Guidelines for Treating Hypothyroidism
Initial Levothyroxine Dosing
Healthy Adults Without Cardiac Disease (<70 years)
Start with full replacement dose of 1.6 mcg/kg/day in otherwise healthy adults under 70 years without cardiac disease. 1, 2 This approach is safe, reaches euthyroidism faster, and is more cost-effective than gradual titration. 3 A prospective randomized trial demonstrated no cardiac events occurred with full-dose initiation in cardiac-asymptomatic patients, with euthyroidism achieved significantly faster (13 patients at 4 weeks vs. 1 patient with low-dose approach). 3
Older Adults (≥65-70 years) or Coronary Artery Disease
For patients over 70 years or with known/suspected cardiac disease, start at 25-50 mcg/day and titrate gradually by 12.5-25 mcg increments every 6-8 weeks. 1, 2, 4 Rapid normalization can unmask or worsen cardiac ischemia, precipitate arrhythmias, or trigger heart failure in this population. 1 Elderly patients with underlying coronary disease face increased risk of cardiac decompensation even with therapeutic levothyroxine doses. 1
Pregnant Women
Women with hypothyroidism who become pregnant should immediately increase their levothyroxine dose by 25-50% (approximately 2 extra doses per week). 1, 4 Levothyroxine requirements typically increase during early pregnancy, and inadequate treatment is associated with preeclampsia, low birth weight, and potential neurodevelopmental deficits in offspring. 1 Target TSH <2.5 mIU/L in the first trimester. 1 Monitor TSH every 4 weeks during pregnancy until stable, then at minimum once per trimester. 1
Subclinical Hypothyroidism Treatment
TSH >10 mIU/L with Normal Free T4
Initiate levothyroxine therapy regardless of symptoms when TSH persistently exceeds 10 mIU/L. 1, 5, 4 This threshold carries approximately 5% annual risk of progression to overt hypothyroidism and is associated with cardiac dysfunction (delayed relaxation, abnormal cardiac output), adverse lipid profiles (elevated LDL cholesterol), and increased cardiovascular risk. 1 Evidence quality is rated as "fair" by expert panels. 1
TSH 4.5-10 mIU/L with Normal Free T4
Routine levothyroxine treatment is NOT recommended for asymptomatic patients with TSH 4.5-10 mIU/L and normal free T4. 1, 4 Randomized controlled trials found no improvement in symptoms with levothyroxine therapy in this range. 1 However, consider treatment in specific situations:
- Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation may benefit from a 3-4 month trial with clear evaluation of benefit 1
- Pregnant women or those planning pregnancy should be treated for any TSH elevation 1, 5
- Positive anti-TPO antibodies predict higher progression risk (4.3% vs 2.6% annually in antibody-negative individuals) 1, 5
- Presence of goiter or infertility 1, 5
Important: Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously. 1
Severe Presentations: Myxedema Coma
Myxedema coma requires immediate aggressive treatment with intravenous levothyroxine and supportive care. 4 Early recognition and appropriate treatment are essential for this life-threatening presentation. 4 Critical safety consideration: Before initiating levothyroxine in suspected central hypothyroidism or concurrent adrenal insufficiency, start corticosteroids (hydrocortisone 20 mg morning, 10 mg afternoon) at least one week prior to thyroid hormone replacement to prevent life-threatening adrenal crisis. 1, 5
Monitoring TSH
During Dose Titration
Monitor TSH every 6-8 weeks while adjusting levothyroxine dose. 1, 2 This interval represents the time needed to reach steady state. 1 Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize. 1
After Stabilization
Once adequately treated with stable TSH (0.5-4.5 mIU/L), repeat testing every 6-12 months or if symptoms change. 1, 2 For pregnant women with pre-existing hypothyroidism, check TSH every trimester after dosage stabilization. 1
Dose Adjustments
Adjust levothyroxine by 12.5-25 mcg increments based on current dose and patient characteristics. 1 Use smaller increments (12.5 mcg) for elderly patients or those with cardiac disease; larger adjustments (25 mcg) may be appropriate for younger patients without cardiac disease. 1 Avoid excessive dose increases that could lead to iatrogenic hyperthyroidism. 1
Alternative Therapy Options
Levothyroxine monotherapy remains the standard of care for hypothyroidism treatment. 2, 5, 6, 7 Adding triiodothyronine (T3) is not recommended, even in patients with persistent symptoms and normal TSH levels. 4 While 15 clinical trials have evaluated combined levothyroxine plus liothyronine treatment, with some showing patient preference for combination therapy, clear advantages have not been demonstrated. 7 Until definitive benefits are proven, levothyroxine alone should remain the treatment of choice. 7
Critical Pitfalls to Avoid
Overtreatment occurs in 14-21% of treated patients and approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH. 1 This increases risk for:
- Atrial fibrillation (3-5 fold increased risk, especially in patients ≥45 years) 1
- Osteoporosis and fractures (particularly in postmenopausal women >65 years with TSH ≤0.1 mIU/L) 1
- Abnormal cardiac output and ventricular hypertrophy 1
- Increased cardiovascular mortality 1
If TSH falls below 0.1 mIU/L, reduce levothyroxine dose by 25-50 mcg immediately. 1 For TSH 0.1-0.45 mIU/L, decrease dose by 12.5-25 mcg, particularly in elderly or cardiac patients. 1
Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism, as this can precipitate adrenal crisis. 1, 5
Do not treat based on a single elevated TSH value without confirmation, as transient elevations are common. 1 Recognize transient causes including acute illness, recovery from thyroiditis, recent iodine exposure, or certain medications. 1