When should thyroid medication, such as levothyroxine (T4), be initiated in a patient with hypothyroidism, elevated thyroid-stimulating hormone (TSH) levels, and symptoms like fatigue, weight gain, or cold intolerance?

When to Start Thyroid Medication for Hypothyroidism

Initiate levothyroxine immediately for patients with TSH >10 mIU/L regardless of symptoms, any TSH elevation with low free T4 (overt hypothyroidism), or symptomatic patients with any degree of TSH elevation. 1

Confirm the Diagnosis Before Treatment

Before starting therapy, confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize spontaneously on repeat testing. 1 This confirmation step prevents unnecessary lifelong treatment for transient thyroid dysfunction. 1

Measure both TSH and free T4 to distinguish between:

• Subclinical hypothyroidism: Elevated TSH with normal free T4 1
• Overt hypothyroidism: Elevated TSH with low free T4 1, 2

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L: Treat Immediately

Initiate levothyroxine therapy regardless of symptoms when TSH persistently exceeds 10 mIU/L. 1 This threshold carries approximately 5% annual risk of progression to overt hypothyroidism and is associated with increased cardiovascular risk. 1 Treatment may improve symptoms, lower LDL cholesterol, and prevent complications in patients who progress. 1

Starting dose for most adults: 1.6 mcg/kg/day for patients under 70 years without cardiac disease. 1

Starting dose for high-risk patients: 25-50 mcg/day for patients over 70 years or those with cardiac disease/multiple comorbidities, titrating gradually. 1, 3

TSH 4.5-10 mIU/L: Individualized Approach

Routine levothyroxine treatment is not recommended for asymptomatic patients with TSH 4.5-10 mIU/L. 1 Instead, monitor thyroid function tests at 6-12 month intervals. 1

Consider treatment in specific situations:

• Symptomatic patients with fatigue, weight gain, cold intolerance, or cognitive symptoms may benefit from a 3-4 month trial of therapy with clear evaluation of benefit. 1, 3
• Positive anti-TPO antibodies (4.3% annual progression risk vs 2.6% in antibody-negative individuals). 1
• Women planning pregnancy or currently pregnant (any TSH elevation warrants treatment). 1, 4
• Patients with goiter or infertility. 1, 5

Overt Hypothyroidism: Immediate Treatment Required

Start levothyroxine without delay when TSH is elevated and free T4 is below the reference range to prevent cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration. 2, 3

Special Populations Requiring Modified Approach

Pregnant Women or Planning Pregnancy

Treat any TSH elevation immediately in women planning pregnancy or currently pregnant, targeting TSH <2.5 mIU/L in the first trimester. 1, 4, 5 Untreated hypothyroidism during pregnancy is associated with preeclampsia, low birth weight, and potential neurodevelopmental effects in the offspring. 1, 3

For pre-existing hypothyroidism, increase levothyroxine dosage by 12.5-25 mcg per day as soon as pregnancy is confirmed, as requirements typically increase by 25-50% during pregnancy. 1, 4

Elderly Patients (>70 years)

Start with lower doses (25-50 mcg/day) and titrate gradually to avoid cardiac complications. 1, 3 The upper limit of normal TSH shifts upward with age, reaching 7.5 mIU/L in patients over 80. 6 Treatment of subclinical hypothyroidism may be harmful in elderly patients, particularly those over 85 years. 5, 6

Patients with Cardiac Disease

For patients with known or suspected ischemic heart disease, coronary artery disease, or atrial fibrillation, start at 12.5-25 mcg/day and titrate slowly. 5, 3 Rapid normalization of thyroid hormone can unmask or worsen cardiac ischemia. 5

Patients on Immune Checkpoint Inhibitors

Consider treatment even for subclinical hypothyroidism if fatigue or other symptoms are present, as thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy and 16% with combination immunotherapy. 1 Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption. 1

Critical Safety Considerations Before Starting Treatment

Rule out concurrent adrenal insufficiency before initiating levothyroxine, especially in suspected central hypothyroidism or hypophysitis, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1, 5 If adrenal insufficiency is present, start physiologic dose steroids 1 week prior to thyroid hormone replacement. 1

Monitoring After Initiation

Monitor TSH every 6-8 weeks while titrating hormone replacement until TSH reaches the target range of 0.5-4.5 mIU/L. 1, 4, 2 Once adequately treated on a stable dose, repeat testing every 6-12 months or whenever symptoms change. 1, 4

Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize. 1

Common Pitfalls to Avoid

Do not treat based on a single elevated TSH value without confirmation, as 30-60% normalize spontaneously. 1, 6 This represents one of the most common errors leading to unnecessary lifelong treatment.

Avoid overtreatment, which occurs in 14-21% of treated patients and increases risk for atrial fibrillation, osteoporosis, fractures, and cardiac complications. 1 Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH. 1

Never assume hypothyroidism is permanent without reassessment—consider transient thyroiditis, especially in the recovery phase where TSH can be elevated temporarily. 1

Development of low TSH (<0.1-0.45 mIU/L) on therapy suggests overtreatment or recovery of thyroid function; dose should be reduced or discontinued with close follow-up. 1