What blood markers are used to diagnose thyroidism, specifically hypothyroidism and hyperthyroidism?

Blood Markers for Diagnosing Thyroid Dysfunction

TSH (thyroid-stimulating hormone) is the primary screening test for thyroid dysfunction, with free T4 measured when TSH is abnormal to distinguish between subclinical and overt disease. 1, 2

Primary Screening Algorithm

Initial Testing

• TSH alone is the recommended first-line test for screening and evaluating suspected thyroid disease, with sensitivity above 98% and specificity greater than 92% 1, 3, 2
• If TSH is abnormal, measure free T4 (FT4) to distinguish between:
  • Subclinical hypothyroidism: elevated TSH with normal FT4 1, 3
  • Overt hypothyroidism: elevated TSH with low FT4 1, 3
  • Subclinical hyperthyroidism: suppressed TSH with normal FT4 3
  • Overt hyperthyroidism: suppressed TSH with elevated FT4 1

Confirmation Testing

• Repeat TSH after 3-6 weeks if initially elevated, as 30-60% of high TSH levels normalize spontaneously 3
• Both TSH and FT4 should be measured together in pregnant women with suspected thyroid dysfunction 1

Specific Diagnostic Patterns

Hypothyroidism Markers

• TSH >10 mIU/L with any FT4 level indicates significant hypothyroidism requiring treatment regardless of symptoms 3
• TSH 4.5-10 mIU/L with normal FT4 defines subclinical hypothyroidism, where treatment decisions depend on symptoms, antibody status, and pregnancy plans 3
• Low or inappropriately normal TSH with low FT4 suggests central (secondary) hypothyroidism from pituitary or hypothalamic dysfunction 2

Hyperthyroidism Markers

• Suppressed TSH (<0.1 mIU/L) with elevated FT4 and/or FT3 confirms overt hyperthyroidism 1, 2
• FT3 measurement is particularly useful when hyperthyroidism is suspected but FT4 is normal, as "T3-toxicosis" can occur with normal T4 4, 2, 5
• Measure free T3 (FT3) if TSH is undetectable and FT4 is normal to detect T3-predominant hyperthyroidism 2

Additional Diagnostic Tests

Antibody Testing

• Anti-thyroid peroxidase (anti-TPO) antibodies should be measured to confirm autoimmune etiology (Hashimoto's thyroiditis), which predicts 4.3% annual progression risk to overt hypothyroidism versus 2.6% in antibody-negative individuals 1, 3
• Anti-thyroglobulin antibodies are less predictive than anti-TPO antibodies but can be measured alongside anti-TPO at diagnosis in children with type 1 diabetes 1
• Consider measuring antibodies soon after diabetes diagnosis or in patients with TSH 4.5-10 mIU/L to guide treatment decisions 1, 3

Critical Interpretation Pitfalls

When TSH is Unreliable

• Euthyroid sick syndrome: TSH may be misleading during acute illness, ketoacidosis, or metabolic instability—recheck after recovery 1
• Recent iodine exposure (CT contrast, amiodarone) can transiently affect thyroid function 3
• Recovery phase from thyroiditis: TSH can be temporarily elevated 3
• Central hypothyroidism: TSH cannot be used as a screening test; must measure FT4 directly 2

Free Hormone Advantages Over Total Hormones

• Free T4 and free T3 are superior to total T4 and T3 because total hormones are influenced by thyroid-binding protein variations (TBG excess/deficiency, familial dysalbuminemic hyperthyroxinemia) 4
• Free hormone measurements correctly establish euthyroidism when binding protein abnormalities exist 4

Monitoring Established Disease

Hypothyroidism on Treatment

• TSH every 6-8 weeks during dose titration until target range (0.5-4.5 mIU/L) is achieved 3
• TSH every 6-12 months once stable on maintenance therapy 3
• Free T4 can help interpret ongoing abnormal TSH during therapy, as TSH may take longer to normalize 3

Special Populations

• Pregnant women: Check TSH every trimester after stabilization, as levothyroxine requirements increase 25-50% during pregnancy 3
• Type 1 diabetes patients: Measure TSH at diagnosis when clinically stable, then every 1-2 years if normal, or sooner if positive antibodies or symptoms develop 1
• Patients on immunotherapy: Monitor TSH every 4-6 weeks for first 3 months, then every second cycle, as thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy 3

Cost-Effective Testing Strategy

Avoid routine ordering of free T4 and free T3 without clinical indication, as inappropriate free thyroid hormone testing accounts for 36% of all thyroid function tests ordered and represents significant unnecessary healthcare expenditure 6. TSH alone is sufficient for initial screening in most cases, with free hormones reserved for abnormal TSH results or specific clinical scenarios 6.