What is the treatment for an elevated Thyroid-Stimulating Hormone (TSH) level indicating hypothyroidism?

Treatment for Elevated TSH

Initiate levothyroxine therapy for patients with TSH persistently >10 mIU/L regardless of symptoms, and consider treatment for symptomatic patients with TSH 4.5-10 mIU/L after confirming the elevation with repeat testing. 1, 2

Confirm the Diagnosis First

• Repeat TSH measurement along with free T4 within 2-3 months before starting treatment, as 30-60% of initially elevated TSH levels normalize spontaneously 1, 2
• Measure thyroid peroxidase (TPO) antibodies to identify autoimmune etiology, which predicts higher progression risk to overt hypothyroidism (4.3% vs 2.6% per year in antibody-negative patients) 1, 2
• Distinguish between subclinical hypothyroidism (elevated TSH with normal free T4) and overt hypothyroidism (elevated TSH with low free T4), as this determines treatment urgency 1

Treatment Algorithm Based on TSH Level

TSH >10 mIU/L

• Start levothyroxine regardless of symptoms 1, 2
• This threshold carries approximately 5% annual risk of progression to overt hypothyroidism 1
• Treatment may prevent cardiovascular dysfunction, lipid abnormalities, and quality of life deterioration 1

TSH 4.5-10 mIU/L

• Do not routinely treat asymptomatic patients 1, 2
• Consider a 3-4 month trial of levothyroxine if the patient has hypothyroid symptoms (fatigue, weight gain, cold intolerance, constipation) 1, 2
• Continue therapy only if clear symptomatic benefit occurs; discontinue if no improvement after achieving normal TSH 1, 2
• Treat regardless of TSH level if positive TPO antibodies, goiter, infertility, or planning pregnancy 1, 2

Levothyroxine Dosing Strategy

Initial Dosing

• For patients <70 years without cardiac disease: Start with full replacement dose of 1.6 mcg/kg/day 1, 3
• For patients >70 years or with cardiac disease/atrial fibrillation risk: Start with 25-50 mcg/day and titrate slowly to avoid cardiac complications 1, 3
• For patients with long-standing severe hypothyroidism: Use lower starting doses regardless of age 4

Administration

• Take on empty stomach, 30-60 minutes before breakfast with full glass of water 3
• Separate from medications that interfere with absorption by at least 4 hours 3

Dose Titration

• Adjust dose by 12.5-25 mcg increments every 4-6 weeks for younger patients, or every 6-8 weeks for elderly/cardiac patients 1, 3
• Larger adjustments risk overtreatment and should be avoided 1

Monitoring Protocol

• Recheck TSH and free T4 every 6-8 weeks during dose titration until target achieved 1, 5
• Target TSH: 0.5-2.5 mIU/L (lower half of reference range) for most adults 5
• Once stable, monitor TSH every 6-12 months or when symptoms change 1, 5
• Free T4 helps interpret persistently abnormal TSH during therapy, as TSH may lag behind clinical response 1

Special Populations

Pregnant Women or Planning Pregnancy

• Treat at any TSH elevation to normalize levels before and during pregnancy 1, 2
• Subclinical hypothyroidism associates with preeclampsia, low birth weight, and potential neurodevelopmental effects 1
• Monitor TSH every 6-8 weeks during pregnancy as levothyroxine requirements typically increase 2

Elderly Patients (>80-85 years)

• Use wait-and-see approach for TSH ≤10 mIU/L in the oldest patients 5
• Limited evidence suggests treatment may not benefit those >85 years with mild TSH elevation 4
• When treating, start with 25-50 mcg/day and titrate very slowly 1

Patients with Cardiac Disease

• Start with lower doses (25-50 mcg/day) and titrate every 6-8 weeks 1, 3
• Consider repeating tests within 2 weeks if atrial fibrillation or serious cardiac conditions present 1

Critical Pitfalls to Avoid

• Overtreatment occurs in 14-25% of patients, causing TSH suppression that increases risk for atrial fibrillation, osteoporosis, fractures, and cardiac complications 1, 4
• Adjusting doses too frequently before reaching steady state (wait full 6-8 weeks between adjustments) 1
• Failing to distinguish placebo effect from true benefit in patients with TSH 4.5-10 mIU/L; reassess after 3-4 months and discontinue if no clear improvement 2
• Missing transient hypothyroidism may lead to unnecessary lifelong treatment; confirm persistence before committing to therapy 1
• In patients with concurrent adrenal insufficiency, always start steroids before thyroid hormone to avoid precipitating adrenal crisis 1

When TSH Remains Elevated Despite Treatment

• Verify medication adherence first 4
• Check for malabsorption issues 4
• Review drug interactions (calcium, iron, proton pump inhibitors, bile acid sequestrants) 4
• Consider timing of levothyroxine administration relative to food and other medications 3, 6
• Inadequate response to doses >300 mcg/day is rare and suggests compliance or absorption problems 3