Diet, environmental factors, and lifestyle underlie the high prevalence of vitamin D deficiency in healthy adults in Scotland, and supplementation reduces the proportion that are severely deficient.

Vitamin D deficiency has recently been implicated as a possible risk factor in the etiology of numerous diseases, including nonskeletal conditions. In humans, skin synthesis following exposure to UVB is a potent source of vitamin D, but in regions with low UVB, individuals are at risk of vitamin D deficiency. Our objectives were to describe the prevalence of vitamin D deficiency and to investigate determinants of plasma 25-hydroxyvitamin D (25-OHD) concentrations in a high northern latitude country. Detailed dietary, lifestyle, and demographic data were collected for 2235 healthy adults (21-82 y) from Scotland. Plasma 25-OHD was measured by liquid chromatography-tandem MS. Among study participants, 34.5% were severely deficient (25-OHD <25 nmol/L) and 28.9% were at high risk of deficiency (25-40 nmol/L). Only 36.6% of participants were at low risk of vitamin D deficiency or had adequate levels (>40 nmol/L). Among participants who were taking supplements, 21.3% had a May-standardized 25-OHD concentration >50 nmol/L, 54.2% had 25-50 nmol/L, and 24.5% had <25 nmol/L, whereas this was 15.6, 43.3, and 41%, respectively, among those who did not take supplements (P < 0.0001). The most important sources of vitamin D were supplements and fish consumption. Vitamin D deficiency in Scotland is highly prevalent due to a combination of insufficient exposure to UVB and insufficient dietary intake. Higher dietary vitamin D intake modestly improved the plasma 25-OHD concentration (P = 0.02) and reduced the proportion of severely deficient individuals (P < 0.0001). In regions with low UVB exposure, dietary and supplement intake may be much more important than previously thought and consideration should be given to increasing the current recommended dietary allowance of 0-10 µg/d for adults in Scotland.

Ethnic differences in aortic pulse wave velocity occur in the descending aorta and may be related to vitamin D.

We studied aortic pulse wave velocity (aPWV), a predictor of cardiovascular events independent of blood pressure, in a multiethnic sample of British men, to investigate the roles for blood levels of vitamin D and aldosterone in total and regional aortic stiffness. Total aPWV was estimated noninvasively by the Arteriograph device (aPWV(AG)) in 198 men, with its length measure calibrated by magnetic resonance. PWVs over the aortic arch and descending aorta were measured by magnetic resonance in a subsample (n=47). Mean (SE) aPWV(AG) in South Asians (n=68; age 55±10 years), at known higher coronary disease risk than other groups, was 0.5 m/s (0.2 m/s) higher than in African Caribbeans (n=67; 55±10 years), at lowest coronary disease risk here, and Europeans (n=63; 57±8 years), adjusted for age, systolic blood pressure, and diabetes mellitus (P=0.01). By magnetic resonance, PWV over the descending aorta in South Asians was 0.7 m/s (0.3 m/s) and 0.8 m/s (0.3 m/s) higher than in African Caribbeans and Europeans, respectively; PWV over the aortic arch was not different. South Asians and African Caribbeans had 21 nmol/L (3 nmol/L) and 14 nmol/L (3 nmol/L) lower mean (SE) 25(OH)D than Europeans (P<0.001). Unlike aldosterone, 25(OH)D was negatively correlated with aPWV(AG) adjusted for age and systolic blood pressure, as well as weakened or removed ethnic differences in aPWV(AG) in regression models. These data suggest that aortic stiffness as aPWV parallels coronary disease risk in ethnic groups, descending aortic but not arch PWV has this feature, and serum 25(OH)D is an independent negative correlate of aPWV and may partly account for ethnicity-related differences in aPWV and coronary disease risk.

Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome.

