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Objectives During 2020, the UK’s Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity. Methods Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study. Results Analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7–39.1) demonstrated diagnostic sensitivity of 92.4% (87.4–95.5), specificity of 97.4% (94.0–98.9) and near total concordance with RT-qPCR (Cohen’s Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1–99.3), specificity 97.4% (94.0–98.9) and Cohen’s Kappa 0.95. Conclusions This unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory.

Background Symptoms of hyperandrogenism are common in patients with Cushing's disease (CD), yet they are not sufficiently explained by androgen concentrations. In this study, we analyzed the contribution of 11-oxygenated C19 steroids (11oxC19) to hyperandrogenemia in female patients with CD. Methods We assessed saliva day profiles in females with CD pre (n = 23) and post (n = 13) successful transsphenoidal surgery, 26 female controls, 5 females with CD treated with metyrapone and 5 treated with osilodrostat for cortisol, cortisone, androstenedione (A4), 11-hydroxyandrostenedione (11OHA4), testosterone (TS), 11-ketotestosterone (11KT), as well as metabolites of classic and 11-oxygenated androgens in 24-h urine. In addition, morning baseline levels of gonadotropins and estradiol, sex hormone-binding globulin, cortisol and dehydroepiandrosterone sulfate (DHEAS) in serum and adrenocorticotrophic hormone in plasma in patients and controls were investigated. Results Treatment-naïve females with CD showed a significantly elevated area under the curve of 11OHA4 and 11KT in saliva throughout the day compared to controls (11OHA4 mean rank difference (mrd) 18.13, P = 0.0002; 11KT mrd 17.42; P = 0.0005), whereas A4, TS and DHEAS were comparable to controls. Gonadotropin concentrations were normal in all patients with CD. After transsphenoidal surgery, 11oxC19 and their metabolites dropped significantly in saliva (11OHA4 P < 0.0001; 11KT P = 0.0010) and urine (11-oxo-androsterone P = 0.0011; 11-hydroxy-androsterone P < 0.0001), treatment with osilodrostat and metyrapone efficaciously blocked 11oxC19 synthesis. Conclusion Hyperandrogenemia in CD is predominantly caused by excess of 11oxC19 steroids.

Background Guidelines recommend the assessment of cortisol secretion in patients with adrenal incidentalomas (AI) using the overnight dexamethasone suppression test (ONDST). This requires attendance to a health care facility and venepuncture. Alternatively, the ONDST can be done by measuring salivary cortisol and cortisone which can be collected at home. We aimed to assess the utility of these measurements in patients with AI. Materials and Methods A retrospective analysis of data from 173 patients with AI who underwent an ONDST and salivary cortisol/cortisone diurnal studies. Serum and salivary cortisol and salivary cortisone were collected at 09:00, late night and at 09:00 post dexamethasone. Dexamethasone levels were measured in the post dexamethasone samples. Serum and salivary samples were analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Stata. Results We identified a strong correlation between salivary cortisone and serum cortisol post 1 mg dexamethasone (r = 0.95). Stepwise multivariate regression showed that post-dexamethasone salivary cortisone, baseline serum cortisol, salivary cortisone suppression (pre: post-dexamethasone ratio) and sex as the only significant or near significant independent variables. Performance of predictive indices using these four parameters (sensitivity = 88.5%, specificity = 91.2%; kappa 0.80) and post-dexamethasone salivary cortisone alone (sensitivity = 85.3%, specificity = 91.7%; kappa 0.77) were comparable when used to predict an ONDST serum cortisol of ≤50 nmol/L. No correlation was observed with any of the other measured parameters. Conclusion In AI patients, post dexamethasone, salivary cortisone correlates very strongly with serum cortisol in the ONDST and could therefore be used as an alternative sampling method which does not require venepuncture or attendance to hospital.

