Bornhorst, Joshua A.

Abstract Introduction Measurement of amyloid beta (Aβ40 and Aβ42) and tau (phosphorylated tau [p‐tau] and total tau [t‐tau]) in cerebrospinal fluid (CSF) can be utilized to differentiate clinical and preclinical Alzheimer's disease dementia (AD) from other neurodegenerative processes. Methods CSF biomarkers were measured in 150 participants from the Mayo Clinic Study of Aging and the Alzheimer's Disease Research Center. P‐tau/Aβ42 (Roche Elecsys, Fujirebio LUMIPULSE) and Aβ42/40 (Fujirebio LUMIPULSE) ratios were compared to one another and to amyloid positron emission tomography (PET) classification. Results Strong correlation was observed between LUMIPULSE p‐tau/Aβ42 and Aβ42/40, as well as Elecsys and LUMIPULSE p‐tau/Aβ42 and Aβ42/40 (Spearman's ρ = –0.827, –0.858, and 0.960, respectively). Concordance between LUMIPULSE p‐tau/Aβ42 and Aβ42/40 was 96% and between Elecsys p‐tau/Aβ42 and both LUMIPULSE ratios was 97%. All ratios had > 94% overall, positive, and negative percent agreement with amyloid PET classification. Discussion These data suggest that p‐tau/Aβ42 and Aβ42/40 ratios provide similar clinical information in the assessment of amyloid pathology.

Abstract Background Pathologic causes of hyperprolactinemia include prolactin-secreting pituitary adenoma (prolactinoma), diseases of the hypothalamus, primary hypothyroidism, and renal failure. Another cause of hyperprolactinemia is the presence of macroprolactin, a high-molecular-mass complex of prolactin and immunoglobulins, which constitutes a biologically inactive form of prolactin. Detection of macroprolactin is important to avoid misdiagnosis and inappropriate treatment; however, relatively little is known about the persistence of macroprolactin in patients over time or how macroprolactin concentrations evolve within patients. The objective of this study was to examine the changes in macroprolactin and prolactin over time in a large clinical population. Methods All physician-ordered macroprolactin tests from December 2011 to October 2018 (n = 5,318 unique patients) were examined. Data were extracted from patients with repeat collections (≥2 timepoints) during this 7-year period (n = 269). Macroprolactin testing was performed using the Roche Elecsys Prolactin II assay. Prior to analysis, an equal volume of 25% polyethylene glycol (PEG) was added to patient serum, causing macroprolactin to precipitate. Following centrifugation, unprecipitated prolactin was measured in the supernatant, as well as an aliquot of the native sample (measuring total prolactin). Macroprolactin (precipitated prolactin) was calculated by subtracting the unprecipitated prolactin from the total prolactin concentration. For this study, a specimen was considered positive for macroprolactin if the percentage of precipitated prolactin was ≥60%. Results A total of 14% (37/269) of patients tested positive for macroprolactin in at least one of the sequential determinations. For all patients with two or more timepoints, the mean interdetermination change in percent macroprolactin was +0.6% and the mean interdetermination change in total prolactin was –11.6 ng/mL. The mean time between determinations in these patients was 303 days. For the 37 patients that had a positive macroprolactin determination, 25 remained positive across all sample collections (mean interdetermination change of +0.5% macroprolactin, mean interdetermination change in total prolactin of +0.4 ng/mL), seven samples went from positive to negative (mean interdetermination change of –10% macroprolactin, mean change in total prolactin of +0.2 ng/mL), and two samples went from negative to positive (mean interdetermination change of +5.5% macroprolactin, mean change in total prolactin of +1.3 ng/mL). The remaining 3 of the 37 specimens had more than two determinations that fluctuated above and below the predefined cutoff. Conclusions The results from this study suggest that the presence of macroprolactin largely but not exclusively persists over time. Additionally, macroprolactin rarely appears after a previously negative assessment (2/235 patients). Furthermore, only small increases in sequential percent macroprolactin determinations were observed in this data set. The prevalence of the persistence of macroprolactin protein over time might have important implications for patient prolactin monitoring.

Background Gadolinium-based contrast agents (GBCAs) have been used in magnetic resonance imaging for the past 30 years, where they have significantly improved the effectiveness of imaging studies. However, the increased usage of gadolinium in the medical community has also resulted in unexpected interferences in other laboratory assays. This has been particularly the case in clinical elemental analysis using inductively coupled plasma mass spectrometry (ICP-MS). Methods By conducting ICP-MS interference experiments, we describe how gadolinium interferes with elemental analysis by space charge effect, double charge effect and the creation of polyatomic interferences. Additionally, by reviewing more than a year of reference laboratory data from our laboratory information system, we determined the number of elemental tests cancelled due to gadolinium interference. Results Interference experiments show that gadolinium normally found in GBCAs can interfere with heavy metals, platinum and selenium analysis of biological fluids using ICP-MS. Within one year, our institution’s metals laboratory had to cancel 42 selenium serum tests and 19 heavy metal urine panels due to potential interference caused by gadolinium. Conclusions GBCAs will continue to be utilized in hospitals around the world. However, clinical laboratories should be wary of potential interferences caused by GBCAs. Relevant interferences include space charge effect, double charge interference, and the formation of polyatomic interferences caused by gadolinium. These interferences can negatively affect patient care by resulting in cancelled laboratory tests and causing patients to have blood redrawn and analysed at a later date leading to delays in their diagnosis/treatment.