Colin Dayan and Vijay Panicker
Keywords: Levothyroxine, Liothyronine, T4, T3, Thyroid hormone replacement
Whilst trials of combination levothyroxine/liothyronine therapy versus levothyroxine monotherapy for thyroid hormone replacement have not shown any superiority, there remains a small subset of patients who do not feel well on monotherapy. Whilst current guidelines do not suggest routine use of combination therapy they do acknowledge a trial in such patients may be appropriate. It appears that use of combination therapy and dessicated thyroid extract is not uncommon but often being used by non-specialists and not adequately monitored. This review aims to provide practical advice on selecting patients, determining dose and monitoring of such a trial.
It is important to select the correct patient for a trial so as to not delay diagnosis or potentially worsen an undiagnosed condition. An appropriate starting dose may be calculated but accuracy is limited by available formulations and cost. Monitoring of thyroid function, benefits and adverse effects are vital in the trial setting given lack of evidence of safe long term use. Also important is that patients understand set up of the trial, potential risks involved and give consent.
- Alternatives to LT4 monotherapy for thyroid hormone replacement are being used in a small percentage of hypothyroid patients and it appears frequently without specialist oversight and appropriate monitoring. If specialists are willing to discuss the available evidence, possible benefits and adverse effects of such therapy with patients, it is likely to make this practice safer.
- Be aware of formulations of LT3 and LT4/LT3 available locally and if possible their pharmacokinetics. Errors in the preparations of compounded preparations have been reported.
- Starting dose in a patient on adequate LT4 monotherapy will always require removal of part of the LT4 dose and replacement with LT3. In practice the dose of LT3 will usually be a dose of 5 – 20 mcg a day in a split dose, by necessity often determined by the availability of low dose formulations of LT3.
- Initial trial 6 months, and then confirm benefit is still present at least 1 year before planning long-term therapy.
- Patients should be monitored indefinitely for cardiovascular, psychological and bone adverse effects.
- Be aware and make patients aware of costs and availability of formulations prior to prescribing.
- Whilst all major endocrine and thyroid societies advise against the use of DTE for hypothyroidism, it is clear that its use remains significant. Better regulated formulations and trials are required to determine its role, if any. Until these are available patients who continue to use DTE should be advised on appropriate safety monitoring as for using T4/T3.
Whilst evidence is lacking on whether a small group of patients may benefit from combination therapy a trial may be indicated in those who remain symptomatic despite adequate levothyroxine monotherapy. This should be undertaken by clinicians experienced in the field with appropriate monitoring for adverse outcomes in both short and long term.
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