RÉSUMÉ
The Vitamin D External Quality Assessment Scheme (DEQAS) distributes serum samples globally, on a quarterly basis, to assess participants' performance of specific methods for 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D). DEQAS occasionally circulates samples containing high levels of substances found in certain clinical situations e.g. 25-OHD2, 24,25-(OH)2D3, hypertriglyceridemia. The increased availability and use of health supplements containing biotin has led to case reports of assay interference in methods utilizing a biotin-streptavidin detection system. In October 2018, DEQAS included a serum sample (545) containing exogenous biotin (concentration =586 µg/L) which was analyzed by a total of 683 laboratories using 35 different methods. The same serum sample (544) without exogenous biotin was also included in the 5-sample set. All methods (760 laboratories) performed satisfactorily on sample 544 giving an All-Laboratory Trimmed Mean = 50.2 ± 6.5 nmol/L (±SD, CV = 12.9 %). The target value for this sample 544 (& 555) was 47.4 nmol/L as determined by Centers for Disease Control and Prevention (CDC) Atlanta, Georgia using their LC-MS/MS reference method. In contrast, #545 containing the exogenous biotin was reported by only 683 laboratories and gave an All-Laboratory Trimmed Mean = 66.8 ± 37.6 nmol/L (±SD, CV = 56.3 %). As expected, LC-MS/MS methods (143 labs) reported similar results for both 544 = 48.9 ± 4.4 nmol/L (±SD) and 545 = 48.3 ± 4.5 nmol/L (±SD) showing that assays involving chromatographic steps are unaffected by the presence of biotin. Several of the antibody-based assays including Abbott Architect, DiaSorin Liaison, Beckman Unicel and Siemens Centaur are also unaffected by the addition of biotin. Two assays, IDS-iSYS and Roche Total 25OHD, both of which use biotin-streptavidin, exhibit biotin interference yielding values with a significant positive bias for 545 of 102.6 nmol/L ± 78.7 nmol/L (±SD) and 517.8 nmol/L ± 209.8 nmol/L (±SD) respectively. Interestingly, the failure to report sample 545 data from 77 laboratories is due solely to those running Roche Total 25OHD or Roche Vitamin D Total II assays. Given the prevalence of the adversely affected assays (25 % of DEQAS users) and the high volume of 25OHD testing, clinicians using these assays should, where possible, only measure 25OHD when patients are off biotin.
Sujet(s)
Dosage biologique/méthodes , Biotine , Compléments alimentaires , Vitamine D/analogues et dérivés , Humains , Ligands , Plan de recherche , Vitamine D/métabolismeRÉSUMÉ
The External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) distributes human serum samples to laboratories across the world to assess their performance in measuring serum total 25-hydroxyvitamin D [25(OH)D], i.e. the sum of the concentrations of serum 25(OH)D2 and 25(OH)D3. In 2013 DEQAS, in collaboration with the Vitamin D Standardization Program (VDSP), became an accuracy-based EQAS when the National Institute for Standards and Technology (NIST) began assigning 25(OH)D target values to DEQAS serum samples using their Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved reference measurement procedure (RMP). Historically, NIST has performed 4 determinations of 25-OHD2 and 25-OHD3 on each sample and used the mean values to calculate a single 'target value' for Total 25-OHD against which performance was judged. By definition the target values cannot be exact and each is associated with a level of uncertainty. The total uncertainty (UNIST) has two components, one from the 25(OH)D2, and 25(OH)D3 measurements and the other associated with the calibration procedure. The total combined uncertainty is calculated by adding up these uncertainties. In future, uncertainties will be attached to the target value in each DEQAS serum sample, starting with the next distribution cycle in 2019. Confidence intervals obtained using these uncertainties will allow DEQAS participants to determine if their result agrees with the NIST assigned target value. Furthermore, if the value falls within the confidence interval the laboratory's assay would be regarded as traceable, i.e. standardized, to the NIST RMP.