Both vitamin D deficiency and polycystic ovary syndrome (PCOS) are associated with aspects of metabolic syndrome, but it is unclear whether vitamin D deficiency contributes to the metabolic disturbances commonly found in women with PCOS. This study sought to investigate (1) the prevalence of vitamin D deficiency in PCOS women in Scotland and (2) the relationship between vitamin D status and metabolic risk factors. This was an observational study on 52 women (25 in PCOS group and 27 in control group). Serum 25-hydroxyvitamin D concentrations less than 25 nmol/L were classified as severe vitamin D deficiency and were found in 44.0% and 11.2% of subjects in the PCOS and control groups, respectively (P = .047). Among the PCOS subjects, 25-hydroxyvitamin D concentrations were negatively correlated with body mass index (P = .033), C-reactive protein (P = .027), and free androgen index (P = .025) and positively correlated with quantitative insulin sensitivity check index (P = .035), high-density lipoprotein cholesterol (HDL-C) (P = .033), and sex hormone binding globulin (P = .038). Associations of vitamin D deficiency with quantitative insulin sensitivity check index and HDL-C were independent of body mass index and waist-to-hip ratio. Vitamin D deficiency is highly prevalent in PCOS women in Scotland, and a larger proportion of PCOS patients than control women were found to be vitamin D deficient. We also demonstrate correlations of vitamin D status with insulin sensitivity, HDL-C, and C-reactive protein in PCOS patients, which support the increasing evidence that vitamin D deficiency is associated with multiple metabolic risk factors in PCOS women.

UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development.

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional DSD team acts as the first point of contact. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents are as fully informed as possible and have access to specialist psychological support. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration.

The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty.

BACKGROUND: Studies indicate that low plasma 25-hydroxyvitamin D [25(OH)D] is associated with a range of disease processes, many of which are inflammatory. However, other lipid-soluble vitamins decrease during the systemic inflammatory response, and this response may confound the interpretation of plasma 25(OH)D. OBJECTIVE: The objective was to examine whether plasma 25(OH)D concentrations change during evolution of the systemic inflammatory response. DESIGN: Patients (n = 33) who underwent primary knee arthroplasty had venous blood samples collected preoperatively and postoperatively (beginning 6-12 h after surgery and on each morning for 5 d) for the measurement of 25(OH) D, vitamin D-binding protein, parathyroid hormone (PTH), calcium, C-reactive protein, and albumin. A final sample was collected at 3 mo. RESULTS: Preoperatively, most patients were 25(OH)D deficient (<50 nmol/L) and had secondary hyperparathyroidism (PTH > 5 pmol/L). Age, sex, body mass index, season, medical history, and medication use were not associated with significant differences in preoperative plasma 25(OH)D concentrations. By day 2 there was a large increase in C-reactive protein concentrations (P < 0.001) and a significant decrease in 25(OH)D of ≈40% (P < 0.001). C-reactive protein, 25(OH)D, and calculated free 25(OH)D had not returned to preoperative concentrations by 5 d postoperatively (all P < 0.001). At 3 mo, 25(OH)D and free 25(OH)D remained significantly lower (20% and 30%, respectively; P < 0.01). CONCLUSION: Plasma concentrations of 25(OH)D decrease after an inflammatory insult and therefore are unlikely to be a reliable measure of 25(OH)D status in subjects with evidence of a significant systemic inflammatory response.

Confirmation of congenital adrenal hyperplasia by adrenal steroid profiling of filter paper dried blood samples using ultra-performance liquid chromatography-tandem mass spectrometry.

BACKGROUND: The specificity of screening for congenital adrenal hyperplasia by direct measurement of 17-hydroxyprogesterone in filter paper dried blood spot samples by immunoassay is low and has a high false-positive rate. In order to reduce the false-positive rate of this test, we developed a rapid, robust, specific confirmatory procedure in which cortisol, 4-androstene-3,17-dione and 17-hydroxyprogesterone were measured simultaneously by ultra-performance liquid chromatography-tandem mass spectrometry. METHODS: After extraction, samples were analysed by ultra-performance liquid chromatography-tandem mass spectrometry and 17-hydroxyprogesterone was quantified accurately. Other steroids were determined using stable deuterated internal standards. In total, 25 patient blood spot samples and 92 control samples were analysed. RESULTS: The assay was linear for 17-hydroxyprogesterone, with a coefficient of determination >0.997 and imprecision ≤ 6.5%. An upper limit of normal for 17-hydroxyprogester-one of 4.45 nmol/L was established by analysing a cohort of samples from unaffected newborns. In addition, a cut-off of 3.5 for the peak areas ratio (17-hydroxyprogesterone+4-androstene-3,17-dione)/cortisol, allows confirmation of the affected steroidogenic enzyme. CONCLUSIONS: A high throughput method for the detection of steroids related to congenital adrenal hyperplasia has been developed, allowing the false-positive rate associated with screening for 17-hydroxyprogesterone by immunoassay to be determined.

