When should subclinical hypothyroidism be treated in adults and children, considering TSH levels, symptoms, anti‑thyroid peroxidase antibodies, pregnancy, cardiovascular disease, dyslipidemia, goiter, rapid TSH rise, and growth or neurocognitive concerns?

Indications to Treat Subclinical Hypothyroidism

Treat subclinical hypothyroidism immediately when TSH is persistently >10 mIU/L, regardless of age or symptoms, as this threshold carries approximately 5% annual risk of progression to overt hypothyroidism and is associated with increased cardiovascular risk. 1

Confirm the Diagnosis First

Before initiating treatment, confirm the elevated TSH with repeat testing after 2-3 months, measuring both TSH and free T4, as 30-60% of elevated TSH levels normalize spontaneously on repeat testing. 1, 2 Exclude transient causes including:

• Recovery from acute illness or hospitalization 1
• Recent iodine exposure (e.g., CT contrast) 1
• Recovery phase from destructive thyroiditis 1
• Medications (dopamine, glucocorticoids, dobutamine) 3
• Laboratory interference from heterophilic antibodies 3

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L with Normal Free T4

Initiate levothyroxine therapy regardless of symptoms or age (except very elderly >80-85 years). 1, 2 This recommendation is supported by:

• Higher progression risk to overt hypothyroidism (~5% per year) 1
• Potential improvement in symptoms and LDL cholesterol 1
• Prevention of cardiovascular dysfunction and adverse lipid profiles 1
• Evidence quality 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. 1 Instead, monitor thyroid function tests every 6-12 months. 1 Randomized controlled trials found no improvement in symptoms with levothyroxine therapy in this population. 1

However, consider treatment in these specific situations:

Mandatory Treatment Indications:

• Pregnancy or planning pregnancy - Target TSH <2.5 mIU/L in first trimester to prevent preeclampsia, low birth weight, and neurodevelopmental effects in offspring 1, 4
• Women contemplating pregnancy - Treat any TSH elevation to decrease risk of pregnancy complications and impaired cognitive development 4

Strong Indications for Treatment:

• Positive anti-TPO antibodies - Progression risk increases to 4.3% per year versus 2.6% in antibody-negative individuals 1, 2, 4
• Age <65-70 years with symptoms - Consider 3-4 month trial of levothyroxine for fatigue, weight gain, cold intolerance, or constipation, with clear evaluation of benefit 1, 2
• Goiter present - Physical enlargement of thyroid gland warrants treatment consideration 1, 4
• Infertility - Treatment may improve fertility outcomes 4, 5

Additional Considerations:

• Cardiovascular disease or dyslipidemia - Younger patients (<70 years) with TSH ≥10 mIU/L have increased risk of coronary heart disease, heart failure, and cerebrovascular disease 6
• Rapid TSH rise - Progressive elevation over time suggests ongoing thyroid failure 1

Special Populations

Children and Adolescents

Treat subclinical hypothyroidism in children due to possible adverse effects on growth and neurocognitive development. 1, 5 Poor cognitive development is associated with untreated subclinical hypothyroidism in this population. 3

Elderly Patients (>80-85 years)

Avoid treatment for TSH ≤10 mIU/L in the oldest old. 2 Use a "wait-and-see" strategy with careful monitoring, as age-specific reference ranges shift upward (upper limit can reach 7.5 mIU/L in patients over 80). 1 Treatment should probably be avoided in those aged >85 years with TSH up to 10 mIU/L. 4

Patients on Immune Checkpoint Inhibitors

Consider treatment even for mild TSH elevation if fatigue or hypothyroid symptoms are present. 1 Thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy and 16% with combination immunotherapy. 1

Critical Safety Considerations

Before initiating levothyroxine, always rule out concurrent adrenal insufficiency, especially in suspected central hypothyroidism or hypophysitis. 1 Starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1 In patients with coexisting conditions, initiate corticosteroid replacement at least 1 week before starting thyroid hormone. 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 2
• Once stable, monitor TSH annually or sooner if symptoms change 1

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH value - 30-60% normalize spontaneously 1
• Avoid overtreatment - Occurs in 14-21% of treated patients and increases risk for atrial fibrillation, osteoporosis, fractures, and cardiac complications 1
• Do not miss transient thyroiditis - May lead to unnecessary lifelong treatment 1
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism 1