Falsely elevated thyroid hormone levels associated with fibrin interference in patients receiving oral anticoagulant therapy.

OBJECTIVE: Unique clinical courses were observed in two asymptomatic patients receiving warfarin who referred to our hospital because of suspected central hyperthyroidism. We eventually diagnosed these patients with falsely elevated thyroid hormone levels caused by macroscopically invisible fibrin. Although false results caused by fibrin interference in vitro have been identified in various immunoassays, especially in blood samples from patients receiving anticoagulant therapy, no studies on thyroid function testing have been reported. The experience in evaluating these cases prompted us to investigate the independent influence of oral anticoagulants via putative fibrin interference on thyroid function testing. METHODS: We retrospectively reviewed known contributing factors that affect thyroid function testing including age, gender, medication history, body mass index, estimated glomerular filtration rate, smoking status, alcohol consumption, and the seasons of hospital visits from participants who presented the Department of Health Checkup between April 2010 and December 2020. RESULTS: A propensity-matched analysis revealed that the median serum free thyroxine levels under oral anticoagulant were significantly higher (17.9 pmol/L, n = 60) than those without anticoagulants (16.0 pmol/L, n = 60; p < 0.001). It was noted that this difference was the largest among contributing factors we analyzed. No significant differences were noted in serum thyroid-stimulating hormone levels. CONCLUSIONS: We report two patients receiving warfarin with falsely elevated thyroid hormone levels caused by fibrin interference resembling central hyperthyroidism for the first time. Our retrospective study suggests that the medication status of oral anticoagulants should be considered when evaluating thyroid function tests.

Abnormal thyroid hormone response to TRH in a case of macro-TSH and the cut-off value for screening cases of inappropriate TSH elevation.

A 74-year-old asymptomatic Japanese man with suspected thyroid dysfunction was referred to our hospital. He had an elevated TSH (53.8 mIU/L; reference interval: 0.5-5.0) despite a free T4 (FT4) level (1.4 ng/dL; reference interval: 0.9-1.6). Further analysis revealed macro-TSH. A notable finding was that a 500-µg TRH stimulation test revealed a blunted free T3 (FT3) response despite a prolonged TSH response. Macro-TSH typically presents with inappropriately marked elevation of serum TSH levels compared with other thyroid hormones, as exhibited in our case. However, the level of TSH elevation that might differentiate macro-TSH from subclinical hypothyroidism is poorly known. We retrospectively analyzed 8,183 concurrent measurements of TSH and FT4 in individuals previously examined in our hospital to define the cut-off value for screening cases of inappropriate TSH elevation. FT4 values were rounded off to one decimal place, and the 97.5th percentile of TSH against each FT4 value was calculated. The data of our patient and that of 30 cases of macro-TSH extracted from the English literature were then assessed. When the approximate curve obtained from the 97.5th percentile of TSH values was defined as the cut-off value [Log10TSH = 0.700 + 1.549/{1 + (FT4/0.844)6.854}], 25 of the 31 (80.6%) macro-TSH cases were identified. In conclusion, we report for the first time a case of macro-TSH demonstrating an abnormal FT3 response to TRH. A cut-off value of TSH adjusted to the FT4 level may be a good method of screening for inappropriate TSH elevation (or inappropriate hyperthyrotropinemia) including those caused by macro-TSH.