Nomogram for the decline in serum antimüllerian hormone: a population study of 9,601 infertility patients.

OBJECTIVE: To define an optimal model for the decline in circulating antimüllerian hormone (AMH) with age and develop a validated age-related nomogram. DESIGN: Cohort study with validation of linear, biphasic linear, differential, power, and quadratic equations undertaken in two additional cohorts. SETTING: United Kingdom infertility clinics. PATIENT(S): Training cohort of 4,590 infertile women. Two separate validation cohorts; 4,588 infertile women, and 423 women with confirmed ovulation and normal pelvic ultrasound who have a male partner with severe oligospermia. INTERVENTION(S): Serum AMH measurement. MAIN OUTCOME MEASURE(S): Optimal fit and age-related AMH nomogram. RESULT(S): The linear model had the largest sum of absolute and squared residuals and provided a less adequate fit than the four nonlinear models. Of these, the R(2) ranged from 19.45% to 19.48% in the training dataset, from 21.30% to 21.36% in the validation dataset, and from 13.29% to 13.75% in the partners of oligospermic males. The parameters of the differential model were difficult to estimate, and the goodness-of-fit of the power model was slightly inferior to the quadratic model. CONCLUSION(S): Circulating AMH concentrations decline with increasing reproductive age in a manner optimally described by a quadratic equation. This validated age-related AMH nomogram will enable counseling of infertility patients regarding reproductive performance.

Functional characterisation of the H365Y mutation of the 21-hydroxylase gene in congenital adrenal hyperplasia.

The study subject was a 13 day-old boy admitted to hospital, with weight loss since birth. He presented with the vomiting and hypotension that are classical features of congenital adrenal hyperplasia (CAH). The most common type of CAH is an autosomal recessive disorder caused by mutations in the 21-hydroxylase (CYP21A2) gene. To examine the CYP21A2 gene, gene-specific PCR was carried out, followed by sequencing. The baby was shown to be a compound heterozygote H365Y/R356W for two CYP21A2 gene mutations each inherited from a different parent. One of the mutations has not previously been functionally characterised. The mutations were reconstructed in an expression plasmid and characterised in vitro after transient transfection into human embryonic kidney (HEK293T) and hepatoblastoma (C3A) cell lines followed by measurement of enzyme activity. The CYP21A2 H365Y mutant exhibited minimal 21-hydroxylase activity to convert 17-hydroxyprogesterone to 11-deoxycortisol or progesterone to 11-deoxycorticosterone. Western immunoblotting indicated that the H365Y enzyme was produced in more variable amounts than wild type; in particular, the H365Y mutant protein may be unstable and/or subject to a more rapid degradation by the human proteosome as well as catalytically inefficient. The double mutant genotype with a severe mutation on each allele is compatible with the clinical presentation.

UK Food Standards Agency Workshop Consensus Report: the choice of method for measuring 25-hydroxyvitamin D to estimate vitamin D status for the UK National Diet and Nutrition Survey.

The consensus workshop, organised on behalf of the Food Standards Agency, was convened to recommend the most appropriate and secure method for measuring vitamin D status in the UK. Workshop participants (the Expert Panel) were invited on the basis of expertise in current 25-hydroxyvitamin D (25OHD) assays, or expertise in vitamin D nutrition and metabolism or detailed knowledge and experience in the National Diet and Nutrition Survey (NDNS). A decision support matrix, which set out the particular criteria by which the different options were scored and evaluated, was used to structure the discussion. The Expert Panel agreed that five methods for measuring 25OHD should be evaluated according to eleven criteria, selected on the basis of their relevance to the NDNS. All three of the evaluating subgroups of the Expert Panel produced similar total scores over the eleven criteria for the different methods; they scored LC-MS/MS and HPLC-UV similarly highly, while the scores for the immunoassay methods were lower. The Expert Panel recommended that an LC-MS/MS method should be the preferred method for the NDNS. A detailed specification for the method will be required to ensure comparability between NDNS and the National Health and Nutrition Examination Survey in the US facilitating future comparisons. The Expert Panel also recommended that the method should be carried out in a laboratory with appropriate expertise, competency and history of records of good performance. The method should be standardised against the National Institute of Standards and Technology SRM 972. If the recommended LC-MS/MS is adopted, the Expert Panel indicated that the method should be able to discriminate the C-3 epimer of 25OHD(3), especially if used to measure 25OHD in young infants in the forthcoming Diet and Nutrition Survey of Infants and Young Children, who are known to have high circulating concentrations of the C-3 epimer.

