Misdiagnosis of Graves' Hyperthyroidism Due to Therapeutic Biotin Intervention

Background: Lately, high dose of biotin is often given orally to patients with a primary progressive multiple sclerosis (PPMS). However, the molecule biotin is also a principle compound in various analytic immunoassays.

Clinical Case: An asymptomatic 60-year-old woman with PPMS on high dose of biotin therapy (3 × 100 mg/d) displayed abnormal thyroid function tests (TSH 0.02 mU/l, fT4 > 103 pmol/l, and fT3 > 46 pmol/l). TSH was determined by a homogeneous sandwich chemiluminescent immunoassay and fT4 and fT3 were both determined by a homogeneous, sequential, chemiluminescent immunoassay. TSH receptor antibodies were found to be markedly elevated (>40 IU/l) using a electrochemiluminescence immunoassay, suggestive for Graves' hyperthyroidism. Due to inconsistency between clinical presentation and laboratory results, thyroid function tests have been repeated with two other immunoassays. A direct, labeled antibody, competitive immunoassay to determine TSH and a luminescent immunometric immunoassay to determine fT4 and fT3 showed a subclinical hyperthyroidism (TSH < 0.02 mU/l, fT4 15.9 pmol/l, and fT3 4.7 pmol/l). Normal thyroid function tests (TSH 1.66 mU/l, fT4 15.3 pmol/l, and fT3 4.7 pmol/l) were obtained by a chemiluminescent microparticle immunoassay. All abnormal levels of TSH, fT4, fT3, and TSH-R-Ab were observed in immunoassays using biotin as a reagent.

Conclusion: Abnormal thyroid function tests in this euthyroid patient were found to be false due to significant interference of supraphysiological levels of plasma biotin. Laboratory tests applying immunoassays using a biotin-containing reagent should be interpreted with caution in patients on biotin substitution.