Asymptomatic elevated parathyroid hormone level due to immunoassay interference.

BACKGROUND: Parathyroid hormone (PTH) measurement using immunoassays is inherently vulnerable to interferences due to the presence of different proteins such as heterophile antibodies, human anti-animal antibodies, auto-analyte antibodies, the rheumatoid factor, and others. The frequency of immunoassay interference can be as high as 6%. We report the case of a patient showing persistent high levels of PTH without impact on calcium and bone metabolism. CASE PRESENTATION: The patient was a 59-year-old asymptomatic woman who consistently showed elevated PTH levels (385-482 pg/ml) using the Roche Elecsys (Cobas e-411) and ADVIA Centaur assays, with normal calcium, phosphorus, vitamin D, and renal function parameters. She had no history of fractures, nephrolithiasis, gastrointestinal complaints, renal insufficiency, or autoimmune diseases. Her physical examination revealed no abnormalities. Biomarkers of bone metabolism were within the reference range. To rule out falsely elevated PTH levels, we initially performed serial dilutions using both assays, which revealed nonlinearity. After a polyethylene glycol precipitation test, less than 10% of PTH was recovered from the supernatant. These results suggested the presence of heterophile antibodies as the cause of the falsely elevated PTH levels. CONCLUSION: Physicians should be aware of this issue in order to avoid unnecessary clinical investigations and inappropriate treatments.

Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway.

Tumor angiogenesis is essential for tumor growth and metastasis and is dependent on key angiogenic factors. Angiogenin (ANG), a 14.2-kDa polypeptide member of the RNase A superfamily, is an angiogenic protein that has been reported to be upregulated and associated with poor prognosis in some human cancers. The mechanisms through which aberrant ANG levels promote specific steps in tumor progression are unknown. Here, we show that ANG expression in human tissues is strongly correlated with an invasive cancer phenotype. We also show that ANG induces cellular survival, proliferation, endothelial tube formation and xenograft angiogenesis and growth. Novel mechanistic investigations revealed that ANG expression stimulated matrix metallopeptidase-2 (MMP2) expression through the phosphorylation of ERK1/2. Targeting ANG in vivo with N65828, a small-molecule inhibitor of the ribonucleolytic activity of human ANG, resulted in the diminution of xenograft tumoral growth through the inhibition of angiogenesis. Our findings support an unrecognized interplay between ANG, ERK1/2 and MMP2 that can impact tumor growth and progression. The targeting of ANG and associated factors could provide a novel strategy to inhibit tumor establishment and growth.