[PP.27.25] DIAGNOSTIC VALUE AND REFERENCE INTERVALS OF PLASMA FREE METANEPHRINES MEASURED BY LC-MS IN A POPULATION REFERRED TO A HYPERTENSION EXCELLENCE CENTER.

Background The Endocrine Society Clinical Practice Guideline on Phaeochomocytoma and Paraganglioma recommends phlebotomy for plasma-free metanephrines with patients fasted and supine using appropriately defined reference intervals. Studies have shown higher diagnostic sensitivities using these criteria. Further, with seated-sampling protocols, for result interpretation, reference intervals that do not compromise diagnostic sensitivity should be employed. Objective To determine the impact on diagnostic performance and financial cost of using supine reference intervals for result interpretation with our current plasma-free metanephrines fasted/seated-sampling protocol. Methods We conducted a retrospective cohort study of patients who underwent screening for PPGL using plasma-free metanephrines from 2009 to 2014 at Galway University Hospitals. Plasma-free metanephrines were measured using liquid chromatography-tandem mass spectrometry. Supine thresholds for plasma normetanephrine and metanephrine set at 610 pmol/L and 310 pmol/L, respectively, were used. Results A total of 183 patients were evaluated. Mean age of participants was 53.4 (±16.3) years. Five of 183 (2.7%) patients had histologically confirmed PPGL (males, n=4). Using seated reference intervals for plasma-free metanephrines, diagnostic sensitivity and specificity were 100% and 98.9%, respectively, with two false-positive cases. Application of reference intervals established in subjects supine and fasted to this cohort gave diagnostic sensitivity of 100% with specificity of 74.7%. Financial analysis of each pretesting strategy demonstrated cost-equivalence (€147.27/patient). Conclusion Our cost analysis, together with the evidence that fasted/supine-sampling for plasma-free metanephrines, offers more reliable exclusion of PPGL mandates changing our current practice. This study highlights the important advantages of standardized diagnostic protocols for plasma-free metanephrines to ensure the highest diagnostic accuracy for investigation of PPGL.

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Standardisation of electrocardiographic examination in corn snakes (Pantherophis guttatus)

Veterinary Record ◽

10.1136/vr.105713 ◽

2020 ◽

Vol 186 (19) ◽

pp. e29-e29

Author(s):

Martyn Lewis ◽

Jonathan Bouvard ◽

Kevin Eatwell ◽

Geoff Culshaw

Keyword(s):

Heart Rate ◽

Cardiac Cycle ◽

Normal Animal ◽

Diagnostic Value ◽

Reference Intervals ◽

Evidence Based ◽

High Quality ◽

Reptile Species ◽

Electrocardiographic Examination ◽

Rhythmic Oscillation

IntroductionCorn snakes are a very common pet reptile species, yet there is an absence of evidence-based literature standardising collection of ECG or detailing ECG deflection morphology in the normal animal. The authors describe a well-tolerated, reproducible technique and detail the cardiac cycle in terms of lead 2 equivalent waveforms and intervals.Animals29 adult corn snakes.Materials and methodsThis prospective study evaluated, under species-appropriate, standardised conditions, a technique for producing standard six-lead ECG tracings. Lead 2 equivalent cardiac cycles were described in detail and statistically analysed for sex, weight, length, heart rate and mean electrical axis.ResultsHigh-quality tracings demonstrated common ECG characteristics for this species, including no Q, S or SV waves, prolonged PR and RT intervals, rhythmic oscillation of the baseline, short TP segments, and a right displaced mean electrical axis. An influence of sex, weight or length on heart rate and mean electrical axis was not identified.ConclusionsTo the authors’ knowledge, this is the first study to describe a standardised technique for recording ECG in significant numbers of normal corn snakes. Ranges have been provided that may be of diagnostic value or form the basis for future development of reference intervals for this species.

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Reference intervals for plasma free metanephrines with an age adjustment for normetanephrine for optimized laboratory testing of phaeochromocytoma

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/acb.2012.012066 ◽

2012 ◽

Vol 50 (1) ◽

pp. 62-69 ◽

Cited By ~ 63

Author(s):

G. Eisenhofer ◽

P. Lattke ◽

M. Herberg ◽

G. Siegert ◽

N. Qin ◽

...

