What labs are recommended to work up hyperthyroidism?

Laboratory Workup for Hyperthyroidism

The initial laboratory workup for suspected hyperthyroidism should include TSH and free T4, followed by total T3 or free T3 if TSH is suppressed, with additional testing guided by the clinical presentation and initial results. 1, 2, 3

Initial Screening Tests

First-Line Laboratory Tests

• Measure serum TSH as the initial screening test - it has sensitivity above 98% and specificity greater than 92% for detecting thyroid dysfunction 1
• Measure free T4 (FT4) simultaneously with TSH to distinguish between overt hyperthyroidism (elevated FT4) and subclinical hyperthyroidism (normal FT4) 1, 3
• TSH values below 0.1 mIU/L are considered suppressed and warrant further evaluation 1

When to Add T3 Testing

• Measure total T3 or free T3 when TSH is suppressed (<0.1 mIU/L) and FT4 is normal or borderline to detect T3 thyrotoxicosis 1, 2, 3
• T3 thyrotoxicosis occurs in approximately 0.5% of newly diagnosed hyperthyroid patients and is most likely when TSH <0.01 μIU/mL 4
• Free T3 testing has limited utility when TSH is not significantly suppressed, with only 1.6% of all tested patients showing biochemical T3 thyrotoxicosis 4

Confirmatory and Repeat Testing

Timing of Repeat Measurements

• If initial TSH is between 0.1-0.45 mIU/L, repeat TSH with FT4 and T3 within 3 months for stable patients without cardiac disease 1
• If initial TSH is <0.1 mIU/L, repeat within 4 weeks along with FT4 and total T3 or FT3 1
• For patients with atrial fibrillation, cardiac disease, or serious medical conditions, repeat testing within 2 weeks is prudent 1

Etiologic Workup After Confirming Hyperthyroidism

Antibody Testing

• Measure TSH-receptor antibodies (TRAb) to diagnose Graves' disease, which accounts for 70% of hyperthyroidism cases 2, 3
• Measure thyroid peroxidase antibodies (TPO) to identify autoimmune thyroid disease 2
• Positive TSH-receptor antibodies confirm Graves' disease without need for imaging 3

Imaging Studies

• Thyroid ultrasonography helps identify nodular disease and assess gland size 2
• Radioactive iodine uptake and scan distinguishes between Graves' disease (diffuse uptake), toxic nodular goiter (focal uptake), and destructive thyroiditis (low uptake) 1, 2, 3
• Scintigraphy is recommended when thyroid nodules are present on examination or ultrasound, or when the etiology remains unclear after antibody testing 3

Special Considerations and Common Pitfalls

Factors Affecting Test Interpretation

• Recent iodine exposure from CT contrast can transiently affect thyroid function tests and should be considered before making treatment decisions 1
• Severe nonthyroidal illness can cause false-positive low TSH results, with positive predictive value of only 0.24 for hyperthyroidism in hospitalized patients 1
• 30-60% of mildly elevated or suppressed TSH values normalize on repeat testing, emphasizing the importance of confirmation before treatment 5

Pregnancy-Specific Testing

• In pregnant women with suspected hyperthyroidism, measure TSH, FT4, and total T3 or FT3 1
• TSH-receptor antibodies should be measured in pregnant women with Graves' disease to assess risk of fetal/neonatal thyroid dysfunction 1
• Thyrotropin-releasing hormone testing may be useful in specific pregnancy situations 1

Monitoring During Treatment

• Monitor TSH and FT4 every 2-4 weeks during initial antithyroid drug therapy until euthyroid state is achieved 1, 6, 7
• Obtain complete blood count if patients develop sore throat or fever to detect agranulocytosis from antithyroid drugs 6, 7
• Monitor prothrombin time before surgical procedures as antithyroid drugs may cause hypoprothrombinemia 6, 7

Critical Diagnostic Distinctions

• Subclinical hyperthyroidism (TSH <0.45 mIU/L with normal FT4 and T3) should be distinguished from overt hyperthyroidism (suppressed TSH with elevated FT4 or T3) as management differs 1, 3
• Grade I subclinical hyperthyroidism (TSH 0.1-0.4 mIU/L) carries lower risk than Grade II (TSH <0.1 mIU/L) and requires different monitoring intervals 8
• Central hypothyroidism must be excluded when TSH is low with low or normal FT4, particularly in patients with pituitary disease or on immunotherapy 1