What is the initial treatment for hypothyroidism (underactive thyroid)?

Initial Treatment for Hypothyroidism

Levothyroxine monotherapy is the first-line treatment for hypothyroidism, initiated immediately upon diagnosis to normalize thyroid-stimulating hormone (TSH) levels and prevent serious complications including cardiovascular disease, heart failure, and myxedema coma. 1, 2, 3

Diagnostic Confirmation Before Treatment

• Confirm the diagnosis with elevated TSH and low free T4 for overt hypothyroidism, or elevated TSH with normal free T4 for subclinical hypothyroidism 1, 2
• Repeat testing after 3-6 weeks is recommended before initiating treatment in asymptomatic patients, as 30-60% of elevated TSH values normalize spontaneously 1
• Measure anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk to overt hypothyroidism (4.3% per year versus 2.6% in antibody-negative patients) 1

Critical Safety Consideration: Rule Out Adrenal Insufficiency

Before initiating levothyroxine, always rule out concurrent adrenal insufficiency, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1

• In patients with suspected central hypothyroidism or hypophysitis, start physiologic dose steroids at least 1 week prior to thyroid hormone replacement 1
• This is particularly important in patients on immune checkpoint inhibitors or those with pituitary disease 1

Initial Levothyroxine Dosing Strategy

For Younger Patients (<70 years) Without Cardiac Disease

• Start with full replacement dose of approximately 1.6 mcg/kg/day 1, 3, 4
• This approach rapidly normalizes thyroid function and prevents cardiovascular complications 1

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

• Start with a lower dose of 25-50 mcg/day and titrate gradually 1, 4
• Elderly patients with coronary disease are at increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic levothyroxine doses 1
• Use smaller dose increments (12.5 mcg) during titration to avoid cardiac complications 1

For Patients With Long-Standing Severe Hypothyroidism

• Initiate at a low dose regardless of age to prevent cardiac overload 4
• Closely monitor for cardiac symptoms during the first 2 weeks of therapy 5

Treatment Thresholds Based on TSH Levels

Overt Hypothyroidism (Elevated TSH + Low Free T4)

• Initiate levothyroxine immediately without delay to prevent cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration 1, 4
• Treatment is mandatory regardless of symptoms 1

Subclinical Hypothyroidism with TSH >10 mIU/L

• Initiate levothyroxine therapy regardless of symptoms, as this level carries approximately 5% annual risk of progression to overt hypothyroidism 1, 4
• Treatment may improve symptoms and lower LDL cholesterol 1

Subclinical Hypothyroidism with TSH 4.5-10 mIU/L

• Treatment decisions should be individualized based on specific factors 1, 4:
  • Pregnant women or those planning pregnancy: Treat at any TSH elevation to prevent adverse pregnancy outcomes including preeclampsia, low birth weight, and impaired fetal neurodevelopment 1, 5
  • Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation: Consider a 3-4 month trial of levothyroxine with clear evaluation of benefit 1
  • Patients with positive anti-TPO antibodies: Consider treatment due to higher progression risk (4.3% per year) 1, 4
  • Patients with infertility or goiter: Consider treatment 4
• For asymptomatic patients without these factors, monitor TSH every 6-12 months without treatment 1

Monitoring and Dose Adjustment

• Recheck TSH and free T4 in 6-8 weeks after initiating therapy or any dose adjustment, as this represents the time needed to reach steady state 1, 3
• Target TSH range is 0.5-4.5 mIU/L with normal free T4 levels 1, 4
• Adjust levothyroxine dose in 12.5-25 mcg increments based on TSH results 1
• Once adequately treated, repeat TSH testing every 6-12 months or if symptoms change 1

Special Populations Requiring Modified Approach

Pregnant Women

• Levothyroxine requirements typically increase by 25-50% during early pregnancy 1
• Monitor TSH more frequently during pregnancy and adjust dose proactively 5
• Return to pre-pregnancy dose immediately after delivery 5

Patients on Immune Checkpoint Inhibitors

• Thyroid dysfunction occurs in 6-20% of patients on anti-PD-1/PD-L1 therapy 1
• Consider treatment even for subclinical hypothyroidism if fatigue or other symptoms are present 1
• Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption 1

Patients With Diabetes

• Addition of levothyroxine may worsen glycemic control and increase insulin requirements 5
• Carefully monitor blood glucose, especially when starting or adjusting thyroid therapy 5

Patients on Oral Anticoagulants

• Levothyroxine increases the response to oral anticoagulants 5
• Closely monitor coagulation tests and decrease anticoagulant dose as needed when correcting hypothyroidism 5

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH value without confirmation, as transient elevations are common 1
• 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, increasing cardiovascular and bone risks 1
• Do not assume hypothyroidism is permanent without reassessment—consider transient thyroiditis, especially in recovery phase 1
• Ensure adequate separation from medications that interfere with absorption: Take levothyroxine at least 4 hours apart from calcium, iron, phosphate binders, bile acid sequestrants, and proton pump inhibitors 5

Why Levothyroxine Is the Standard of Care

• Levothyroxine monotherapy remains the current standard for management of both primary and central hypothyroidism 4, 6
• Its effects are more predictable and reliable than other thyroid preparations 6
• It is one of the world's most widely prescribed medicines with decades of clinical experience 3
• When properly dosed, levothyroxine is safe for lifelong use 1