Hyperthyroidism Laboratory Workup
Begin with serum TSH as the single most sensitive initial screening test, followed immediately by free T4 (FT4) to distinguish between subclinical and overt hyperthyroidism. 1
Initial Laboratory Panel
Essential First-Line Tests
- TSH (thyroid-stimulating hormone): The most sensitive initial screening test that should be performed first in all suspected cases 1, 2
- Free T4 (FT4): Must be measured simultaneously with TSH to differentiate subclinical from overt hyperthyroidism 1, 3
- Free T3 (FT3): Should be included in the initial workup, as approximately 8% of hyperthyroid patients present with T3 toxicosis (elevated T3 with normal T4 and suppressed TSH) 4
Interpretation of Initial Results
- TSH < 0.1 mU/L with elevated FT4 and/or FT3: Overt hyperthyroidism 1, 2
- TSH < 0.1 mU/L with normal FT4 and FT3: Subclinical hyperthyroidism requiring close monitoring 1
- Low TSH with low FT4: Suggests central hypothyroidism from pituitary dysfunction, not hyperthyroidism 1
Additional Diagnostic Tests for Etiology
Once biochemical hyperthyroidism is confirmed, determine the underlying cause:
Antibody Testing
- TSH receptor antibodies (TRAb): Essential for diagnosing Graves' disease, which accounts for 70% of hyperthyroidism cases 2
- Thyroid peroxidase antibodies (TPO-Ab): Helpful in identifying autoimmune thyroid disease 2, 5
- TRAb is particularly important in pregnant women as maternal antibodies can cross the placenta and affect the fetus 6
Imaging Studies
- Thyroid ultrasonography: Recommended to evaluate thyroid structure and identify nodular disease 2, 5
- Thyroid scintigraphy (radioiodine uptake scan): Useful for differentiating Graves' disease (diffuse uptake) from toxic nodular goiter (focal uptake) or thyroiditis (low uptake) 2, 7
Supporting Laboratory Tests
Basic Metabolic Assessment
- Basic metabolic panel: Assess for electrolyte abnormalities (particularly hypokalemia in thyrotoxic periodic paralysis) 1
- Complete blood count: Baseline assessment before initiating antithyroid drugs, as agranulocytosis is a serious potential complication 8
- Liver function tests: Baseline values needed as antithyroid medications can cause hepatotoxicity 8
Cardiovascular Evaluation
- Electrocardiogram: Recommended in patients over 50 years or with cardiovascular symptoms to detect atrial fibrillation or other arrhythmias 1
Confirmation and Monitoring
- Repeat testing after 2-4 weeks: Confirm persistent abnormalities before initiating treatment, as transient thyroid dysfunction can occur 1
- Monitor thyroid function every 2-3 weeks initially after diagnosis to detect transition to hypothyroidism, the most common outcome of transient thyroiditis 6
Common Pitfalls to Avoid
- Do not rely on total T4 and T3 alone: These are influenced by thyroid-binding protein abnormalities and can be misleading in euthyroid patients with TBG excess or deficiency 3
- Do not assume elevated FT4 always means hyperthyroidism: Patients on chronic amiodarone or levothyroxine therapy may have elevated FT4 while remaining euthyroid 3
- Do not overlook T3 toxicosis: Approximately 8% of hyperthyroid patients have isolated T3 elevation with normal T4 4
- TSH may remain suppressed for months after achieving euthyroid state in treated Graves' disease, making it unreliable for monitoring during early treatment 7
Special Populations
- Patients on immune checkpoint inhibitors: Require thyroid function monitoring every cycle for the first 3 months, then every second cycle, as these medications commonly cause thyroiditis 6
- Elderly patients: Low TSH is often not associated with true hyperthyroidism; confirm with elevated thyroid hormones before diagnosing 7
- Hospitalized patients: May have low T3 syndrome (sick euthyroid syndrome) without true thyroid dysfunction 4