Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism.

Male hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with a multidisciplinary approach to treating patients with MH. This guideline has been compiled using expertise from endocrine (medical and nursing), primary care, clinical biochemistry, urology and reproductive medicine practices. These guidelines also provide a patient perspective to help clinicians best manage MH.

A global multicenter study on reference values: 1. Assessment of methods for derivation and comparison of reference intervals.

OBJECTIVES: The IFCC Committee on Reference Intervals and Decision Limits coordinated a global multicenter study on reference values (RVs) to explore rational and harmonizable procedures for derivation of reference intervals (RIs) and investigate the feasibility of sharing RIs through evaluation of sources of variation of RVs on a global scale. METHODS: For the common protocol, rather lenient criteria for reference individuals were adopted to facilitate harmonized recruitment with planned use of the latent abnormal values exclusion (LAVE) method. As of July 2015, 12 countries had completed their study with total recruitment of 13,386 healthy adults. 25 analytes were measured chemically and 25 immunologically. A serum panel with assigned values was measured by all laboratories. RIs were derived by parametric and nonparametric methods. RESULTS: The effect of LAVE methods is prominent in analytes which reflect nutritional status, inflammation and muscular exertion, indicating that inappropriate results are frequent in any country. The validity of the parametric method was confirmed by the presence of analyte-specific distribution patterns and successful Gaussian transformation using the modified Box-Cox formula in all countries. After successful alignment of RVs based on the panel test results, nearly half the analytes showed variable degrees of between-country differences. This finding, however, requires confirmation after adjusting for BMI and other sources of variation. The results are reported in the second part of this paper. CONCLUSION: The collaborative study enabled us to evaluate rational methods for deriving RIs and comparing the RVs based on real-world datasets obtained in a harmonized manner.

NICE-Accredited Commissioning Guidance for Weight Assessment and Management Clinics: a Model for a Specialist Multidisciplinary Team Approach for People with Severe Obesity.

Despite increasing prevalence of obesity, no country has successfully implemented comprehensive pathways to provide advice to all the severely obese patients that seek treatment. We aimed to formulate pathways for referral into and out of weight assessment and management clinics (WAMCs) that include internal medicine/primary care physicians as part of a multidisciplinary team that could provide specialist advice and interventions, including referral for bariatric surgery. Using a National Institute of Health and Care Excellence (NICE)-accredited process, a Guidance Development Group conducted a literature search identifying existing WAMCs. As very few examples of effective structures and clinical pathways existed, the current evidence base for optimal assessment and management of bariatric surgery patients was used to reach a consensus. The model we describe could be adopted internationally by health services to manage severely obese patients.

An evidence-based approach to the assessment of heart-type Fatty Acid binding protein in acute coronary syndrome.

Cardiac troponins have been the biomarkers of choice for the diagnosis of acute coronary syndrome (ACS) for over a decade. There has, however, been considerable interest over the last two decades for newer biomarkers that would bring added value to the measurement of troponin such as the provision of prognosis and assistance in the choice of therapeutic interventions. In this manuscript, we review the development of heart-type fatty acid binding protein (H-FABP) in patients with ACS using the evidence-based laboratory medicine format.Phase I studies have established that H-FABP reference intervals and pre-analytical factors influencing H-FABP. Phase II studies have confirmed a) that H-FABP is elevated in patients with established myocardial infarction; b) that its serum concentration is related to the extent of infarction using survival as a surrogate; and c) that its use in chest pain patients can identify ACS patients and also provide prognostic information on survival. Furthermore, it is an independent prognostic marker for patients with suspected ACS who are troponin negative. Phase III studies involving randomised control trials for diagnosis and prognosis have not yet been performed and Phase IV studies await uptake of H-FABP in a routine service.

An assessment of the concentration-related prognostic value of cardiac troponin I following acute coronary syndrome.

In 2004 the British Cardiac Society redefined myocardial infarction by cardiac troponin I (cTnI) concentration: ≤ 0.06 µg/L (unstable angina), >0.06 to < 0.5 µg/L (myocardial necrosis), and ≥ 0.5 µg/L (myocardial infarction). We investigated the effects of this classification on all-cause mortality in 1,285 patients from the Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-2 registry. There were 528 deaths (6.6-year all-cause mortality 41.1%). Survival was greatest in the cTnI ≤ 0.06-µg/L subgroup at 30 days (p = 0.005), 6 months (p = 0.015), 1 year (p = 0.002), and 6.6 years (p = 0.045). After adjustment there was no significant difference in survival between the cTnI >0.06- to < 0.5-µg/L and ≥ 0.5-µg/L subgroups. Increased mortality (hazard ratio, 95% confidence interval) was associated with ages 70 to 80 years (2.58, 1.17 to 3.91) and >80 years (3.30, 3.50 to 5.06), peripheral vascular disease (1.50, 1.16 to 1.94), heart failure (1.36, 1.05 to 1.83), diabetes mellitus (1.68, 1.36 to 2.07), severe left ventricular systolic dysfunction (1.50, 1.00 to 2.21), and creatinine per 10 µmol/L (1.65, 1.02 to 1.08), whereas ages 50 to 60 years (0.55, 0.32 to 0.96), ß blockers (0.53, 0.44 to 0.64), aspirin (0.80 0.65 to 0.99), angiotensin-converting enzyme inhibitors (0.67, 0.56 to 0.80), statins (0.73, 0.59 to 0.90), and revascularization (0.33, 0.12 to 0.92) were associated with a lower risk of death. In conclusion, although quantitative evaluation of cTnI concentration in patients with acute coronary syndrome with cTnI > 0.06 µg/L was associated with no added prognostic information, the dichotomization of patients by cTnI status ("positive" and "negative") facilitates acute coronary syndrome risk stratification.

An audit of the laboratory interpretation of growth hormone response to insulin-induced hypoglycaemia in the assessment of short stature in children.

INTRODUCTION: Measurement of serum growth hormone (GH) concentration in response to insulin-induced hypoglycaemia remains an important investigation in the assessment of pituitary disease. METHODS: In this audit, laboratories were presented with aliquots of sera with GH concentrations likely to be found in an insulin stress test (IST). They were invited to analyse the specimens for GH and comment on their results. RESULTS AND DISCUSSION: A number of laboratories appeared to be using out-of-consensus cut-off concentrations that sometimes were unrelated to the bias of their GH assay. The specimens were chosen to mimic those seen in an IST that was clearly not indicative of GH deficiency, so there was reasonable consensus in the interpretation of results. However, five laboratories (9.6%) did indicate that their results were equivocal.