Diagnostic Thyroid Testing: Serum Free T4

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Bioactive free T4 concentrations:
    • Can be estimated using a variety of indirect (analog, immunometric, and two-step labeled hormone assays) or direct methods (equilibrium dialysis, ultrafiltration), and are the most commonly used measurements of circulating thyroid hormone levels
  • Generally, most laboratories estimate free T4 by either the analog immunoassay or a calculated FT4I corrected to thyroid hormone binding capacity:
    • The former is readily available and provides quick results; it does not directly measure the free T4 concentration but is a reliable estimate of FT4 levels in most patients, based on one-step, two-step, or labeled antibody approaches
  • This type of free T4 estimate is especially sensitive to abnormal serum albumin levels and should not be used with conditions such as:
    • Familial dysalbuminemic hyperthyroxinemia, pregnancy, or severe nonthyroidal illness:
      • For example, it is common to have a free T4 lower than the reference range in a euthyroid pregnant woman:
        • Due to the high estrogen state of pregnancy greatly increasing serum TBG concentrations, thus resulting in inaccurate FT4 measurements
  • The serum FT4I measurement is a calculated value that is the product of the total T4 concentrations and a correction factor related to the number of available thyroid hormone binding sites:
    • This correction factor may be called:
      • A thyroid hormone binding ratio (THBR), T3 resin uptake (T3RU), or T3 uptake (T3U)
      • The T3RU is inversely related to the free thyroid hormone binding sites but is now used in only a few laboratories
  • Free T4 by equilibrium dialysis:
    • Is the gold standard and measures the 0.03% of T4 that is biologically active and unbound to protein
    • This assay is available only at reference laboratories and is useful to directly determine free T4 levels when other testing does not provide a clear result
  • Although a TSH-first testing algorithm is suffcient for general screening:
    • Both FT4 and TSH assays are needed for:
      • Diagnosing subclinical thyroid dysfunction, central hypothyroidism, and in the assessment of elderly and hospitalized patients, as well as for accurate assessment of treatment effects
  • Guidelines from multiple thyroid and endocrine societies:
    • Have also endorsed a TSH-first strategy in most clinical scenarios with FT4 testing when clinically indicated or TSH is found to be abnormal
    • Work by Henze et al. goes even further suggesting that a TSH-first strategy can be further perfected by:
      • Widening the TSH reference range from 0.4 to 4.0 mIU/L to 0.2–6.0 mIU/L with minimal impact on case detection
      • They found that only 4.2% of TSH values between 0.2 mIU/L and 0.4 mIU/L would not have led to detection of a high FT4 and equally, only 2.5% of TSH values between 4.0 mIU/L and 6.0 mIU/L were associated with low FT4 level
      • It is likely that this small additional group of patients outside the wider range with abnormal FT4 is clinically unimportant in most cases
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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