Treatment of Subclinical Hypothyroidism
Treat subclinical hypothyroidism with levothyroxine when TSH is persistently >10 mIU/L regardless of symptoms, and consider treatment for TSH 4.5-10 mIU/L only in pregnant women, those planning pregnancy, or patients with positive TPO antibodies. 1, 2
Confirm the Diagnosis First
Before initiating any treatment, confirm the elevated TSH with repeat testing after 2 weeks to 3 months, as 30-60% of elevated TSH levels normalize spontaneously on repeat testing. 1, 2, 3 This critical step prevents unnecessary lifelong treatment for transient thyroid dysfunction. 1
Measure both TSH and free T4 to distinguish subclinical hypothyroidism (elevated TSH with normal free T4) from overt hypothyroidism (elevated TSH with low free T4). 1
Treatment Algorithm Based on TSH Level
TSH >10 mIU/L with Normal Free T4
Initiate levothyroxine therapy regardless of symptoms. 1, 2, 4 This threshold carries approximately 5% annual risk of progression to overt hypothyroidism and may prevent cardiovascular complications, improve symptoms, and lower LDL cholesterol. 1, 5
The evidence supporting treatment at this level is rated as "fair" by expert panels, but the potential benefits of preventing progression outweigh the risks of therapy. 1
TSH 4.5-10 mIU/L with Normal Free T4
Do not routinely treat, but monitor TSH every 6-12 months. 1, 2 Double-blinded randomized controlled trials show that treatment does not improve symptoms or cognitive function when TSH is less than 10 mIU/L. 3
However, treat in these specific situations:
- Pregnant women or women planning pregnancy (treat at any TSH elevation to prevent preeclampsia, low birth weight, and impaired fetal neurocognitive development) 1, 2, 6, 4
- Positive TPO antibodies (progression risk increases to 4.3% per year versus 2.6% in antibody-negative patients) 1, 2
- Symptomatic patients may receive a 3-4 month trial of therapy with clear evaluation of benefit 1, 2
Levothyroxine Dosing Strategy
For Patients <70 Years Without Cardiac Disease
Start with full replacement dose of approximately 1.6 mcg/kg/day. 1, 2, 7 A prospective randomized trial demonstrated this approach is safe and more cost-effective than gradual titration in cardiac asymptomatic patients. 7
For Patients >70 Years or With Cardiac Disease
Start with 25-50 mcg/day and titrate gradually by 12.5-25 mcg increments every 6-8 weeks. 1, 2, 4 This prevents exacerbation of cardiac symptoms and reduces risk of atrial fibrillation. 1
Monitoring Protocol
Check TSH and free T4 every 6-8 weeks during dose titration until target TSH of 0.5-2.0 mIU/L is achieved. 1, 2, 4 Once stable, monitor TSH every 6-12 months or if symptoms change. 1, 2
Critical Pitfalls to Avoid
Overtreatment occurs in 14-21% of treated patients and 25% are inadvertently maintained on doses sufficient to fully suppress TSH. 1, 2 This increases risk for atrial fibrillation (especially in elderly), osteoporosis, fractures, and cardiovascular mortality. 1, 4
Never treat based on a single elevated TSH value without confirmation testing, as this leads to unnecessary lifelong treatment. 1, 3
Do not treat elderly patients (>85 years) with TSH ≤10 mIU/L, as treatment may be harmful rather than beneficial in this population. 4, 3 TSH goals are age-dependent, with upper limit of normal being 7.5 mIU/L for patients over age 80. 3
In patients with suspected central hypothyroidism, always rule out adrenal insufficiency and start corticosteroids before levothyroxine to avoid precipitating adrenal crisis. 1, 4
Special Considerations for Pregnancy
Pregnant women require immediate treatment at any degree of TSH elevation. 1, 2, 6, 4 Levothyroxine requirements increase by 25-50% during pregnancy, so increase the weekly dosage by 30% (take one extra dose twice per week) as soon as pregnancy is confirmed. 6, 8 Monitor TSH every 6-8 weeks during pregnancy and adjust accordingly. 2, 6
Return to pre-pregnancy dose immediately after delivery, as postpartum TSH levels revert to preconception values. 6
When Treatment Fails to Improve Symptoms
If symptoms persist despite normalized TSH on levothyroxine monotherapy, reassess for poor compliance, malabsorption, drug interactions, or other causes of symptoms rather than adding triiodothyronine. 4, 8 Most patients with persistent symptoms have other underlying conditions causing their complaints, not inadequate thyroid replacement. 3, 5