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Figure. Differential Diagnosis of Hyperthyroxinemia and Nonsuppressed TSH High Total or Free T4 (analogue method) Normal/high TSH Rule out levothyroxine therapy, acute non-thyroidal illness, and drug effects Free T4, Direct Dialysis (DFT4) and TSH Normal DFT4 Normal/high TSH High DFT4 Normal/high TSH Hyperthyroxinemia not confirmed Suspect resistance to thyroid hormone (RTH) Resistance to Thyroid Hormone (RTH) Mutation Analysis (THRB gene mutation) Suspect analytical interference T4 Antibody T4 Binding Proteins TSH Antibody TSH, with HAMA Treatment No abnormalities detected Negative Positive RTH very likely Suspect TSH-secreting pituitary tumor Possible RTH without THRB mutation (15% of cases) Alpha Subunit and TSH Alpha subunit:TSH ratio >1 Consider THRB mutation testing on 1st degree relatives Alpha subunit:TSH ratio <1 T3 Suppression Test (unless contraindicated) TSH not suppressed TSH partially suppressed TSH-secreting pituitary adenoma probable Analytical interference in the direct dialysis free T4 and TSH assays could result from benign conditions such as abnormal T4 binding proteins (eg, familial dysalbuminemic hyperthyroxinemia), autoantibodies to T4 or TSH, or exposure to mouse monoclonal antibodies resulting in production of human anti-mouse antibodies (HAMA). Adapted from references 1 and 2. Quest, Quest Diagnostics, any associated logos, and all associated Quest Diagnostics registered or unregistered trademarks are the property of Quest Diagnostics. All third party marks - and - are the property of their respective owners. © 2012 Quest Diagnostics Incorporated. All rights reserved. Content reviewed 12/2012