Keyword(s):

Laboratory Testing ◽

Reference Intervals ◽

Plasma Free Metanephrines

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Case report of a phantom pheochromocytoma

Biochemia Medica ◽

10.11613/bm.2020.021003 ◽

2020 ◽

Vol 30 (2) ◽

pp. 325-330

Author(s):

Caroline M Joyce ◽

Audrey Melvin ◽

Paula M O’Shea ◽

Seán J Costelloe ◽

Domhnall J O’Halloran

Keyword(s):

Reference Intervals ◽

Patient Anxiety ◽

Biochemical Tests ◽

Drug Interference ◽

High Clinical Suspicion ◽

Liquid Chromatography Tandem Mass ◽

History Of ◽

Plasma Metanephrines ◽

Plasma Free Metanephrines ◽

Test Probability

Plasma free metanephrines or urinary fractionated metanephrines are the biochemical tests of choice for the diagnosis of pheochromocytoma as they have greater sensitivity and specificity than catecholamines for pheochromocytoma detection. This case highlights the preanalytical factors which can influence metanephrine measurement and cause a false positive result. It describes a patient with a high pre-test probability of pheochromocytoma due to hypertension and a past medical history of adrenalectomy for a purported pheochromocytoma in her home country. When biochemical screening revealed grossly elevated urine normetanephrine in the presence of a previously identified right adrenal lesion, there was high clinical suspicion of a pheochromocytoma. However, functional imaging did not support this view which prompted additional testing with plasma metanephrines. Results for plasma and urine metanephrines were discordant and preanalytical drug interference was suspected. Patient medications were reviewed and sulfasalazine, an anti-inflammatory drug was identified as the most likely analytical interferent. Urinary fractionated metanephrines were re-analysed using liquid chromatography tandem mass spectrometry (LC-MS/MS) and all metanephrines were within their reference intervals. This case illustrates how method-specific analytical drug interference prompted unnecessary expensive imaging, heightened patient anxiety and resulted in lengthy investigations for what turned out to be a phantom pheochromocytoma.

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Testosterone, free testosterone, and free androgen index in women: Reference intervals, biological variation, and diagnostic value in polycystic ovary syndrome

Clinica Chimica Acta ◽

10.1016/j.cca.2015.08.019 ◽

2015 ◽

Vol 450 ◽

pp. 227-232 ◽

Cited By ~ 20

Author(s):

H.N. Bui ◽

P.M. Sluss ◽

F.J. Hayes ◽

S. Blincko ◽

D.L. Knol ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Free Testosterone ◽

Diagnostic Value ◽

Reference Intervals ◽

Biological Variation ◽

Ovary Syndrome ◽

Free Androgen Index

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Advances in catecholamine and metabolite measurements for diagnosis of pheochromocytoma

Clinical Chemistry ◽

10.1093/clinchem/37.10.1854 ◽

1991 ◽

Vol 37 (10) ◽

pp. 1854-1867 ◽

Cited By ~ 83

Author(s):

T G Rosano ◽

T A Swift ◽

L W Hayes

Keyword(s):

High Performance ◽

Diagnostic Value ◽

Reference Intervals ◽

Plasma Norepinephrine ◽

Analytical Sensitivity ◽

Vanillylmandelic Acid ◽

Sample Collection ◽

Urinary Catecholamines ◽

Patient Preparation ◽

Biochemical Detection

Abstract Assessment of catecholamine production and excretion is important in the laboratory detection of pheochromocytoma, a rare but curable cause of hypertension. Advances in catecholamine and metabolite methodologies have enhanced the diagnostic acumen by increasing analytical sensitivity and eliminating many of the interferences observed with earlier methods. Estimation of urinary catecholamines metanephrine and vanillylmandelic acid is routinely used in the biochemical detection of pheochromocytoma and in monitoring the completeness of tumor excision as well as the possibility of recurrence. Traditional spectrophotometric and fluorometric methods for urinary catecholamines and their metabolites are being replaced by highly sensitive and selective chromatographic methods. The ability to quantify individual catecholamines and metanephrines by high-performance liquid chromatography is of particular value for detecting familial forms of the tumor that may secrete epinephrine. Plasma norepinephrine and epinephrine measurements are of additional diagnostic value in determining recent catecholamine release and response to clonidine suppression. For either urine or plasma measurements, appropriate patient preparation, sample collection, and method validation along with an understanding of the variable pattern of catecholamine secretion and metabolism in pheochromocytoma are essential. Advances in laboratory methodology and reference intervals for catecholamines for clinical interpretation are reviewed.

