What is the typical treatment for hypothyroidism?

Treatment of Hypothyroidism

Levothyroxine monotherapy is the standard treatment for hypothyroidism, initiated immediately upon diagnosis to normalize thyroid function and prevent serious complications including cardiovascular disease, heart failure, and myxedema coma. 1, 2

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm the diagnosis with appropriate testing:

• Measure both TSH and free T4 to distinguish between overt hypothyroidism (elevated TSH with low free T4) and subclinical hypothyroidism (elevated TSH with normal free T4) 1, 3
• Repeat testing after 3-6 weeks if TSH is initially elevated, as 30-60% of elevated TSH levels normalize spontaneously 1, 4
• Check anti-TPO antibodies to confirm autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk to overt disease (4.3% per year versus 2.6% in antibody-negative patients) 1

Critical Safety Consideration

In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, always initiate corticosteroids at least 1 week before starting levothyroxine to prevent life-threatening adrenal crisis. 1, 3 This is particularly important in patients with autoimmune hypothyroidism who have increased risk of concurrent autoimmune adrenal insufficiency (Addison's disease) 1.

Initial Levothyroxine Dosing

For Patients Under 70 Years Without Cardiac Disease

• Start with full replacement dose of approximately 1.6 mcg/kg/day taken on an empty stomach 1, 4, 5
• This approach rapidly normalizes thyroid function and prevents complications 1

For Elderly Patients or Those With Cardiac Disease

• Start with lower dose of 25-50 mcg/day and titrate gradually 1, 6, 4
• Elderly patients and those with coronary artery 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 Pregnant Women

• Initiate treatment immediately as maternal hypothyroidism is associated with spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, premature delivery, low birth weight, and impaired fetal neurocognitive development 1, 3, 6
• Pregnancy increases levothyroxine requirements by 25-50% above pre-pregnancy doses 1, 6
• Monitor TSH levels closely during pregnancy and adjust dosage as needed 6
• Return to pre-pregnancy dose immediately after delivery as postpartum TSH levels return to preconception values 6

Treatment Thresholds Based on TSH Levels

TSH >10 mIU/L (Overt or Severe Subclinical Hypothyroidism)

• Initiate levothyroxine therapy regardless of symptoms 1, 7
• This threshold carries approximately 5% annual risk of progression to overt hypothyroidism 1
• Treatment may improve symptoms and lower LDL cholesterol 1

TSH 4.5-10 mIU/L (Mild Subclinical Hypothyroidism)

• Routine levothyroxine treatment is not recommended 1
• Consider treatment in specific situations:
  • Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation 1, 3
  • Pregnant women or those planning pregnancy 1
  • Patients with positive anti-TPO antibodies (higher progression risk) 1
  • Patients with infertility or goiter 7
• Monitor thyroid function tests every 6-12 months if not treating 1

Monitoring and Dose Adjustment

Initial Titration Phase

• Recheck TSH and free T4 every 6-8 weeks after initiating therapy or changing dose 1, 2
• This interval represents the time needed to reach steady state 1
• Adjust dose by 12.5-25 mcg increments based on patient's current dose and clinical characteristics 1
• Use smaller increments (12.5 mcg) for elderly patients or those with cardiac disease 1

Target TSH Range

• Target TSH 0.5-4.5 mIU/L with normal free T4 levels for primary hypothyroidism 1, 7
• Slightly higher targets (up to 5-6 mIU/L) may be acceptable in very elderly patients to avoid overtreatment risks, though this remains controversial 1

Long-Term Monitoring

• Once stable, monitor TSH annually or sooner if symptoms change 1, 2
• Approximately 25% of patients are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for complications 1

Risks of Overtreatment

Overtreatment occurs in 14-21% of treated patients and significantly increases morbidity and mortality risks: 1

• Atrial fibrillation and cardiac arrhythmias, especially in elderly patients (5-fold increased risk in patients ≥45 years with TSH <0.4 mIU/L) 1
• Osteoporosis and fractures, particularly in postmenopausal women (increased risk of hip and spine fractures in women >65 years with TSH ≤0.1 mIU/L) 1, 4
• Left ventricular hypertrophy and abnormal cardiac output 1
• Increased cardiovascular mortality 1

Common Pitfalls to Avoid

• Never treat based on single elevated TSH value without confirmation, as transient elevations are common 1, 4
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism 1, 3
• Avoid adjusting doses too frequently before reaching steady state—wait 6-8 weeks between adjustments 1
• Do not overlook transient hypothyroidism (recovery phase from thyroiditis, recent illness, or medication-induced), which may not require lifelong treatment 1, 4
• Recognize factors affecting levothyroxine absorption: iron, calcium, and certain medications reduce gastrointestinal absorption; enzyme inducers reduce efficacy 4, 7

Special Populations

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
• Monitor TSH every cycle for first 3 months, then every second cycle thereafter 1

Patients With Long-Standing Severe Hypothyroidism

• Start at lower doses even in younger patients to avoid cardiac complications 4
• Titrate gradually as rapid normalization may unmask or worsen cardiac ischemia 1

Ensuring Adequate Bone Health During Treatment

• Patients on long-term levothyroxine should ensure adequate calcium intake (1200 mg/day) and vitamin D (1000 units/day) to prevent osteoporosis and fractures, especially if TSH is chronically suppressed 1