What is the accurate way to measure Thyroid-Stimulating Hormone (TSH) and Triiodothyronine (T3), Thyroxine (T4) levels?

Accurate Measurement of TSH, T3, and T4 Levels

TSH is the primary and most accurate screening test for thyroid dysfunction, and should be measured first; if TSH is abnormal, then measure free T4 to distinguish subclinical from overt disease, and only measure T3 in specific situations such as suspected hyperthyroidism with normal T4. 1

Initial Testing Strategy

Start with TSH Alone

• TSH has high sensitivity (98%) and specificity (92%) when used to confirm suspected thyroid disease and should be the first-line test 2, 1
• Do not routinely order T3 or T4 alongside initial TSH screening 1
• Reverse T3 has no role in screening or diagnosis 1

Confirm Abnormal Results

• If TSH is abnormal, repeat the measurement along with free T4 (and sometimes T3) to confirm the finding 2
• For TSH between 0.1-0.45 mIU/L: repeat within 2 weeks if cardiac disease/atrial fibrillation present, otherwise within 3 months 2
• For TSH <0.1 mIU/L: repeat within 4 weeks along with free T4 and total T3 or free T3 2
• For elevated TSH: repeat over 3-6 month intervals before making treatment decisions, unless TSH >10.0 mIU/L 2

Interpretation Thresholds

TSH Reference Values

• TSH <0.1 mIU/L is considered low 2, 1
• TSH >6.5 mIU/L is considered elevated 2, 1
• Values between 0.1-0.45 mIU/L represent mild suppression requiring confirmation 2

Distinguishing Subclinical from Overt Disease

• Measure free T4 when TSH is persistently abnormal to differentiate subclinical (normal T4) from overt (abnormal T4) thyroid dysfunction 2, 1
• Subclinical hypothyroidism: elevated TSH with normal T4 and T3 2
• Overt hypothyroidism: elevated TSH with low T4 2
• Subclinical hyperthyroidism: low TSH with normal T4 and T3 2
• Overt hyperthyroidism: low TSH with elevated T4 or T3 2

When to Measure T3

Specific Indications for T3 Testing

• Measure T3 only when TSH is suppressed (<0.1 mIU/L) and free T4 is normal, to detect T3 toxicosis 2, 3, 4
• Approximately 5% of hyperthyroid patients have selective T3 elevation (T3 thyrotoxicosis) with normal T4 5
• Measure total T3 or free T3 when confirming hyperthyroidism with very low TSH 2

When NOT to Measure T3

• Do not measure T3 to assess levothyroxine over-replacement in hypothyroid patients—it adds no diagnostic value 6
• T3 levels bear little relation to thyroid status in patients on levothyroxine replacement 6
• Normal T3 can be seen in over-replaced patients, making it unreliable for this purpose 6
• Most circulating T3 (80%) comes from peripheral conversion of T4, not thyroid secretion, making it less reliable than T4 for assessing thyroid function 7

Monitoring Established Thyroid Disease

Primary Hypothyroidism on Treatment

• Monitor TSH levels 6-8 weeks after any dosage change 8
• Once stable, evaluate every 6-12 months 8
• TSH is the most important parameter for monitoring adequacy of replacement 3
• Free T4 measurement is not routinely needed if TSH is in target range 8

Central (Secondary/Tertiary) Hypothyroidism

• TSH cannot be used for monitoring—measure free T4 and maintain in upper half of normal range 8, 3
• This applies to hypothalamic-pituitary dysfunction where TSH is diagnostically misleading 7

Pediatric Patients

• Monitor TSH and total or free T4 at 2 and 4 weeks after treatment initiation, 2 weeks after dosage changes, then every 3-12 months 8
• Failure of T4 to increase into upper half of normal range within 2 weeks, or TSH to decrease below 20 IU/L within 4 weeks, indicates inadequate therapy 8

Critical Pitfalls to Avoid

Measurement Variability

• Single abnormal TSH measurements require confirmation due to measurement variability and sensitivity to non-thyroidal conditions 2
• Laboratory reference intervals are based on statistical distribution rather than clinical outcomes, leading to uncertainty about true "abnormal" cutpoints 2
• TSH secretion is sensitive to conditions other than thyroid dysfunction 2

False Reassurance from Normal T3

• A normal T3 does not exclude thyroid dysfunction or over-replacement with levothyroxine 6
• Clinicians often inappropriately reassure patients based on normal T3 when TSH and T4 indicate problems 6

Population-Specific Considerations

• TSH reference ranges shift higher in older adults—age-specific ranges may be more appropriate 2
• Pregnant patients require trimester-specific TSH reference ranges 8
• Measure TSH and free T4 as soon as pregnancy is confirmed in patients with pre-existing hypothyroidism 8