Rare coincidence: Macro-thyroid-stimulating hormone and multiple manufacturer-specific interferences in thyroid hormone immunoassays.

Immunoassays are widely used for laboratory assessment of endocrine functions including thyroid hormones. While usually adequate for patient evaluation, they are known to potentially suffer from interference from a variety of factors. We report the case of a 44 year-old male patient without clinical symptoms of thyroid disease who presented for specialist evaluation after pathological thyroid function tests prompted a transferal by his primary care practitioner. Thyroid function tests showed discrepant results across immunoassays and platforms of different manufacturers. Polyethylene glycol precipitation prompted the diagnosis of macro-thyroid-stimulating hormone, while heterophilic and non-specific antibody blocking reagents proved ineffective in eliminating the interference in thyroid-stimulating hormone, free triiodothyronine and free thyroxine measurements. Further assessment ruled out a diagnosis of familial dysalbuminemic hyperthyroxinemia, leaving an exclusion diagnosis of manufacturer-specific interference in free triiodothyronine and free thyroxine assays due to unknown factors. Both clinicians and laboratory specialists must be aware of potential interference in immunoassays which otherwise might be misleading, potentially triggering unnecessary (invasive) follow-up procedures or therapeutic interventions. Close communication is required for successful troubleshooting. To our knowledge, no other case of both macro-thyroid-stimulating hormone and manufacturer-specific interference in a single patient has been documented thus far.

Identification of Paraproteins via Serum Immunofixation or Serum Immunosubtraction and Immunoturbidimetric Quantitation of Serum Immunoglobulins in the Laboratory Testing for Monoclonal Gammopathies.

CONTEXT.­: In laboratory testing for monoclonal gammopathies, paraproteins are identified via serum immunofixation or serum immunosubtraction, and immunoturbidimetric quantitation of serum immunoglobulins is often used. OBJECTIVE.­: To evaluate methodologic differences between serum immunofixation and serum immunosubtraction, as well as in the quantitation of serum immunoglobulins on different clinical chemical platforms. DESIGN.­: Three hundred twenty-two unique routine patient samples were blinded and used for comparison between serum immunofixation on Sebia's HYDRASIS 2 and serum immunosubtraction on Sebia's CAPILLARYS 2, as well as between quantitation results of immunoglobulin A, G, and M on Abbott's ARCHITECT c16000PLUS and Roche's Cobas c 502 module. Microsoft Excel 2019 with the add-on Abacus 2.0 and MedCalc were used for statistical analysis and graphic depiction via bubble diagram, Passing-Bablok regressions, and Bland-Altman plots. RESULTS.­: The median age of patients was 75 years, and samples with paraproteinemia were nearly evenly split between sexes. Paraprotein identification differed remarkably between immunofixation and immunosubtraction. Quantitation of serum immunoglobulins showed higher values on Abbott's ARCHITECT c16000PLUS when compared with Roche's Cobas c 502 module. CONCLUSIONS.­: Identification of paraproteins via serum immunosubtraction is inferior to serum immunofixation, which can have implications on the diagnosis and monitoring of patients with monoclonal gammopathy. If immunoturbidimetric quantitation of immunoglobulins is used for follow-up, the same clinical-chemical platform should be used consistently.

Gamma Heavy Chain Disease - Diagnostic Challenges in an Unusual Case and a Brief Synopsis of the Current Literature.

BACKGROUND: Gamma heavy chain disease is a disorder characterized by the production of truncated heavy chains without associated light chains. Clinical manifestations differ greatly. Thus far no standard treatment has been formulated. METHODS: We report a case of Franklin's disease, which proved diagnostically challenging due to the absence of symptoms and disorders frequently associated with the disease. RESULTS: Standard screening tests for monoclonal gammopathy remained unremarkable. Serum immunofixation detected monoclonal truncated gamma heavy chains. CONCLUSIONS: Serum immunofixation should be performed, if heavy chain disease is strongly suspected. Flow cytometry and genetic evaluation are needed to provide additional insights into Franklin's disease.

Interference From High-Dose Biotin Intake in Immunoassays for Potentially Time-Critical Analytes by Roche.

CONTEXT.­: Immunoassays using the interaction between streptavidin and biotin are used for clinical chemical analytes on platforms by many different manufacturers. The design can be susceptible to interference from high-dose biotin intake in patients, which remains an often-overlooked confounder despite recently increased awareness. OBJECTIVE.­: To evaluate an easily implementable method of in vitro biotin depletion for the removal of biotin interference in immunoassays for potentially time-critical analytes. DESIGN.­: A biotin stock solution was made and de-identified patient samples were spiked to reach a biotin concentration of 1.126 × 106 pg/mL, the maximum reported biotin concentration 1 to 2 hours after a single oral dose of 300 mg biotin. Then, the resulting interference in Elecsys immunoassays for cortisol, cyclosporine A, tacrolimus, digitoxin, thyroid-stimulating hormone, free triiodothyronine, free thyroxine, C-peptide, insulin, N-terminal pro-B-type natriuretic peptide, troponin T high sensitive, human immunodeficiency virus, procalcitonin, ß human chorionic gonadotropin, toxoplasma immunoglobulin M, and toxoplasma immunoglobulin G was evaluated before and after biotin depletion using streptavidin particles. RESULTS.­: All tested immunoassays, with the exception of toxoplasma immunoglobulin M and toxoplasma immunoglobulin G, suffered from significant biotin interference. The depletion protocol removed assay interference due to biotin and produced results that were close or identical to initial prespike measurements. CONCLUSIONS.­: Despite an increase in turnaround times, biotin adsorption is a feasible countermeasure for biotin interference in Elecsys immunoassays. Until test kits with an increased resistance to the interference from high-dose biotin intake are distributed, the evaluated protocol can provide results properly reflecting the patient's clinical condition.