DIAGNOSIS OF ENDOCRINE DISEASE: How reliable are free thyroid and total T3 hormone assays?

Abstract

Hypothyroidism is a very common disorder worldwide, for which the usual treatment is monotherapy with levothyroxine (L-T 4 ). However, a number of patients treated with L-T 4 continue to report symptoms of hypothyroidism despite seemingly normal levels of thyroid-stimulating hormone (TSH), free-T 3 (FT 3 ) and free-T 4 (FT 4 ) measured by immunoassay. This review summarizes the limitations of the immunoassays commonly used to measure thyroid hormone levels and emphasizes the advantages of the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Immunoassays for free thyroid hormone are affected by alterations in serum binding proteins that occur in many physiological and disease states. Multiple studies show falsely normal values for T 3 , FT 3 and FT 4 by immunoassay that are below the reference interval when measured by (ultrafiltration) LC-MS/MS, a reference method. We suggest evaluation of thyroid hormone levels by ultrafiltration LC-MS/MS for patients who continue to experience hypothyroid symptoms on LT-4. This may help identify the approximately 20% subset of patients who would benefit from addition of T 3 to their treatment regimen (combination therapy).