What additional testing is indicated with decreased Thyroid-Stimulating Hormone (TSH) levels?

Additional Testing for Decreased TSH

When TSH is decreased, you must measure free T4 (FT4) and free T3 (FT3) to distinguish between hyperthyroidism and central hypothyroidism, as a low TSH alone cannot differentiate these conditions. 1

Initial Diagnostic Algorithm

For TSH Between 0.1-0.45 mIU/L

• Confirm the result by repeating TSH measurement along with FT4 and either total T3 or FT3 1
• Timing of repeat testing depends on clinical context:
  • Within 2 weeks if patient has atrial fibrillation, cardiac disease, or serious medical conditions 1
  • Within 3 months if these factors are absent 1
• If FT4 is low with low TSH, this indicates central hypothyroidism—evaluate for hypophysitis and measure morning cortisol and ACTH 1
• If FT4 is normal or elevated, this suggests primary hyperthyroidism or thyrotoxicosis 1

For TSH <0.1 mIU/L

• Repeat TSH measurement within 4 weeks along with FT4 and total T3 or FT3 1
• Shorten this interval if patient has cardiac symptoms, atrial fibrillation, or signs of hyperthyroidism 1
• T3 measurement is particularly helpful in highly symptomatic patients with minimal FT4 elevations, as T3 thyrotoxicosis can occur with normal FT4 1, 2
• The likelihood of detecting clinically significant T3 thyrotoxicosis increases substantially when TSH <0.01 μIU/mL (27.6% positive rate) 3

Additional Workup After Confirming Hyperthyroidism

Once biochemical hyperthyroidism is confirmed (low TSH with elevated FT4 and/or FT3):

• TSH receptor antibodies (TRAb) if clinical features suggest Graves' disease, such as ophthalmopathy or T3 toxicosis 1, 2
• Thyroid peroxidase antibodies (TPO) to assess for autoimmune thyroid disease 2
• Radioactive iodine uptake and scan to distinguish between Graves' disease, toxic nodular goiter, and destructive thyroiditis 1, 2
• Thyroid ultrasonography for structural assessment, particularly if nodular disease is suspected 2

Critical Pitfalls to Avoid

• Never assume low TSH means hyperthyroidism without checking FT4—central hypothyroidism presents with low TSH and low FT4, requiring entirely different management including evaluation for adrenal insufficiency before thyroid hormone replacement 1
• In elderly patients, low TSH is often not associated with true hyperthyroidism, making FT4 and FT3 measurement essential 4
• Drawing both TSH and FT4 is especially important when patients are symptomatic because in hypophysitis, TSH can remain within the reference range despite hypothyroidism 1
• Consider medication effects: patients on levothyroxine may have iatrogenic suppression, and drugs like amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors can cause thyroid dysfunction 2
• In patients on antithyroid drugs for Graves' disease, TSH may remain low for months after achieving euthyroid status, while FT4 may drop below normal with T3 remaining elevated—making T3 measurement crucial for accurate assessment 5

Context-Specific Considerations

• In immune checkpoint inhibitor therapy patients: Monitor TSH every 4-6 weeks routinely, and always measure both TSH and FT4 for symptomatic patients, as thyroiditis commonly progresses from thyrotoxicosis to hypothyroidism 1
• In pregnancy or with suspected nonthyroidal illness: Free hormone assays are essential as total hormone levels are unreliable due to binding protein alterations 6