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

Management of Elevated FT3, Elevated FT4, and Normal TSH

Immediate Diagnostic Consideration

This biochemical pattern (elevated FT3 and FT4 with normal TSH) is highly unusual and requires confirmation with repeat testing before initiating treatment, as it does not represent typical primary hyperthyroidism. 1

The most common causes include:

• Assay interference (heterophile antibodies, biotin supplementation) 1, 2
• TSH-secreting pituitary adenoma (TSHoma) - rare but important 1, 2
• Thyroid hormone resistance syndrome 1, 2
• Recovery phase from non-thyroidal illness 1
• Medication interference with laboratory testing 1, 2

Initial Management Algorithm

Step 1: Confirm Results and Assess Clinical Context

• Repeat thyroid function tests in 3-6 weeks, as 30-60% of abnormal results normalize spontaneously 1
• Review medication history for drugs affecting thyroid function or assays (amiodarone, biotin, heparin, tyrosine kinase inhibitors, immune checkpoint inhibitors) 1, 3, 2
• Evaluate for recent iodine exposure (CT contrast) that can transiently affect results 4
• Assess for non-thyroidal illness, as severe illness can cause discordant thyroid function tests 2

Step 2: Rule Out Assay Interference

• Screen for biotin supplementation and discontinue 72 hours before retesting 2
• Consider heterophile antibody interference if results remain discordant 2
• Request alternative assay methods from the laboratory if interference is suspected 2

Step 3: Clinical Assessment for True Hyperthyroidism

If hyperthyroid symptoms are present (tachycardia, tremor, heat intolerance, weight loss):

• Initiate beta-blocker therapy (atenolol or propranolol) for symptomatic relief while awaiting definitive diagnosis 1
• Monitor thyroid function tests every 2-3 weeks initially to detect transition to typical hyperthyroid pattern 1

Step 4: Specialized Testing if Pattern Persists

If elevated FT3/FT4 with normal TSH persists on repeat testing:

• Measure TSH-receptor antibodies to evaluate for Graves' disease 3
• Check thyroid peroxidase antibodies for autoimmune etiology 1, 3
• Obtain thyroid ultrasound to assess for nodular disease 3
• Consider thyroid scintigraphy if nodular disease is present 3, 5
• Refer to endocrinology for evaluation of TSH-secreting pituitary adenoma or thyroid hormone resistance syndrome 1, 2

Critical Management Principles

What NOT to Do

Do not initiate antithyroid drugs (methimazole or propylthiouracil) when both TSH and thyroid hormones are elevated, as this pattern does not represent typical primary hyperthyroidism. 1 Starting antithyroid medication without proper diagnosis risks:

• Unnecessary exposure to serious adverse effects (agranulocytosis, hepatotoxicity, vasculitis) 6, 7
• Masking the underlying diagnosis 1
• Inappropriate treatment if TSHoma or resistance syndrome is present 2

Symptomatic Management

For patients with hyperthyroid symptoms while awaiting diagnosis:

• Beta-blockers are safe and effective for controlling tachycardia, tremor, and anxiety 1
• Propranolol 10-40 mg three times daily or atenolol 25-100 mg once daily 1
• Beta-blockers do not interfere with diagnostic workup 1

Special Considerations

Pregnancy Context

If this pattern occurs in pregnancy:

• Normal TSH in pregnancy may be lower than non-pregnant reference ranges 8
• Hyperemesis gravidarum can cause biochemical hyperthyroidism (low TSH, elevated FT4/FT3) that rarely requires treatment 8
• Avoid radioiodine imaging in pregnant women 8
• Consult maternal-fetal medicine if true hyperthyroidism is confirmed 8

Monitoring Protocol

• Recheck TSH, FT4, and FT3 in 4-6 weeks after initial abnormal results 1
• If pattern persists, endocrinology referral is mandatory 1
• Monitor for symptom development in either direction (hypothyroid or hyperthyroid) 1
• Once diagnosis is established, repeat testing every 6-12 months or with symptom changes 1

Common Pitfalls to Avoid

• Treating based on single abnormal test without confirmation 4, 1
• Assuming primary hyperthyroidism without considering alternative diagnoses 1, 2
• Failing to check for medication/supplement interference (especially biotin) 2
• Initiating antithyroid drugs before establishing definitive diagnosis 1
• Missing TSH-secreting pituitary adenoma, which requires entirely different management (transsphenoidal surgery, not antithyroid drugs) 2