What is the difference between thyroxine (T4) preparations, including synthetic levothyroxine, liothyronine (T3), and natural desiccated thyroid (NDT) extracts like Armour Thyroid (liothyronine and levothyroxine)?

Differences Between Thyroid Hormone Preparations

Levothyroxine (T4) is the standard first-line treatment for hypothyroidism due to its consistent hormone levels and established safety profile, while liothyronine (T3) and natural desiccated thyroid extracts are generally reserved for specific cases where patients remain symptomatic despite optimal T4 therapy. 1

Levothyroxine (T4)

• Composition: Synthetic crystalline L-3',5'-tetraiodothyronine sodium salt, chemically identical to naturally produced T4 2
• Mechanism: Acts as a prohormone that is converted peripherally to the active T3 form
• Advantages:
  • Long half-life allowing once-daily dosing
  • Provides stable hormone levels without diurnal fluctuations
  • Missing occasional doses causes minimal disruption
  • Maintains the body's natural T4-to-T3 conversion mechanisms 3
• Dosing: Typically 1.6 mcg/kg/day, adjusted based on TSH levels 1
• Monitoring: TSH levels every 6-8 weeks during dose adjustments and every 6-12 months once stable 1

Liothyronine (T3)

• Composition: Synthetic form of triiodothyronine (T3), the active thyroid hormone 4
• Mechanism: Direct action as the active thyroid hormone without requiring conversion
• Characteristics:
  • Short half-life requiring multiple daily doses
  • Causes more rapid changes in thyroid hormone levels
  • May cause transient episodes of hypertriiodothyroninemia 5
• Clinical use: Generally reserved for specific situations:
  • As add-on therapy for patients symptomatic on levothyroxine alone
  • Typical starting dose when adding to levothyroxine: 2.5-7.5 mcg once or twice daily 5

Natural Desiccated Thyroid (NDT)

• Composition: Animal-derived thyroid extract containing both T4 and T3 in approximately a 4:1 ratio 4, 5
• Examples: Armour Thyroid, ERFA Thyroid
• Characteristics:
  • Contains multiple thyroid hormones in fixed ratios
  • Less standardized than synthetic preparations
  • Not under formal FDA oversight; consistency monitored by manufacturers 5
• Clinical use:
  • May be considered for patients who remain symptomatic on levothyroxine
  • Mean daily dose typically contains ~11 mcg T3 5
  • Some studies show improved quality of life metrics in levothyroxine-unresponsive patients 6

Comparative Efficacy and Safety

• First-line recommendation: Levothyroxine is recommended by the American Thyroid Association as first-line therapy 1
• Combination therapy: For patients who remain symptomatic on levothyroxine alone, guidelines suggest a trial of combination therapy (T4+T3) 5
• Safety considerations:
  • Overtreatment with any preparation can lead to bone mineral density loss, particularly in postmenopausal women 1, 3
  • Elderly patients and those with cardiac disease require more conservative dosing due to increased risk of complications 1
  • T3-containing preparations may cause more pronounced cardiac effects due to rapid absorption and serum level fluctuations 7

Clinical Decision Making

1. Start with levothyroxine for newly diagnosed hypothyroid patients 5
2. Monitor response using TSH levels (target 1-2 mU/L for primary hypothyroidism) 3
3. For persistent symptoms despite normal TSH:
   • Consider trial of combination therapy (reducing levothyroxine by 25 mcg and adding 2.5-7.5 mcg liothyronine) 5
   • OR consider natural desiccated thyroid as an alternative 6
4. Monitor closely for overtreatment (TSH <0.2 mU/L) which increases risk of atrial fibrillation and bone loss 7

Important Caveats

• Bioequivalence may differ among generic and brand name levothyroxine preparations 7
• Some patients may have tissue-specific T3 requirements not reflected in serum TSH measurements 7
• Patients with diabetes may experience worsened glycemic control even with optimal thyroid hormone doses 1
• Iron is crucial for thyroid function; iron deficiency anemia can be associated with thyroid dysfunction 8