We report a falsely elevated blood spot thyrotrophin (TSH) concentration caused by a TSH-IgG complex. A routine blood spot screen returned a whole blood TSH of 213 mU/l from a one week-old neonate using the Wallac DELFIA method. Measurement in serum confirmed elevated TSH (826 mU/l, Roche Elecsys assay) but free thyroxine (17.2 pmol/l) was normal. The babys mother was clinically euthyroid but also showed discordant high serum TSH (287 mU/l) with normal free thyroxine (13.5 pmol/l). Low recovery of immunoreactive TSH following PEG precipitation and Protein A- Sepharose absorption of the maternal serum suggested the presence of an interfering antibody. Gel-filtration chromatography of serum from mother and child showed the presence of high molecular weight TSH immuno-reactivity consistent with a TSH-IgG complex. Incubation of maternal serum with serum from an unrelated hypothyroid patient (TSH 103 mU/l - Roche Elecsys) removed low molecular weight TSH from the hypothyroid serum confirming interference due to a TSH binding immunoglobulin rather than a heterophilic antibody. Serum TSH in the infant decreased to 210 mU/l after 14 days but remained elevated 3 months later (>100) suggesting a TSH-IgG complex with long plasma half-life and an IgG component possibly derived from placental transfer of maternal IgG. Interference was assay platform dependent; TSH on mothers serum was 4.0 mU/l using the Bayer Centaur, 16 mU/l using the DPC Immulite 2000 and 287 mU/l using the Roche Elecsys. Elevated TSH levels detected by newborn bloodspot screening should be interpreted with caution and we recommend that follow up routinely includes checking mothers thyroid hormone status. Furthermore this case demonstrates that macro-TSH should also be considered when elevated serum TSH levels are discordant with free thyroxine or clinical findings.
01 - 05 Apr 2006
European Society of Endocrinology