Optimal Prescribing of Levothyroxine Study (OPAL)
Research type
Research Study
Full title
Optimal Prescribing of Levothyroxine Study (OPAL)
IRAS ID
313119
Contact name
Simon Pearce
Contact email
Sponsor organisation
Newcastle upon Tyne NHS Foundation Trust
ISRCTN Number
ISRCTN65030272
Duration of Study in the UK
1 years, 3 months, 31 days
Research summary
Levothyroxine is the third most commonly prescribed medication in the UK and at 4 pence per 100mcg tablet is amongst the cheapest. The general assumption has been that when patients are prescribed levothyroxine for a diagnosis of hypothyroidism (thyroid underactivity), that the treatment is life-long. However, the commonest cause of hypothyroidism is Hashimoto’s (autoimmune) thyroiditis, which may result in a variable degree of mild hypothyroidism or even have a relapsing/remitting course in some patients. In addition, serum TSH may rise transiently following any ‘non-thyroidal illness’ and this physiological phenomenon may easily be mistaken for mild hypothyroidism in someone who doesn’t feel well following an intercurrent infection or other health issue. Therefore, guidelines suggest observing such patients for 3 to 6 months to see if the elevation of TSH is persistent, and then considering a trial of levothyroxine treatment in younger patients with compatible hypothyroid symptoms. Unfortunately, not all transient, variable or mild hypothyroidism is recognised as such, leading to overtreatment.
Recent evidence both from the US and UK suggests that many patients with only mildly abnormal or even normal thyroid blood tests are being prescribed levothyroxine in primary care settings. A complementary meta-analysis of 11 studies show that if levothyroxine therapy is withdrawn (“de-prescription”), 30-50% of patients remain euthyroid (with normal TSH). Thus, overprescribing of levothyroxine is a potentially detrimental situation, not only because of wasted resources in medication prescriptions and monitoring blood tests, but also because out-of-range thyroid tests are found in around 50% of people taking levothyroxine, which are associated with several undesirable health outcomes, including fractures, heart problems and increased mortality. Because levothyroxine is taken by around 3 million people in the UK, overprescribing could be adversely affecting the health of around half a million people. This study aims to address how this important public health issue can be best addressed.
The study will invite 130 patients identified from GP databases as taking levothyroxine for more than 6 months and ask them to temporarily stop taking their levothyroxine for 6 weeks. Thyroid blood tests will be done at the end of 6 weeks and quality of life will be measured at the start and end of the study. Patients will be asked what they thought about stopping their medication, how they felt during the period off levothyroxine and whether they would recommend trying off thyroid medications to a friend. After 6 weeks, patients will have the option of staying on medication if they prefer, but if their thyroid tests are suitable, they will be offered the chance to remain off levothyroxine.
REC name
West of Scotland REC 4
REC reference
22/WS/0067
Date of REC Opinion
16 May 2022
REC opinion
Favourable Opinion