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Testicular Ultrasound to Stratify Hormone References in a Cross-Sectional Norwegian Study of Male Puberty

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz094 ◽

2019 ◽

Vol 105 (6) ◽

pp. 1888-1898 ◽

Cited By ~ 3

Author(s):

André Madsen ◽

Ninnie B Oehme ◽

Mathieu Roelants ◽

Ingvild S Bruserud ◽

Geir Egil Eide ◽

...

Keyword(s):

Serum Testosterone ◽

Diagnostic Value ◽

Reference Intervals ◽

Sex Hormone Binding Globulin ◽

Clinical Variable ◽

Chronological Age ◽

Total Testosterone ◽

Serum Samples ◽

Cross Sectional ◽

Male Puberty

Abstract Context Testicular growth represents the best clinical variable to evaluate male puberty, but current pediatric hormone references are based on chronological age and subjective assessments of discrete puberty development stages. Determination of testicular volume (TV) by ultrasound provides a novel approach to assess puberty progression and stratify hormone reference intervals. Objective The objective of this article is to establish references for serum testosterone and key hormones of the male pituitary-gonadal signaling pathway in relation to TV determined by ultrasound. Design, Setting, and Participants Blood samples from 414 healthy Norwegian boys between ages 6 and 16 years were included from the cross-sectional “Bergen Growth Study 2.” Participants underwent testicular ultrasound and clinical assessments, and serum samples were analyzed by liquid chromatography tandem–mass spectrometry and immunoassays. Main Outcome Measures We present references for circulating levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin in relation to TV, chronological age, and Tanner pubic hair stages. Results In pubertal boys, TV accounted for more variance in serum testosterone levels than chronological age (Spearman r = 0.753, P < .001 vs r = 0.692, P < .001, respectively). Continuous centile references demonstrate the association between TV and hormone levels during puberty. Hormone reference intervals were stratified by TV during the pubertal transition. Conclusions Objective ultrasound assessments of TV and stratification of hormone references increase the diagnostic value of traditional references based on chronological age or subjective staging of male puberty.

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Comparison of the Schirmer tear test I values after placement in ventral and dorsal conjunctival fornices in healthy cats

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x17733207 ◽

2017 ◽

Vol 20 (12) ◽

pp. 1169-1172 ◽

Cited By ~ 2

Author(s):

Ghazal Aftab ◽

Seyed Mehdi Rajaei ◽

Houman Faghihi

Keyword(s):

Body Weight ◽

Confidence Interval ◽

Diagnostic Value ◽

Reference Intervals ◽

Clinically Normal ◽

Normal Reference ◽

Schirmer Tear Test ◽

Significant Difference ◽

Study Population ◽

The Difference

Objectives The objective of this study was to compare the Schirmer tear test I values obtained from placement of Schirmer tear test (STT) strips in ventral and dorsal conjunctival fornices and to investigate any correlation between age, body weight and STT values in clinically normal cats. Methods Twenty-eight intact adult domestic shorthair and Persian cats were used in this study. The cats were gently physically restrained in a sternal position, and a Schirmer tear strip was placed on each eye in the ventral conjunctival fornix at one-third of the distance from the temporal to nasal canthus for 60 s. Then, the wetted portion of the strips was measured as mm/min (L-STT I). After 48 h, the same procedure was performed on each eye in the dorsal conjunctival fornix (U-STT I). Results Mean ± SD STT values of the ventral and dorsal conjunctival fornices were 20.80 ± 2.25 mm/min (range 14–25 mm/min; 95% confidence interval [CI] 19.92–21.67) and 18.28 ± 2.27 mm/min (range 15–22 mm/min; 95% CI 17.39–19.16) in all of the study population, respectively. A significant difference was found between STT values obtained from the ventral and dorsal conjunctival fornices ( P <0.001). There was no correlation between the age and body weight of the animals and STT I values. Conclusions and relevance This study compared the STT I values of the dorsal and ventral conjunctival fornices in cats. The difference was significant between the L-STT I and U-STT I values; however, the L-STT I and U-STT I values were within normal reference intervals. The U-STT I data have diagnostic value that might be of benefit in cases where there is a problem in the ventral conjunctival fornix.

