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本篇文章截止時間為：2020年12月20日
A 40 year old woman complains of tiredness over the past few weeks. She had atotal thyroidectomy three years ago for Graves′ thyrotoxicosis and has been taking levothyroxine since then. She weighs 80 kg and is taking 150 μg daily. A blood test done in the previous week showed thyroid stimulating hormone(TSH)levels above 30mU/L (reference range 0.4-4.5mU/L).
Some hypothyroid patients continue to have symptoms or biochemical evidence of hypothyroidism (serum TSH above the upper laboratory reference range) despitestandard thyroid replacement therapy. The prevalence of treatment-refractory hypothyroidism is not established.Studies in different populations report about a third ofpatients taking thyroid medications have TSH levels above the reference range,suggesting inadequate thyroid hormone replacement1-2.
Further dose increase may not always be appropriate.Patients may not be taking the treatment regularly as advised.Conditions that decrease absorption or increase demand for thyroxine may also be responsible (see box 1). A recent expert consensus report recommends identifying and addressing the likely cause before increasing the daily dose of levothyroxine above 1.9μg/kg body weight3.
What you should cover
Look for possible causes
•Ask about adherence to treatment. Is the patient taking the levothyroxine tablets regularly?
•Is she taking levothyroxine alongside other medications or with meals? Several foods and medications interfere with the absorption of levothyroxine in the intestine (see box 1).Certain medications increase the metabolism oflevothyroxine.
•Review her medication list, tablet box, and prescription history.
•If the patient acknowledges non ⁃ adherence, explore the reasons for it in the context of herlife. What else is going on in her life? Is she stressed? Does she understand what the tablets are for? Has she searched for information on the internet? Has she any concerns about side effects? Does she miss tablets because she finds it hard to wake up and because it says take on an empty stomach? Is the drug well tolerated?
•Is the patient pregnant? Pregnancy increases the demand for levothyroxine.
•Has the patient got any symptoms or signs to suggest malabsorption? Vomiting, diarrhoea, or weight loss accompanied by anaemia can suggest malabsorption.However, many patients have no symptoms.
What you should do
Explain why regular treatment is important and how it is to be taken
Draw up a shared management plan that incorporates the patient′s goals and preferences. Inform patients that not taking recommended levothyroxine replacement puts them at risk of weight gain, raised cholesterol levels,tiredness, depression,and, over a longer time period, myxoedema coma, which can be fatal4.
Explain that the absorption of levothyroxine tablets can be affected by other substances taken at the same time.Advise the patient to take levothyroxine on an empty stomach with water at least an hour before breakfast or any other tablets in the morning. This has been shown to optimise absorption5.
Discuss other ways to improve adherence (such as a dosette box, alarms or reminders on phone, tablet counting,etc). Measures such as taking levothyroxine at bed time,trying a different preparation of levothyroxine (brand, liquid formulation), or supervised weekly dose may be considered in patients who find it hard to adhere to treatment, but there is no evidence to support these.
Dose increase
Levothyroxinedose increment of 25-50 μg may be appropriate for patients taking other medications that decrease its bioavailability. Increasing the dose by 25-50 μg is also advised in pregnant women taking levothyroxine for optimal fetal growth and development. Monitor serum TSH every 6-8weeks, aiming to keep it<2.5mU/L throughout pregnancy6.
Assess the effect of advised changes
Offer the patient an initial full thyroid function test (TSH and free thyroxine levels in the blood)as well as simple screening tests for malabsorption (such as full blood count,serum levels of vitamin B12, folate, ferritin, calcium, and albumin, and coeliac antibody test).Recheck thyroid function after six weeks to see the effect of the above changes.
Referral
Consider referral to an endocrinologist if:
•TSH levels remain elevated after six weeks despite the above advice and changes in the absence of malabsorption.An endocrinologist may perform levothyroxine absorption challenge tests to differentiate true malabsorption from non-adherence to treatment(pseudomalabsorption)3,7⁃8. Paired blood samples may need to be sent to an alternative laboratory to rule out TSH assay interference.
•Symptoms or blood test results suggest true malabsorption(for example,deficiencies of vitamin B12, folate, ferritin, or calcium and positive coeliac antibody test).
Laura J McNally clinicalfellow 1,
Catherine I Ofiaeli general practitioner 2,
Samson O Oyibo consultantendocrinologist 1
1PeterboroughCity Hospital, Peterborough PE3 9GZ, UK;
2NewQueen Street Surgery, Peterborough PE7 1AT
Correspondence to: S O Oyibo samoyibo@yahoo.co.uk
BMJ 2019;364 doi: https://doi.org/10.1136/bmj.l579