What are the normal levels of Thyroid-Stimulating Hormone (TSH), free Triiodothyronine (T3), and free Thyroxine (T4)?

Normal Thyroid Function Test Reference Ranges

The normal reference ranges for thyroid function tests are: TSH 0.4-4.5 mIU/L, free T4 within laboratory-specific reference ranges, and free T3 within laboratory-specific reference ranges. 1, 2

TSH Reference Range

• The standard reference interval for TSH is approximately 0.4 to 4.5 mIU/L 1
• This range represents the 95% confidence interval of TSH values in a normal population
• Important considerations for TSH interpretation:
  • Age-specific variations exist: In older adults (70-79 years), the upper limit may extend to 5.9 mIU/L 3
  • Modern immunometric TSH assays have a functional sensitivity of at least 0.10 mU/L 3
  • Day-to-day variability: TSH levels can vary by up to 50% of mean values 1
  • Serial measurements are essential to confirm persistent thyroid dysfunction 1

Free T4 and Free T3 Reference Ranges

• Reference ranges for free T4 and free T3 are laboratory-specific and assay-dependent 2
• These tests are typically ordered when TSH values are abnormal to confirm thyroid dysfunction 4

Clinical Interpretation Algorithm

1. Initial Assessment: TSH is the most appropriate initial thyroid function test with high sensitivity (98%) and specificity (92%) 2, 4

2. Interpreting Results:

   • Normal TSH (0.4-4.5 mIU/L): Indicates euthyroidism with >99% accuracy 3
   • Abnormal TSH: Requires free T4 measurement for confirmation 3

3. Pattern Recognition:

   • Overt Hyperthyroidism: Low/suppressed TSH + elevated free T4 and/or free T3
   • Subclinical Hyperthyroidism: Low/suppressed TSH + normal free T4 and free T3
   • T3-Toxicosis: Low TSH + normal free T4 + elevated free T3
   • Overt Hypothyroidism: Elevated TSH + low free T4
   • Subclinical Hypothyroidism: Elevated TSH + normal free T4 2

Important Caveats

• Physiologic Variations: TSH secretion varies by race/ethnicity, sex, and age 1
• Non-thyroidal Influences: TSH can be affected by:
  • Acute illness (often suppresses TSH) 1
  • Medications: iodine, dopamine, glucocorticoids, octreotide, bexarotene 1
  • Medical conditions: adrenal insufficiency, pregnancy, anorexia nervosa, autoimmune diseases, pituitary disorders 1
• Laboratory Interference: Heterophilic antibodies may cause falsely elevated TSH values 3
• Treatment Targets: Target TSH values during treatment may differ from reference ranges:
  • For primary hypothyroidism: Target TSH 0.25-2.0 mU/L 3
  • For differentiated thyroid cancer after ablation: Target TSH ≤0.10 mU/L 3

Pitfalls to Avoid

• Relying on a single TSH measurement for diagnosis 1
• Failing to consider age-specific reference ranges, especially in older adults 1
• Ordering unnecessary thyroid hormone panels when TSH alone is often sufficient for initial screening 4
• Missing central hypothyroidism (rare) which presents with low/normal TSH and low free T4 3
• Overlooking medication effects and non-thyroidal illness on TSH values 1, 2