Sometimes laboratory results are puzzling: Results don’t match the patient’s clinical picture, or even more perplexing, the results of complementary analytes are contradictory. In times such as these, what’s a clinician to do? Call the friendly local laboratory expert of course.
Fortunately, Tuesday’s morning session, “Clinical Assay Issues: What Endocrinologists Will Ask You,” helped equip laboratorians to answer three of the most common laboratory queries facing endocrinologists. Mark Gurnell, MBBS, PhD, spoke about the difficulties in interpreting thyroid function tests when the results are discordant or when the results contradict the clinical picture. He reminded attendees to take a systematic approach to troubleshooting and provided five illustrative clinical vignettes of cases that presented to his laboratory.
First, look at the clinical setting and determine if there are any potential confounders such as pregnancy, non-thyroidal illness or medications such thyroxine, amiodarone, heparin, or glucocorticoids. Once these have been eliminated, the next step is to consider laboratory artefacts and assay interferences. Finally, once these have been excluded, consider genetic or acquired disorders.
In the second presentation, Nikola Baumann, PhD, spoke about how biotin can sometimes interfere with lab measurements. It is essential for clinical laboratorians to know not only how assays in their lab work, but also how to explain potential interferences to clinicians.
Biotin supplements (also known as vitamin B7) have been promoted for thickening hair, strengthening nails, and improving skin, leading to an increase in their use. Previously, high-dose biotin therapy was confined to patients with biotinidase deficiency, certain forms of alopecia, or multiple sclerosis. Now the popularity of biotin supplement use has also led to an increase in reported cases of biotin interferences, increasing the potential for misdiagnoses.
Based on a survey of nearly 200 patients, Baumann and her colleagues discovered that only 8% of outpatients were aware that they were taking biotin supplements. Biotin interference can affect an extensive range of assays. These include assays used to diagnose and monitor malignancies (Tg, calcitonin, gastrin), thyroid disorders (TSH, free T4, total T4, free T3, total T3), bone and calcium homeostasis (PTH, 25-OH vitamin D), reproductive hormones (progesterone, LH, FSH, estradiol, DHEAS, testosterone, beta-hCG), anemia (ferritin), and cardiac markers (NT-pro-BNP, troponin).
Biotin interference can happen because most immunoassay manufacturers rely on biotin-streptavidin capture in their assays. Biotin interference can cause a falsely increased result in competitive assays and a falsely low result in sandwich assays. A complicating factor is that the concentration of biotin that causes interferences is assay-dependent.
To identify biotin interference, Baumann suggested that labs can perform serial dilution checks to see if they are linear. Labs can also test the sample on a platform that does not use biotin-streptavidin capture. Most manufacturers suggest that patients taking biotin supplements wait 8 hours before having laboratory testing, however, according to Baumann, “we have learned some additional lessons on this journey.”
For instance, biotin is not readily cleared in patients with impaired renal function, and biotin concentrations that affect assays can still be observed in these patients up to 72 hours post-consumption. In addition, the majority of cases reviewed did not list biotin supplements in the electronic medication list.
The third speaker, David Sacks, MB ChB, FRCPath, explained how factors independent of glucose concentration changes can alter HbA1c. HbA1c reflects the estimated average glucose concentrations over approximately 8-12 weeks and is used by endocrinologists to diagnose diabetes, monitor long-term glucose control, alter medication dosages in diabetic patients and measure the risk of cardiovascular complications in diabetic patients. Hemoglobin variants, elevations of hemoglobin F, and renal failure all can cause analytical interferences.
When a lab suspects one of these, Sachs explained that testing by an alternative method can often provide an accurate result. For conditions that affect the lifespan of red blood cells—for example, chronic renal failure, hereditary spherocytosis, hemolytic anemia or some medications—or when blood transfusions or blood loss occur, the lab should use alternate measurements such as fructosamine of glycated albumin.