The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

To circumvent the Tg-Ab interference, Hoofnagle and Wener developed and validated a MS Tg method (Tg-MS) using tryptic digestion and immunocapture of Tg-specific peptides followed by MS focused on those peptides. 167 They demonstrated the Tg-MS method accurately measures Tg in the presence of Tg-Ab. 162 The tryptic digestion destroys the Tg-Ab, eliminating their interference with the assay. Four national reference laboratories have adopted versions of this method, and harmonization efforts are underway. A recent clinical outcome study compared Tg-IA, Tg-RIA, and Tg-MS in both Tg-Ab À and Tg-Ab þ patients. As predicted from the assay designs, all methods were equivalent for Tg-Ab À cases, but the Tg-MS was more accurate for Tg-Ab þ cases. Tg-IA methods had more false negatives and Tg-RIA had more false positives. 168 Although Tg-MS has not yet been incorporated into the current guidelines, the ATA guideline mentions it as a promising new technique. Without Tg-MS, thyroid cancer recurrence in Tg-Ab þ patients can be missed, thus delaying follow-up and creating patient harm.