Treatment for Elevated TSH
Initiate levothyroxine therapy for patients with TSH persistently >10 mIU/L or for symptomatic patients with any degree of TSH elevation. 1
Initial Assessment Before Treatment
Before starting therapy, confirm the elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize spontaneously on repeat testing 1, 2. This critical step prevents unnecessary lifelong treatment for transient thyroiditis 1.
Measure both TSH and free T4 simultaneously to distinguish between:
- Subclinical hypothyroidism: elevated TSH with normal free T4 1
- Overt hypothyroidism: elevated TSH with low free T4 1, 3
Treatment Algorithm Based on TSH Levels
TSH >10 mIU/L
Start levothyroxine regardless of symptoms 1. This threshold carries approximately 5% annual risk of progression to overt hypothyroidism and warrants treatment to prevent complications including heart failure, cardiovascular dysfunction, and metabolic derangements 1, 3.
TSH 4.5-10 mIU/L
Treatment decisions require more nuance 1:
- Treat if: symptomatic (fatigue, weight gain, cold intolerance, constipation), positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk), pregnant or planning pregnancy, or presence of goiter 1, 4
- Monitor without treatment if: asymptomatic, antibody-negative, and no pregnancy plans—recheck TSH every 6-12 months 1
Special Population: Pregnancy
Treat at any TSH elevation in pregnant women or those planning pregnancy, as subclinical hypothyroidism is associated with preeclampsia, low birth weight, and potential neurodevelopmental effects in offspring 1, 5. Pre-pregnancy levothyroxine doses typically increase by 25-50% during pregnancy 5.
Levothyroxine Dosing Strategy
Initial Dosing
For patients <70 years without cardiac disease: Start with full replacement dose of approximately 1.6 mcg/kg/day 1, 5, 4
For patients >70 years OR with cardiac disease/multiple comorbidities: Start with 25-50 mcg/day and titrate gradually 1, 2, 6. Elderly patients and those with coronary artery disease risk cardiac decompensation even with therapeutic doses 1.
Dose Adjustments
Increase by 12.5-25 mcg increments based on current dose 1. Use smaller increments (12.5 mcg) for elderly or cardiac patients; larger increments (25 mcg) may be appropriate for younger, healthier patients 1. Avoid excessive increases that could cause iatrogenic hyperthyroidism 1.
Monitoring Protocol
During titration: Check TSH every 6-8 weeks after any dose change 1, 5, 6. Free T4 can help interpret ongoing abnormal TSH levels, as TSH may take longer to normalize 1.
Once stable: Monitor TSH every 6-12 months or when symptoms change 1, 5. Target TSH within reference range of 0.5-4.5 mIU/L 1, 4.
For pregnant patients: Check TSH every 4 weeks until stable, then each trimester at minimum 5.
Critical Pitfalls to Avoid
Never start levothyroxine before ruling out adrenal insufficiency in patients with suspected central hypothyroidism, as this can precipitate adrenal crisis 1. Corticosteroids must be initiated first 1.
Avoid overtreatment: Approximately 25% of patients on levothyroxine are unintentionally maintained on doses that fully suppress TSH 1. Even slight overdose increases risk for atrial fibrillation (especially in elderly), osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 1, 2, 4.
Do not treat based on single elevated TSH: Confirm with repeat testing to avoid treating transient elevations 1, 2.
Recognize drug interactions: Iron, calcium, and enzyme inducers reduce levothyroxine efficacy 2. Take levothyroxine on empty stomach 2.
When TSH Becomes Low on Therapy
If TSH becomes suppressed (<0.1 mIU/L) during treatment, this suggests overtreatment or recovery of thyroid function 1. Reduce dose by 25-50 mcg and recheck in 6-8 weeks 1. The exception is thyroid cancer patients requiring intentional TSH suppression—consult endocrinology for target levels 1.