Treating an underactive thyroid

on Wed 8 Feb


Every day over one million people in the UK take the thyroid hormone Levothyroxine sodium (L-T4) for an underactive thyroid (hypothyroidism). The goal of therapy is to


  • restore well-being
  • normalise the serum thyroid-stimulating hormone (TSH) level


 - TSH being the hormone which is secreted by the pituitary gland and which regulates thyroid hormone (thyroxine (T4) and triiodothyronine (T3)) production.


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.


Diagnosis and Evidence

The diagnosis of primary hypothyroidism is based on the clinical features of hypothyroidism supported by biochemical evidence of an elevated serum TSH together with low free T4 (overt hypothyroidism).


The earliest evidence of an underactive thyroid (hypothyroidism) is an elevated serum TSH.


About serum TSH levels

There has been a growing controversy about the upper limit of the reference range for serum TSH and at what point patients actually benefit from thyroid hormone replacement.


To establish a “normal” reference range in the first place we look at large group of people who do not have thyroid disease and are otherwise well. By convention this only comprises 95% of a reference population.


Therefore it is understood that, 2.5% of ‘normal’ individuals will fall above the reference range and 2.5% will fall below the range.


By doing this the reference range for serum TSH in thyroid- disease- free individuals is accepted as between 0.4 and 4.0 mU/l.


Studies and Trials

Studies addressing the relationship between symptoms suggestive of thyroid hormone deficiency and the biochemical finding of a mildly elevated TSH and a normal T4 (subclinical hypothyroidism) have produced conflicting results.


What’s more, in randomised controlled trials, there is inconsistent evidence for the benefit of thyroid hormone treatment in subclinical hypothyroidism.


The conclusion is that Primary hypothyroidism should not be diagnosed in individuals with a serum TSH within the population reference range and who have intact pituitary function.


Thyroid Function

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.


So would patients be better off with potentially more physiological combination treatment with synthetic human L-T4 and L-T3 than with L-T4 monotherapy?


In considering this The British Thyroid Association recently published a peer-reviewed position statement in the leading UK endocrine journal Clinical Endocrinology on the management of primary hypothyroidism. See here


This is based on a review of the recently published positions of the American Thyroid Association (ATA) and the European Thyroid Association (ETA); upon current literature and upon the best principles of good medical practice.


This statement has been endorsed by the Association of Clinical Biochemistry (ACB);  the British Thyroid Foundation (BTF);  the Royal College of Physicians (RCP);  and the Society for Endocrinology (SFE).


In brief the conclusion is that 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.


Our advice to the medical community

People may 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-specific symptoms associated with thyroid failure such as lethargy and weight gain. However, patients should be thoroughly evaluated for other modifiable conditions such as other autoimmune conditions and mood disorders.


This may mean that in some cases a retrospective review of the original diagnosis of hypothyroidism may prove to be necessary.


Symptom and lifestyle management support should be provided and further dose adjustments may be required.


L-T4 is considered the most effective 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.



Although every effort is made to ensure that all health advice on this website is accurate and up to date it is for information purposes and should not replace a visit to your doctor or health care professional.


As the advice is general in nature rather than specific to individuals the BTA cannot accept any liability for actions arising from its use nor can he be held responsible for the content of any pages referenced by an external link.