Thyroid Function Tests (TFTs)

Definition & Overview

Hormones Measured

1. Thyroxine (T4) - a prohormone; most circulating T4 is converted peripherally to T3
2. Triiodothyronine (T3) - the active hormone

• Circulating T4 is slowly metabolized, mostly to T3, and a smaller amount is converted to the inactive metabolite reverse T3 (rT3).
• T4 and T3 are highly protein-bound in serum (primarily to thyroid-binding globulin [TBG] and prealbumin/transthyretin).
• Only ~0.02% of T4 and ~0.2% of T3 circulate as free, biologically active hormones.

Tests in the Panel

1. Thyroid-Stimulating Hormone (TSH / Thyrotropin)

• A pituitary hormone that stimulates production and release of thyroid hormones.
• Through a tightly regulated negative feedback loop, TSH rises when T3/T4 fall, and falls when T3/T4 rise.
• Small changes in free T3 and T4 produce large changes in TSH, making it the most sensitive indicator.
• Normal range: 0.3 - 3.3 mU/L.
• TSH is the best first-line test for thyroid function. A normal TSH essentially excludes thyroid dysfunction.
• Measured by immunochemiluminometric assay (can detect very low levels).

2. Free T4 (fT4)

• Measured when TSH is abnormal.
• Normal range: 10-30 nmol/L.
• Not affected by TBG fluctuations (unlike total T4).
• Elevated in hyperthyroidism; low in hypothyroidism.

3. Free T3 (fT3)

• Measured in select circumstances: to diagnose T3 toxicosis, investigate analytical interference with fT4 assay, assess impaired T4-to-T3 conversion, or monitor patients on oral T3 therapy.
• Normal range: 3.5-7.5 µmol/L.

4. Thyroid Autoantibodies (supplementary)

• Anti-thyroid peroxidase (TPO) antibody and anti-thyroglobulin antibody - useful for determining the cause of thyroid dysfunction (e.g., Hashimoto's thyroiditis).
• TSH receptor antibodies (TRAb/TSI) - present in Graves' disease.

Interpretation of TFT Patterns

Factors Affecting TBG (and hence Total T3/T4)

Testing Strategy

1. Start with TSH - best initial screening test.
2. If TSH is abnormal, add free T4.
3. Add free T3 only in select situations (T3 toxicosis, monitoring T3 therapy).

When NOT to Rely on TSH Alone:

• Critically ill patients (euthyroid sick syndrome): low T4, T3, and normal-to-low TSH without true thyroid disease.
• Early thyroid replacement therapy: TSH may remain abnormally low for a prolonged period due to long-term thyrotroph cell suppression.
• Pituitary/hypothalamic disease (secondary hypothyroidism): TSH may be inappropriately low/normal despite low T4.

Radioactive Iodine Uptake (RAIU) - Additional Test

• Increased RAIU: Graves' disease, functioning adenoma.
• Decreased RAIU: Thyroiditis, struma ovarii, exogenous thyroid hormone ingestion.