Background/Aims MTX non-adherence is associated with reduced response, increased healthcare costs to the NHS and reduced quality of life for the patient. Often the prescriber is unable to determine if a patient is taking their medication as prescribed. There is a need to measure adherence directly to facilitate more precise and objective measurements of adherence to add to the clinicians tools and help to open up honest discussions and supportive interventions with patients. Our group has previously developed a sensitive biochemical assay for the detection of MTX adherence, MIRA is a feasibility trial designed to assess the feasibility of a randomised controlled trial of MTX biochemical adherence biofeedback. Methods MIRA is a prospective multi-centre randomised controlled trial to examine the feasibility of a fully powered randomised controlled trial to examine if a biochemical adherence guided intervention is superior to standard clinical care in RA patients prescribed MTX. RA patients prescribed oral MTX for ≥ two years were randomised 1:1 to receive biochemical adherence biofeedback or control. Clinico-demographics, biochemical MTX adherence and DAS-28 and were measured at baseline and three months. Participants in the intervention cohort were telephoned with their biochemical adherence results and adherence was explored. Ethical approval for MIRA was given by the North West - Haydock Research Ethics Committee (19/NW/0047) and all participants provided written informed consent. Results 57 participants were recruited, withdrawal rate was 14% and reasons given were intercurrent illness, lost contact, withdrawn consent and one patient died during follow-up leaving full outcome data available for 49 participants. Baseline clinico-demographics were similar in control and intervention cohorts (Table 1). Biochemical adherence worsened in the control cohort and improved in the intervention cohort (17 to 30%, 15 to 8% respectively). Change in DAS(CDP)-28 during the trial worsened in the control cohort but improved in the intervention cohort (-0.04 STD 1.26 and 0.38 STD 0.78 respectively). Conclusion The results of the MIRA trial have demonstrated that the use of a biochemical adherence blood test with biofeedback is feasible as part of a clinical trial. The intervention demonstrated early evidence for efficacy justifying the need for a full definitive trial. Disclosure J. Bluett: None. K.L. Hyrich: None. B. Keevil: None. P. Doran: None. A. Barton: None.

Objective There is limited knowledge on the onset of comorbidities in congenital adrenal hyperplasia (CAH) during childhood. We aimed to establish the health status of children with CAH in the UK. Design and methods This cross-sectional multicentre study involved 14 tertiary endocrine UK units, recruiting 101 patients aged 8–18 years with classic 21-hydroxylase deficiency and 83 controls. We analysed demographic, clinical and metabolic data, as well as psychological questionnaires (Strengths and Difficulties (SDQ), Paediatric Quality of Life (PedsQL)). Results Patient height SDS in relation to mid-parental height decreased with age, indicating the discrepancy between height achieved and genetic potential height. Bone age was advanced in 40.5% patients, with a mean difference from the chronological age of 1.8 (±2.3) years. Patients were more frequently overweight (27%) or obese (22%) compared to controls (10.8% and 10.8%, respectively, P < 0.001). No consistent relationship between glucocorticoid dose and anthropometric measurements or hormonal biomarkers was detected. A small number of patients had raised total cholesterol (3.0%), low HDL (3.0%), raised LDL (7.0%) and triglycerides (5.0%). SDQ scores were within the ‘high’ and ‘very high’ categories of concern for 16.3% of patients. ‘School functioning’ was the lowest PedsQL scoring dimension with a median (interquartile range) of 70 (55–80), followed by ‘emotional functioning’ with a median of 75 (65–85). Conclusions Our results show an increased prevalence of problems with growth and weight gain in CAH children and suggest reduced quality of life. This highlights the urgent need to optimise management and monitoring strategies to improve long-term health outcomes.

