Is thyroxine (T4) the same as levothyroxine?

Thyroxine vs. Levothyroxine: Understanding the Difference

Yes, thyroxine (T4) and levothyroxine are essentially the same thing - levothyroxine is the synthetic form of the naturally occurring thyroid hormone thyroxine. 1, 2

Detailed Explanation

• Levothyroxine sodium is the synthetic preparation of the natural thyroid hormone thyroxine (T4) found in the body 3, 1
• Synthetic T4 (levothyroxine) is chemically identical to the T4 hormone produced naturally in the human thyroid gland 1, 2
• Levothyroxine sodium has the chemical formula C₁₅H₁₀I₄NNaO₄•H₂O and a molecular weight of 798.86 (anhydrous) 1, 2

Clinical Applications

• Levothyroxine is the principal treatment for hypothyroidism, administered as oral T4 monotherapy (levothyroxine sodium) 3
• Treatment of hypothyroidism with levothyroxine generally continues for many years, often lifelong 3
• Levothyroxine was widely used in the United States before receiving FDA approval in 2000 3
• The mean T4 dose required to normalize serum TSH is approximately 1.6 μg/kg per day, though daily maintenance doses vary widely between 75 and 250 μg 4

Mechanism of Action

• Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis 1
• T4 (thyroxine) diffuses into cell nuclei and binds to thyroid receptor proteins attached to DNA 1
• The majority (approximately 80%) of the active thyroid hormone T3 is derived from T4 through deiodination in peripheral tissues 1, 4
• Oral levothyroxine sodium exerts the same physiologic effect as endogenous T4, maintaining normal T4 levels when a deficiency exists 1

Pharmacokinetics

• Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80%, with most absorption occurring in the jejunum and upper ileum 1
• T4 absorption is increased by fasting and decreased by certain foods (such as soybeans), dietary fiber, and malabsorption syndromes 1
• Circulating thyroid hormones are more than 99% bound to plasma proteins 1
• The higher affinity of binding proteins for T4 explains its higher serum levels, slower metabolic clearance, and longer half-life compared to T3 1

Monitoring Considerations

• Serum TSH test is the primary screening test for thyroid dysfunction 3
• Multiple tests should be done over a 3-6 month interval to confirm abnormal findings 3
• Follow-up testing of serum T4 levels in persons with persistently abnormal TSH levels can differentiate between subclinical and overt thyroid dysfunction 3
• Patients on levothyroxine may have slightly elevated serum T4 levels but normal T3 levels and appear clinically euthyroid 5, 6

Potential Risks of Treatment

• Overtreatment with levothyroxine can lead to iatrogenic hyperthyroidism 3
• One quarter of patients on levothyroxine may be inadvertently maintained on doses high enough to make TSH levels undetectable 3
• Long-term overdosing with levothyroxine could potentially increase risk for osteoporosis, fractures, abnormal cardiac output, or ventricular hypertrophy 3, 6
• The product label cites possible adverse effects on bone mineral density and the cardiovascular system, including angina, arrhythmia, and increased cardiac wall thickness 3

Special Populations

• In elderly patients, treatment should be initiated at less than the full replacement dose due to increased prevalence of cardiovascular disease 1
• Atrial arrhythmias, particularly atrial fibrillation, can occur in elderly patients with levothyroxine overtreatment 1
• TSH values ≤0.1 mU/L carry a risk of developing atrial fibrillation and are associated with bone loss 4

In summary, while thyroxine and levothyroxine refer to the same hormone, in clinical practice, "levothyroxine" typically refers to the synthetic medication used for thyroid hormone replacement, while "thyroxine" may refer to either the naturally occurring hormone or the medication.