What is the workup for hyperthyroidism?

Workup for Hyperthyroidism

The workup for hyperthyroidism should begin with TSH and free T4 measurements, followed by targeted testing based on clinical presentation to determine the underlying etiology. 1, 2

Initial Laboratory Evaluation

• TSH is the primary screening test for thyroid dysfunction and should be the first test ordered when hyperthyroidism is suspected 1
• Free T4 should be measured simultaneously with TSH or as a follow-up to an abnormal TSH 1, 3
• T3 measurement can be helpful in highly symptomatic patients with minimal FT4 elevations 1, 2
• Multiple tests should be done over a 3-6 week interval to confirm abnormal findings 1

Additional Testing Based on Initial Results

For Confirmed Low TSH with Elevated Free T4/T3:

• TSH receptor antibody (TRAb) testing should be performed when Graves' disease is suspected, especially if clinical features such as ophthalmopathy are present 1, 3
• If TRAb testing is negative or unavailable, radioiodine uptake should be performed to distinguish between causes of hyperthyroidism 3, 2
• Consider thyroid peroxidase antibodies to help identify autoimmune thyroid disease 2

Imaging Studies:

• Thyroid ultrasound can help identify nodules and evaluate thyroid morphology when toxic multinodular goiter or toxic adenoma is suspected 1
• Doppler ultrasound may help distinguish between causes of thyrotoxicosis by assessing thyroid blood flow (increased in Graves' disease and toxic nodules; decreased in thyroiditis) 1
• Radioiodine uptake and scan is valuable when the etiology remains unclear after antibody testing, particularly to differentiate between Graves' disease, toxic multinodular goiter, toxic adenoma, and thyroiditis 1, 4

Special Considerations

• Low TSH with low FT4 suggests central hypothyroidism and requires evaluation for hypophysitis 1
• For patients with thyroid nodules, additional workup may be needed to evaluate for malignancy 1
• In pregnant patients, radioactive iodine scanning is contraindicated; rely on clinical features, laboratory tests, and ultrasound 2
• For patients on immune checkpoint inhibitors, TSH should be checked every 4-6 weeks as part of routine monitoring 1

Common Pitfalls and Caveats

• Amiodarone-induced thyrotoxicosis requires special consideration and can be type I (iodine-induced hyperthyroidism) or type II (destructive thyroiditis) 1, 2
• Subclinical hyperthyroidism (low TSH with normal FT4/T3) should be distinguished from overt hyperthyroidism as management differs 4
• Thyroiditis causes transient hyperthyroidism that typically resolves spontaneously and may progress to hypothyroidism; serial monitoring is essential 1, 5
• Failure to consider rare causes of hyperthyroidism such as struma ovarii, thyroid hormone resistance, or factitious thyrotoxicosis may lead to misdiagnosis 1
• TSH may remain suppressed for weeks to months after resolution of hyperthyroidism, so free T4 and T3 are more reliable indicators of current thyroid status during treatment 1, 2

The diagnostic approach should be systematic, starting with basic thyroid function tests and proceeding to more specialized testing based on clinical suspicion of the underlying cause, as this directly impacts treatment decisions and patient outcomes 2, 4.