Case 1 A 19 year old primigravida, 35 weeks gestation, presented with acute severe right flank pain and vomiting. She underwent a MR cholangiopancreatography following advice from the gastroenterologists. This revealed a right adrenal gland haemorrhage 46×24×40 mm. CRP was raised at 151mg/l. Random cortisol, potassium and plasma metanephrines (pMET) were normal. She was delivered by Caesarian Section at term with 100 mg IV hydrocortisone cover and with no complications to either mother or baby. CT adrenals performed 8 weeks postpartum was entirely normal with no evidence of residual haemorrhage or adrenal mass. Case 2 A 63 man with hypertension presented with acute severe left flank pain. CT renal and CT angiogram showed a large left adrenal and perinephric haemorrhage. This was treated with coil embolization of the left suprarenal artery. Initial biochemistry showed mildly raised plasma normetanephines at 2211 pmol/l which subsequently normalised. Overnight dexamethasone suppression test (ONDST) and aldosterone/plasma renin activity were normal. Serial CT scan showed gradual resolution of the adrenal haemorrhage with no underlying adrenal lesion. Case 3 A 56 year old man presented with a 3 day history of epigastric and left sided abdominal pain with nausea and fever. CT scan of the abdomen revealed a 5 cm adrenal haemorrhage which was contained within the gland. ONDST, pMET and aldosterone/plasma renin activity were normal. Serial scans showed resolution of the adrenal haemorrhage and a residual 14×13 mm adrenal nodule with a density of 20 Hounsfield Units but which remained unchanged in size. Case 4 A 72 year old man with generalised abdominal pain a week after hip replacement surgery. He developed a fever and his inflammatory markers were raised. CT abdomen showed non-enhancing bilateral adrenal lesions consistent with adrenal haemorrhage. He was taking Apixaban for thromboprophylaxis following hip replacement. A short synacthen test performed to rule out adrenal insufficiency showed a suboptimal cortisol response and treatment with hydrocortisone was commenced. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Background Symptoms of hyperandrogenism are common in patients with Cushing's disease (CD), but they cannot be sufficiently explained by measured concentrations of circulating androgens. In this study we analyzed the contribution of 11-oxygenated (11oxC19) androgens to hyperandrogenemia in female patients with CD as well as the influence of treatment with steroidogenesis inhibitors osilodrostat and metyrapone on 11oxC19 and classic androgens. Methods In this single-center study, we assessed saliva day profiles of 23 females with treatment naïve CD, 26 female controls, 5 females with CD treated with metyrapone and 5 treated with osilodrostat for cortisol, cortisone, androstenedione (A4), 11-hydroxyandrostenedione (11OHA4), testosterone (T), 11-ketotestosterone (11KT) by by liquid chromatography tandem mass spectrometry as well as morning baseline levels of gonadotropins and estradiol, sex hormone-binding globulin, cortisol anddehydroepiandrosterone sulfate (DHEAS) in serum and adrenocorticotropic hormone in plasma. Results Treatment naïve females with CD showed significantly elevated area under the curve (AUC) of 11OHA4 and 11KT throughout the day compared to controls (11OHA4 mean rank difference (mrd) 18.13, p = 0.0002; 11KT mrd 17.42; p = 0.0005) whereas A4, T and DHEAS were comparable to controls. Patients with more symptoms of hyperandrogenism displayed higher concentrations of 11oxC19 androgens and had significantly lower SHBG concentrations. Gonadotropin levels were normal in all patients with CD (LH 7.18 U/l (SD 14.28 U/l); FSH 7.68 U/l (SD 12.0 U/l)) and did not correlate with any other parameters. Treatment with osilodrostat and metyrapone efficaciously blocked 11oxC19 synthesis. In metyrapone but not in osilodrostat treatment a trend towards increased concentrations of T and significantly increased A4-concentrations were observed (A4 mrd 23.07, p = 0.0119). Conclusion Hyperandrogenemia in CD is predominantly caused by excess of 11oxC19 androgens. Due to lower compensatory increase of A4 and T, osilodrostat seems to be more suitable for treatment of females with CD and hyperandrogenism than metyrapone. Presentation: Tuesday, June 14, 2022 9:45 a.m. - 10:00 a.m.

Accurate assessment of anterior pituitary function requires a sound knowledge of its normal physiology together with careful integration of clinical and biochemical information. The optimum methods of testing anterior and posterior pituitary function and the interpretation of the results are subjects of continuing debate. The syndromes associated with and consequences of hypo- and hyperpituitarism; and the diagnosis and treatment of diabetes insipidus are all discussed elsewhere in this book. The intention of this chapter is to describe the physiological basis and evidence in favour of the various available tests of anterior pituitary function, while at the same time acknowledging their limitations and appreciating the importance of the clinical context of testing.

