BACKGROUND:Thyroid testing strategies vary across laboratories. First-line combined thyroid stimulating hormone (TSH) and freeT4 (FT4) have historically been preferred by many laboratories as this detects individuals with undiagnosed central hypothyroidism who can be missed with a first-line TSH-only strategy. However, an up-to-date evaluation of the utility of this approach is lacking.OBJECTIVES:We investigated the clinical utility of first-line TSH and FT4 in the detection of central hypothyroidism in current day practice.DESIGN, PATIENTS, AND MEASUREMENTS:The All-Wales laboratory information system was queried to identify thyroid function tests in patients aged ≥16 years with decreased FT4 and inappropriate TSH (low-FT4). The 1-year incidence of low-FT4 was determined using mid-year population data. Clinical information of patients with low-FT4 was reviewed to determine causes of low-FT4 and the incidence of central hypothyroidism.RESULTS:The incidence of low-FT4 varied according to FT4 assay method (range: 98-301 cases/100,000 population/year). Fifteen new cases of central hypothyroidism were detected in two health boards, equivalent to 2 cases/100,000 population/year. Positive predictive value of low-FT4 for central hypothyroidism was 2%-4%. In a cross-section of primary care patients, low-FT4 was detected in 0.5% of all thyroid tests with assay-related differences in detection rates.CONCLUSIONS:Although low-FT4 is a common laboratory finding, the incidence of central hypothyroidism remains rare. With the currently increased rates of thyroid testing and increased use of medications that decrease FT4, low-FT4 has a much lower predictive value for central hypothyroidism than previously reported. Thyroid screening strategies will need to balance the yield from first line TSH and FT4 testing with the cost of investigating individuals with non-pathological laboratory abnormalities.

Objective To investigate the final diagnosis and clinical outcome of patients referred to endocrinology in our district general hospital with biochemical isolated central hypothyroidism (CeH), and whether there is an association between this biochemical picture and treatment with antidepressant and antipsychotic medications. Methods We performed a retrospective observational study of patients referred to endocrinology with unexplained biochemical isolated CeH over a 5-year period. Results Of the 29 patients included in the study, 4 were found to have a partially empty or empty sella and 1 to have a bulky pituitary gland which was deemed to be an incidental radiological finding. No patients had any clinically significant pathology. On reviewing their medications, 18/29 (62%) were found to be on psychotropic medications. Conclusions Our study suggests a relationship between patients on psychotropic medications and biochemical isolated CeH, an association only described in a very limited amount of literature prior to this. The mechanism behind this may be suppression of TSH secretion via antagonism of the dopamine-serotoninergic pathway. Determining a correlation between psychotropic medications and isolated CeH could lead to the avoidance of further radiological investigations and unnecessary anxiety for patients. However, a larger observational study is needed to provide further evidence to support/refute our finding.

BackgroundElectronic AKI alerts highlight changes in serum creatinine compared to the patient's own baseline. Our aim was to identify all AKI alerts and describe the relationship between electronic AKI alerts and outcome for AKI treated in the Intensive Care Unit (ICU) in a national multicentre cohort.MethodsA prospective cohort study was undertaken between November 2013 and April 2016, collecting data on electronic AKI alerts issued.Results10% of 47,090 incident AKI alerts were associated with ICU admission. 90-day mortality was 38.2%. Within the ICU cohort 48.8% alerted in ICU. 51.2% were transferred to ICU within 7days of the alert, of which 37.8% alerted in a hospital setting (HA-AKI) and 62.2% in a community setting (CA-AKI). Mortality was higher in patients transferred to ICU following the alert compared to those who had an incident alert on the ICU (p<0.001), and was higher in HA-AKI (45.3%) compared to CA-AKI (39.5%) (35.0%, p=0.01). In the surviving patients, the proportion of patient recovering renal function following, was significantly higher in HA-AKI alerting (84.2%, p=0.004) and CA-AKI alerting patients (87.6%, p<0.001) compared to patients alerting on the ICU (78.3%).ConclusionThe study provides a nationwide characterisation of AKI in ICU highlighting the high incidence and its impact on patient outcome. The data also suggests that within the cohort of AKI patients treated in the ICU there are significant differences in the presentation and outcome between those patients that require transfer to the ICU after AKI is identified and those who develop AKI following ICU admission. Moreover, the study demonstrates that using AKI e-alerts provides a centralised resource which does not rely on clinical diagnosis of AKI or coding, resulting in a robust data set which can be used to define the incidence and outcome of AKI in the ICU setting.

