In the overnight dexamethasone suppression test, 1.0 mg loading is superior to 0.5 mg loading for diagnosing subclinical adrenal Cushing’s syndrome based on plasma dexamethasone levels determined using liquid chromatography-tandem mass spectrometry

Sasaki, Yasutsuna; Katabami, Takuyuki; Asai, Shiko; Fukuda, Hisashi; Tanaka, Yasushi

doi:10.1507/endocrj.ej17-0083

Cited by 12 publications

(11 citation statements)

References 29 publications

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“…This helps to maximize analytical recovery and reduce matrix effects, thus allowing for an efficient and sensitive method capable of measuring dexamethasone down to concentrations of 0.25 nmol/L. SLE methods hold an advantage over SPE [5][6][7][8] as they are considerably quicker, require fewer steps (thereby reducing inter-operator variation) and are generally less expensive. In addition, the SLE extracts are stable for up to 96 h when stored at either 10 C or À20 C allowing samples to be reinjected or temporarily stored should there be unforeseen instrument downtime.…”

Section: Discussionmentioning

confidence: 99%

“…3 More recently, several liquid chromatography tandem mass spectrometry (LC-MS/MS) methods have been published. Many of these rely on solid phase extraction (SPE) for sample preparation, 5–8 protracted run-times, 9 or are not sensitive enough to be used in combination with the ONDST. 10,11 These issues have limited the widespread application of serum dexamethasone measurement into the workflow of busy, high-throughput clinical laboratories.…”

Section: Introductionmentioning

confidence: 99%

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Development of a rapid liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone and its clinical verification

et al. 2018

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Background Measurement of serum dexamethasone during the overnight dexamethasone-suppression test has been recommended to reduce false-positive results when investigating Cushing's syndrome or increasingly commonly found adrenal incidentalomas. Despite this, there remains a paucity of well-validated dexamethasone methods currently available. Here, we describe the development of a rapid and sensitive liquid chromatography tandem mass spectrometry serum dexamethasone assay and verify its utility in a cohort of postmenopausal females. Method Isotopically labelled internal standard was added to samples prior to supported liquid extraction. Extracts were analysed using liquid chromatography tandem mass spectrometry in the positive electrospray ionization mode. Multiple reaction monitoring was used to detect dexamethasone and its corresponding internal standard transitions. Normal healthy postmenopausal women ( n = 95) were recruited and underwent an overnight dexamethasone suppression test, with serum dexamethasone and cortisol measurements at 09:00 after administration of oral dexamethasone 1 mg at 23:00 the night before. Results Mean intra- and inter-assay imprecision were 4.1% and 2.9%, respectively, for dexamethasone concentrations of 1.5, 6.0 and 12.0 nmol/L. Matrix effects were found to be negligible at 106-109% with recovery ranging from 96 to 100%. The limit of quantitation was 0.25 nmol/L, and structural analogue analysis proved the method to be robust against interferences. Applying a serum dexamethasone cut-off of >3.3 nmol/L was associated with a serum cortisol ≤50 nmol/L in 84/95 individuals. Conclusion We have developed a sensitive and robust liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone. The method can be used to identify false-positive results during the overnight dexamethasone suppression test or for pharmacokinetic studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a rapid liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone and its clinical verification

et al. 2018

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“…The blood concentration of DEX after loading with 1 mg of DEX was about twice that after loading with 0.5 mg of DEX. Also, the blood concentration of DEX was not associated with body weight, body surface area or the body mass index [22]. From these findings, it was concluded that a 1-mg DST was more effective than a 0.5-mg DST in terms of reducing the risk of false-positive results in the DST due to insufficient suppression of ACTH.…”

Section: Evidence For the Proposal Of New Diagnostic Criteria For Scsmentioning

confidence: 87%

“…Katabami et al [22] investigated the adoption of 0.5 mg or 1 mg for the DST. They measured the blood concentration of dexamethasone (DEX) in SCS cases using LC-MS/MS.…”

Section: Evidence For the Proposal Of New Diagnostic Criteria For Scsmentioning

confidence: 99%

New diagnostic criteria of adrenal subclinical Cushing’s syndrome: opinion from the Japan Endocrine Society