Sujet(s)
Vitamine D/analogues et dérivés , Algorithmes , Humains , Normes de référence , Taille de l'échantillon , Incertitude , Vitamine D/sang , Vitamine D/métabolismeRÉSUMÉ
The discovery that mutations of the CYP24A1 gene are a cause of idiopathic infantile hypercalcemia (IIH) has revived interest in measuring serum 24,25(OH)2D3. Several studies have also suggested that a high 25-hydroxyvitamin D3(25-OHD3):24,25(OH)2D3 ratio might provide additional diagnostic information in the investigation of vitamin D deficiency. Measurement of 24,25(OH)2D3 is necessarily restricted to laboratories with mass spectrometry methods although cross reactivity of the metabolite in immunoassays for 25-OHD is a potential cause of misleading results. The international External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) was set up in 1989. In 2013 DEQAS became an accuracy based EQA for 25-OHD with 'target values' assigned by the National Institute of Standards and Technology (NIST) Reference Measurement Procedure (RMP). A pilot scheme for serum 24,25(OH)2D3 was started in 2015 and participants were asked to measure the metabolite on each of the 5 samples sent out for 25-OHD. Inter-laboratory agreement was poor but this may reflect methodological differences, in particular different approaches to assay standardization. An important potential contribution to reducing variability among assays was the development by NIST of a 24,25(OH)2D3 RMP and its use in assigning values to SRMs 972a, 2973 and 2971, supported by the NIH Office of Dietary Supplements (ODS) as part of the Vitamin D Standardization Program (VDSP) effort.
Sujet(s)
Spectrométrie de masse en tandem/méthodes , Vitamine D/analogues et dérivés , Vitamines/sang , Chromatographie en phase liquide/méthodes , Chromatographie en phase liquide/normes , Humains , Contrôle de qualité , Normes de référence , Spectrométrie de masse en tandem/normes , Vitamine D/sangRÉSUMÉ
Recent years have seen a substantial increase in demand for 25-hydroxyvitamin D (25-OHD) assays. DEQAS (the Vitamin D External Quality Assessment Scheme) has been monitoring the performance of these assays since 1989. The first DEQAS distribution was in June 1989 and results were submitted by 13 laboratories in the UK, two of which used HPLC/UV; the rest used ligand binding assays with a tritium tracer. Inter-laboratory CVs (ALTM) ranged from 29.3% (42.7nmol/L) to 53.7% (20.0nmol/L). Currently the scheme has participants in 56 countries using 30 methods or variants of methods. In January 2017, 918 participants returned results and inter-laboratory CVs (ALTM) ranged from 10.3% (73.1nmol/L) to 15.3% (29.4nmol/L). Over the last 27 years, there have been a number of significant milestones in assay development. The first major advance was the development of an iodinated 25-OHD tracer by Hollis and Napoli in 1992, subsequently used in an RIA kit marketed by DiaSorin. This and other commercial radioimmunoassays that followed brought 25-OHD assays within reach of many more non-specialist routine laboratories. With the introduction of fully automated non-isotopic assays without solvent extraction, measurement of 25-OHD became available to any clinical chemistry laboratory with an appropriate analytical platform. However, as the limitations of these non-extraction assays became apparent more laboratories started using LC-MS/MS methodology. Meanwhile the variable accuracy of 25-OHD methods has been addressed by the Vitamin D Standardization Program (VDSP) which encourages manufacturers to produce methods traceable to the reference measurement procedures (RMPs) of NIST, University of Ghent and the Centers for Disease Control and Prevention (CDC). DEQAS changed to an accuracy-based scheme in 2013 and now assesses assay accuracy against the NIST RMP. This review will use DEQAS results and statistics to chart the historical development in 25-OHD assay technology and highlight some of the problems encountered in obtaining reliable results for this most challenging of analytes.