OBJECTIVE: Limited evidence supports the use of free testosterone (FT) for diagnosing hypogonadism when sex hormone-binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). DESIGN: Prospective observational study with a median follow-up of 4.3 years. PATIENTS: Three thousand three hundred sixty-nine community-dwelling men aged 40-79 years from eight European centres. MEASUREMENTS: Subjects were categorized according to baseline and follow-up biochemical status into persistent eugonadal (referent group; n = 1880), incident LNSH (eugonadism to LNSH; n = 101) and incident LLSH (eugonadism to LLSH; n = 38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. RESULTS: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9%, respectively. Baseline obesity predicted both LNSH and LLSH, but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR = 2.67 (1.27-5.60)], erectile dysfunction [OR = 4.53 (2.05-10.01)] and infrequent morning erections [OR = 3.40 (1.48-7.84)]. CONCLUSIONS: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obese men with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT. ispartof: CLINICAL ENDOCRINOLOGY vol:89 issue:4 pages:459-469 ispartof: location:England status: published

Summary Introduction Hypogonadism is more prevalent in men with type 2 diabetes (T2DM) (25%‐40%) than in men without T2DM. Hypogonadism has been associated with poorer glycaemic outcomes and increased cardiovascular morbidity/mortality. We report a 14‐year follow‐up study to evaluate the influence of baseline testosterone level on T2DM outcomes. Research design and methods A total of 550 men with T2DM underwent baseline total testosterone and dihydrotestosterone measurement by tandem mass spectrometry. Mean age of the men was 59.7 ± 12 (mean ± SD) years. Sex hormone‐binding globulin (SHBG) was measured and free testosterone estimated. Patients were followed up between 2002 and 2016. Mean follow‐up period was 12.2 ± 4 years using the Salford (UK) Integrated Health Records system. Results Mean baseline total testosterone was 13.7 ± 5.8 nmol/L, and mean free testosterone was 245.7 ± 88.0 pmol/L. Mean for low total testosterone (

Salivary cortisol measurement is used as a practical surrogate for serum free cortisol. However, parotid tissue harbors 11β-hydroxysteroid dehydrogenase (11β-HSD2) activity converting cortisol to cortisone.This study was designed to assess the impact of parotid 11β-HSD2 activity on the measurement of salivary cortisol. PATIENTS, DESIGN, AND OUTCOME MEASURES: Study participants with changes in circulating corticosteroid-binding globulin (CBG) (±oral contraceptive, functionally CBG null) and controls were studied during adrenal stimulation by ACTH and postoral and iv hydrocortisone administration. Simultaneous serum and saliva samples were collected for the measurement of total serum cortisol (SerF) by immunoassay, and unbound cortisol and cortisone in serum (FreeF and FreeE) and saliva (SalF and SalE) by liquid chromatography-tandem mass spectrometry.ACTH stimulation increased SerF, FreeF, SalF, SalE, but not FreeE in all individuals. SerF significantly decreased after stopping oral contraceptive administration, but FreeF, SalF and SalE remained unchanged. In the hydrocortisone administration study, individual FreeF and SalE curves were nearly identical and SalE closely reflected FreeF in all participants, irrespective of CBG changes. The highest correlation in all (n = 537) matched serum-saliva samples was between SalE and FreeF (r = 0.95, P0.0001), and there was no evidence of 11β-HSD2 saturation.Salivary cortisol is a useful surrogate for circulating free cortisol, but its concentration is determined both by serum free cortisol and parotid metabolism to cortisone. We have shown that salivary cortisone closely reflects free serum cortisol after adrenal stimulation and hydrocortisone administration and is unaffected by CBG changes. Salivary cortisone has potential as a useful surrogate for serum free cortisol in research and clinical assessment, and further research in states of chronic glucocorticoid excess is now needed.

Background Current gold standard markers for myocardial damage are troponins I and T, which are both sensitive and specific for the detection of myocardial infarction, but require up to 6 h to become reliably elevated in serum. Investigation into markers with potential to identify patients with early ischaemic changes is therefore intense. Choline is reported to be prognostic in patients presenting with acute coronary syndromes via its release from ischaemic cell membranes. Methods Liquid chromatography tandem mass spectrometry was used to develop a method to quantitate choline in plasma and blood. The method involves addition of a deuterated internal standard to an aliquot of plasma or blood followed by organic solvent addition, which precipitates the proteins in the sample. Preparation was carried out directly into a 96-deep-well plate. Chromatography of choline used a strong cation exchange column and separation used a Waters Atlantis dC18 analytical column positioned directly before the mass spectrometer source, allowing on-line preanalytical clean up of the sample. Results The lower limit of quantitation was 0.38 μmol/L, linearity was observed up to 754 μmol/L, with a working concentration range of 0.38–224 μmol/L, inter- and intra-assay coefficients of variation were Conclusions The assay was successfully validated in accordance with FDA guidelines and is suitable for quantitation of choline in research and clinical settings.

