LC-MSMS assays of urinary cortisol, a comparison between four in-house assays

2018 ◽  
Vol 56 (7) ◽  
pp. 1109-1116 ◽  
Author(s):  
Julie Brossaud ◽  
Monique Leban ◽  
Jean-Benoit Corcuff ◽  
Florence Boux de Casson ◽  
Anne-Gaëlle Leloupp ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
High Performance ◽  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Normal Ranges ◽  
Free Cortisol ◽  
Solid Liquid

Abstract Background: Twenty-four hour urinary free cortisol (UFC) determination can be used for screening and follow-up of Cushing syndrome (CS). As immunoassay methods lack specificity for UFC measurement, the use of high-performance liquid chromatography coupled to mass spectrometer (LC-MSMS) is recommended. The aim of our study was to compare UFC results using four LC-MSMS methods performed in four independent laboratories in order to evaluate interlaboratory agreement. Methods: Frozen aliquots of 24-h urine samples (78 healthy volunteers and 20 patients with CS) were sent to four different laboratories for analysis. Following liquid-liquid or solid-liquid extraction, UFC were determined using four different LC-MSMS assay. Results: UFC intra- and interassays variation coefficients were lower than 10% for each centre. External quality control results were not significantly different. UFC normal ranges (established from healthy volunteers) were 17–126, 15–134, 12–118 and 27–157 nmol/day, respectively. Classification of UFC from healthy volunteers and patients with CS using a 95th percentile threshold was similar. However, for extreme UFC values (<50 or >270 nmol/day), negative or positive bias was noted. Conclusions: Even for highly specific methods such as LC-MSMS, variations of results can be found depending on analytical process. Validation of LC-MSMS methods including determination of the reference range is essential.

scholarly journals Hypercoagulability in Cushing Syndrome, Prevalence of Thrombotic Events: A Large, Single-Center, Retrospective Study

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Maria Gabriela Suarez ◽  
Madeleine Stack ◽  
Jose Miguel Hinojosa-Amaya ◽  
Michael D Mitchell ◽  
Elena V Varlamov ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Cushing Syndrome ◽  
Thrombotic Event ◽  
Urinary Free Cortisol ◽  
Bilateral Adrenalectomy ◽  
Bleeding Complications ◽  
Single Center ◽  
Free Cortisol ◽  
Prophylactic Anticoagulation

Abstract Background The risk of Cushing syndrome (CS) patients experiencing a thrombotic event (TE) is significantly higher (odds ratio; OR 18%) than that of the general population. However, there are currently no anticoagulation guidelines. Methods A retrospective, single-center, longitudinal study of patients undergoing all types of treatment—surgical (pituitary, unilateral, and bilateral adrenalectomy) and medical treatment—was undertaken. TEs were recorded at any point up until last patient follow-up; myocardial infarction (MI), deep venous thrombosis (DVT), and pulmonary embolism (PE) or stroke. Patients’ doses and complications of anticoagulation were recorded. Results Included were 208 patients; a total of 165 (79.3%) were women, and mean age at presentation was 44 ± 14.7 years. Thirty-nine (18.2%) patients had a TE; extremity DVT (38%), cerebrovascular accident (27%), MI (21%), and PE (14%). Of 56 TEs, 27 (48%) were arterial and 29 (52%) were venous. Patients who underwent bilateral adrenalectomy (BLA) had an odds ratio of 3.74 (95% CI 1.69-8.27) of developing a TE. Of patients with TEs, 40.5% experienced the event within the first 60 days after surgery. Baseline 24-hour urinary free cortisol levels did not differ in patients with or without TE after BLA. Of 197 patients who underwent surgery, 50 (25.38%) received anticoagulation after surgery, with 2% having bleeding complications. Conclusions The risk of TEs in patients with CS was approximately 20%. Many patients had more than 1 event, with higher risk 30 to 60 days postoperatively. The optimal prophylactic anticoagulation duration is unknown, but most likely needs to continue up to 60 days postoperatively, particularly after BLA.

scholarly journals Pseudo-Cushing Syndrome Caused by Fenofibrate Interference with Urinary Cortisol Assayed by High-Performance Liquid Chromatography

