Functional vitamin B12 deficiency: Improving methylmalonic acid reference intervals in urine.

BACKGROUND-AIM: Most laboratory requests focus on the detection of possible vitamin B12 deficiency. In this context, methylmalonic acid (MMA) is reported as the best biomarker. The aim of our study was to establish the biological reference interval for MMA in urine, and assess the influence of age, sex, and vitamin B12 status on MMA concentrations. METHODS: This is a prospective observational study considering individuals with normal results for blood count and liver and kidney function. Individuals who presented supplementation, any pathology or treatment that could cause cobalamin metabolism disorders, and pregnant women were excluded. Likewise, individuals whose vitamin B12 result presented antibody-mediated interference were excluded. Individuals were grouped by age-group and sex. Reference intervals were determined by non-parametric calculation (percentiles 1-99). RESULTS: It was established a single reference interval [0.52 (CI90%: 0.50-0.54) - 5.75 (CI90%: 5.57-6.17) mmolMMA/mol creatinine], with 100 % of individuals with MMA above the upper limit of reference presenting a total vitamin B12 concentration ≤ 238 pmol/L. CONCLUSION: The establishment of optimal reference intervals for methylmalonic acid excretion in urine is crucial in individuals with a suspicion of functional vitamin B12 deficiency. However, the possibility of establishing a cut-off value for total vitamin B12 suggesting subclinical deficiency remains a challenge for this magnitude.

Challenges in the diagnosis of hypervitaminemia B12. Interference by immunocomplexes.

BACKGROUND-AIM: High vitamin B12 concentrations are considered a common finding in clinical practice. Thanks to immunoassay accessibility, vitamin B12 has become a usual test in routine health checkups. However, these analytical methods usually present antibody-mediated interferences. Our aim was to propose an algorithm for the screening of antibody-mediated analytical interferences on vitamin B12 immunoassays on the Alinity platform. METHODS: Observational, prospective, case-control study was performed during 12 months. Individuals with persistently elevated cobalamin concentrations [>554 pmol/L] were considered as cases in the absence of supplementation or other justifying cause. Individuals under treatment with vitamin B12, or in the context of alcoholism were included as controls. A thorough interference study by macromolecules in immunoassays was performed in serum samples: PEG precipitation, rheumatoid factor, heterophile antibodies and gel permeation chromatography (GPC). Albumin, total B12, IgG and IgM were measured in every GPC collected fraction and chromatograms were drafted. RESULTS: Up to 45% of cases presented interference by B12-immunocomplexes and the precipitation for all of them was >50%. The individual with the lowest interfered vitamin B12 result was 661 pmol/L. CONCLUSION: The presence of antibody-mediated interferences, mainly B12-immunocomplexes, is a relatively common phenomenon. A simple algorithm for the screening of interferences is useful and reliable in ruling out healthy individuals and highly cost-effective.

Thyroid panel reference intervals in healthy children and adolescents: A Spanish cohort.

OBJECTIVES: In children, thyroid hormones are essential for correct physical and neurological development. The recommended process for defining reference intervals (RIs) is the direct approach; however, indirect methods are an effective alternative. This study aimed to explore age- and sex-dependent relationships between serum concentrations of thyroid hormones in a large population-based cohort of healthy Spanish Caucasian children and calculate RIs. MATERIAL AND METHODS: Results of serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were collected from laboratory data of N (TSH = 23201; fT4 = 20728) patients aged 1 month - 15 years. These results were validated with a prospective study. Analyses of serum concentrations of TSH and fT4 were performed on ARCHITECT i2000 (Abbott Diagnostics, US). Percentiles (2.5th to 97.5th) were determined for each variable and taken as the RI. RESULTS: No difference was found between serum TSH concentrations in male and female children of all age groups. A difference between serum fT4 concentrations in males and females and an age-dependent correlation for both sexes were found. CONCLUSION: There is very little consensus on RIs in children. Our data confirm it is possible to use data mining techniques to calculate reliable and clinically useful RIs.

Optimization of the thyroid panel for diagnostic purposes: Thyrotropin cut-off values for the reflex addition of free thyroxine.

BACKGROUND-AIM: Measurement of serum thyrotropin is currently the recommended test for the screening of thyroid dysfunction, while serum free thyroxine is kept as a reflex test. In our laboratory, the strategy followed in adult individuals from Primary Care includes a 'safety margin' for requests with a thyrotropin ≤1.0 or ≥4.0 mIU/L (normal: 0.35-4.95 mIU/L). Our aim was to optimize the thyrotropin cut-off values for the addition of free thyroxine and, based on these cut-offs, to retrospectively analyze avoidable free thyroxine measurements and possible adverse clinical consequences. METHODS: Retrospective observational study performed in a tertiary care hospital between 2013 and 2018. We considered all laboratory requests for screening of thyroid dysfunction (TD) in adult patients from Primary Care. Requests from patients with a previous diagnosis of thyroid disease or pregnant women were excluded. Different receiver operating characteristic (ROC) curves were performed and the obtained thyrotropin cut-off values were compared. Economic savings were assessed considering the current cost of free thyroxin assays in our laboratory. RESULTS: From a total of 554,529 TD protocols included, 119,504 requests had free thyroxine added. From the ROC curve that enables ≥95% of abnormal free thyroxine results to be detected, the thyrotropin values obtained were ≥4.58 mIU/L and ≤0.94 mIU/L. These thyrotropin cut-off values would lead to a saving of 22.7% of annual free thyroxine measurements without adverse clinical consequences. DISCUSSION: Setting optimized thyrotropin cutoffs for reflex testing of free thyroxine would reduce the need for this test. Clinical laboratories need to offer not only true results, but also become the cornerstone in the optimization of resources.

Assessment of a laboratory critical risk result notification protocol in a tertiary care hospital and their use in clinical decision making.

INTRODUCTION: Communication of laboratory critical risk results is essential for patient safety, as it allows early decision making. Our aims were: 1) to retrospectively evaluate the current protocol for telephone notification of critical risk results in terms of rates, efficiency and recipient satisfaction, 2) to assess their use in clinical decision making and 3) to suggest alternative tools for a better assessment of notification protocols. MATERIALS AND METHODS: The biochemical critical risk result notifications reported during 12 months by routine and STAT laboratories in a tertiary care hospital were reviewed. Total number of reports, time for the notification and main magnitudes with critical risk results were calculated. The use of notifications in clinical decision making was assessed by reviewing medical records. Satisfaction with the notification protocol was assessed through an online questionnaire to requesting physicians and nurses. RESULTS: Critical result was yielded by 0.1% of total laboratory tests. Median time for notification was 3.2 min (STAT) and 16.9 min (routine). The magnitudes with a greater number of critical results were glucose and potassium for routine analyses, and troponin, sodium for STAT. Most notifications were not reflected in the medical records. Overall mean satisfaction with the protocol was 4.2/5. CONCLUSION: The results obtained indicate that the current protocol is appropriate. Nevertheless, there are some limitations that hamper the evaluation of the impact on clinical decision making. Alternatives were proposed for a proper and precise evaluation.