What is the most likely test to reveal the cause of hyperthyroidism (elevated thyroid hormone levels) in a patient with undetectable Thyroid-Stimulating Hormone (TSH) and elevated Free Thyroxine (FT4) levels?

Thyroid Scintigraphy and Radioactive Iodine Uptake is the Most Appropriate Test to Determine the Cause of Hyperthyroidism

Thyroid scintigraphy and radioactive iodine uptake (RAIU) is the most appropriate test to reveal the cause of hyperthyroidism in this patient with undetectable TSH and elevated FT4 levels. 1, 2

Clinical Presentation Analysis

The patient presents with:

• Palpitations most days of the week
• Occasional diarrhea
• Fidgety behavior and constant movement
• Undetectable TSH and elevated FT4
• No palpable thyroid nodules, no exophthalmos, no pretibial edema
• Normal BMI of 19

These findings are consistent with hyperthyroidism, but the etiology needs to be determined for appropriate management.

Diagnostic Test Selection Rationale

Why Thyroid Scintigraphy and RAIU is the Best Choice:

• The American Thyroid Association recommends radioactive iodine uptake measurement and scan to distinguish between different causes of hyperthyroidism, including destructive thyroiditis, Graves' disease, and nodular goiter 1
• Thyroid scintigraphy provides specific patterns that help differentiate between Graves' disease, toxic multinodular goiter, toxic adenoma, and destructive thyroiditis 2
• RAIU not only helps establish the cause but also provides information for planning potential radioiodine therapy 2

Why Other Options Are Less Appropriate:

1. MRI of the pituitary - Not indicated as first-line test for this presentation. While central hyperthyroidism from a TSH-secreting pituitary adenoma is possible, it's extremely rare compared to primary hyperthyroidism. The clinical presentation (fidgety behavior, palpitations) is more consistent with primary hyperthyroidism 3

2. Ultrasound-guided biopsy - Not appropriate as an initial test for hyperthyroidism. Biopsy is used to evaluate thyroid nodules for malignancy, but this patient has no palpable nodules 1

3. Serum thyroglobulin levels - Primarily used for monitoring differentiated thyroid cancer, not for diagnosing the cause of hyperthyroidism 1

4. Serum reverse T3 (rT3) - Not helpful in determining the etiology of hyperthyroidism 4

Diagnostic Algorithm for Hyperthyroidism

1. Confirm biochemical hyperthyroidism: Low/undetectable TSH with elevated FT4/FT3 (already established in this case)

2. Determine etiology with thyroid scintigraphy and RAIU:

   • High uptake: Graves' disease or toxic nodular disease
   • Low uptake: Thyroiditis, exogenous thyroid hormone, or iodine-induced hyperthyroidism

3. Additional testing based on scintigraphy results:

   • If high uptake pattern suggests Graves' disease: Check TSH receptor antibodies
   • If nodular pattern: Consider thyroid ultrasound for better characterization

Clinical Pearls and Pitfalls

• Pearl: The combination of undetectable TSH, elevated FT4, and symptoms like palpitations and fidgeting strongly suggests hyperthyroidism, with Graves' disease being the most common cause (70% of cases) 5

• Pitfall: Relying solely on clinical features without appropriate imaging can lead to misdiagnosis, as different causes of hyperthyroidism require different treatment approaches 5

• Caution: Radioactive iodine studies should be avoided in pregnant patients; thyroid ultrasound would be the preferred imaging modality in such cases 5

• Important: Thyroid scintigraphy with either radioiodine or 99mTc-pertechnetate can be used, with specific scintigraphic patterns for different etiologies of hyperthyroidism 2

By performing thyroid scintigraphy and RAIU, the clinician can confidently determine whether this patient has Graves' disease, toxic nodular disease, or thyroiditis, which will guide appropriate treatment selection.