When should subclinical hypothyroidism be treated considering TSH level, age, symptoms, thyroid peroxidase antibodies, pregnancy, goitre, cardiovascular disease, or dyslipidaemia?

When to Treat Subclinical Hypothyroidism

Treat subclinical hypothyroidism immediately if TSH is persistently >10 mIU/L, regardless of age or symptoms, because this threshold carries approximately 5% annual risk of progression to overt hypothyroidism and is associated with cardiac dysfunction and adverse lipid profiles. 1, 2

Confirm the Diagnosis First

Before making any treatment decision, always confirm the elevated TSH with repeat testing after 2-3 months, as 30-60% of initially elevated TSH values normalize spontaneously 1, 2. Measure both TSH and free T4 on repeat testing to distinguish subclinical (normal free T4) from overt (low free T4) hypothyroidism 1.

Treatment Algorithm Based on TSH Level

TSH >10 mIU/L with Normal Free T4

Initiate levothyroxine therapy immediately, regardless of symptoms or age (except in patients >80-85 years). 1, 2, 3

• This TSH level carries 5% annual progression risk to overt hypothyroidism 1, 4
• Treatment may improve symptoms and lower LDL cholesterol, though mortality benefit is unproven 1, 2
• Evidence quality is rated as "fair" by expert panels 1

TSH 4.5-10 mIU/L with Normal Free T4

Do NOT routinely treat asymptomatic patients in this range, as randomized controlled trials show no symptomatic benefit from levothyroxine 1, 2, 5. Instead, monitor thyroid function tests every 6-12 months 1, 2.

However, TREAT in these specific situations:

Pregnancy or Planning Pregnancy (Absolute Indication)

• Treat any TSH elevation immediately in pregnant women or those planning pregnancy 1, 2, 4
• Target TSH <2.5 mIU/L in the first trimester 1
• Untreated subclinical hypothyroidism increases risk of preeclampsia, low birth weight, and potential neurodevelopmental effects in offspring 1

Positive Anti-TPO Antibodies

• Consider treatment if anti-TPO antibodies are positive, as this indicates autoimmune etiology with higher progression risk (4.3% vs 2.6% per year in antibody-negative individuals) 1, 2, 3

Symptomatic Patients

• Offer a 3-4 month trial of levothyroxine to symptomatic patients (fatigue, weight gain, cold intolerance, constipation) 1, 2, 3
• Clearly evaluate response after TSH normalizes 1, 3
• Discontinue levothyroxine if no symptom improvement after 3-4 months, as this likely represents placebo effect 1, 3

Cardiovascular Disease or Dyslipidaemia

• Consider treatment in younger patients (<65 years) with cardiovascular disease, as subclinical hypothyroidism is associated with increased coronary heart disease risk, particularly with TSH ≥10 mIU/L 6
• Treatment may reduce cardiovascular risk in this age group, though randomized trial evidence is lacking 6

Goitre

• Consider treatment if goitre is present, as this may indicate more significant thyroid dysfunction 2, 4

Age-Specific Considerations

Elderly Patients (>80-85 Years)

Generally avoid treatment in the oldest old with TSH ≤10 mIU/L, as treatment may be harmful rather than beneficial in this age group 3, 5. The upper limit of normal TSH shifts upward with age, reaching 7.5 mIU/L in patients over 80 5. Use a "wait-and-see" strategy with careful monitoring 3.

Younger Patients (<65-70 Years)

Treat more liberally in younger patients, especially those with TSH >10 mIU/L, as cardiovascular benefits may be greater and risks of progression higher 3, 6.

Critical Pre-Treatment Evaluation

Before initiating levothyroxine, always:

• Rule out adrenal insufficiency, especially in suspected central hypothyroidism, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 1, 4
• Measure anti-TPO antibodies to identify autoimmune etiology and predict progression risk 1, 2
• Review lipid profile, as subclinical hypothyroidism affects cholesterol levels 1, 2

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH value without confirmation, as transient elevations are common 1, 2
• Avoid overtreatment, which occurs in 14-21% of treated patients and increases risk for atrial fibrillation (3-5 fold), osteoporosis, fractures, and cardiovascular mortality 1, 2, 5
• Do not treat asymptomatic patients with TSH 4.5-10 mIU/L unless specific risk factors are present, as evidence shows no benefit 1, 2, 5
• Recognize that approximately 25% of patients on levothyroxine are unintentionally overtreated with suppressed TSH, increasing serious complication risks 1

Monitoring After Treatment Initiation

• Recheck TSH and free T4 every 6-8 weeks during dose titration 1
• Target TSH 0.4-2.5 mIU/L (lower half of reference range) for most adults 3, 7
• Once stable, monitor TSH annually or sooner if symptoms change 1, 3