What is the diagnosis and treatment for a patient with elevated Free Triiodothyronine (FT3), normal Free Thyroxine (FT4), and normal Thyroid-Stimulating Hormone (TSH) levels?

Elevated FT3 with Normal FT4 and TSH: T3 Toxicosis Until Proven Otherwise

This pattern—isolated elevation of FT3 with normal FT4 and normal TSH—most commonly represents T3 toxicosis, a variant of hyperthyroidism where the thyroid gland selectively overproduces triiodothyronine. 1

Diagnostic Approach

Confirm the Finding First

• Repeat thyroid function tests (TSH, FT4, FT3) in 2-4 weeks to confirm the pattern, as approximately 30-60% of single abnormal thyroid values normalize spontaneously 2
• Measure total T3 (TT3) alongside FT3 to validate the elevation, as FT3 immunoassays can exhibit significant inter-assay variation and false elevations 3, 4
• If TT3 is normal while FT3 remains elevated, this suggests an analytical artifact rather than true T3 toxicosis 4

Rule Out Assay Interference

• Consider switching to an alternative FT3 assay with different methodology (e.g., from Cobas to Architect or Liaison) if clinical presentation doesn't match laboratory findings 4
• Measure TT3 as a confirmatory test—if TT3 is within reference range while FT3 is elevated, this indicates assay interference rather than true hyperthyroidism 4
• Heterophilic antibodies can cause spurious FT3 elevations, though heterophilic blocking tubes may not always resolve this issue 4

Differential Diagnosis

Primary Causes of Isolated FT3 Elevation

T3 Toxicosis (Most Common)

• Accounts for approximately 5% of all hyperthyroidism cases 1
• Caused by selective T3 hypersecretion from toxic nodular goiter, toxic adenoma, or early Graves' disease 1
• TSH will be suppressed (<0.1 mIU/L) in true T3 toxicosis, not normal—if TSH is truly normal, reconsider the diagnosis 1

Exogenous T3 Administration

• Patients taking liothyronine (Cytomel) or desiccated thyroid preparations will have elevated FT3 5
• Review medication history carefully, including over-the-counter supplements and compounded preparations 5

Thyroiditis (Transient Phase)

• Subacute thyroiditis or painless postpartum thyroiditis can cause transient elevations in FT3, FT4, and TT3 during the thyrotoxic phase 5
• These elevations are typically accompanied by elevated FT4 as well, making isolated FT3 elevation less common 5

Analytical Artifacts

Assay-Specific Interference

• Different FT3 immunoassays show only moderate correlation (r = 0.589-0.790), with significant inter-assay variation 3
• Some assays are more prone to interference from binding proteins, heterophilic antibodies, or other serum factors 3, 4
• If clinical suspicion is low and FT3 is only mildly elevated, measure TT3 to confirm 4

Clinical Algorithm

Step 1: Verify TSH is Truly Normal

• If TSH is between 0.1-0.45 mIU/L (low-normal), this suggests early hyperthyroidism with selective T3 production 6
• Repeat TSH with FT4 and FT3 in 3-6 weeks 2
• If TSH is solidly within 0.5-4.5 mIU/L range, proceed to Step 2 2

Step 2: Confirm FT3 Elevation with TT3

• Measure total T3 (TT3) on the same sample 4
• If TT3 is normal, the elevated FT3 is likely an assay artifact—no treatment needed 4
• If TT3 is also elevated, proceed to Step 3 4

Step 3: Assess for Hyperthyroid Symptoms

• Evaluate for tachycardia, tremor, heat intolerance, weight loss, anxiety, or palpitations 1
• If symptomatic with confirmed elevated FT3 and TT3, treat as T3 toxicosis even if TSH appears normal 1
• Obtain thyroid ultrasound and radioactive iodine uptake scan to identify nodular disease 1

Step 4: Consider Medication History

• Review all thyroid medications, including liothyronine, desiccated thyroid, and compounded preparations 5
• Check for recent amiodarone use, which can transiently elevate thyroid hormones 5
• If taking exogenous T3, reduce or discontinue and recheck in 6-8 weeks 2

Step 5: Monitor if Asymptomatic with Borderline Values

• If patient is completely asymptomatic, TSH is solidly normal (1.0-3.0 mIU/L), and FT3 is only mildly elevated, repeat testing in 3 months 2
• Consider switching to a different FT3 assay to rule out method-specific interference 4
• Do not initiate antithyroid treatment based on isolated FT3 elevation without confirming with TT3 and clinical correlation 4

Critical Pitfalls to Avoid

• Never treat based on a single elevated FT3 value without confirming with TT3, as FT3 assays have significant inter-method variability and are prone to interference 3, 4
• Do not assume T3 toxicosis if TSH is truly normal (>0.5 mIU/L)—true T3 toxicosis suppresses TSH below 0.1 mIU/L 1
• Avoid missing exogenous T3 administration by failing to obtain a complete medication and supplement history 5
• Do not overlook transient thyroiditis, which can cause temporary hormone elevations that resolve spontaneously within weeks to months 5
• If clinical presentation doesn't match laboratory findings, always measure TT3 and consider assay interference before initiating treatment 4

When to Refer to Endocrinology

• Confirmed T3 toxicosis with suppressed TSH (<0.1 mIU/L) and elevated FT3/TT3 requires endocrinology referral for radioactive iodine uptake scan and definitive treatment 1
• Discordant results (elevated FT3 with normal TT3 and normal TSH) that persist despite repeat testing warrant endocrinology consultation to determine if specialized testing is needed 4
• Patients with thyroid nodules or goiter on examination should be referred for ultrasound and possible fine-needle aspiration 7