What are the risks of overtreatment with levothyroxine (thyroid hormone replacement medication) for hypothyroidism?

From the Guidelines

Overtreatment with levothyroxine for hypothyroidism poses significant risks, including cardiac strain, bone health issues, and nervous system overstimulation, emphasizing the need for careful dosing and regular monitoring of thyroid function tests, as highlighted in the most recent guideline update 1. The goal of treatment should be to normalize TSH levels, typically between 0.4-4.0 mIU/L, though target ranges may vary by age and condition, rather than simply relieving symptoms. Key considerations for managing levothyroxine treatment include:

• Starting with a lower dose in older or frail patients and titrating up as needed
• Monitoring for signs of overtreatment, such as low TSH levels, and adjusting the dose accordingly
• Being aware of the potential for thyroiditis and the need for close follow-up in asymptomatic patients with elevated TSH and normal FT4 levels Regular monitoring, typically every 6-12 months once stable, is essential to ensure proper dosing and avoid complications, as noted in earlier guidelines 1. However, the most recent update 1 provides the most current and relevant guidance on managing levothyroxine treatment, emphasizing the importance of individualized care and careful monitoring to minimize the risks of overtreatment. Some of the key risks associated with overtreatment include:
• Cardiac strain, leading to heart palpitations, rapid or irregular heartbeat, and increased risk of atrial fibrillation
• Bone health issues, including accelerated bone resorption, osteoporosis, and increased fracture risk, particularly in postmenopausal women
• Nervous system overstimulation, resulting in anxiety, irritability, insomnia, and tremors
• Other symptoms, such as unexplained weight loss, heat intolerance, increased sweating, muscle weakness, and menstrual irregularities in women. Long-term overtreatment can potentially increase mortality risk, underscoring the need for careful management and monitoring of levothyroxine treatment, as emphasized in the most recent guideline update 1.

From the FDA Drug Label

Levothyroxine sodium tablets has a narrow therapeutic index. Overtreatment or undertreatment with levothyroxine sodium tablets may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, gastrointestinal function, and glucose and lipid metabolism in adult or pediatric patients Over-treatment with levothyroxine may cause an increase in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients In pediatric patients with congenital and acquired hypothyroidism, undertreatment may adversely affect cognitive development and linear growth, and overtreatment is associated with craniosynostosis and acceleration of bone age

The risks of overtreatment with levothyroxine for hypothyroidism include:

• Negative effects on cardiovascular function, such as increased heart rate, cardiac wall thickness, and cardiac contractility, which may precipitate angina or arrhythmias
• Negative effects on bone metabolism, such as acceleration of bone age in pediatric patients
• Negative effects on cognitive function and linear growth in pediatric patients
• Increased risk of craniosynostosis in pediatric patients
• Potential negative effects on reproductive function, gastrointestinal function, and glucose and lipid metabolism 2

From the Research

Risks of Overtreatment with Levothyroxine

The risks of overtreatment with levothyroxine for hypothyroidism include:

• Cardiac arrhythmias and heart failure, as excessive thyroid hormone can lead to increased heart rate and cardiac output 3
• Osteoporosis, as excessive thyroid hormone can lead to increased bone turnover and decreased bone density 3
• Adverse pregnancy outcomes, as overtreatment with levothyroxine can lead to increased risk of miscarriage, premature birth, and low birth weight 3, 4
• Unintentional weight loss, as excessive thyroid hormone can lead to increased metabolism and weight loss 3
• Increased mortality, as overtreatment with levothyroxine can lead to increased risk of cardiovascular disease and other complications 3

Patient-Specific Risks

Certain patient populations may be at higher risk for overtreatment with levothyroxine, including:

• Older adults, who may be more susceptible to the cardiac and osteoporotic effects of excessive thyroid hormone 3, 4
• Patients with ischemic heart disease, who may be at increased risk for cardiac arrhythmias and heart failure 5
• Pregnant women, who may be at increased risk for adverse pregnancy outcomes 5, 4
• Patients with subclinical hypothyroidism, who may not require treatment with levothyroxine and may be at risk for overtreatment 6, 4

Monitoring and Management

To minimize the risks of overtreatment with levothyroxine, it is essential to:

• Monitor thyroid-stimulating hormone (TSH) levels regularly to ensure that the patient is not overtreated 5, 7
• Adjust the dose of levothyroxine based on TSH levels and clinical symptoms 5, 7
• Consider alternative treatment options, such as watchful waiting or treatment with triiodothyronine, in patients with subclinical hypothyroidism 6, 4