et al. 2018

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Abstract. New diagnostic criteria and the treatment policy for adrenal subclinical Cushing's syndrome (SCS) are proposed on behalf of the Japan Endocrine Society. The Japanese version has been published, and the essential contents are presented in this English-language version. The current diagnostic criteria for SCS have elicited two main problems: (i) the relatively low reliability of a low range of serum cortisol essential for the diagnosis by an overnight 1-mg dexamethasone suppression test (DST); (ii) different cutoff values for serum cortisol after a 1-mg DST compared with those of other countries. Thus, new criteria are needed. In the new criteria, three hierarchical cortisol cutoff values, 5.0, 3.0 and 1.8 μg/dL, after a 1-mg DST are presented. Serum cortisol ≥5 μg/dL after a 1-mg DST alone is considered sufficient to judge autonomous cortisol secretion for the diagnosis of SCS, and the current criterion based on serum cortisol ≥3 μg/dL after a 1-mg DST can continue to be used. Clinical evidence suggests that serum cortisol ≥1.8-2.9 μg/dL after a 1-mg DST is not always normal, so cases who meet the cutoff value as well as a basal adrenocorticotropic hormone (ACTH) level <10 pg/mL (or poor ACTH response to corticotropin-releasing hormone (CRH)) and nocturnal serum cortisol ≥5 μg/dL are proposed to have SCS. We suggest surgery if cases show serum cortisol ≥5 μg/dL after a 1-mg DST (or are disheartened by treatment-resistant problems) or suspicious cases of adrenal cancer according to tumor imaging. [7,8] and a reduction in bone quality when evaluated by the Spinal Density Index [9]. However, with changes in the measurement system (from radioimmunoassay to enzyme immunoassay) of cortisol in blood, four main discussions have arisen: (i) the relatively low reliability of a low range of cortisol concentrations (<3 μg/dL) essential for the diagnosis after an overnight 1-mg DST [10]; (ii) the inconsistency of the screening criteria of SCS with those proposed by the American Endocrine Society (serum cortisol ≥1.8 μg/dL after a 1-mg DST) [11] or other countries [1]; (iii) the "globalization" of diagnostic criteria; (iv) the necessity of a 8-mg DST for the SCS diagnosis [12]. Thus, new diagnostic criteria for adrenal SCS have become an important agenda for the Japan Endocrine Society (JES).The current task force was organized officially in 2012 and multicenter collaborative research was done to collect evidence for a revision. Based on the results of the research and peer reviews of articles focusing on SCS, the final new diagnostic criteria for adrenal SCS and the treatment policy were proposed. These evidence-based diagnostic criteria and the treatment policy for adrenal SCS were reviewed by a JES subcommittee and approved. These documents were also approved by Research Committee on Disorders of Adrenal Hormones from the MHLW, Japan and Japan Hormonal Steroid Association. The Japanese version has been published and the English-language version has been described here. The new diagnostic criteria for adrenal SCS ...

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“…A concordant result of ≥1.8 μg/dL (50 nM) is confirmation of hypercortisolism [14]. An LDDST should be validated with a serum dexamethasone level of >220 ng/dL (5.6 nM) to avoid the possibility of a false-positive result [30].…”

Section: Biochemical Evaluationmentioning

confidence: 99%

Adrenal Hypercortisolism: A Closer Look at Screening, Diagnosis, and Important Considerations of Different Testing Modalities

Chiodini

Ramos-Rivera

Marcus

et al. 2019

Journal of the Endocrine Society

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Although prolonged hypercortisolism is associated with increased mortality and substantial morbidity, the clinical signs and symptoms are wide ranging and often nonspecific, contributing to challenges in diagnosis, as well as treatment delays. Greater awareness is needed among clinicians to help identify which patients should undergo biochemical screening for excess cortisol. Several biochemical tests are available, each with important caveats that should be considered in the context of the individual patient. Cortisol secretion varies widely, further complicating the biochemical diagnosis of hypercortisolism, which relies on the use of definitive cutoff values. Patients with hypercortisolism resulting from adrenal adenomas, including those discovered incidentally, often do not present with overt Cushingoid features (plethora, striae, muscle weakness, moon facies, etc. ). However, the consequences of prolonged exposure to even slight elevations in cortisol levels are profound, including increased risk of diabetes, hypertension, fractures, cardiovascular events, and mortality. Because most cases of hypercortisolism resulting from an adrenal adenoma can be managed, it is imperative to identify patients at risk and initiate testing early for the best outcomes. The aim of this report is to increase awareness of the indications for screening for hypercortisolism and to review the biochemical screening tests and diagnosis for hypercortisolism associated with adrenal adenomas.

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In the overnight dexamethasone suppression test, 1.0 mg loading is superior to 0.5 mg loading for diagnosing subclinical adrenal Cushing’s syndrome based on plasma dexamethasone levels determined using liquid chromatography-tandem mass spectrometry

Cited by 12 publications

References 29 publications

Development of a rapid liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone and its clinical verification

Development of a rapid liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone and its clinical verification

New diagnostic criteria of adrenal subclinical Cushing’s syndrome: opinion from the Japan Endocrine Society

Adrenal Hypercortisolism: A Closer Look at Screening, Diagnosis, and Important Considerations of Different Testing Modalities

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