Serum steroid profiling for congenital adrenal hyperplasia using liquid chromatography-tandem mass spectrometry.

BACKGROUND: Diagnosis of Congenital Adrenal Hyperplasia (CAH) is based on the quantification of 17-hydroxyprogesterone (17-OHP), usually by immunoassay. During the neonatal period the specificity of screening for CAH by blood spot 17-OHP immunoassay is low. High false-positive rates result in a relatively high demand for a second-tier serum confirmation test. A robust, specific and selective method for measurement of cortisol, 21-deoxycortisol, 11-deoxycortisol, 4-androstene-3,17-dione (A4) and 17-OHP in serum has been developed. The method involves a simple extraction procedure and a fast analysis using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS). METHODS: The steroids were extracted from 50microl of serum using methyl-tert-butyl-ether. Analysis was performed on a UPLC tandem quadrupole mass spectrometer system in positive mode electrospray ionization and multiple reaction monitoring acquisition. RESULTS: The assay was linear over each analyte concentration range with all correlation coefficients (r(2))>0.996. Inter- and intra-day CVs were

The relationship between the insulin-like growth factor-1 axis, weight loss, an inflammation-based score and survival in patients with inoperable non-small cell lung cancer.

BACKGROUND & AIMS: The involvement of a systemic inflammatory response, as evidenced by the Glasgow Prognostic Score (GPS), is associated with weight loss and poor outcome in patients with non-small cell lung cancer. There is good evidence that nutritional and functional decline in patients with advanced malignant disease is associated with catabolic changes in metabolism. However, defects in anabolism may also contribute towards nutritional decline in patients with cancer. The aim of the present study was to examine the relationship between IGF-1 and IGFBP-3, performance status, mGPS and survival in patients with inoperable NSCLC. METHODS: 56 patients with inoperable NSCLC were studied. The plasma concentrations of IGF-1, IGFBP-3 and leptin were measured using ELISA and RIA. RESULTS: The patients were predominantly male (61%), over 60 years old (80%), with advanced (stage III or IV) disease (98%), with a BMI> or =20 (84%), an ECOG-ps of 0 or 1 (79%), a haemoglobin (59%) and white cell count (79%) in the reference range. On follow-up 43 patients died of their cancer. On univariate analysis, BMI (p<0.05), Stage (p<0.05), ECOG-ps (p<0.05), haemoglobin (p<0.05), white cell count (p<0.05) and mGPS (p<0.05) were associated with cancer specific survival. There was no association between age, sex, treatment, IGF-1, IGFBP-3, IGF-1:IGFBP-3 ratio, or leptin and cancer specific survival. With an increasing mGPS concentrations of haemoglobin (p<0.005) and IGFBP-3 (p<0.05) decreased. mGPS was not associated with either IGF-1(p>0.20), or leptin (p>0.20). CONCLUSIONS: In summary, the results of this study suggest that anabolism (IGF-1 axis) does not play a significant role in the relationship between nutritional and functional decline, systemic inflammation and poor survival in patients with inoperable NSCLC.

Familial and phenotypic associations of the aldosterone Renin ratio.

