Initial Laboratory Evaluation for Suspected Thyroid Disorders
Primary Screening Test
TSH is the single most important initial test for evaluating suspected thyroid dysfunction, with sensitivity >98% and specificity >92%. 1, 2 This should be your first-line test in nearly all cases of suspected primary thyroid disease.
When to Add Free T4 Immediately
Measure both TSH and free T4 simultaneously in these specific situations:
- Suspected central (secondary/tertiary) hypothyroidism – TSH is diagnostically misleading when pituitary or hypothalamic dysfunction is present 3, 4
- Patients on immune checkpoint inhibitors – Risk of hypophysitis requires monitoring both parameters 1, 3
- Pregnant women or those planning pregnancy – Untreated thyroid dysfunction has significant maternal and fetal consequences 1
- Hospitalized or critically ill patients – Non-thyroidal illness dramatically reduces TSH's positive predictive value to only 0.24 1
- Patients with known pituitary disease – TSH cannot be relied upon 3
Algorithmic Approach Based on TSH Results
If TSH is Elevated (>4.5-6.5 mIU/L):
- Measure free T4 to distinguish subclinical hypothyroidism (normal T4) from overt hypothyroidism (low T4) 5, 3
- Consider anti-TPO antibodies if TSH is 4.5-10 mIU/L to identify autoimmune etiology and predict progression risk (4.3% vs 2.6% annually) 5
- Repeat testing in 3-6 weeks before treatment decisions, as 30-60% of elevated TSH values normalize spontaneously 5, 1
If TSH is Suppressed (<0.1-0.4 mIU/L):
- Measure free T4 to confirm hyperthyroidism versus subclinical hyperthyroidism 3
- Add T3 measurement if free T4 is normal but TSH remains suppressed – this identifies T3-toxicosis or early hyperthyroidism 3, 4
If TSH is Normal:
- No further thyroid testing needed in asymptomatic patients 2
- Measure free T4 anyway if strong clinical suspicion for central hypothyroidism exists 3, 4
When to Measure T3
T3 testing is not part of routine initial evaluation. Order T3 only in these specific scenarios:
- TSH suppressed but free T4 normal – suggests T3-toxicosis 3, 4
- Confirming overt hyperthyroidism – when TSH is low/undetectable, measure both T4 and T3 3
- Monitoring central hypothyroidism – use free T4 and T3 since TSH is unreliable 4
Autoimmune Thyroid Disease Evaluation
Anti-TPO antibodies should be measured when:
- TSH is 4.5-10 mIU/L to guide treatment decisions 5
- Confirming Hashimoto's thyroiditis or Graves' disease is clinically important 5
- Patient has other autoimmune conditions 6
Do not routinely measure thyroglobulin antibodies, TSI, or TBII in initial evaluation unless specific clinical scenarios warrant them 7
Critical Pitfalls to Avoid
- Never treat based on single abnormal TSH – 30-60% normalize on repeat testing 5, 1
- Never rely on physical examination alone – signs have poor diagnostic accuracy (LR+ range 1.0-3.88) and cannot confirm or exclude hypothyroidism 8
- Never order TSH in hospitalized patients unless thyroid disease is strongly suspected – positive predictive value is only 0.24 1
- Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism – this precipitates adrenal crisis 1, 3
- Never assume normal TSH excludes all thyroid disease – central hypothyroidism presents with low/normal TSH and low T4 3, 4
High-Risk Populations Requiring Aggressive Case Finding
Screen with TSH in these groups even without symptoms 6:
- Women >60 years
- Personal history of autoimmune disease
- Family history of thyroid disease
- Type 1 diabetes mellitus
- Previous thyroid surgery or radioactive iodine treatment
- Atrial fibrillation
- Postpartum women 1
- Patients on immune checkpoint inhibitors (check every 4-6 weeks) 1
Population Screening Not Recommended
Do not perform routine TSH screening in asymptomatic general populations – evidence is insufficient to support population-based screening 6. Focus instead on aggressive case finding in high-risk groups.