When should medication be started for hypothyroidism (underactive thyroid gland)?

When to Start Medication for Hypothyroidism

Start levothyroxine immediately for all patients with TSH >10 mIU/L, regardless of symptoms, and for symptomatic patients with any degree of TSH elevation. 1

Confirm the Diagnosis First

Before initiating treatment, confirm the diagnosis with repeat testing after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously. 1 This critical step prevents unnecessary lifelong treatment for transient thyroid dysfunction.

• Measure both TSH and free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4). 1
• Consider checking anti-TPO antibodies to identify autoimmune etiology, which predicts higher progression risk (4.3% per year vs 2.6% in antibody-negative individuals). 1

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L: Always Treat

Initiate levothyroxine therapy regardless of symptoms or age when TSH exceeds 10 mIU/L. 1 This threshold carries approximately 5% annual risk of progression to overt hypothyroidism and may prevent cardiovascular complications, heart failure, and other manifestations of thyroid hormone deficiency. 1, 2

• Treatment may improve symptoms and lower LDL cholesterol, though evidence for mortality benefit is limited. 1
• The evidence quality is rated as "fair" by expert panels, but the potential benefits of preventing progression outweigh the risks of therapy. 1

TSH 4.5-10 mIU/L: Selective Treatment

Do not routinely treat patients with TSH 4.5-10 mIU/L; instead, monitor thyroid function tests every 6-12 months. 1 Randomized controlled trials found no improvement in symptoms with levothyroxine therapy in this range. 1

However, consider treatment in specific high-risk situations:

• Pregnant women or those planning pregnancy: Subclinical hypothyroidism during pregnancy is associated with preeclampsia, low birth weight, and potential neurodevelopmental effects in offspring. 1 Treatment should be initiated to normalize TSH.
• Positive anti-TPO antibodies: These patients have 4.3% annual progression risk versus 2.6% in antibody-negative individuals. 1
• Symptomatic patients: Those with fatigue, weight gain, cold intolerance, constipation, or cognitive symptoms may benefit from a 3-4 month trial of therapy with clear evaluation of benefit. 1
• Patients on immune checkpoint inhibitors: Consider treatment even with mild TSH elevation if symptomatic, as thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy. 1

TSH <4.5 mIU/L: Do Not Treat

Normal TSH values do not warrant treatment, even if trending upward within the normal range. 1 TSH values can naturally vary due to pulsatile secretion, time of day, and physiological factors. 1

Initial Dosing Strategy

For Patients <70 Years Without Cardiac Disease

Start with full replacement dose of 1.6 mcg/kg/day. 1, 2 This approach achieves therapeutic levels more rapidly in young, healthy patients without cardiac risk factors.

For Patients >70 Years or With Cardiac Disease

Start with a lower dose of 25-50 mcg/day and titrate gradually. 3, 1 Elderly patients with coronary disease are at increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic levothyroxine doses. 1 Rapid normalization can unmask or worsen cardiac ischemia. 1

Critical Safety Consideration: Rule Out Adrenal Insufficiency

In patients with suspected central hypothyroidism or hypophysitis, always start corticosteroids before initiating thyroid hormone to prevent adrenal crisis. 3, 1 This is particularly important in patients on immune checkpoint inhibitors, where >75% of patients with hypophysitis have both central hypothyroidism and adrenal insufficiency. 3

Monitoring and Dose Adjustment

• Recheck TSH and free T4 every 6-8 weeks while titrating the dose until TSH normalizes within the reference range (0.5-4.5 mIU/L). 1, 4
• Adjust dose by 12.5-25 mcg increments based on TSH response. 3 Larger adjustments risk overtreatment, especially in elderly patients or those with cardiac disease. 3
• Once adequately treated, monitor TSH every 6-12 months or sooner if symptoms change. 1, 4

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH value without confirmation testing, as 30-60% normalize spontaneously. 1
• Avoid overtreatment: Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiac complications. 1
• Do not start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism, as this can precipitate adrenal crisis. 3, 1
• Recognize transient hypothyroidism: Failure to distinguish transient thyroiditis (such as immune checkpoint inhibitor-induced) from permanent hypothyroidism may lead to unnecessary lifelong treatment. 1

Special Populations

Pregnant Women

Treat any degree of TSH elevation in pregnant women or those planning pregnancy. 1 Inadequate treatment is associated with increased risk of preeclampsia, low birth weight, and impaired neurodevelopmental outcomes. 1 Levothyroxine requirements typically increase 25-50% during pregnancy. 1

Elderly Patients

Use conservative dosing (25-50 mcg/day initially) and accept slightly higher TSH targets (up to 5-6 mIU/L may be acceptable in very elderly patients) to avoid overtreatment risks. 1 The risks of overtreatment—including atrial fibrillation, fractures, and cardiovascular mortality—are particularly pronounced in elderly patients. 1

Patients on Immune Checkpoint Inhibitors

Monitor TSH every 4-6 weeks initially, then every cycle for the first 3 months, then every second cycle thereafter. 1 Thyroid dysfunction occurs in 6-20% of patients on immunotherapy. 3 Continue immune checkpoint inhibitor therapy in most cases, as high-dose corticosteroids are rarely required for thyroid dysfunction. 1