What target serum TSH range should be aimed for in a patient with primary hypothyroidism treated with levothyroxine?

Target TSH for Hypothyroid Patients on Levothyroxine

For adults with primary hypothyroidism treated with levothyroxine, target a serum TSH of 0.5–4.5 mIU/L with normal free T4 levels. 1, 2

Standard TSH Target Range

The goal of levothyroxine therapy is to normalize TSH into the reference range of 0.5–4.5 mIU/L, which represents the 2.5th to 97.5th percentile in disease-free populations. 1 This target applies to the vast majority of patients with primary hypothyroidism and ensures adequate thyroid hormone replacement while avoiding the risks of both under- and overtreatment.

• Aim for TSH in the lower half of the normal range (0.5–2.5 mIU/L) for optimal symptom control in most patients, as this more closely approximates the physiologic set point for many individuals 1, 3
• Maintain normal free T4 levels alongside normalized TSH to confirm adequate peripheral thyroid hormone availability 1, 2

Age-Adjusted Considerations

TSH reference ranges shift upward with advancing age, requiring modified targets in elderly patients. 1, 4

• For patients over 70–80 years, slightly higher TSH targets (up to 5–6 mIU/L) may be acceptable to reduce the risk of overtreatment-related complications including atrial fibrillation and fractures 1, 4
• The upper limit of normal TSH reaches approximately 7.5 mIU/L in patients over age 80, reflecting physiologic age-related changes 1, 4
• Approximately 12% of individuals ≥80 years have TSH >4.5 mIU/L without underlying thyroid disease, underscoring the need for age-adjusted interpretation 1

Special Populations Requiring Different Targets

Thyroid Cancer Patients

TSH targets in thyroid cancer survivors depend on risk stratification and treatment response, often requiring intentional suppression below the normal range. 1, 5

• Low-risk patients with excellent response: TSH 0.5–2.0 mIU/L 1
• Intermediate-to-high-risk patients with biochemical incomplete response: TSH 0.1–0.5 mIU/L 1
• Structural incomplete response (any risk level): TSH <0.1 mIU/L 1
• Always consult with the treating endocrinologist before adjusting levothyroxine in thyroid cancer patients, as intentional TSH suppression may be required 1

Pregnant Women

Pregnant women with hypothyroidism require trimester-specific TSH targets, ideally <2.5 mIU/L in the first trimester. 1, 6, 2

• Maintain serum TSH within trimester-specific reference ranges throughout pregnancy 6
• Monitor TSH every 4 weeks during pregnancy until stable, then at minimum once per trimester 6
• Levothyroxine requirements typically increase by 25–50% during pregnancy, necessitating proactive dose adjustments 1

Central (Secondary) Hypothyroidism

In central hypothyroidism, TSH cannot be used as a reliable monitoring parameter; instead, target free T4 in the upper half of the normal range. 6, 2

• Monitor serum free T4 levels and maintain in the upper half of the normal range 6
• TSH levels are inappropriately normal or low in central hypothyroidism despite inadequate thyroid hormone, making TSH an unreliable marker 1

Monitoring Protocol to Achieve Target

Check TSH and free T4 every 6–8 weeks after any dose adjustment until the target range is reached. 1, 2, 3

• This 6–8 week interval represents the time needed for levothyroxine to reach steady-state concentrations 1, 5
• Adjust levothyroxine dose by 12.5–25 mcg increments based on TSH response, using smaller increments (12.5 mcg) in elderly patients or those with cardiac disease 1, 5
• Once a stable dose is established with TSH in target range, monitor TSH every 6–12 months or sooner if clinical status changes 1, 6, 2

Critical Risks of Missing the Target

Overtreatment (TSH <0.5 mIU/L)

Approximately 25% of patients on levothyroxine are unintentionally overtreated with suppressed TSH, significantly increasing morbidity and mortality risks. 1, 2, 4

• TSH suppression <0.1 mIU/L increases atrial fibrillation risk 3–5-fold, especially in patients ≥60 years 1
• Prolonged TSH suppression causes accelerated bone loss and increases fracture risk, particularly in postmenopausal women 1
• All-cause mortality increases up to 2.2-fold and cardiovascular mortality up to 3-fold in individuals >60 years with TSH <0.5 mIU/L 1
• If TSH falls below 0.1 mIU/L, reduce levothyroxine dose by 25–50 mcg immediately 1, 3
• For TSH 0.1–0.45 mIU/L, decrease dose by 12.5–25 mcg, especially in elderly or cardiac patients 1

Undertreatment (TSH >4.5 mIU/L)

Persistent TSH elevation above the target range indicates inadequate replacement and carries cardiovascular and metabolic risks. 1

• TSH >10 mIU/L is associated with cardiac dysfunction (delayed relaxation, reduced cardiac output), adverse lipid profiles (elevated LDL cholesterol), and ~5% annual risk of progression to overt hypothyroidism 1, 2
• Even TSH 4.5–10 mIU/L may cause persistent hypothyroid symptoms and adverse cardiovascular effects in some patients 1
• Increase levothyroxine by 12.5–25 mcg when TSH remains elevated above target 1

Common Pitfalls in Achieving Target TSH

• Adjusting doses too frequently before reaching steady state—always wait 6–8 weeks between adjustments 1
• Failing to check free T4 alongside TSH during titration, which can help interpret discordant results 1, 2
• Not recognizing factors that interfere with levothyroxine absorption (iron, calcium, proton pump inhibitors taken within 4 hours) or increase requirements (pregnancy, malabsorption, certain medications) 1, 7
• Overlooking transient causes of TSH elevation (acute illness, recovery from thyroiditis, iodine exposure) that may resolve without dose adjustment 1
• Using population reference ranges in elderly patients without considering age-adjusted norms 1, 4