Objectives Choline has been identified as a promising marker of coronary inflammation, plaque destabilisation and ischaemia. We sought to evaluate plasma choline levels for rapid confirmation or exclusion of acute myocardial infarction (AMI) in the Emergency Department (ED) and for predicting major adverse cardiac events (MACE). Methods We prospectively recruited 361 patients who presented to the ED with suspected cardiac chest pain within the previous 24 h. Blood was drawn at the time of presentation for plasma choline levels. All patients underwent troponin T testing ≥ 12 h after symptom onset and were followed up for the occurrence of MACE within 6 months. Whole blood choline (WBCho) levels were also measured in a convenience sample of 39 patients. Results Plasma choline levels did not help to predict a diagnosis of AMI (odds ratio (OR) 1.00 (95% confidence intervals (CI) 0.91–1.10, p = 0.98). For a diagnosis of AMI the area under the receiver operating characteristic (ROC) curve was 0.48. Plasma choline was not predictive of the combined endpoint of MACE (OR 1.03, 95% CI 0.95–1.12, p = 0.45) but predicted AMI within 6 months (OR 1.31, 95% CI 1.09–1.56, p = 0.003). WBCho levels were significantly different to plasma levels and were predictive of MACE. Conclusions Plasma choline, measured at the time of ED presentation, is not a diagnostic marker of AMI but predicts AMI within 6 months. While plasma choline failed to predict MACE, WBCho was predictive and warrants further evaluation.

Background Little is known about how socioeconomic position (SEP) across life impacts on different axes of the endocrine system which are thought to underlie the ageing process and its adverse consequences. We examined how indicators of SEP across life related to multiple markers of the endocrine system in late midlife, and hypothesized that lower SEP across life would be associated with an adverse hormone profile across multiple axes. Methods Data were from a British cohort study of 875 men and 905 women followed since their birth in March 1946 with circulating free testosterone and insulin-like growth factor-I (IGF-I) measured at both 53 and 60–64 years, and evening cortisol at 60–64 years. Indicators of SEP were ascertained prospectively across life—paternal occupational class at 4, highest educational attainment at 26, household occupational class at 53, and household income at 60–64 years. Associations between SEP and hormones were investigated using multiple regression and logistic regression models. Results Lower SEP was associated with lower free testosterone among men, higher free testosterone among women, and lower IGF-I and higher evening cortisol in both sexes. For example, the mean standardised difference in IGF-I comparing the lowest with the highest educational attainment at 26 years (slope index of inequality) was −0.4 in men (95% CI -0.7 to −0.2) and −0.4 in women (−0.6 to −0.2). Associations with each hormone differed by SEP indicator used and sex, and were particularly pronounced when using a composite adverse hormone score. For example, the odds of having 1 additional adverse hormone concentration in the lowest compared with highest education level were 3.7 (95% CI: 2.1, 6.3) among men, and 1.6 (1.0, 2.7) among women (P (sex interaction) = 0.02). We found no evidence that SEP was related to apparent age-related declines in free testosterone or IGF-I. Conclusions Lower SEP was associated with an adverse hormone profile across multiple endocrine axes. SEP differences in endocrine function may partly underlie inequalities in health and function in later life, and may reflect variations in biological rates of ageing. Further studies are required to assess the likely functional relevance of these associations., Highlights • Socioeconomic position (SEP) across life was related to multiple hormone measures. • Lower SEP was related to lower testosterone in men, higher testosterone in women. • Lower SEP was related to lower IGF-I and higher evening cortisol in both sexes. • SEP differences in multiple hormone axes may underlie later life health inequality.

Background: Dehydroepiandrosterone sulphate (DHEAS) is a steroid that is increasingly being recognized as a potential drug of abuse in many countries. This is due to its reputation as a hormone that may be able to retard the ageing process. The measurement of DHEAS is useful in the diagnosis of medical conditions such as congenital adrenal hyperplasia and polycystic ovary syndrome. Thus, a liquid chromatography-tandem mass spectrometry method has been developed to determine DHEAS concentrations in human serum. Method: The chromatography was performed using a WatersTM 2795 Alliance HT LC system coupled to a Mercury Fusion-RP column fitted with a SecurityGuardTM column. Results: DHEAS and the internal standard, deuterated DHEAS, both had a retention time of 1.5 min. The transition determined by the Micromass QuattroTM tandem mass spectrometer for DHEAS was m/z 367.3>96.7 and for the internal standard m/z 369.3>96.6. The method was linear up to 20 µmol/L; the lower limit of detection and the lower limit of quantitation were both 1 µmol/L. The intra- and interassay imprecision were Conclusion: The measurement of DHEAS by liquid chromatography-tandem mass spectrometry is robust and has a simple sample preparation procedure with a rapid cycle time of only 4 min.