CONTEXT: The aldosterone to renin ratio (ARR) is a marker of aldosterone excess, widely used to screen for primary aldosteronism (PA). The significance of a raised ARR in normotensive and hypertensive subjects and the phenotypic and familial factors affecting it are unclear. OBJECTIVE: We estimated the distribution and heritability of the ARR and tested for associations between ARR and blood pressure (BP) with 11 polymorphisms at the CYP11B1/CYP11B2 locus. DESIGN AND SETTING: A total of 1172 individuals from 248 Caucasian families ascertained via a hypertensive proband were evaluated. MAIN OUTCOME MEASURE: Plasma aldosterone was measured by RIA, and plasma renin concentration was measured by the LIAISON Direct Renin chemiluminescent immunoassay. RESULTS: Unadjusted and adjusted ARR were continuously distributed in normotensives and hypertensives, with no evidence of a cutoff that would identify a separate population with PA. Median ARR was 4.19 ng/liter per mIU/liter (range, 0.04-253.16). ARR levels were higher in females and associated with age, body mass index, and potassium. Antihypertensive agents had significant predictable effects on the ARR. Renin was negatively associated, and ARR was positively associated with ambulatory BP readings (P < 0.001) in subjects not taking antihypertensives. The heritability of the ARR was 38.1% (P < 10(-8)). Plasma aldosterone, but not ARR, was influenced by the intron 2 conversion variation in the CYP11B2 gene (beta = -0.07; P = 0.04). CONCLUSIONS: The ARR is continuously distributed, is influenced by genetic and environmental factors, and is not a marker of a distinct pathological abnormality but possibly reflects the long-term influence of aldosterone on cardiovascular homeostasis.

A re-investigation of saliva collection procedures that highlights the risk of potential positive interference in cortisol immunoassay.

BACKGROUND: The use of saliva for measurement of cortisol permits non-invasive study of adrenal function, but collection can be technically difficult, particularly in small infants. Saliva collection can be assisted by citric acid to increase saliva flow, or by the use of cotton or polyester swabs in the mouth. AIM: To determine whether different methods of saliva collection affect cortisol radioimmunoassay (RIA) performance. EXPERIMENTAL: Cortisol was measured in saliva collected from 16 adults using intra-oral cotton swabs or polyester swabs, compared with saliva dribbled directly into a pot either alone (plain saliva) or after citric acid had been placed on the tongue. An in-house RIA, without prior extraction, was used to measure cortisol with an encapsulated sheep antibody. RESULTS: Mean (median) salivary cortisol was 10.9 (10.5) nmol L(-1) in plain saliva, 10.4 (8.4) nmol L(-1) in citric acid stimulated saliva; 25.3 (25.1) nmol L(-1) in saliva collected on cotton swabs, and 27.9 (27.3) nmol L(-1) collected on polyester swabs. Cortisol in saliva collected using citric acid was not significantly different from plain saliva (p=0.997), but cortisol in saliva collected using cotton and polyester swabs was significantly higher than that of plain saliva (p<0.01). CONCLUSION: The use of cotton or polyester swabs for collection of saliva can result in spuriously high levels of cortisol when measured by RIA.

A simple automated solid-phase extraction procedure for measurement of 25-hydroxyvitamin D3 and D2 by liquid chromatography-tandem mass spectrometry.

BACKGROUND: Measurement of 25-hydroxyvitamin D(3) (25OHD(3)) and D(2) (25OHD(2)) is challenging. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been described but they are often complex and difficult to automate. We have developed a simplified procedure involving an automated solid-phase extraction (SPE). METHODS: Internal standard (hexadeuterated 25-hydroxyvitamin D(3)) was added to serum or plasma followed by protein precipitation with methanol. Following centrifugation, a robotic instrument (CTC PAL [Presearch] for ITSP SPE [MicroLiter Analytical Supplies, Inc]) performed a six-step SPE procedure and the purified samples were injected into the LC-MS/MS. Quantification of 25OHD(3) and 25OHD(2) was by electrospray ionization MS/MS in the multiple-reaction monitoring mode. RESULTS: The lower limit of quantitation was 4.0 nmol/L for 25OHD(3) and 7.5 nmol/L for 25OHD(2). Within- and between-assay precision was below 10% over the concentration range of 22.5-120 nmol/L for D(3) and 17.5-70 nmol/L for D(2) (n = 10). The calibration was linear up to 2500 nmol/L (r = 0.99). Recoveries ranged between 89% and 104% for both metabolites and no ion suppression was observed. The results obtained compared well (r = 0.96) with the IDS-OCTEIA 25-hydroxyvitamin D enzyme immunoassay for samples containing less than 125 nmol/L, at higher concentrations the immunodiagnostic system (IDS) method showed positive bias. CONCLUSIONS: Our simplified sample preparation and automated SPE method is suitable for the measurement of 25OHD(3) and D(2) in a routine laboratory environment. The system can process up to 300 samples per day with no cumbersome solvent evaporation step and minimal operator intervention.

