Persistent symptoms in patients treated for hypothyroidism are common. Despite more than 20 years of debate, the use of liothyronine for this indication remains controversial, as numerous randomised trials have failed to show a benefit of treatment regimens that combine liothyronine (T3) with levothyroxine over levothyroxine monotherapy. This consensus statement attempts to provide practical guidance to clinicians faced with patients who have persistent symptoms during thyroid hormone replacement therapy. It applies to non-pregnant adults and is focussed on care delivered within the UK National Health Service, although it may be relevant in other healthcare environments. The statement emphasises several key clinical practice points for patients dissatisfied with treatment for hypothyroidism. Firstly, it is important to establish a diagnosis of overt hypothyroidism; patients with persistent symptoms during thyroid hormone replacement but with no clear biochemical evidence of overt hypothyroidism should first have a trial without thyroid hormone replacement. In those with established overt hypothyroidism, levothyroxine doses should be optimised aiming for a TSH in the 0.3-2.0 mU/L range for 3 to 6 months before a therapeutic response can be assessed. In some patients, it may be acceptable to have serum TSH below reference range (e.g. 0.1-0.3 mU/L), but not fully suppressed in the long term. We suggest that for some patients with confirmed overt hypothyroidism and persistent symptoms who have had adequate treatment with levothyroxine and in whom other comorbidities have been excluded, a trial of liothyronine/levothyroxine combined therapy may be warranted. The decision to start treatment with liothyronine should be a shared decision between patient and clinician. However, individual clinicians should not feel obliged to start liothyronine or to continue liothyronine medication provided by other health care practitioners or accessed without medical advice, if they judge this not to be in the patient's best interest.

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