Thyroid Laboratory Tests
  • Thyroid Function: Direct tests
    • Involve in vivo radioactive iodine administration
    • Most common:
      • thyroid radioactive iodine uptake (RAIU)
      • 131I or 125I (preferable due to lower radiation dose)
      • Method:
        • radioiodine equilibrates with endogenous iodide pool
        • determined what percentage of iodide entering & leaving the extracellular space/unit time is accumulated by the thyroid
        • RAIU measured 24 hours following isotope administration (plateau period) {severe thyroid hyperfunction may cause earlier plateau period}
        • RAIU varies inversely with plasma iodide concentration indirectly with thyroid functional status
      • Normal RAIU results:
        • (United States)-1 mg/day I uptake: normal 24-hour RAIU= 10%-30% of administered dose.
        • Discriminates poorly between normal and hypothyroid states
        • Discriminates well in diagnosing hyperthyroid states
      • Utility of RAIU: when thyrotoxicosis is associated with a low RAIU:
        • iodine-induced hyperthyroidism
        • thyrotoxicosis factitia
        • "hamburger toxicosis" -- eating meat containing thyroid glands
        • spontaneously resolving thyrotoxicosis, e.g. associated with:
          • painless, chronic thyroiditis
          • postpartum thyroiditis
          • subacute thyroiditis
  • Hormone Concentration & Hormonal Binding in Blood
    • Highly specific/sensitive radioimmunoassays for serum T4 & T3 concentrations and rarely serum rT3 concentration {used less since development of highly sensitive TSH assays}: Purpose- diagnosis of hypothyroidism or hyperthyroidism
    • Normal values:
      1. 60-150 nmols/L (5-12 ug/dL) for T4
      2. 1-3 nmols/L (70-190 ng/dL) for T3
      3. 0.2-0.6 nmols/L (10-40 ng/dL) for rT3
    • Some factors that influence blood-hormone concentration
      • changes in hormone-plasma protein binding
      • changes in hormonal secretion rates
    • Only changes in hormone secretion lead to new steady-state changes in free hormone levels
      • Free hormone concentrations correlate better with metabolic state than the total levels, since they most consistently reflect hormonal production rates
      • Free T4 (FT4) concentration measured by equilibrium dialysis of serum containing tracer quantities of labeled T4.
        • Percentage of dialyzable {free} label is an estimate of free T4 (FT4)
      • Indirect assays are now more commonly done so:
        • "free T4 estimate, FT4E" may refer to
          1. an equilibrium dialysis estimation
          2. the derived free T4 estimate
          3. or to any indirectly measured or calculated free T4 level
        • Example of an indirect assay:
          • in vitro uptake test --
            • labeled T4 or labeled T3 is added to serum
            • incubation with insoluble particulate (resin or charcoal) which binds free hormone (resin T3 uptake, RT3U)
            • Percent of labeled hormone taken up by charcoal varies inversely with both (1) concentration of unoccupied serum protein sites and (2) their affinity for the particular hormone used
            • RT3U is often called thyroid hormone binding ratio (THBR) which reduces confusion between assays for T3 and T3 uptake
        • Clinical conditions & results
          • Usually values of RT3U and THBR or FTE proportional to the percent of FT4 and free T3, since in normal serum both hormones bind to a common TBG binding sites
            • Accordingly, changes in binding as a result of excess or reduced TBG or binding excess or insufficient T4 do not significantly change intensity of binding relationships of T4 & T3.
            • a free T4 index (FT4I) and a free T3 (FT3I) index {product of the RT3U new and the total T4 and T3 concentrations} are proportional to the actual free T4 and free T3 concentrations
        • Consequences of Changes in TBG concentrations
          • Changes in TBG concentration cause inverse changes in RT3U and are proportional to changes in serum T4 and serum T3 levels therefore FT4I and FT3I remain normal
        • Consequences of Changes in T4 Secretion
          • cause changes in percent FT4 and in RT3U in the same direction as those in serum T4
          • FT4& FT4I change from normal values more substantially then do percent FT4 and RT3U by themselves
      • Current Methodologies:
        • Immunoradiometric (IRMA) and chemiluminescent assays for direct FT4 measurement provide reliable results in many disorders; they could replace measurement of total T4, RT3U, and FT4I
        • Highly sensitive TSH assay: most sensitive thyroid function test
        • Determination of TSH level and a FT4E or FT4I: sufficient for most diagnostic and patient management requirements.
Increased TBG (From table 331-2; Harrison's)

pregnancy

newborn state

oral contraceptives/estrogen ingestion

tamoxifen (Nolvadex) use

infectious/chronic, active hepatitis

biliary cirrhosis

acute intermittent porphyria

perphenazine (Trilafon)

genetic determination

 

Decreased TBG (From table 331-2; Harrison's)

androgen use

genetic determination

large dose glucocorticoid use

chronic hepatic disease

severe systemic illness

active acromegaly

 

 

nephrosis

 
Wartofsky, L., Diseases of the Thyroid, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2012-2034