A novel CYP11B2 gene mutation in an Asian family with aldosterone synthase deficiency.

CONTEXT: Three siblings of Pakistani origin presented neonatally with isolated hyperreninemic hypoaldosteronism and were well controlled on fludrocortisone therapy during childhood and adolescence. OBJECTIVE/DESIGN: These individuals were reevaluated as adults after fludrocortisone withdrawal to investigate the biochemical and molecular basis of their disorder. RESULTS: When reassessed off fludrocortisone treatment, hyperreninemic hypoaldosteronism was confirmed in all subjects but with significant hyperkalemia in only one case. Profiling of urinary steroid metabolites showed a biochemical pattern (elevated tetrahydrocorticosterone to 18-hydroxytetrahydro-11-dehydrocorticosterone ratio but normal 18-hydroxytetrahydro-11-dehydrocorticosterone to tetrahydroaldosterone ratio) consistent with partial type 1 aldosterone synthase deficiency. Sequencing of the CYP11B2 gene showed that affected subjects were homozygous for a single nucleotide substitution (T925C) in exon 5, corresponding to a serine to proline mutation (S308P) in the predicted protein, with unaffected family members being heterozygous. Consistent with structural modeling showing that the mutated residue is located within the alpha-helix I, close to the hemebinding, active site of the enzyme, functional characterization of the S308P mutant protein in vitro showed complete loss of enzyme activity. However, administration of dexamethasone further reduced levels of circulating aldosterone and its urinary metabolites in affected subjects, suggesting that some mineralocorticoid biosynthesis occurs in vivo. CONCLUSION: We have identified the first CYP11B2 gene defect in a family of Asian origin, associated with a type 1 aldosterone synthase deficiency phenotype. Preservation of some aldosterone production suggests either residual mutant CYP11B2 enzyme activity in vivo or mineralocorticoid biosynthesis via an alternative pathway.

Leptin and coronary heart disease: prospective study and systematic review.

OBJECTIVES: This study sought to better determine the link between leptin and coronary heart disease (CHD). BACKGROUND: Circulating leptin is considered a risk factor for CHD but larger studies are needed. METHODS: Leptin levels were measured in 550 men with fatal CHD or nonfatal myocardial infarction and in 1,184 controls nested within a prospective study of 5,661 British men and set in context with a meta-analysis. RESULTS: Baseline leptin correlated with body mass index (BMI), blood pressure, total cholesterol, triglyceride, and inflammatory markers; correlations persisted after BMI adjustment. The within-person consistency of leptin values over 4 years (correlation coefficient: 0.79; 95% confidence interval [CI]: 0.73 to 0.83) was higher than those of some established cardiovascular risk factors. In a comparison of individuals in the top third with those in the bottom third of baseline leptin, the age- and town-adjusted odds ratio for CHD was 1.25 (95% CI: 0.96 to 1.62), decreasing to 0.98 (95% CI: 0.72 to 1.34) after adjustment for BMI. A systematic review identified 7 prospective reports with heterogeneous findings (I(2) = 60%, 13% to 82%). The combined adjusted risk ratio across all studies was 1.44 (95% CI: 0.95 to 2.16) in a comparison of extreme thirds of leptin levels. The inconsistency between studies was partially explained by sample size, with combined estimates from studies involving >100 CHD cases (1.28, 95% CI: 0.80 to 2.04) being somewhat weaker than those from smaller studies (1.81, 95% CI: 0.76 to 4.31). CONCLUSIONS: Previous studies appear to have overestimated associations of leptin and CHD risk. Our results suggest a moderate association that is largely dependent on BMI.

The changing role of the clinical laboratory in the investigation of polycystic ovarian syndrome.

In this review we outline clinical features, presentation and pathogenesis of polycystic ovarian syndrome (PCOS), treatment objectives and therapeutic options. We focus on and outline the changing role of the clinical laboratory in diagnosis and treatment of this condition. We also review recent information on the involvement of insulin resistance in the syndrome. We provide some explanation for confusion over the selection of the best hormone measurements for diagnosis. Finally, we outline the best current and future laboratory support for this common condition in young women.