Background Tandem mass spectrometry (MS/MS) has recently become an alternative method for the newborn screening of sickle cell disorders (SCD), as it is able to detect haemoglobin (Hb) peptides following digestion of bloodspots with trypsin. Using the SpOtOn Diagnostics Reagent Kit, we previously developed a screening protocol to detect only the disease states of SCD, using action values based on the ratio between the variant Hb peptide to wild-type peptide abundances for the HbS, C, DPunjab, OArab, E and Lepore peptides. Methods Action values using the ratios between the wild type HbA (ßT1-3) peptides and the foetal Hb (γT2) peptide were developed to identify bloodspot samples from premature and transfused infants. An evaluation was undertaken to assess the transferability of the action values onto an additional MS/MS instrument. We report here our experience using this MS/MS protocol. Results During a three-year period, we screened 100,456 babies and identified 10 SCD cases (1 HbS/HPFH, 5 HbS/S and 4 HbS/C) and a case of HbE/ß-thalassaemia that was identified as a by-product. The Hb variant to wild-type peptide ratio action values were transferable to a second MS/MS instrument. Our protocol prevented the identification of an estimated 810 carrier infants. Gestational age-related action values for HbA to HbF peptide ratios were required to minimize the number of samples referred for second-line testing to exclude ß-thalassaemia. Conclusion MS/MS is a robust alternative screening technology for SCD; in addition, it also optimizes the use of equipment and expertise that currently exist in newborn screening laboratories.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Background Considerable intermethod bias has been observed between cortisol immunoassays, with some also displaying a gender difference. Cortisol immunoassay performance is affected by serum matrix effects such as changes in steroid binding proteins and presence of interfering steroids which can be altered in various clinical settings. This study investigates cortisol immunoassay bias in pregnancy, renal failure and intensive care patients. Methods Serum remaining after routine analysis from pregnant patients, patients on the intensive care unit and patients with renal failure were obtained prior to disposal and used to create 20 anonymous samples per group. A male and female serum pool was prepared and spiked with cortisol. Samples were aliquoted and distributed to four hospitals for cortisol analysis by immunoassays from four different manufacturers. Cortisol was also measured by an isotope dilution-gas chromatography–mass spectrometry method for comparison of assay bias. Results Differences in cortisol immunoassay bias were observed across the different patient groups. A negative bias compared to pooled serum samples was observed for pregnancy serum, whilst a more positive bias was seen in renal failure and intensive care patients. Variation in bias was greatest in renal failure with the Roche E170 the most affected and the Abbott architect the least (interquartile ranges 44% and 14%, respectively). Conclusions Cortisol immunoassay bias may be affected by gender and differences in serum matrix from patients with various clinical conditions. Users of cortisol assays should be aware of differing matrix effects on their assay and the relevance of these for the interpretation of clinical results.

Background:Paediatric reference intervals are less well characterized than in adults. An initiative for harmonization of pathology across the United Kingdom has recommended an interval for sodium of 133-146mmol/L at all ages. Methods:To assess the validity of this, the laboratory database was interrogated for all renal profiles (sodium, potassium, urea and creatinine) for children presenting to primary care over a 13-year period. While the primary interest was in sodium results, sufficient current data were also available for potassium and creatinine and so these were included for study. The electrolyte results were filtered to include only normal renal function and the remaining data were analysed for age-related differences. Results:Sodium concentrations were observed to be lower for infants (1-5 years of age) with a mean of 138mmol/L, increasing towards adult concentrations (mean 140mmol/L) by teenage years. A similar pattern was seen for potassium results, and creatinine was seen to increase with age. At all ages, the distributions of sodium concentrations measured in this population were observably tighter than the interval of 133-146mmol/L recommended by Pathology Harmony. Conclusions:We suggest that this interval is too wide, and more work is needed to establish more appropriate paediatric ranges.