What are the long-term side effects of taking Synthroid (levothyroxine)?

Long-Term Side Effects of Synthroid (Levothyroxine)

When properly dosed, levothyroxine is generally safe for long-term use with minimal side effects, but overtreatment—which occurs in approximately 25% of patients—can lead to serious complications including osteoporosis, fractures, cardiac arrhythmias, and ventricular hypertrophy. 1, 2

Primary Risks from Overtreatment

The most significant long-term risks arise from excessive dosing that suppresses TSH levels, not from the medication itself at appropriate doses:

Bone Health Complications

• Decreased bone mineral density is a well-documented consequence of levothyroxine over-replacement, particularly in postmenopausal women 3
• Increased bone resorption occurs with TSH suppression, associated with elevated serum calcium and phosphorous levels, increased bone alkaline phosphatase, and suppressed parathyroid hormone 3
• Increased fracture risk, including stress fractures, has been reported with chronic overtreatment 4
• One case study demonstrated severe osteoporosis with bilateral femoral stress fractures in a 38-year-old woman from excessive levothyroxine, which reversed rapidly after dose correction 4

Cardiovascular Complications

• Atrial fibrillation and cardiac arrhythmias are more common with TSH suppression, especially in elderly patients 1, 2, 3
• Potential for angina, myocardial infarction, and cardiac arrest with overdosage 3
• Left ventricular hypertrophy and abnormal cardiac output may develop with long-term TSH suppression 1, 5
• Increased pulse, blood pressure, and heart failure risk 3
• Shortening of systolic time intervals and increased frequency of atrial premature beats 5

Side Effects from Appropriate Dosing

When levothyroxine is dosed correctly to maintain normal TSH levels, long-term studies show no increase in morbidity or mortality 6:

• A 12-year population study of women on levothyroxine found no increased morbidity, mortality, or decreased quality of life compared to women without thyroid disease 6
• Patients with properly monitored therapy showed identical clinical outcomes to controls 6

Common Adverse Effects (Usually from Overdosage)

The FDA label identifies these adverse reactions, primarily occurring with therapeutic overdosage 3:

General Symptoms

• Fatigue, increased appetite, weight loss (or gain with undertreatment) 7, 3
• Heat intolerance, fever, excessive sweating 3

Neurological Effects

• Headache, hyperactivity, nervousness, anxiety, irritability 3
• Emotional lability, insomnia 3
• Rarely, seizures with therapy initiation 3

Musculoskeletal Effects

• Tremors, muscle weakness, muscle spasm 3
• Joint pain and muscle cramps 8

Other Systems

• Hair loss (temporary, often resolves) 3, 8
• Menstrual irregularities, impaired fertility 3
• Gastrointestinal symptoms: diarrhea, vomiting, abdominal cramps 3
• Elevated liver function tests 3

Critical Monitoring Requirements

The key to preventing long-term complications is appropriate monitoring and dose adjustment 2:

• TSH should be checked every 6-8 weeks during dose titration 2
• Once stable, monitor TSH every 6-12 months 2
• Approximately 25% of patients are inadvertently maintained on doses high enough to suppress TSH completely, increasing risks for osteoporosis, fractures, and cardiac complications 1, 2

Special Populations at Higher Risk

Elderly Patients

• Greater susceptibility to cardiac complications from overtreatment 2, 3
• Should start with lower doses (25-50 mcg/day) and titrate slowly 2

Postmenopausal Women

• Highest risk for bone density loss with TSH suppression 3
• Should ensure adequate calcium (1200 mg/day) and vitamin D (1000 units/day) intake if TSH chronically suppressed 2

Patients with Cardiac Disease

• Increased risk of angina, arrhythmias, and coronary insufficiency 3
• Require more conservative dosing and frequent monitoring 2

Important Caveats

The FDA approval process for levothyroxine in 2000 did not include studies evaluating short- or long-term adverse effects, despite its widespread prior use 1. Most safety data comes from post-marketing surveillance and observational studies rather than controlled trials designed to assess long-term harms 1.

Hypersensitivity reactions to inactive ingredients (not levothyroxine itself) can occur, including urticaria, rash, angioedema, and gastrointestinal symptoms 3. Some formulations contain tartrazine (FD&C Yellow No. 5), which may cause allergic reactions in susceptible individuals 3.

Bottom Line

Levothyroxine is safe for lifelong use when properly dosed and monitored 9, 6. The primary long-term risks—bone loss, fractures, and cardiac complications—result from overtreatment, not from the medication itself at replacement doses 1, 4. Regular TSH monitoring and maintaining levels within the reference range (0.5-4.5 mIU/L for most patients) effectively prevents these complications 2.