When to Order TSH and Free T4 Testing
Order TSH and free T4 together as initial tests when evaluating suspected thyroid dysfunction, with TSH serving as the primary screening test and free T4 distinguishing between subclinical and overt disease. 1
Initial Diagnostic Evaluation
For suspected primary hypothyroidism:
- TSH is the preferred first-line test due to its sensitivity above 98% and specificity greater than 92% 1, 2
- Add free T4 when TSH is elevated to distinguish subclinical hypothyroidism (normal free T4) from overt hypothyroidism (low free T4) 1
- Measure both tests together if you need immediate diagnostic clarity, as the combination definitively excludes or confirms thyroid dysfunction 1
For suspected hyperthyroidism:
- TSH with free T3 is the optimal initial strategy, since free T4 may be falsely elevated in euthyroid patients on amiodarone or levothyroxine 3
- Free T4 becomes essential when TSH is suppressed to quantify the degree of thyroid hormone excess 4
Monitoring During Levothyroxine Therapy
Check TSH and free T4 every 6-8 weeks during dose titration until TSH reaches the target range of 0.5-4.5 mIU/L 1
Key monitoring timepoints:
- 6-8 weeks after any dose adjustment (the time required to reach steady state) 1
- Free T4 helps interpret persistently abnormal TSH during therapy, as TSH may lag behind free T4 normalization 1
- Every 6-12 months once stable on maintenance therapy 1
For patients with cardiac disease or atrial fibrillation: Consider repeating tests within 2 weeks rather than waiting 6-8 weeks after dose changes 1
Confirmation Testing for Abnormal Results
When TSH is initially elevated:
- Repeat TSH with free T4 after 3-6 weeks minimum, as 30-60% of elevated TSH values normalize spontaneously 1
- This confirmation step prevents unnecessary lifelong treatment for transient thyroiditis 1
When TSH is suppressed (<0.1 mIU/L):
- Measure free T4 and free T3 to distinguish subclinical from overt hyperthyroidism 1
- Repeat in 3-6 weeks to confirm, as acute illness and medications can transiently suppress TSH 1
Special Clinical Scenarios Requiring Modified Testing
Central hypothyroidism (pituitary/hypothalamic disease):
- TSH is unreliable—use free T4 as the primary monitoring parameter 5, 2
- Low or inappropriately normal TSH with low free T4 is the diagnostic pattern 5
- Monitor free T4 every 6-8 weeks during dose adjustments, targeting the upper half of normal range 5
Pregnancy or planning pregnancy:
- Check TSH and free T4 every 4 weeks until stable, then at minimum once per trimester 1
- Target TSH <2.5 mIU/L in the first trimester 1
- Levothyroxine requirements increase 25-50% during pregnancy, necessitating proactive monitoring 1
Patients on immune checkpoint inhibitors:
- Monitor TSH (with optional free T4) every 4-6 weeks for the first 3 months, then every second cycle 1
- Thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy and 16% with combination immunotherapy 1
Critical Situations Requiring Urgent Testing
Recheck within 2 weeks (not 6-8 weeks) when:
- Patient has atrial fibrillation or cardiac arrhythmias 1
- Serious cardiac disease or multiple comorbidities are present 1
- TSH is severely suppressed (<0.1 mIU/L) in elderly patients 1
Common Pitfalls to Avoid
- Never treat based on a single abnormal TSH value without confirmation testing, as 30-60% normalize spontaneously 1
- Don't recheck TSH too frequently (before 6-8 weeks after dose changes), as this leads to inappropriate adjustments before steady state is reached 1
- Don't rely on TSH alone in central hypothyroidism—it will be misleadingly low or normal despite true hypothyroidism 5, 2
- Don't assume normal free T4 excludes all thyroid dysfunction—subclinical hypothyroidism (elevated TSH with normal free T4) represents clinically significant disease requiring treatment when TSH >10 mIU/L 1
- Approximately 25% of patients on levothyroxine are unintentionally overtreated with fully suppressed TSH, increasing risks for atrial fibrillation, osteoporosis, and cardiac complications 1