BACKGROUND: Cardiovascular mortality in end-stage renal failure patients is high and early risk stratification in these patients may aid clinical management improving outcomes. Cardiac troponin T (cTnT) is a component of the cardiac myocyte which is released into the circulation following myocardial necrosis. It has been shown to be of prognostic significance in patients with unstable angina. The role of cTnT in patients with renal disease remains unclear. The aim of this investigation, therefore, was to assess the prognostic significance of cTnT in chronic renal impairment patients, pre-dialysis.METHODS: Ninety-six patients with chronic renal impairment were followed prospectively after cTnT determination by a quantitative laboratory method. The clinical outcomes after 2 years were determined. The measured cTnT values were correlated with biochemical parameters and clinical end-points.RESULTS: A cut-off of 0.1 ng/ml was used in assessing the prognostic significance of cTnT. Twenty-five patients had a cTnT >0.1 ng/ml, whilst 71 had a cTnT 0.1 ng/ml was 42% compared with 14% in those with levels below the cut-off. Thirty-three patients died or had a vascular event. The rate of death or a vascular event in the elevated group was 64% compared with 24% in those with levels below the cut-off. At the end of the study, 23 patients were treated by continuous ambulatory peritoneal dialysis, 29 by haemodialysis, 22 had functioning renal transplants and one patient was not on renal replacement therapy. Factors that were found to significantly affect cTnT were diabetes, age and urea. cTnT was found to be a significant predictor of survival in these patients. Patients with high cTnT values were more likely to end up on haemodialysis. No relation of renal function to cTnT level was found.CONCLUSIONS: These results show that in patients with renal impairment, the measurement of cTnT prior to commencing renal replacement is a significant independent predictor of survival. cTnT did show potential as a prognostic test to stratify patients with a high cardiovascular risk and may enable intensive risk factor modification in this patient group. This may be of further use in selection of patients' suitability for renal transplantation.

Objective Randomized trials in men with testosterone deficiency have provided evidence of short‐term effects of testosterone therapy on muscle and fat mass but it is unclear whether this persists over a longer period or how testosterone affects women. We examined whether the midlife decline in testosterone relates to fat and lean mass in both sexes. Methods Data were collected from 440 men and 560 women participating in the 1946 British birth cohort study with testosterone measured at 53 and/or 60‐64 years. Fat and appendicular lean mass were measured at 60‐64 years using dual‐energy X‐ray absorptiometry. Results Mean free testosterone concentrations were lower at 60‐64 than 53 years, by 26% in both sexes. At both ages testosterone was negatively associated with fat mass in men and positively associated in women. A larger decline in free testosterone was associated with higher fat mass in men but with lower fat mass among women. In contrast, declines in testosterone were not associated with lean mass in either sex. Conclusions Our findings suggest sex‐divergent relationships between testosterone and fat mass and their distribution but do not support the hypothesis that midlife declines in testosterone lead to lower lean mass.

An interlaboratory comparison study for melatonin, cortisol and testosterone in saliva in which five laboratories participated is reported in this study. Each laboratory blindly measured eight samples prepared from natural saliva spiked with melatonin, cortisol and testosterone in the range 0-579 pmol/L for melatonin, 0-90 nmol/L for cortisol, and 0-622 pmol/L for testosterone. The recovery of spiked material for melatonin ranged from 91-110%, from 83-100% for cortisol and from 80-94% for testosterone. The content of natural hormone in saliva was estimated to be between 0.278 and 6.90 pmol/L for melatonin, 0.56 and 6.72 nmol/L for cortisol and 11.9 and 73.8 pmol/L for testosterone. This indicates a large interlaboratory variation. The present study emphasizes the importance of external quality control for the analysis of melatonin, cortisol and testosterone in saliva.