SAT-613 Heterophile Antibody Interference Causing Elevated TSH Levels: A Challenging Diagnosis

Introduction Patients with persistently abnormal thyroid function tests despite increasing thyroid hormone supplementation should be investigated for several clinically important causes. We present an interesting such case in which widely fluctuating TSH measurements were caused by assay-interfering heterophile antibodies. Clinical Case A 57-year-old female with primary hypothyroidism was referred to our clinic for widely fluctuating TSH levels despite adjustment of levothyroxine dose. Indeed, her TSH levels over the previous year were as high as 24.56 μIU/ml (reference range 0.27-4.20) with normal or even elevated Free T4 (up to 1.64 ng/dl, reference range 0.70-1.48), but with no symptoms of hypo- or hyperthyroidism. Laboratory assessment at our institution revealed a TSH of 0.13 µIU/ml without change in the dose of levothyroxine since the prior measurement. It was assumed that the patient had trouble with medication compliance. Over the subsequent year, serial thyroid function tests (TFTs) done at an outside institution showed TSH elevated between 18-28 µIU/ml with elevated free T4 levels. Multiple possibilities were considered as the cause of discordant TFTs including poor compliance (although she denied missing any levothyroxine doses), thyroid hormone resistance syndrome, TSH producing tumor, interference from biotin supplementation and antibody interference. Upon further review, a pattern was evident in the TFTs, with marked elevations in TSH levels noted when labs were done locally, but normal or low TSH levels when done at our institution, raising the suspicion of interfering antibodies. The majority of commercially available TSH assays use an automated chemiluminescence system with two-site sandwich antibody assay. Antibodies including heterophile antibodies (human anti-mouse monoclonal antibodies or HAMAs), autoantibodies and rheumatoid factors can interfere with immunoassays. HAMAs are the most common cause of interference. Clinical laboratory personnel can employ several techniques to investigate potential antibody interference. In our case, the clinical pathologist ran the TSH assay with dilution analysis at our institution and showed a linear pattern, indicating no interference. However, a dilutional analysis of this same sample at the outside lab did not demonstrate dilutional linearity confirming the presence of an interfering antibody. Thus, the TSH values obtained at the outside institution were erroneous. The patient’s actual TSH was low at 0.21 µIU/ml, hence solving mystery of her discordant TFTs. Conclusion Interfering antibodies such as HAMAs should be suspected whenever thyroid function tests done at different laboratories conflict with each other, conflict with the clinical picture, or form an unusual pattern. Reference: N Bolstad et al. Best Pract Res Clin Endocrinol Metab. 2013; 27(5):647-61