How should I manage a patient with elevated thyroid‑stimulating hormone (TSH), normal free triiodothyronine (FT3) and free thyroxine (FT4), who has symptoms of hypothyroidism?

Management of Elevated TSH with Normal FT3/FT4 and Hypothyroid Symptoms

Initiate levothyroxine therapy for symptomatic patients with elevated TSH, even when free T3 and free T4 are normal, as this represents subclinical hypothyroidism that warrants treatment to prevent progression and improve quality of life. 1

Confirm the Diagnosis First

Before starting treatment, you must confirm the TSH elevation is persistent and not transient:

• Repeat TSH measurement after 3-6 weeks along with free T4, as 30-60% of elevated TSH levels normalize spontaneously on repeat testing 1
• Exclude transient causes: recent illness, recovery from thyroiditis, iodine exposure (CT contrast), or medications that affect thyroid function 1
• Measure anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk to overt hypothyroidism (4.3% vs 2.6% annually in antibody-negative patients) 1

Treatment Algorithm Based on TSH Level

TSH >10 mIU/L with normal free T4:

• Treat immediately with levothyroxine regardless of symptoms 1
• This threshold carries ~5% annual risk of progression to overt hypothyroidism 1
• Treatment may improve symptoms and lower LDL cholesterol 1

TSH 4.5-10 mIU/L with normal free T4:

• Treat if the patient has symptoms (fatigue, weight gain, cold intolerance, constipation, dry skin, hair loss) 1, 2
• Treat if positive anti-TPO antibodies (higher progression risk) 1
• Treat if pregnant or planning pregnancy (any TSH elevation warrants treatment to prevent adverse pregnancy outcomes) 1
• Consider a 3-4 month trial of levothyroxine with clear evaluation of symptom improvement 1

Levothyroxine Dosing Strategy

For patients <70 years without cardiac disease:

• Start with full replacement dose of approximately 1.6 mcg/kg/day 1, 3
• Take on empty stomach, 30-60 minutes before breakfast 3
• Titrate by 12.5-25 mcg increments every 6-8 weeks based on TSH response 1, 3

For patients >70 years OR with cardiac disease:

• Start with lower dose of 25-50 mcg/day 1, 3
• Titrate more slowly every 6-8 weeks to avoid cardiac complications 1, 3
• Rapid normalization can unmask cardiac ischemia or precipitate arrhythmias 1

Monitoring Protocol

• Recheck TSH and free T4 every 6-8 weeks during dose titration until TSH normalizes to 0.5-4.5 mIU/L 1, 3
• Once stable, monitor TSH every 6-12 months or sooner if symptoms change 1
• Target TSH within reference range (0.5-4.5 mIU/L) with normal free T4 1, 3

Critical Safety Considerations

Before starting levothyroxine, rule out adrenal insufficiency:

• In suspected central hypothyroidism or patients with autoimmune disease, check morning cortisol and ACTH 1, 4
• Always start corticosteroids before thyroid hormone if adrenal insufficiency is present, as thyroid hormone can precipitate life-threatening adrenal crisis 1, 4

Common Pitfalls to Avoid

• Don't treat based on single elevated TSH without confirmation testing 1
• Don't ignore symptoms just because free T4 is normal—subclinical hypothyroidism can cause significant symptoms 1, 2
• Don't overtreat: Approximately 25% of patients on levothyroxine are unintentionally maintained on excessive doses, increasing risks for atrial fibrillation, osteoporosis, and cardiac complications 1
• Don't assume hypothyroidism is permanent without reassessment—some cases are transient (recovery phase thyroiditis) 1

Special Populations

Pregnant women or planning pregnancy:

• Treat any TSH elevation immediately, targeting TSH <2.5 mIU/L in first trimester 1
• Untreated hypothyroidism increases risk of preeclampsia, low birth weight, and neurodevelopmental effects in offspring 1

Elderly patients:

• Use more conservative dosing (25-50 mcg starting dose) 1, 3
• Monitor closely for cardiac complications and atrial fibrillation 1

Why Symptoms Persist Despite Normal Free Hormones

The presence of symptoms with elevated TSH but normal free T3/T4 reflects:

• Early thyroid gland failure where compensatory TSH elevation maintains normal circulating hormone levels temporarily 2
• Tissue-level hypothyroidism where cellular thyroid hormone action is impaired despite normal serum levels 5
• Metabolic consequences including delayed relaxation, abnormal cardiac output, and lipid abnormalities that cause fatigue, cold intolerance, and weight gain 1, 5, 2

Treatment with levothyroxine addresses the underlying thyroid insufficiency and typically resolves symptoms within 6-8 weeks of achieving target TSH 1, 2