All physicians will see some patients who do not feel totally well even after normalising thyroid blood tests using just thyroxine. These patients complain of a variety of symptoms such as fatigue, lethargy, weight gain and general poor health despite a long period of normal blood test results. The symptoms suggest persistence of hypothyroidism which in some cases gets better when T4/T3 combinations are tried out.

Some doctors dismiss these symptoms as being part of another disease process such as depression and that the resolution on T4/T3 as being a placebo effect. There does however remain a theoretical basis for an improvement when T3 is added to the mix. Not all tissues may not be able to generate T3 from T4, this process is governed by enzymes and a defective conversion process in the brain for example could result in persistence of hypothyroid symptoms.