What do T3 (triiodothyronine) and T4 (thyroxine) levels monitor?

T3 and T4 Monitoring in Thyroid Function

T3 (triiodothyronine) and T4 (thyroxine) levels monitor thyroid hormone status in the body, with T4 functioning primarily as a prohormone that converts to the more biologically active T3 in peripheral tissues. 1

Basic Function and Relationship

• T4 (thyroxine) is the main hormone produced by the thyroid gland, while T3 (triiodothyronine) is the more biologically active form 2
• Approximately 80% of circulating T3 is derived from peripheral conversion of T4 through deiodination in tissues such as the liver and kidney 3
• T3 has approximately 4 times the biological potency of T4, making it the major active thyroid hormone despite its lower concentration in circulation 3
• Both hormones are primarily bound to plasma proteins (>99%), with only the small unbound fraction being metabolically active 3

Clinical Significance in Thyroid Disorders

Hypothyroidism

• "Overt" hypothyroidism is biochemically defined by an elevated TSH level and a low T4 level, regardless of symptom presence 2
• In primary hypothyroidism (thyroid gland failure), TSH is elevated while T4 is decreased, with TSH elevation being the most sensitive indicator 4
• Central (secondary/tertiary) hypothyroidism presents with low T4 but normal or low TSH due to pituitary or hypothalamic dysfunction 5
• When monitoring levothyroxine replacement therapy, both TSH and T4 levels are used to assess adequacy of treatment 3

Hyperthyroidism

• "Overt" hyperthyroidism is biochemically defined by a low or undetectable TSH level and elevated T4 or T3 levels 2
• Subclinical hyperthyroidism presents with TSH below the reference range (usually <0.4 mIU/L) but normal T4 and T3 levels 2
• T3 thyrotoxicosis (approximately 5% of hyperthyroid cases) presents with normal T4 but elevated T3 levels 4
• Thyrotoxicosis due to thyroiditis typically shows high free T4 or T3 with low/normal TSH, occurring about one month after starting immunotherapy drugs 2

Monitoring Considerations

• TSH is the most sensitive marker for primary thyroid dysfunction and should be the first test ordered 2, 6
• Laboratory reference intervals for TSH are based on statistical distribution rather than clinical outcomes, leading to some professional disagreement about appropriate cut points 6
• Multiple tests should be performed over a 3-6 month interval to confirm abnormal findings, especially in asymptomatic individuals 6
• T3 measurement adds little value in assessing levothyroxine over-replacement, as normal T3 levels can be seen in over-replaced patients 7

Special Situations

• In patients receiving immunotherapy, thyroid dysfunction (hypothyroidism, hyperthyroidism, and thyroiditis) may occur in 6-20% of cases 2
• During pregnancy, both TSH and free-T4 should be measured at minimum during each trimester 3
• In pediatric patients with hypothyroidism, both serum TSH and total or free-T4 should be monitored at 2 and 4 weeks after treatment initiation, 2 weeks after any dosage change, and then every 3-12 months 3
• For patients with central hypothyroidism, serum free-T4 levels should be maintained in the upper half of the normal range 3

Pitfalls in Interpretation

• TSH secretion can be affected by conditions other than thyroid dysfunction, requiring careful interpretation 6
• T3 levels bear little relation to thyroid status in patients on levothyroxine replacement, making T3 testing of doubtful clinical value in this situation 7
• Extrathyroidal T4 conversion to T3 is decreased in patients with various acute and chronic illnesses, which can lead to low T3 levels despite normal thyroid function 1
• When T4 conversion to T3 is impaired, serum concentrations of biologically inactive reverse T3 (rT3) may increase 1

Understanding the relationship between T3 and T4 is crucial for proper interpretation of thyroid function tests and appropriate management of thyroid disorders.