What is the first line of treatment for elevated Thyroid-Stimulating Hormone (TSH) levels?

Treatment of Elevated TSH

Levothyroxine is the first-line treatment for elevated TSH, with the decision to treat and initial dosing determined by the TSH level, patient age, cardiac status, and symptom presence. 1, 2, 3

Confirm the Diagnosis First

• Repeat TSH and free T4 testing after 3-6 weeks before initiating treatment, as 30-60% of elevated TSH levels normalize spontaneously 1, 4
• Measure both TSH and free T4 to distinguish subclinical hypothyroidism (elevated TSH, normal free T4) from overt hypothyroidism (elevated TSH, low free T4) 1, 2
• Consider checking thyroid peroxidase (TPO) antibodies, as positive antibodies indicate autoimmune etiology with higher progression risk (4.3% vs 2.6% per year) 1, 5

Treatment Algorithm Based on TSH Level

TSH >10 mIU/L

Initiate levothyroxine therapy regardless of symptoms or age. 1, 2, 6

• This threshold carries approximately 5% annual risk of progression to overt hypothyroidism 1
• Treatment prevents complications in patients who progress and may improve symptoms and lower LDL cholesterol 1

TSH 4.5-10 mIU/L

Monitor without treatment for most asymptomatic patients, but consider treatment in specific high-risk situations. 1, 2, 5

• Recheck thyroid function every 6-12 months if stable 1, 2
• Treat if: pregnant or planning pregnancy, symptomatic with clear hypothyroid features, or positive TPO antibodies with symptoms 1, 2, 5
• For symptomatic patients in this range, consider a 3-4 month trial of levothyroxine and discontinue if no symptom improvement 5

Initial Levothyroxine Dosing

Younger Patients (<65-70 years) Without Cardiac Disease

• Start with full replacement dose of approximately 1.6 mcg/kg/day 1, 3
• This approach achieves target TSH more rapidly in healthy adults 1

Elderly Patients (>70 years) or Those With Cardiac Disease

• Start with 25-50 mcg/day and titrate gradually. 1, 3, 6
• This conservative approach prevents exacerbation of cardiac symptoms, particularly atrial fibrillation 1, 4
• Use smaller dose increments (12.5 mcg) in this population 1

Pregnant Patients

• For new-onset hypothyroidism with TSH ≥10 mIU/L: start 1.6 mcg/kg/day 3
• For new-onset hypothyroidism with TSH <10 mIU/L: start 1.0 mcg/kg/day 3
• For pre-existing hypothyroidism: increase pre-pregnancy dose by 12.5-25 mcg/day 3
• Monitor TSH every 4 weeks during pregnancy to maintain trimester-specific reference ranges 3

Monitoring and Dose Adjustment

• Recheck TSH and free T4 every 6-8 weeks during dose titration 1, 3, 5
• Target TSH: 0.4-2.5 mIU/L (lower half of reference range) for most adults 5
• Once stable, monitor TSH every 6-12 months or with symptom changes 1, 3
• Adjust levothyroxine dose by 12.5-25 mcg increments based on TSH response 1

Critical Pitfalls to Avoid

• Do not adjust doses more frequently than every 6-8 weeks, as levothyroxine has a long half-life and steady state takes time to achieve 1, 6
• Avoid overtreatment: approximately 25% of patients on levothyroxine are inadvertently maintained on doses that suppress TSH, increasing risks for atrial fibrillation, osteoporosis, and fractures 1
• Do not treat transient hypothyroidism: recognize that some TSH elevations are temporary and may not require lifelong treatment 6, 4
• Counsel patients on proper administration: take levothyroxine on an empty stomach, separate from iron, calcium, and other medications that impair absorption 6

Age-Specific Considerations

• TSH reference ranges increase with age: upper limit of normal is 3.6 mIU/L for patients <40 years but 7.5 mIU/L for patients >80 years 4
• For patients >80-85 years with TSH ≤10 mIU/L: adopt a "wait-and-see" strategy rather than treating, as treatment may be harmful in this population 5, 4
• Treatment of subclinical hypothyroidism in elderly patients has not shown benefit in randomized trials and may increase cardiovascular risk 4

Special Clinical Scenarios

Thyroid Cancer Patients

• TSH suppression targets differ based on cancer risk stratification 1, 3
• Higher doses (often 2.0-2.2 mcg/kg/day) are required to suppress TSH in patients after total thyroidectomy compared to primary hypothyroidism (1.6 mcg/kg/day) 7

Patients With Adrenal Insufficiency

• Always start corticosteroids before initiating levothyroxine to avoid precipitating adrenal crisis 1