What is the initial evaluation for a patient with suspected thyroid dysfunction, including relevant lab tests and considerations for those with a history of thyroid disease or taking thyroid hormone replacement therapy?

Initial Thyroid Function Evaluation

Primary Recommendation

TSH is the single best initial test for evaluating suspected thyroid dysfunction, followed by free T4 measurement only if TSH is abnormal. 1, 2

Testing Algorithm for New Suspected Thyroid Dysfunction

Step 1: Initial TSH Measurement

• Order TSH as the first-line test for all patients with suspected thyroid dysfunction 1, 3
• TSH demonstrates 98% sensitivity and 92% specificity when confirming suspected thyroid disease 3, 1
• Interpret TSH values as:
  • Low: <0.1 mU/L
  • Elevated: >6.5 mU/L (some sources use >4.5 mU/L)
  • Normal range: 0.45-4.5 mU/L 3, 1

Step 2: Reflex Testing Based on TSH Results

If TSH is elevated (>6.5 mU/L):

• Measure free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 1, 2
• Consider thyroid peroxidase (TPO) antibodies if biochemical hypothyroidism is confirmed 3

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

• Measure free T4 to confirm hyperthyroidism versus subclinical hyperthyroidism 3, 1
• If free T4 is normal but clinical suspicion remains high, measure total T3 or free T3 to detect T3 toxicosis 3, 2
• Repeat testing within 4 weeks for confirmation 3
• Consider thyroid antibodies (TRAb or TSI) and radioactive iodine uptake scan to distinguish Graves disease from thyroiditis 3

If TSH is mildly suppressed (0.1-0.45 mU/L):

• Repeat TSH measurement for confirmation 3
• Measure free T4 and T3 to exclude central hypothyroidism or nonthyroidal illness 3
• Timing of repeat testing depends on clinical urgency: within 2 weeks if cardiac disease/atrial fibrillation present, otherwise within 3 months 3

Critical Exception: Central Hypothyroidism

When central (secondary/tertiary) hypothyroidism is suspected, TSH is diagnostically misleading and should NOT be used alone. 1, 2

• Measure free T4 directly as the primary test 1, 2
• TSH may be low, normal, or even slightly elevated in central hypothyroidism 3
• Clinical clues include: headache, visual changes, other pituitary hormone deficiencies, history of pituitary disease 3

Special Considerations for Patients on Thyroid Hormone Replacement

For patients already taking levothyroxine:

• TSH remains the primary monitoring parameter for adequacy of replacement in primary hypothyroidism 2
• Target TSH should be within normal reference range (0.45-4.5 mU/L) unless specific indications exist for suppression 3

If TSH is 0.1-0.45 mU/L on levothyroxine:

• Review indication for therapy—many patients are overtreated 3
• Decrease levothyroxine dose to allow TSH to rise toward normal range, unless patient has thyroid cancer or nodules requiring suppression 3

If TSH is <0.1 mU/L on levothyroxine:

• Review indication immediately 3
• Decrease levothyroxine dose unless intentional suppression is indicated for thyroid cancer or nodules 3
• Prolonged suppression increases risks of atrial fibrillation and bone loss 3

Important Pitfalls to Avoid

• Always confirm abnormal results with repeat testing before initiating treatment, as nonthyroidal illness can cause spurious results 1, 4
• Do not order T3 routinely—reserve for cases where TSH is suppressed but free T4 is normal and hyperthyroidism is still suspected 1, 2
• In hospitalized or acutely ill patients, TSH has low positive predictive value and results are frequently confounded by nonthyroidal illness 3, 1
• Free thyroid hormones are superior to total hormones because total levels are affected by binding protein abnormalities (pregnancy, estrogen, familial dysalbuminemic hyperthyroxinemia) 5
• In suspected hypophysitis (particularly with immunotherapy), morning cortisol/ACTH must be checked alongside thyroid function, and steroids must be started before thyroid hormone if both deficiencies exist to avoid adrenal crisis 3