Improved liquid chromatography–tandem mass spectrometry method in clinical utility for the diagnosis of Cushing’s syndrome

Fong, Bonnie Mei-Wah; Tam, Sidney; Leung, Kelvin Sze-Yin
January 2010
Analytical & Bioanalytical Chemistry;Jan2010, Vol. 396 Issue 2, p783
Academic Journal
Determination of urinary free cortisol is one of the first lines in screening for the diagnosis of Cushing’s syndrome where its measurement is mostly done by immunoassay. Although easy to perform, immunoassays suffer from the problem of assay interferences and are unable to measure cortisone levels. To enhance such techniques for clinical diagnosis, an improved liquid chromatography–tandem mass spectrometric (LC–MS/MS) method was developed for the simultaneous determination of urinary free cortisol and cortisone. The leftover urine samples from immunoassay were collected and subjected to facile solid-phase extraction cleanup. In the analysis of 130 urine samples from patients, 65 (50%) were found to have elevated urinary free cortisol (UFC) by immunoassay; but only 13 (10.8%) were found to have elevated UFC by this improved LC–MS/MS method. Nine out of the 13 patients, which showed elevated UFC by LC–MS/MS, were surgically confirmed to have Cushing’s syndrome/disease. By setting a two times upper limit as a cut-off, the immunoassay gave a positive predictive value of 43.5%, whilst by using the improved method, a positive predictive value of 90% was obtained. Although several tests have been used extensively in first line screening for the diagnosis of Cushing’s syndrome, none has ever shown with full capability of distinguishing all cases of Cushing’s syndrome from normal and/or obese individuals. This method has shown superior analytical advantages over existing immunoassay type in terms of sensitivity, specificity and capability to diagnose Cushing’s syndrome. Comparison between existing spectrometric methods, the reported developed method shown here, provides a simpler sample preparation procedure and meets with the high throughput demand of clinical laboratories.


Related Articles

  • Diagnosing hypercortisolism. Singh, Ravinder J. // MLO: Medical Laboratory Observer;Dec2006, Vol. 38 Issue 12, p20 

    The article focuses on the development of the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in diagnosing for hypercortisolism. Cortisol is a glucocortoid hormone responsible to the adaptation of stress and regulation of metabolism. It is associated with Cushing's syndrome and...

  • Dexamethasone suppression test: development of a method for simultaneous determination of cortisol and dexamethasone in human plasma by liquid chromatography/tandem mass spectrometry. Hempen, C.; Elfering, S.; Mulder, A. H. L.; van den Bergh, F. A. J. T. M.; Maatman, R. G. H. J. // Annals of Clinical Biochemistry;Mar2012, Vol. 49 Issue 2, p170 

    Background: Dexamethasone is a synthetic glucocorticoid and is analogous to cortisol. It is used in the low-dose overnight dexamethasone suppression test (LDODST) to diagnose hypercortisolism in patients suspected to be suffering from Cushing's syndrome (CS). Measuring plasma dexamethasone in...

  • Concordance of the late night salivary cortisol in patients with Cushing's syndrome and elevated urine-free cortisol. Doi, Suhail; Clark, Justin; Russell, Anthony // Endocrine (1355008X);Apr2013, Vol. 43 Issue 2, p327 

    The concordance of the late night salivary cortisol (LNSC) results with the 24-h urine-free cortisol (UFC) results in the biochemical screening for Cushing's syndrome is unknown. We investigated this in a population of Cushing's syndrome subjects. We used meta-analytic methods to pool...

  • Cortisone/hydrocortisone.  // Reactions Weekly;9/7/2013, Issue 1468, p16 

    The article presents a case study of a 75-year old woman who developed Cushing's syndrome after receiving a herbal medicine enriched with cortisone and hydrocortisone.

  • Cortisol measurement in patients receiving metyrapone therapy. Owen, L. J.; Halsall, D. J.; Keevil, B. G. // Annals of Clinical Biochemistry;Nov2010, Vol. 47 Issue 6, p573 

    Current guidance recommends titrating the dose of metyrapone against serum cortisol concentration, in patients under medical management of Cushing's syndrome. In the UK, this almost always involves measuring serum cortisol concentration by immunoassay, the performance of which is questionable in...

  • Quantification of urinary 18-hydroxycortisol using LC-MS/MS. Jin, Shigeki; Wada, Norio; Takahashi, Yuji; Hui, Shu-Ping; Sakurai, Toshihiro; Fuda, Hirotoshi; Takeda, Seiji; Fujikawa, Masato; Yanagisawa, Katsuyuki; Ikegawa, Shigeo; Kurosawa, Takao; Chiba, Hitoshi // Annals of Clinical Biochemistry;Sep2013, Vol. 50 Issue 5, p450 

    The article presents a study which proposes a method for the measurement of urinary 18-hydroxycortisol via liquid chromatography-tandem mass spectrometry (LC-MS/MS) and its usefulness for differential diagnosis of aldosterone-producing adenoma (APA). Urine samples were collected over 24 hours in...

  • Measurement of Plasma Cortisol in the Diagnosis of Cushing's Syndrome. Sawin, Clark T. // Annals of Internal Medicine;Mar68, Vol. 68 Issue 3, p624 

    Provides information on a study which used the measurement of plasma cortisol in the diagnosis of Cushing's syndrome. Methods for estimating plasma cortisol; Effect of a corticotropin simulation test on the diagnosis of the syndrome; Diurnal variation of plasma cortisol.

  • Naturally occurring isotopes of an analyte can interfere with doubly deuterated internal standard measurement. Duxbury, K; Owen, L; Gillingwater, S; Keevil, B // Annals of Clinical Biochemistry;Mar2008, Vol. 45 Issue 2, p210 

    Background: Internal standards are essential in quantitative mass spectrometry (MS) assays to correct for variability in sample extraction and ionization at the source. In liquid chromatography MS assays, analogues of the analyte with several atoms replaced by their stable isotopes, e.g. 2H (D,...

  • Determination of serum cortisol using isotope dilution-liquid chromatography-mass spectrometry as a candidate reference method. Jung, Pyong; Kim, Byungjoo; Park, Sang-Ryoul; So, Hun-Young; Shi, Lian; Kim, Yongseong // Analytical & Bioanalytical Chemistry;Nov2004, Vol. 380 Issue 5/6, p782 

    We propose isotope-dilution mass spectrometry as a candidate reference method for determination of serum cortisol. The method uses liquid chromatography-mass spectrometry (LC-MS), interfaced with electrospray ionization, and selective monitoring of the [M+H]+ ions of cortisol and isotopically...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics