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Side Effects by Body System
General

Levothyroxine is usually well tolerated. Side effects associated with levothyroxine therapy typically resulted from therapeutic overdosage and included the signs and symptoms of hyperthyroidism. Weight loss, increased appetite, insomnia, anxiety, heat intolerance, diarrhea or increase in bowel frequency, palpitations, hypertension, tachycardia, angina, and menstrual irregularities may be reported. Given the long half-life of levothyroxine, such effects may not be present for several weeks after therapy initiation or dosage increases.
Cardiovascular

Cardiac function was evaluated in twenty patients requiring TSH suppression for either thyroid goiter or following thyroidectomy and radioactive iodine therapy for thyroid cancer and in twenty age- and sex-matched controls. TSH suppression was associated with an increased incidence of premature ventricular beats, an increased left ventricular mass index, and enhanced left ventricular systolic function. The clinical significance of these changes remains to be determined.

A 38-year-old female experienced with severe hypothyroidism experienced myxedema coma and cardiac ischemia coincident with levothyroxine therapy. After 3 months of levothyroxine therapy (initial dose: 12.5 mcg/d; maintenance dose: 125 mcg/d), all abnormal laboratory values associated with hypothyroidism returned to normal. However, three weeks after initiating treatment, the patient reported intermittent chest pains during the course of treatment, and a coronary artery angiogram revealed diffuse stenosis of all 3 branches. She underwent coronary artery bypass grafting, with subsequent improvement in coronary perfusion.

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Cardiovascular side effects have included symptoms of palpitations, hypertension, tachycardia, and angina which may be exacerbated in patients with underlying cardiovascular disorders. Ischemic heart disease and significant effects on cardiac function including an increased incidence of premature ventricular beats, an increased left ventricular mass index, and enhanced left ventricular systolic function have been reported in clinical trials.
Endocrine

Endocrine side effects have included changes in symptom presentation for diabetes and adrenal cortical insufficiency.
Nervous system

Nervous system side effects have rarely included seizures during initiation of therapy.
Dermatologic

Dermatologic side effects including transient dermatologic effect and hair loss have been reported during the initial months of therapy.
Musculoskeletal

Musculoskeletal side effects have included an increase risk of osteoporosis. However, data from long-term studies are conflicting.

A study evaluated the effect of long-term thyroid hormone therapy on bone mineral density in 196 women (mean age, 74.4 years) compared to a control group comprised of 795 women (mean age, 72.1 years). The mean daily thyroxine dose was 1.99 mcg/kg (range, 0.3 to 6.6 mcg/kg) with a mean duration of therapy of 20.4 years (range, less than 1 to 68 years). Women taking daily doses of 1.6 mcg/kg or more had significantly lower bone mineral density levels at the ultradistal radius, midshaft radius, hip, and lumbar spine compared to controls. However, estrogen use appeared to negate the adverse effects of thyroid hormone on bone mineral density.

Higher rates of femur fractures have been found in males (p=0.008) prescribed long-term thyroid hormone therapy as compared to controls in a case-control analysis of 23,183 patients, from the United Kingdom General Practice Research Database, prescribed thyroid hormone.

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