndrome/disease is strongly suspected, multiple tests assessing hypercortisolism should be performed on subsequent occasions, especially when the patient is experiencing signs and symptoms of short-term hypercortisolism.

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“…Androgens in seminal plasma were significantly lower by RIA after paper chromatography (Zalata et al, 1995). Measurement of cortisol in patients with chronic renal failure, who were given dexamethasone to suppress the cortisol production, were superior after paper chromatography than by direct RIA (Van Herle et al, 1998). It is our experience that paper chromatography using Bush systems is time-consuming and significant amounts of potentially interfering non-specific material is usually eluted from the paper together with the steroid of interest, giving rise to high blank values.…”

Section: Paper Chromatographymentioning

confidence: 99%

General Methods for the Extraction, Purification, and Measurement of Steroids by Chromatography and Mass Spectrometry

Makin

Honour

Shackleton³

et al. 2010

Steroid Analysis

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Paper Chromatography prior to Cortisol RIA Allows for Accurate Use of the Dexamethasone Suppression Test in Chronic Renal Failure

Cited by 9 publications

References 13 publications

Cortisol excess in chronic kidney disease – A review of changes and impact on mortality

Cortisol excess in chronic kidney disease – A review of changes and impact on mortality

High Prevalence of Normal Tests Assessing Hypercortisolism in Subjects with Mild and Episodic Cushing's Syndrome Suggests that the Paradigm for Diagnosis and Exclusion of Cushing's Syndrome Requires Multiple Testing

General Methods for the Extraction, Purification, and Measurement of Steroids by Chromatography and Mass Spectrometry

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