What are the initial investigations for hyperthyroidism?

Initial Investigations for Hyperthyroidism

The initial laboratory workup for suspected hyperthyroidism should include measurement of thyroid stimulating hormone (TSH) and free thyroxine (FT4), with additional testing of free triiodothyronine (FT3) when TSH is suppressed but FT4 is normal. 1, 2

Primary Laboratory Assessment

• TSH is the most sensitive initial screening test for thyroid dysfunction and should be performed first 3, 1
• Free thyroxine (FT4) should be measured simultaneously with TSH to distinguish between subclinical and overt hyperthyroidism 1, 2
• Free triiodothyronine (FT3) should be added when TSH is suppressed but FT4 is normal (to detect T3 toxicosis) 2, 4
• Low TSH with elevated FT4 and/or FT3 confirms biochemical hyperthyroidism 2, 5
• Low TSH with normal FT4 and FT3 indicates subclinical hyperthyroidism 3, 1
• Low TSH with low FT4 suggests central hypothyroidism, requiring evaluation for pituitary dysfunction 3, 1

Etiological Diagnosis

After confirming biochemical hyperthyroidism, additional tests should be performed to determine the underlying cause:

• TSH receptor antibodies (TRAb) to diagnose Graves' disease, which accounts for approximately 70% of hyperthyroidism cases 2, 6
• Thyroid peroxidase antibodies (anti-TPO) to help identify autoimmune thyroid disease 1, 2
• Thyroid ultrasonography to evaluate for nodularity, size, and vascularity 2, 5
• Radioactive iodine uptake scan (when available and not contraindicated) to differentiate between causes of hyperthyroidism:
  • Increased uptake suggests Graves' disease or toxic nodular goiter 2, 7
  • Decreased uptake suggests thyroiditis or exogenous thyroid hormone 2, 7

Special Considerations

• Basic metabolic panel to assess for electrolyte abnormalities that may accompany hyperthyroidism 3
• Complete blood count to evaluate for concurrent hematologic abnormalities 3
• Liver function tests, particularly in patients who will be started on antithyroid medications 3
• Electrocardiogram in patients over 50 years or with cardiovascular symptoms to assess for atrial fibrillation or other arrhythmias 3
• In pregnant women, TRAb testing is essential as maternal antibodies can cross the placenta and affect the fetus 3, 2
• In patients on immune checkpoint inhibitors, regular monitoring of thyroid function is recommended as these medications can cause thyroiditis 3

Interpretation of Results

• TSH values below 0.1 mU/L are considered significantly suppressed 3
• The FT4/TSH ratio may help distinguish Graves' disease from other causes of hyperthyroidism, with higher ratios suggesting Graves' disease 6
• Patients with subclinical hyperthyroidism (low TSH, normal FT4/FT3) should be monitored closely as they may progress to overt hyperthyroidism or revert to normal thyroid function 3
• Repeat testing after 2-4 weeks is recommended to confirm persistent abnormalities before initiating treatment 3, 1

Common Pitfalls to Avoid

• Relying solely on TSH without measuring FT4 can lead to misdiagnosis 1, 4
• Failing to consider non-thyroidal illness which can cause transient TSH suppression 3, 1
• Not recognizing that medications (amiodarone, glucocorticoids, dopamine) can affect thyroid function tests 1, 2
• Overlooking the possibility of thyroiditis, which typically presents with a triphasic course (hyperthyroidism followed by hypothyroidism, then recovery) 3, 1
• Not distinguishing between Graves' disease and gestational thyrotoxicosis in pregnant women 3, 2