Is Armour Thyroid (thyroid extract) more effective than thyroxine (T4) for treating hypothyroidism?

Levothyroxine Monotherapy Remains Superior to Armour Thyroid for Hypothyroidism Treatment

Levothyroxine (T4) alone should remain the treatment of choice for hypothyroidism, as studies show no clear advantages of combination therapy or desiccated thyroid extract (Armour Thyroid) over levothyroxine monotherapy, and the potential risks of supraphysiologic T3 levels outweigh any uncertain benefits. 1

Evidence Against Armour Thyroid and Combination Therapy

Limited and Inconsistent Benefits

• Out of 15 clinical trials evaluating combined levothyroxine plus liothyronine treatment, only 2 studies showed beneficial effects on mood, quality of life, and psychometric performance compared to levothyroxine alone 1
• The majority of trials (13 out of 15) failed to demonstrate superiority of combination therapy over levothyroxine monotherapy 1
• Patient preference for combination therapy in some studies must be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine 1

Specific Concerns with Desiccated Thyroid Extract (Armour Thyroid)

• Desiccated thyroid extract contains a T4/T3 ratio of approximately 4:1, with the mean daily dose needed to normalize serum TSH containing approximately 11 mcg T3, though some patients may require higher doses 2
• DTE remains outside formal FDA oversight, and consistency of T4 and T3 contents is monitored by manufacturers only, raising significant quality control concerns 2
• Desiccated thyroid preparations frequently cause serum T3 to rise to supranormal values during the absorption phase, associated with palpitations and other symptoms of excess thyroid hormone 3

Why Levothyroxine Monotherapy Is Preferred

Pharmacologic Advantages

• Levothyroxine has a long half-life allowing once-daily administration, and occasional missed doses cause no harm 3
• The extrathyroidal conversion of T4 into T3 (normally providing 80% of the daily T3 production rate) remains fully operative with levothyroxine monotherapy, which may have protective value during illness 3
• Long-term use of levothyroxine is not associated with excess mortality when properly dosed 3

Safety Profile

• Levothyroxine monotherapy avoids the risk of transient hypertriiodothyroninemia that occurs with combination therapy or desiccated thyroid extract 3
• Recent evidence from two independent large population studies shows that mortality of hypothyroid patients treated with levothyroxine is increased only when serum TSH falls outside the normal reference range, supporting the safety of properly dosed levothyroxine monotherapy 4

When Combination Therapy Might Be Considered

Limited Indications

• A trial of combination therapy with LT4+LT3 can be considered only for patients who have unambiguously not benefited from LT4 monotherapy despite achieving biochemical euthyroidism 2
• For patients remaining symptomatic on LT4 therapy, clinical guidelines recommend, on a trial basis only, therapy with LT4+LT3 2

Appropriate Dosing if Combination Therapy Is Attempted

• Reducing the LT4 dose by 25 mcg/day and adding 2.5-7.5 mcg liothyronine once or twice daily is an appropriate starting point 2
• Trials following almost 1000 patients for almost 1 year indicate that therapy with LT4+LT3 can restore euthyroidism while maintaining normal serum TSH, similar to LT4 alone 2
• An observational study of 400 patients with mean follow-up of approximately 9 years did not indicate increased mortality or morbidity risk due to cardiovascular disease, atrial fibrillation, or fractures after adjusting for age when compared with patients taking only LT4 2

Critical Pitfalls to Avoid

• Do not initiate desiccated thyroid extract as first-line therapy for newly diagnosed hypothyroid patients—levothyroxine monotherapy should always be the initial treatment 2
• Avoid using desiccated thyroid extract due to lack of FDA oversight and inconsistent T4 and T3 content between batches 2
• Do not prescribe combination therapy or desiccated thyroid extract for patients who have not first been optimally managed on levothyroxine monotherapy with confirmed normal TSH levels 2
• Approximately 25% of patients on thyroid hormone therapy are unintentionally maintained on doses high enough to suppress TSH completely, risking osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy—this risk applies to all forms of thyroid hormone replacement 5

Monitoring Requirements

• The recommended full replacement dose of levothyroxine is approximately 1.6 mcg/kg/day for patients under 70 years without cardiac disease 5
• TSH should be monitored every 6-8 weeks during dose titration, with target TSH in the reference range (0.5-4.5 mIU/L) 6, 5
• Once adequately treated with stable dose, repeat TSH testing every 6-12 months 6