Sujet(s)
Dosage biologique/tendances , Vitamine D/analogues et dérivés , Vitamines/sang , Dosage biologique/normes , Humains , Vitamine D/sangRÉSUMÉ
The Vitamin D External Quality Assessment Scheme (DEQAS) was launched in 1989 and monitors the performance of 25-hydroxyvitamin D (25-OHD) and 1,25- dihydroxyvitamin D (1,25(OH)2D) assays. In April 2015 a pilot scheme for 24,25-dihydroxyvitamin D (24,25(OH)2D) was introduced. The 25-OHD scheme is accuracy - based with target values assigned by the NIST Reference Measurement Procedure (RMP) for 25-OHD2 and 25-OHD3. A similar method is used to assign values for 3-epi-25-OHD. Five samples of human serum are distributed quarterly to over 1000 participants in 58 countries (April 2016) and clinical laboratories are expected to submit results within approximately 5 weeks. Research laboratories with assays run less frequently are not given a deadline. Archived samples with NIST- assigned values are also available. Performance is assessed on the first four samples with the fifth reserved for investigations e.g. recovery experiments or to assess the influence of other serum constituents such as lipids. DEQAS provides rapid feedback, with an on-line preliminary report available immediately after a participant submits results and a comprehensive report soon after the results deadline. In 2015, DEQAS investigations revealed that several 25-OHD immunoassays under-recovered 25-OHD2 and 25-OHD results were falsely low on a sample with a modestly raised triglyceride concentration. An RMP for 1,25 (OH)2D is not yet available and results are judged against the Method Mean. Free advice is available from the DEQAS Advisory Panel which includes experts on methodology and biostatistics. DEQAS collaborates closely with the Vitamin D Standardization Program (VDSP) and both organizations have successfully worked with participants and manufacturers to improve the accuracy of vitamin D assays.
Sujet(s)
Techniques de chimie analytique/méthodes , Ergocalciférol/sang , Vitamine D/analogues et dérivés , Vitamines/sang , Techniques de laboratoire clinique/méthodes , Humains , Contrôle de qualité , Vitamine D/sangRÉSUMÉ
Substantial variability is associated with laboratory measurement of serum total 25-hydroxyvitamin D [25(OH)D]. The resulting chaos impedes development of consensus 25(OH)D values to define stages of vitamin D status. As resolving this situation requires standardized measurement of 25(OH)D, the Vitamin D Standardization Program (VDSP) developed methodology to standardize 25(OH)D measurement to the gold standard reference measurement procedures of NIST, Ghent University and CDC. Importantly, VDSP developed protocols for standardizing 25(OH)D values from prior research based on availability of stored serum samples. The effect of such retrospective standardization on prevalence of "low" vitamin D status in national studies reported here for The Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and the German Health Interview and Examination Survey for Children and Adolescents (KIGGS, 2003-2006) was such that in NHANES III 25(OH)D values were lower than original values while higher in KIGGS. In NHANES III the percentage with values below 30, 50 and 75 nmol/L increased from 4% to 6%, 22% to 31% and 55% to 71%, respectively. Whereas in KIGGS after standardization the percentage below 30, 50, and 70 nmol/L decreased from 28% to 13%, 64% to 47% and 87% to 85% respectively. Moreover, in a hypothetical example, depending on whether the 25(OH)D assay was positively or negatively biased by 12%, the 25(OH)D concentration which maximally suppressed PTH could vary from 20 to 35ng/mL. These examples underscore the challenges (perhaps impossibility) of developing vitamin D guidelines using unstandardized 25(OH)D data. Retrospective 25(OH)D standardization can be applied to old studies where stored serum samples exist. As a way forward, we suggest an international effort to identify key prior studies with stored samples for re-analysis and standardization initially to define the 25(OH)D level associated with vitamin D deficiency (rickets/osteomalacia). Subsequent work could focus on defining inadequacy. Finally, examples reported here highlight the importance of suspending publication of meta-analyses based on unstandardized 25(OH)D results.
