What is the appropriate management for a 16-year-old female with a normal TSH (Thyroid-Stimulating Hormone) level and an elevated free T4 (Thyroxine) level?

Elevated Free T4 with Normal TSH in a 16-Year-Old Female

Immediate Assessment: Rule Out Assay Interference First

The most likely explanation for a normal TSH (2.180 mIU/L) with elevated free T4 (1.64, above normal range) in an otherwise healthy adolescent is laboratory assay interference, not true thyroid disease. This pattern occurs in approximately 3.3% of thyroid function tests and requires systematic evaluation before any treatment consideration 1.

Critical First Steps

• Repeat thyroid function tests using a different laboratory platform/assay method to confirm the elevated free T4 2, 3. Discrepant thyroid hormone measurements using two different immunoassay methods strongly suggest analytical interference rather than true thyroid dysfunction 2.

• Measure total T4 and thyroid-binding globulin (TBG) to distinguish between true hyperthyroxinemia and assay interference 2, 4. If total T4 is elevated with normal TBG, this suggests familial dysalbuminemic hyperthyroxinemia (FDH) 2, 4.

• Obtain a detailed medication and supplement history, as certain substances can interfere with free T4 assays 1, 3.

Differential Diagnosis for Normal TSH with Elevated Free T4

Most Common Causes in Adolescents

1. Laboratory assay interference (most common) - occurs in 3.3% of combined TSH/free T4 measurements 1

   • Heterophilic antibodies interfering with immunoassays 3
   • Anti-thyroid antibodies (anti-TPO, anti-Tg) causing assay interference 3

2. Familial dysalbuminemic hyperthyroxinemia (FDH) - inherited condition with mutant albumin that binds T4 excessively 2, 4

   • Characterized by elevated total T4, spuriously elevated free T4, normal TBG, and normal TSH 2, 4
   • Patients remain clinically euthyroid 4
   • Confirmed by ALB gene sequencing showing R218H or similar variants 2

3. Early/evolving thyroiditis - particularly if transitioning between phases 5

   • Silent thyroiditis can present with transient biochemical abnormalities 5
   • Would expect symptoms of hyperthyroidism if clinically significant 5

Management Algorithm

If Patient is Clinically Euthyroid (No Symptoms)

No treatment is indicated. The management priority is diagnostic clarification, not intervention 4.

1. Repeat testing on different platform within 2-4 weeks 2, 3

   • If free T4 normalizes on different assay: confirms interference, no further action needed 3
   • If free T4 remains elevated on different assay: proceed to step 2

2. Measure total T4, TBG, and consider anti-thyroid antibodies 2, 4

   • Elevated total T4 + normal TBG + normal TSH = likely FDH 2, 4
   • Normal total T4 despite elevated free T4 = assay interference 3

3. If FDH suspected, check family members for similar pattern 4

   • FDH is inherited; family screening helps confirm diagnosis 4
   • No treatment required as patients remain euthyroid 4

If Patient Has Hyperthyroid Symptoms

• Check TSH receptor antibodies if clinical features suggest Graves' disease 5
• Monitor with repeat thyroid function tests every 2-3 weeks to track evolution 5
• Consider beta-blockers for symptomatic relief if moderately symptomatic 5
• Refer to endocrinology if hyperthyroidism persists beyond 6 weeks 5

Critical Pitfalls to Avoid

• Never initiate antithyroid medication based solely on elevated free T4 with normal TSH without confirming true hyperthyroidism 2. The case report describes a patient who developed profound hypothyroidism (TSH 138 mIU/L) from low-dose propylthiouracil when the elevated free T4 was actually due to FDH 2.

• Do not assume thyroid disease without clinical correlation 3. A normal TSH with elevated free T4 in a clinically euthyroid patient almost always represents assay interference or FDH, not true hyperthyroidism 1, 4.

• Avoid over-testing or treating based on a single discordant result 1. In one study, when medical records were thoroughly reviewed, a causative factor for the discordant results was identified in 30.9% of cases 1.

• TSH remains the most reliable marker when assay interference is present 2. When autoimmune thyroid disease coexists with FDH, TSH levels are the most reliable biochemical marker of thyroid status 2.

When to Refer to Endocrinology

• Persistent elevation of free T4 on multiple platforms with normal TSH and unclear etiology 5
• Development of hyperthyroid symptoms with evolving thyroid dysfunction 5
• Suspected FDH requiring genetic confirmation 2
• Any consideration of antithyroid medication in this clinical scenario 2

Bottom Line for This 16-Year-Old

This patient requires repeat testing on a different assay platform, measurement of total T4 and TBG, and clinical assessment for hyperthyroid symptoms—but no treatment at this time. The combination of normal TSH with isolated elevated free T4 in a presumably asymptomatic adolescent most likely represents laboratory interference or FDH, both of which require no intervention 1, 4. TSH is the most sensitive test for thyroid dysfunction with sensitivity above 98% and specificity greater than 92% 6, and a normal TSH of 2.180 mIU/L strongly argues against clinically significant thyroid disease 6.