What are the best laboratory tests for diagnosing and managing hypothyroidism?

Best Laboratory Tests for Hypothyroidism

TSH is the single best initial screening test for hypothyroidism, followed by free T4 measurement when TSH is abnormal to distinguish between subclinical and overt disease. 1, 2, 3, 4

Primary Diagnostic Algorithm

First-Line Testing

• Measure serum TSH as the initial test with sensitivity above 98% and specificity greater than 92% for detecting thyroid dysfunction 1, 2, 3
• If TSH is elevated (>4.5 mIU/L), measure free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 1, 2
• Confirm any abnormal TSH with repeat testing after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously 1

Additional Diagnostic Tests

• Measure anti-thyroid peroxidase (anti-TPO) antibodies when TSH is elevated to confirm autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk to overt hypothyroidism (4.3% vs 2.6% per year in antibody-negative individuals) 1, 2
• Anti-thyroglobulin antibodies can also be measured alongside anti-TPO for comprehensive autoimmune assessment 2
• T3 measurement is NOT routinely recommended for diagnosing primary hypothyroidism, as it does not add diagnostic value in most cases 1, 3

Monitoring During Treatment

Initial Titration Phase

• Recheck TSH and free T4 every 6-8 weeks after initiating levothyroxine or changing the dose, as this represents the time needed to reach steady state 1, 5
• Target TSH within the reference range (0.5-4.5 mIU/L) with normal free T4 levels 1

Maintenance Monitoring

• Once stable, monitor TSH every 6-12 months or whenever clinical status changes 1, 5, 6
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1

Special Populations

Pregnant Patients

• Measure TSH and free T4 as soon as pregnancy is confirmed and at minimum during each trimester 1, 5
• Target TSH <2.5 mIU/L in the first trimester and within trimester-specific reference ranges thereafter 1, 5
• Monitor TSH every 4 weeks until stable, then at least once per trimester 5

Pediatric Patients

• Monitor both TSH and total or free T4 at 2 and 4 weeks after treatment initiation, 2 weeks after any dose change, then every 3-12 months until growth is completed 5
• Include assessment of development, mental and physical growth, and bone maturation at regular intervals 5

Central Hypothyroidism

• TSH cannot be used as a reliable screening test in suspected pituitary or hypothalamic disease 1
• Monitor free T4 levels and maintain in the upper half of the normal range, as TSH may be inappropriately normal or low despite hypothyroidism 5, 3

Critical Pitfalls to Avoid

• Never treat based on a single abnormal TSH value without confirmation, as transient elevations are common 1
• Do not measure T3 routinely in primary hypothyroidism evaluation, as it adds no diagnostic value and may cause confusion 1, 3
• Avoid checking TSH too frequently (before 6-8 weeks after dose changes), as this leads to inappropriate adjustments before steady state is reached 1
• Remember that TSH levels vary with age, sex, and ethnicity—12% of persons aged 80+ without thyroid disease have TSH >4.5 mIU/L 2
• Consider non-thyroidal factors that can affect TSH: acute illness, medications (amiodarone, lithium, immune checkpoint inhibitors), recent iodine exposure, pregnancy, and recovery from thyroiditis 1, 2
• Approximately 25% of patients on levothyroxine are unintentionally overtreated with fully suppressed TSH, increasing risks for atrial fibrillation, osteoporosis, and cardiac complications 1