Sujet(s)
Techniques de chimie analytique/normes , Vitamine D/analogues et dérivés , Vitamines/sang , Techniques de chimie analytique/méthodes , Humains , Vitamine D/sang , Carence en vitamine D/sangRÉSUMÉ
The vitamin D External Quality Assessment Scheme (DEQAS) for 25-hydroxyvitamin D (25-OHD) has approximately 1100 participants in 53 countries using 26 different methods or variants of methods (October 2014). In April 2015, the scheme was extended to cover 24,25-dihydroxyvitamin D (24,25(OH)2D). Since 2013, the 25-OHD scheme has been accuracy-based with values assigned by the NIST reference measurement procedure (RMP). DEQAS is uniquely placed to assess the accuracy (bias) and specificity of 25-OHD methods in a routine laboratory setting. Other vitamin D metabolites are known to interfere in 25-OHD assays and DEQAS has distributed samples spiked with 3-epi-25-OHD3 (52.4nmol/L), 24R,25(OH)2D3 (14.4nmol/L) and 24S,25(OH)2D3 (57.9nmol/L). The 3-epimer showed a cross reactivity of 56% in a competitive protein binding assay but was not detected in any antibody-based methods. Not all HPLC/UV or LC-MS/MS methods were able to resolve 3-epi-25-OHD3 from 25-OHD3 and thus overestimated total 25-OHD. The cross reactivity of 24R,25(OH)2D3 (24S,25(OH)2D3) ranged from <5% (<5%) to 548% (643%) in ligand binding assays. Both 24-hydroxylated metabolites were resolved by HPLC/UV and LC-MS/MS methods and thus caused no complications in the measurement of 25-OHD. Most antibodies to 25-OHD are known to cross-react with dihydroxylated metabolites but interference in some assays was far greater than expected. This may be related to the anomalous behaviour of exogenously added metabolites in these 25-OHD methods.
Sujet(s)
Calcifédiol/sang , Chromatographie en phase liquide à haute performance/méthodes , Dosage immunologique/méthodes , Spectrométrie de masse en tandem/méthodes , 24,25-Dihydroxyvitamine D3/analyse , 24,25-Dihydroxyvitamine D3/sang , 24,25-Dihydroxyvitamine D3/métabolisme , Calcifédiol/analyse , Calcifédiol/métabolisme , Humains , Sensibilité et spécificité , Stéréoisomérie , Vitamine D/analogues et dérivés , Vitamine D/analyse , Vitamine D/sang , Vitamine D/métabolismeRÉSUMÉ
Unstandardized laboratory measurement of 25-hydroxyvitamin D (25(OH)D) confounds efforts to develop clinical and public health vitamin D guidelines. The Vitamin D Standardization Program (VDSP), an international collaborative effort, was founded in 2010 to correct this problem. Nearly all published vitamin D research is based on unstandardized laboratory 25(OH)D measurements. While it is impossible to standardize all old data, it may be possible to identify a small subset of prior studies critical to guidelines development. Once identified it may be possible to calibrate their 25(OH)D values to the NIST and Ghent University reference measurement procedures using VDSP methods thereby permitting future guidelines to be based on standardized results. We simulated the calibration of a small set of ten clinical trials of vitamin D supplementation on achieved 25(OH)D under minimal sun exposure. These studies were selected because they played a prominent role in setting the 2010 vitamin D dietary reference intakes (DRI). Using random-effects meta-regression analysis, Vitamin D External Quality Assessment (DEQAS) data on assay bias was used to simulate the potential bias due to the lack of assay standardization by calibrating the achieved 25(OH)D levels from those 10 studies to: (1) the largest negative, and (2) the largest positive bias from the DEQAS all laboratory trimmed mean (ALTM) for the appropriate assay and year of analysis. For a usual vitamin D intake of 600IU/day the difference in mean achieved 25(OH)D values for those two options was 20nmol/L. However, without re-calibration of 25(OH)D values it is impossible to know the degree to which any of the current guidelines may have been biased. This approach may help stimulate the search for and standardization of that small subset of key studies and, in the cases where standardization is impossible, to identify areas of urgently needed vitamin D research.
Sujet(s)
Analyse chimique du sang/normes , Apports nutritionnels recommandés , Vitamine D/analogues et dérivés , Vitamine D/administration et posologie , Calibrage , Humains , Essais contrôlés randomisés comme sujet , Analyse de régression , Reproductibilité des résultats , Vitamine D/sang , Vitamine D/normesRÉSUMÉ
The international quality assessment scheme for vitamin D metabolites (DEQAS) was established in 1989. The scheme involves the quarterly distribution of 5 serum samples prepared from blood collected in plain plastic bags. Following transfer of the donors to a clinic using different bags, sera were found to contain a contaminant that interfered in both the local LC-MS/MS assay and the NIST reference measurement procedure for 25-OHD. It seemed likely that the contaminant was a substance, possibly a plasticiser, leached from the plastic bag. It was subsequently suggested that the unidentified contaminant might also cause interference in certain automated non-extraction assays for 25-OHD. This was investigated in 3 automated immunoassays by comparing serum 25-OHD results from blood collected simultaneously into plain glass tubes and plastic bags. There was no significant difference in results, indicating that the leached substance had no effect on any of the 3 immunoassays examined.
