Dr Vijay Panicker

While there’s no evidence of benefit of T4/T3 (liothyronine) combination therapy in hypothyroidism for most patients, some  may be considered for a trial of treatment, according to endocrinologists in WA.

A subgroup of patients with hypothyroidism have persistent symptoms and poor wellbeing despite T4 (levothyroxine) monotherapy, and may turn to alternative practitioners or self treat with potentially risky treatments such as dessicated thyroid extract, according to Dr Vijay Panicker, of the department of endocrinology at the Sir Charles Gairdner Hospital in Perth.

Writing in Thyroid Research, Dr Panicker and co-author Professor Colin Dayan from the UK, say that alternatives to T4 monotherapy are already being used by some hypothyroid patients without adequate oversight or appropriate monitoring.

To avoid this they suggest endocrinologists identify patients who do not respond well to monotherapy and select those who may be suitable for a trial of combination T4/T3 therapy.

The clinicians stress it is important to clarify the initial diagnosis of hypothyroidism, ensure that an adequate dose of T4 has been used and consider co-morbidities – especially psychological ones. Patients with cardiovascular disease, arrhythmia, pregnancy or thyroid cancer, would be at risk of adverse effects and would be excluded, they add.

An initial trial of six months is suggested because it may take three months for steady state to be achieved,  and some initial benefit of T3 treatment may be due to euphoria or placebo effect.

The authors say that when starting a trial of combination therapy, the dose of T4 will have to be reduced, and the dose of T3 should be carefully calculated and given in a split dose or as a sustained release formulation. However they caution that the pharmacokinetics of slow release formulations prepared by compounding pharmacies may be inconsistent and require careful monitoring.

“Patients should be monitored indefinitely for cardiovascular, psychological and bone adverse effects,” they add.

In Australia liothyronine is available on the PBS for patients who have a documented intolerance or resistance to thyroxine, “which is open to the interpretation of the treating physician,” the authors note. It is available on private prescription for a cost of about about A$142 for a year.

They say large randomised controlled trials are still needed to provide evidence of T3 efficacy in subgroups of patients who do not respond to T4 monotherapy. But until these trials are done it may be reasonable to offer such patients a trial of combination therapy.

“It is important that this be performed by a clinician with adequate knowledge and experience in the area, with appropriate patient selection, clear explanation of risks and benefits to the patient for consent and careful monitoring and follow-up,” they conclude.