The diagnosis of an underactive thyroid (hypothyroidism) is confirmed by the presence of an elevated serum thyroid-stimulating hormone (TSH) level which is the hormone secreted by the pituitary gland that regulates thyroid hormone (thyroxine (T4) and triiodothyronine (T3)) production. Every day over one million people in the UK take the thyroid hormone Levothyroxine sodium (L-T4). The goal of therapy is to restore well-being and normalise the TSH. Most patients respond satisfactorily but a minority of treated individuals experience persistent symptoms despite adequate biochemical correction. The care of such individuals is challenging and remains the subject of considerable public interest.
The healthy thyroid produces mainly T4 and much smaller amounts of the physiologically more active T3. Approximately 80% of T3 is provided by conversion of T4 to T3 with the remaining 20% of the T3 secreted direct from the thyroid. In contrast, people with hypothyroidism are treated with T4 alone, so all of their T3 is produced as a result of conversion from T4. It has been suggested that one reason why some people are not happy with L-T4 treatment is that they are not getting their supply of T3 in a physiological way, as all of it is coming from the conversion from T4. Would patients be better off with potentially more physiological combination treatment with synthetic human L-T4 and L-T3 than with L-T4 monotherapy? The British Thyroid Association has recently published a peer-reviewed position statementon the management of primary hypothyroidism (http://www.british-thyroid-association.org/sandbox/bta2016/bta_statement_on_the_management_of_primary_hypothyroidism.pdf). The benefits of combination therapy with LT-4 and LT-3 are still unproven and the potential for harm exists with unregulated use of unapproved therapies especially the lack of long term L-T3 safety data and the unavailability of L-T3 formulations which accurately mimic natural physiology.
People now have high expectations about how energetic they should feel but that does not mean that tiredness and depression should be ignored. It has been demonstrated that up to one-quarter of the healthy population have the non-symptoms associated with thyroid failure such as lethargy and weight gain. Patients should be thoroughly evaluated for other conditions that could be modified such as other autoimmune conditions and mood disorders. In some cases a retrospective review of the original diagnosis of hypothyroidism may be necessary. Symptom and lifestyle management support should be provided and further dose adjustments may be required. L-T4 is considered the most perfect hormone replacement that has yet been devised for endocrine conditions, but there are undoubtedly people who fall outside the current treatment model. Animal-derived products that contain T4 and T3 are not physiological and are not the answer in the longer term, but we do need to find ways to ensure that all our patients with hypothyroidism feel the full benefits of replacement therapy.