Sujet(s)
Dosage immunologique/méthodes , Plastifiants/analyse , Vitamine D/analogues et dérivés , Vitamines/sang , Vitamines/immunologie , Automatisation , Humains , Vitamine D/sang , Vitamine D/immunologieRÉSUMÉ
The Vitamin D External Quality Assessment Scheme (DEQAS) has been monitoring 25-OHD assay performance since 1989. The scheme has expanded rapidly in recent years and has 670 participants in 35 countries (July 2009). Five samples of human serum are distributed quarterly and the results analyzed to give an All-Laboratory Trimmed Mean (ALTM) and SD. Each participant has internet access to a preliminary report after submission of results and, following the results deadline, a final report is e-mailed to designated staff in each laboratory. The last 15 years has seen an improvement in mean inter-laboratory imprecision (CV), from 32.0% (1994) to 15.3% (2009) and most major methods are now giving results within plus or minus 7.4% of the ALTM (2009). DEQAS has regularly conducted and reported on a number of investigations into the performance of 25-OHD methods. A gas chromatography-mass spectrometry (GC-MS) reference method for 25-OHD is under development and will be used to assess whether the ALTM remains the most appropriate target for DEQAS samples.
Sujet(s)
Chromatographie gazeuse-spectrométrie de masse/normes , Vitamine D/analogues et dérivés , Dosage biologique , Tests de chimie clinique , Techniques de laboratoire clinique/normes , Systèmes informatiques , Chromatographie gazeuse-spectrométrie de masse/méthodes , Humains , Laboratoires/normes , Reproductibilité des résultats , Vitamine D/sangRÉSUMÉ
The Vitamin D International External Quality Assessment Scheme (DEQAS) was established in 1989 to monitor the performance of assays for 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (I,25(OH)(2)D). This is achieved through the quarterly distribution of five samples of human serum. Results are used to calculate an All-Laboratory Trimmed Mean and a Method Mean for each of the methods used by participants. In July 2005, participants were asked to assay serum to which 50.9 nmol of either 25-OHD(3) or 25-OHD(2) had been added as ethanolic solutions. The final concentration of ethanol in the serum was 0.7%. The distribution also included a sample of the original serum (OS) containing 0.7% pure ethanol. The percentage recoveries of exogenous 25-OHD(3) (R1) and 25-OHD(2) (R2) were calculated for each method. Results (OS nM, R1 and R2) were as follows: DiaSorin RIA (n=53); 39.2, 82.1%, 83.3%, DiaSorin Liason (n=16); 36.8, 81.4%, 88.6%, IDS RIA (n=21); 36.4, 54.2%, 29.1%, IDS OCTEIA (n=16); 47.3, 78.8%, 56.4%, Nichols Advantage (n=21); 58.9, 46.4%, 43.2%, HPLC (n=9); 42.6, 112.2%, 97.1%, LC-MS (n=4); 34.0, 111.5%, 118.1%. The IDS RIA and Nichols assays gave unexpectedly low recoveries. This does not appear to be a calibration problem or the effect of ethanol.
Sujet(s)
Vitamine D/analogues et dérivés , Fixation compétitive , Humains , Vitamine D/sangRÉSUMÉ
The International Quality Assessment Scheme for Vitamin D metabolites (DEQAS) was introduced in 1989. Initially, the aim was to improve the reliability of 25-hydroxyvitamin D (25-OHD) assays but the scheme was extended in 1997 to include 1,25-dihydroxyvitamin D (1,25(OH)(2)D). DEQAS has 95 members in 18 countries (January 2003). Five serum samples are distributed quarterly and participants are given up to 6 weeks to return their results for statistical analysis. The majority of participants use commercial kits for both analytes. A performance target was set by an advisory panel in 1997 and, at present, requires participants to get 80% or more of their results within +/-30% of the All-Laboratory Trimmed Mean (ALTM). The performance targets are under continual review. In 2003, 59% of participants met the target (cf. 52% in 2000). A questionnaire, distributed in January 2003, requested information on methods and the interpretation of results. Reference ranges varied but there was reasonable agreement on the 25-OHD concentrations below which Vitamin D supplementation was advised. A minority (22%) of respondents was unsure whether Vitamin D(3) or Vitamin D(2) was used to treat patients in their locality. The majority (52%) of assays for 1,25(OH)(2)D were done 'on demand' and others for apparently spurious reasons. Most respondents thought participation in DEQAS extremely important and the planned introduction of on-line reporting should enhance its value.
