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Third of patients on levothyroxine have no reason to take the drug, claim researchers

UK researchers claim that up to a third of patients in primary care taking levothyroxine could be prescribed the drugs ‘without an accepted indication’.

The Cardiff University team found many patients were prescribed levothyroxine at TSH levels below 10.0 mIU/L, but with thyroxine (T4) levels in the reference range and no hypothyroidism symptoms.

The researchers looked at UK Clinical Practice Research Datalink records for over 50,000 patients prescribed levothyroxine between 2001 and 2009, and found there had been a 30% increase in the likelihood of treatment being started at TSH levels below 10.0 mIU/L – the usual cut-off for diagnosing overt hypothyroidism – over this time.

Among the 67% of patients who also had free T4 data available, around 30% had levothyroxine prescribed at a TSH level below 10.0 mIU/L and with T4 levels in the reference range, indicating subclinical hypothyroidism, despite having no classic hypothyroidism symptoms or cardiovascular risk factors.

The researchers said their results showed an increasing trend towards prescribing levothyroxine in patients with subclinical hypothyroidism, where the evidence base is weak and the risks might outweigh the benefits.

Overall, the researchers found older people were the most likely to be started on levothyroxine at borderline TSH levels of between 4.0 and 10.0 mIU/L, even with normal T4 levels, which they said was concerning because ‘treatment of subclinical hypothyroidism in individuals older than 70 years has less cardiovascular benefit than that in younger persons, and overtreatment in older patients may cause net harm’.

Even marginal overtreatment with levothyroxine can lead to low TSH levels, putting elderly patients at risk of osteoporotic fractures and atrial fibrillation, the researchers noted.

The team concluded in JAMA Internal Medicine this month: ‘In the United Kingdom, 1.6 million individuals are on long-term levothyroxine regimens, most of whom have been prescribed it for primary hypothyroidism. If current practice continues, up to 30% of persons receiving levothyroxine may have been prescribed it without an accepted indication and with the potential for net harm if they develop even a low thyrotropin level.’

Professor Simon Pearce, professor of endocrinology at Newcastle University, commented: ‘In contrast to the lack of prognostic benefits of levothyroxine therapy for subclinical hypothyroidism, there is known to be an excess of fractures in those taking levothyroxine who have a suppressed TSH (<0.05 mU/l), and in patients over 70 years taking larger doses of levothyroxine (>100 mcg daily).

‘There is also a small excess risk of cardiac events and atrial fibrillation in those with a fully suppressed TSH (<0.05 mU/l).’

He added: ‘The take-home message should be that many older patients without symptoms of subclinical hypothyroidism would have been safer living with a serum TSH in the 4 to 10mU/l range than being over-treated to a suppressed TSH level.’

Professor Pearce said optimal practice would be to simply monitor these untreated patients once or twice yearly for the development of symptoms and for progression to overt hypothyroidism, although the risk of progression is small, at less than 5% per year.

He said: ‘If levothyroxine treatment is started, the aims should be to alleviate symptoms (if present) and to keep the TSH in the reference interval. Nevertheless, and in contrast to what is generally believed, there is no hard evidence to show that patients who are slightly over-treated with levothyroxine as judged by a serum TSH in the 0.1-0.4mU/l range have any untoward outcomes.’