What are the best labs to order for a comprehensive thyroid workup?

Best Labs for Thyroid Workup

Order TSH as the initial screening test, followed by free T4 if TSH is abnormal—this two-step approach provides the most cost-effective and accurate assessment of thyroid function in the vast majority of patients. 1, 2

Initial Screening Strategy

• TSH is the single most sensitive and specific test for detecting primary thyroid dysfunction, with sensitivity of 98% and specificity of 92% 1
• Order TSH alone for initial screening in patients with suspected thyroid disease or for routine screening in high-risk populations 1, 2
• TSH values below 0.1 mU/L indicate hyperthyroidism, while values above 6.5 mU/L indicate hypothyroidism 1

Reflex Testing Based on TSH Results

If TSH is Elevated (>4.5 mU/L):

• Add free T4 to distinguish subclinical hypothyroidism (normal free T4) from overt hypothyroidism (low free T4) 2, 3
• Measure anti-TPO antibodies to confirm autoimmune etiology, which predicts 4.3% annual progression risk to overt hypothyroidism versus 2.6% in antibody-negative patients 4
• Free T4 is more reliable than total T4 because it is not affected by thyroid-binding protein abnormalities 5

If TSH is Suppressed (<0.1 mU/L):

• Measure free T4 and total T3 to confirm hyperthyroidism, as free T3 is often the first hormone elevated in early hyperthyroidism 2, 6
• If free T4 is normal but TSH remains suppressed, measure free T3 to detect T3 toxicosis 3
• Consider TRAb (TSH receptor antibodies) to diagnose Graves' disease if hyperthyroidism is confirmed 7

If TSH is Normal (0.45-4.5 mU/L):

• No additional testing is needed in asymptomatic patients, as normal TSH combined with normal free T4 definitively excludes both overt and subclinical thyroid dysfunction 4
• In sick hospitalized patients, a normal TSH with normal free T4 suggests the patient has neither hypothyroidism nor thyrotoxicosis 2

Essential Tests for Comprehensive Workup

The complete initial thyroid panel should include:

• TSH (always first) 1, 2, 3
• Free T4 (if TSH abnormal) 2, 5, 3
• Free T3 (if TSH suppressed with normal free T4, or monitoring certain hyperthyroid conditions) 6, 3
• Anti-TPO antibodies (if TSH elevated, to confirm autoimmune etiology) 4, 7

Special Circumstances Requiring Modified Testing

Suspected Central Hypothyroidism:

• Measure both TSH and free T4 simultaneously, as TSH cannot be used as a screening test when pituitary or hypothalamic disease is suspected 3
• A low or inappropriately normal TSH with low free T4 indicates central hypothyroidism 4

Monitoring Thyroid Cancer:

• Measure serum thyroglobulin (Tg) with anti-Tg antibodies 6-12 months after initial treatment 1
• Thyroglobulin antibodies can interfere with Tg measurement, making the test unreliable 7

Suspected Medullary Thyroid Cancer:

• Measure basal serum calcitonin and CEA before surgery in patients with suspicious nodules 1
• Some guidelines recommend routine calcitonin screening for all thyroid nodules, though this remains controversial in the United States 1

Pregnancy or Planning Pregnancy:

• TSH and free T4 should be measured, with target TSH <2.5 mIU/L in first trimester 4
• Levothyroxine requirements increase 25-50% during pregnancy, necessitating more frequent monitoring 4

Critical Pitfalls to Avoid

• Never rely on total T4 or total T3 alone, as these are affected by thyroid-binding protein abnormalities (TBG excess/deficiency, familial dysalbuminemic hyperthyroxinemia) and will give false results in euthyroid patients 5
• Do not order free T3 routinely—it adds no diagnostic value in primary hypothyroidism and should be reserved for suspected T3 toxicosis or monitoring specific hyperthyroid conditions 6, 7
• Avoid testing during acute illness, as nonthyroidal illness can cause transient TSH abnormalities that normalize after recovery; wait 3-6 weeks after illness resolution 4
• Confirm abnormal results with repeat testing after 3-6 weeks, as 30-60% of elevated TSH values normalize spontaneously 4
• Be aware of assay interferences—heterophilic antibodies, biotin supplementation, and certain medications can cause spurious results 7
• Never treat based on a single abnormal TSH value without confirmation and clinical correlation 4

Algorithm for Test Selection

1. Start with TSH alone for screening 1, 2, 3
2. If TSH >4.5 mU/L: Add free T4 and anti-TPO antibodies 4, 2
3. If TSH <0.1 mU/L: Add free T4 and free T3 2, 6, 3
4. If TSH normal (0.45-4.5 mU/L): Stop—no further testing needed unless central hypothyroidism suspected 4, 2
5. If central hypothyroidism suspected: Order TSH and free T4 simultaneously 3