Sujet(s)
Vitamine D/métabolisme , Humains , Internationalité , Enquêtes et questionnairesRÉSUMÉ
The British National Diet and Nutrition Survey of people aged 65 years and over in 1994-5 provided nationally representative estimates of food and nutrient intakes and biochemical status indices. In a further analysis study, parathyroid hormone (PTH) concentrations were measured in plasma samples from 773 subjects and were analyzed with the existing data on vitamin D intake, plasma 25-hydroxyvitamin D (25OHD), total plasma calcium and albumin. As predicted, a strong inverse relationship was observed between PTH and 25OHD. In the free-living respondents aged 65-84 years (n=507) there was a continuous decline in PTH with increasing 25OHD and no plateau, whereas in free-living people aged 85+ years (n=86) there was a significant deviation from a simple inverse relationship, with unexpectedly high PTH values in some people with satisfactory 25OHD status. There was a relationship between both PTH (inverse) and plasma 25OHD (direct) with calcium intake. A direct relationship between 25OHD and total plasma calcium was not significant when calcium was corrected for albumin. Geographically, 25OHD, and to a lesser extent PTH, exhibited a north-south gradient, and 25OHD was associated with self-reported health status. Both 25OHD and PTH were associated with self-reported physical activity. Low calcium intake and 25OHD was associated with receipt of state benefits. The relationship between plasma 25OHD and vitamin D intake revealed a striking seasonal cycle. 25OHD was strongly influenced by vitamin D intake in the winter in free-living subjects, but this was not observed in the summer. In people living in institutions such as nursing homes, who are less likely to be exposed to sunlight throughout the year, plasma 25OHD levels were lower throughout the year.
Sujet(s)
État nutritionnel , Hormone parathyroïdienne/sang , Vitamine D/analogues et dérivés , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Enquêtes nutritionnelles , Royaume-Uni , Vitamine D/administration et posologie , Vitamine D/sangRÉSUMÉ
The aim of the study was to investigate maternal thyroid function in pregnancy by monitoring the circulating concentrations of thyroid stimulating hormone (TSH), free thyroxine (fT(4)) and human chorionic gonadotrophin (hCG) in multifetal pregnancies before and after embryo reduction. We studied two groups of women: group 1 comprised singleton (n=12) and twin (n=12) pregnancies achieved after superovulation and in vitro fertilisation and embryo transfer (IVF-ET), and group 2 were multifetal pregnancies (n=39) undergoing selective fetal reduction to twin pregnancies. Blood samples were obtained initially at 10-12 weeks gestation (before fetal reduction) and then 4 and 8 weeks afterwards. Before fetal reduction, the circulating concentrations of fT(4) in multifetal pregnancies were significantly greater than those in singleton or twin pregnancies (singleton, mean 16.49 pmol/l (interquartile range 14.09-18.13 pmol/l); twins, 15.84 (15.36-16.95 pmol/l); multifetal, 21.08 (16. 64-26.29 pmol/l); P<0.005 for singleton and twins), and in a multiple regression analysis, fT(4) was significantly related to the number of fetuses (F=23.739, P=0.0001), but not to hCG. After fetal reduction to twins, the circulating concentrations of fT(4) in multifetal pregnancies decreased progressively towards those in control twin pregnancies, but remained significantly greater at both 4 (P=0.003) and 8 weeks (P=0.050). This pattern of change in the concentrations of fT(4) is similar to, but lags behind, that of hCG, which attains twin levels 4 weeks after fetal reduction. This may represent a delayed thyroid response to the decreasing concentrations of hCG, but the alternative is that the maternal thyroid function is controlled by a fetal factor in addition to hCG.
