What are the potential side effects of levothyroxine (thyroxine) tablets in adults with hypothyroidism?

Side Effects of Levothyroxine (Thyroxine) Tablets

The side effects of levothyroxine are primarily manifestations of excessive thyroid hormone (iatrogenic hyperthyroidism) when the dose is too high, though proper dosing at replacement levels is generally safe and well-tolerated. 1

Common Side Effects from Overtreatment

Cardiovascular Effects

• Palpitations, tachycardia, arrhythmias, increased pulse and blood pressure are among the most concerning cardiac manifestations of levothyroxine overdose 1
• Heart failure, angina, myocardial infarction, and cardiac arrest can occur, particularly in elderly patients and those with underlying cardiovascular disease 1
• Even slight overdose carries a 3-5 fold increased risk of atrial fibrillation, especially in patients over 60 years 2

Neurological and Psychiatric Effects

• Headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, and insomnia are common central nervous system manifestations 1
• Tremors and muscle weakness frequently occur with overtreatment 1
• Seizures have been reported rarely with institution of levothyroxine therapy 1

Metabolic and General Effects

• Fatigue (paradoxically), increased appetite, weight loss, heat intolerance, fever, and excessive sweating result from the hypermetabolic state 1
• Hair loss, flushing, and rash may occur as dermatologic manifestations 1

Gastrointestinal Effects

• Diarrhea, vomiting, abdominal cramps, and elevations in liver function tests can develop 1

Bone and Reproductive Effects

• Decreased bone mineral density and increased risk of osteoporotic fractures, particularly in postmenopausal women, result from chronic TSH suppression 1, 2
• Menstrual irregularities and impaired fertility may occur 1

Special Risks in Vulnerable Populations

Elderly Patients and Those with Heart Disease

• Overtreatment may precipitate angina or arrhythmias in patients with cardiovascular disease and elderly patients 1
• Increased heart rate, cardiac wall thickness, and cardiac contractility can unmask or worsen cardiac ischemia 1
• Lower starting doses (25-50 mcg/day) are essential in this population to avoid cardiac complications 2

Pediatric Patients

• Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine 1
• Overtreatment may result in craniosynostosis in infants with open fontanelles and premature closure of epiphyses, compromising adult height 1

Critical Safety Concerns

Adrenal Crisis Risk

• Initiating levothyroxine before treating adrenal insufficiency can precipitate life-threatening adrenal crisis, as thyroid hormone increases metabolic clearance of glucocorticoids 1
• Patients with adrenal insufficiency must receive replacement glucocorticoids prior to starting levothyroxine 1

Worsening Diabetic Control

• Addition of levothyroxine in patients with diabetes may worsen glycemic control and increase insulin or antidiabetic agent requirements 1
• Careful monitoring of blood glucose is essential after starting or changing levothyroxine doses 1

Narrow Therapeutic Index

• Levothyroxine has a narrow therapeutic index, meaning small changes in dose can lead to significant clinical effects 1, 3
• Both undertreatment and overtreatment carry risks affecting growth, cardiovascular function, bone metabolism, reproductive function, cognitive function, and metabolic parameters 1

Hypersensitivity Reactions

• Hypersensitivity reactions to inactive ingredients can occur, including urticaria, pruritus, skin rash, flushing, angioedema, gastrointestinal symptoms (abdominal pain, nausea, vomiting, diarrhea), fever, arthralgia, serum sickness, and wheezing 1
• The 50 mcg tablet contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions including bronchial asthma in susceptible persons, particularly those with aspirin hypersensitivity 1
• Hypersensitivity to levothyroxine itself is not known to occur 1

Prevalence of Overtreatment

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses high enough to suppress TSH completely, increasing risks for osteoporosis, fractures, atrial fibrillation, and cardiac complications 2, 4
• About 14-21% of treated patients develop iatrogenic subclinical hyperthyroidism from overtreatment 2

Key Monitoring to Prevent Side Effects

• TSH monitoring every 6-8 weeks during dose titration, then every 6-12 months once stable, is essential to prevent both overtreatment and undertreatment 2, 4
• Target TSH should remain within the reference range (0.5-4.5 mIU/L) for most patients with primary hypothyroidism 2
• Avoid TSH suppression below 0.1 mIU/L in patients without thyroid cancer, as this dramatically increases cardiovascular and bone risks 2