2003 ◽  
Vol 88 (8) ◽  
pp. 3521-3524 ◽  
Author(s):  
A. Wayne Meikle ◽  
James Findling ◽  
Mark M. Kushnir ◽  
Alan L. Rockwood ◽  
Gordon J. Nelson ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance ◽  
Cushing Syndrome ◽  
Urinary Free Cortisol ◽  
Urinary Cortisol ◽  
Free Cortisol ◽  
Hplc Peak ◽  
Major Transition ◽  
Single Transition ◽  
Mass Spectrometry Mass Spectrometry

Urinary free cortisol (UFC) excretion over 24 h reflects the production rate of cortisol and is used commonly in the diagnosis of Cushing syndrome. We report on two patients evaluated for Cushing syndrome who had elevated UFC when analyzed by HPLC but normal values for the analysis performed by RIA and HPLC-mass spectrometry/mass spectrometry (HPLC-MS/MS). Other laboratory testing was inconsistent with the diagnosis of Cushing syndrome and raised doubts about the diagnosis. We identified a probable cause of analytical interference as coming from fenofibrate (Tricor), medication taken by the patients. Fenofibrate peak overlapped with the HPLC peak of cortisol and produced an MS/MS transition overlapping the major transition of cortisol. A second MS/MS transition was free from interference. In summary, fenofibrate administration may cause false elevation of UFC values determined by HPLC or HPLC-MS/MS in patients evaluated for Cushing syndrome. An HPLC-MS/MS method using multiple mass transitions, rather than a single transition, allows accurate quantitation of urinary cortisol in patients taking fenofibrate.

scholarly journals Clinical features, risk of mass enlargement, and development of endocrine hyperfunction in patients with adrenal incidentalomas: a long-term follow-up study

Endocrine ◽  
2020 ◽  
Author(s):  
Pierpaolo Falcetta ◽  
Francesca Orsolini ◽  
Elena Benelli ◽  
Patrizia Agretti ◽  
Paolo Vitti ◽  
...  
Keyword(s):  
Adrenal Incidentaloma ◽  
Plasma Renin ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Endocrine Function ◽  
Adrenal Tumors ◽  
Hormonal Function ◽  
Free Cortisol ◽  
Hormonal Evaluation

Abstract Purpose To evaluate the risk of mass enlargement and endocrine function modification in patients with adrenal incidentaloma (AI). Methods In this retrospective study, we examined clinical and hormonal characteristics of 310 patients with AI (200 females and 110 males; age: 58.3 ± 12.9 years), followed up for a median (interquartile range) of 31.4 months (13.0–78.6) and evaluated for possible modification in adrenal mass size and hormonal function. The hormonal evaluation included morning serum cortisol and plasma ACTH at 8 a.m., aldosterone, plasma renin activity/direct renin concentration, and 24-h urine metanephrines/normetanephrines. One microgram overnight dexamethasone suppression test (DST) was performed. Autonomous cortisol secretion (ACS) was diagnosed in the presence of cortisol after 1 mg DST > 5 μg/dl (138 nmol/l) or >1.8 and ≤5 μg/dl (50–138 nmol/l) and at least one of the following: (i) low ACTH; (ii) increased 24-h urinary-free cortisol; (iii) absence of cortisol rhythm; and (iv) post-LDDST cortisol level > 1.8 μg/dl (50 nmol/l). When there was no biochemical evidence of adrenal hormonal hyperactivity, AIs were classified as nonfunctioning (NFAIs). The mass was considered significantly enlarged when the size increase was more than 20% and at least 5 mm compared to baseline. Results At diagnosis, NFAIs were found in 209 patients, while ACS and overt adrenal hyperfunction were diagnosed in 81 and 20 patients, respectively. During follow-up, 3.3% and 1.5% of patients with NFAI developed subtle and overt endocrine hyperfunction, respectively, while a significant mass enlargement was observed in 17.7% of all AIs. The risk of developing ACS was significantly higher in patients with adenoma >28 mm (hazard ratio [HR] 12.4; 95% confidence interval [CI], 2.33–66.52, P = 0.003), in those with bilateral adrenal tumors (HR: 5.36; 95% CI, 1.17–24.48, P = 0.030), and with low/suppressed ACTH values (HR: 11.2, 95% CI 2.06–60.77; P = 0.005). The risk of mass enlargement was lower for patients in the fourth quartile of body mass index than those in the first quartile (HR 0.33; 95% CI, 0.14–0.78; P = 0.012). Conclusions In patients with AI, the risk of developing hormonal hyperfunction and mass enlargement is overall low, although some tumor characteristics and anthropometric features might increase this risk. Taking account of all these aspects is important for planning a tailored follow-up in AI patients.

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