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Evaluation of the diagnostic possibility of hemorrhagic risk in pregnant women with severe preeclampsia by rotational thromboelastography

Journal of obstetrics and women s diseases ◽

10.17816/jowd71083 ◽

2021 ◽

Vol 70 (2) ◽

pp. 37-44

Author(s):

Ilya S. Peretyatko ◽

Elena V. Mozgovaya

Keyword(s):

Pregnant Women ◽

Normal Pregnancy ◽

Diagnostic Value ◽

Reference Intervals ◽

Severe Preeclampsia ◽

Screening Tests ◽

Control Group ◽

Hemorrhagic Complications ◽

Hemorrhagic Risk ◽

Coagulation Pathway

AIM: The aim of this study was to determine the risk of hemorrhagic complications in pregnant women with severe preeclampsia using rotational thromboelastometry (ROTEM) in two screening tests EXTEM and INTEM. MATERIALS AND METHODS: We examined 30 pregnant women with severe preeclampsia, who were observed in the intensive care unit, the Department of Obstetrics and Perinatology, the Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott, Saint Petersburg. The control group consisted of 10 patients with normal pregnancy, delivered by caesarean section for reasons not related to obstetric complications. RESULTS: When interpreting the ROTEM results, the reference intervals for pregnant women in the third trimester were used, as determined in the study by J. Lee et al. (2019). According to the analysis of thromboelastograms of pregnant women with severe preeclampsia, 9 (30%) of them had a tendency towards hypocoagulation. Of these, 3 thromboelastograms had deviations via the intrinsic coagulation pathway (in the INTEM tests), 3 thromboelastograms via the extrinsic coagulation pathway (in the EXTEM tests), and the rest combined both options. Two patients with severe preeclampsia developed a complication in the form of HELLP syndrome, and the phenomena of hypocoagulation, according to the results of ROTEM performed before delivery, were observed in only one patient. A comparative analysis of ROTEM parameters among pregnant women with severe preeclampsia and normal pregnancy did not reveal statistically significant differences. CONCLUSIONS: The use of the ROTEM method with the main screening tests (EXTEM and INTEM) did not show diagnostic value in assessing the risk of hemorrhagic complications of severe preeclampsia.

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Chitinase-3-like protein 1: reference interval of a healthy population and its diagnostic value for liver fibrosis in Pakistan

BioMedica ◽

10.51441/biomedica/5-499 ◽

2021 ◽

Vol 37 (3) ◽

pp. 1-13

Author(s):

Faryal Husnain ◽

Muhammad Dilawar Khan ◽

Omar Rasheed Chughtai ◽

Akhtar Rasheed Chughtai ◽

Shakeel Ashraf ◽

...

Keyword(s):

Liver Fibrosis ◽

Hepatic Fibrosis ◽

Reference Interval ◽

Diagnostic Value ◽

Reference Intervals ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Population ◽

International Studies ◽

Cross Sectional ◽

Pakistani Population

Background and Objective: Chitinase-3-like protein 1 (CHI3L1) is an upcoming biomarker for the diagnosis of liver fibrosis. The reference intervals (RIs) for CHI3L1 have not been established in the Pakistani population. Thus, this study aimed to determine the RIs in our population and the cut-off value for diagnosis of hepatic fibrosis. Methods: This is a cross-sectional study. A total of 408 participants (202 healthy and 206 diagnosed liver fibrosis cases) were recruited. Serum CHI3L1 level was measured on CHI3L1 kits (Proprium Biotech Co. Ltd) by manual enzyme-linked immunosorbent assay. The RIs were estimated by percentile and working normal method. Results: The distribution of CHI3L1 values showed no remarkable variation with gender and age. The 95% RI of CHI3L1 was 12.80-81.80 ng/ ml in healthy Pakistani subjects and the cut-off for the diagnosis was 102.12 ng/ml in hepatic fibrosis cases. Conclusion: The RIs in healthy adults and the cut-off for the diagnosis of hepatic fibrosis of serum CHI3L1 were determined in a selective adult Pakistani population. This will be a useful reference for further local and international studies.

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