Sujet(s)
Réduction embryonnaire de grossesse multifoetale , Grossesse multiple/physiologie , Glande thyroide/physiologie , Gonadotrophine chorionique/sang , Transfert d'embryon , Femelle , Fécondation in vitro , Humains , Grossesse , Deuxième trimestre de grossesse , Grossesse multiple/sang , Analyse de régression , Statistique non paramétrique , Thyréostimuline/sang , Thyroxine/sangRÉSUMÉ
BACKGROUND: Insulin resistance is associated with ischaemic heart disease and has been proposed as a risk factor for subsequent myocardial infarction. AIM: To investigate the potential use of a recently proposed insulin resistance index in identifying insulin resistance in patients admitted with an acute coronary syndrome. METHODS: Single centre study of 441 non-diabetic patients admitted with chest pain to a coronary care unit and followed prospectively for a median of three years for outcome. Admission glucose and insulin concentrations were measured and from these values an admission index of insulin resistance (AIRI) calculated. Its association with other known factors in the insulin resistance syndrome, and subsequent outcome, was examined. RESULTS: The AIRI was greater in patients with myocardial infarction than in a control group without myocardial infarction (p < 0.0001). A Cox regression model for subsequent cardiac death identified previous myocardial infarction (p < 0.0001), infarct size (p < 0.0001), and AIRI (p = 0. 0033) as positive risk predictors. Patients of Indian subcontinent ethnic origin had greater AIRI values than white patients: mean (SD) 7.5 (1.3) v 4.6 (0.2), p < 0.001. CONCLUSIONS: A simple index of insulin resistance measured on patients admitted with myocardial infarction provides an important predictive measure of poor outcome and is superior to admission glucose measurement. It may be useful in identifying patients admitted with myocardial infarction who could benefit from alternative early management strategies.
Sujet(s)
Insulinorésistance , Infarctus du myocarde/thérapie , Angor instable/sang , Angor instable/mortalité , Angor instable/thérapie , Glycémie/analyse , Unités de soins intensifs cardiaques , Femelle , Études de suivi , Humains , Insuline/analyse , Mâle , Adulte d'âge moyen , Infarctus du myocarde/sang , Infarctus du myocarde/mortalité , Pronostic , Études prospectives , Récidive , Analyse de régression , Facteurs de risqueRÉSUMÉ
The cortisol responses to hypoglycaemia (insulin tolerance test, ITT) and tetracosactrin (short Synacthen test, SST) were compared after hypophysectomy to evaluate the SST for the assessment of hypothalamo-pituitary-adrenocortical (HPA) axis function in the immediate post-operative period. In 12 patients who were tested a mean of 21 months postoperatively (range 1-96) peak plasma cortisol in the SST correlated with that in the ITT (r = 0.90). Correlation was also seen in 12 patients tested a mean of 9 days (range 4-18) after hypophysectomy (r = 0.73). Basal-peak cortisol increments did not correlate. The peak plasma cortisol response in each test was classified by comparison with a reference value of 550 nmol/L. On this basis there was a notable discrepancy between the ITT and SST results in only one patient who was tested 4 days after hypophysectomy. The close correlation between ITT and SST responses after pituitary surgery extends into the immediate post operative period and indicates that the latter test can be used to screen HPA axis function at this time.
Sujet(s)
Tétracosactide , Hydrocortisone/sang , Hypophysectomie , Axe hypothalamohypophysaire/physiologie , Insuline , Axe hypophyso-surrénalien/physiologie , Adolescent , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Période postopératoireRÉSUMÉ
The aim of this study was to examine the possible correlations between follicular fluid insulin-like growth factor binding protein 1 (IGFBP-1) and follicular fluid and serum parameters of granulosa cell function. Twenty-six subjects undergoing diagnostic laparoscopy for infertility had follicular fluid samples collected. Subjects were aged 20-42 years, were having regular ovulatory cycles and either had tubal disease or a partner with male factor infertility. Sex steroids, insulin-like growth factor 1 (IGF-1) and IGFBP-1 were measured by radioimmunoassay. Follicular fluid levels of IGFBP-1 were significantly correlated with levels of estradiol, progesterone in follicular fluid and with serum IGFBP-1 levels, and negatively correlated with follicular fluid androstenedione levels. These results suggests that IGFBP-1 may have a role in the regulation of human ovarian follicles.