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Treatment-refractory hypothyroidism

BMJ 2019; 364 doi: (Published 25 February 2019) Cite this as: BMJ 2019;364:l579
  1. Laura J McNally, clinical fellow1,
  2. Catherine I Ofiaeli, general practitioner2,
  3. Samson O Oyibo, consultant endocrinologist1
  1. 1Peterborough City Hospital, Peterborough PE3 9GZ, UK
  2. 2New Queen Street Surgery, Peterborough PE7 1AT
  1. Correspondence to: S O Oyibo samoyibo{at}

What you need to know

  • Persistent symptoms of hypothyroidism or raised serum levels of thyroid stimulating hormone (TSH) despite optimum thyroid hormone replacement (up to 2.0 μg/kg body weight of levothyroxine) suggest treatment-refractory hypothyroidism

  • Explore adherence to treatment and conditions that impair absorption (taking the drug with medications or food, coeliac disease, etc) or increase demand (pregnancy, other medications)

  • Discuss measures such as taking the tablet on an empty stomach in the morning an hour before other food or medications and using reminders, such as dosette boxes, to improve adherence

A 40 year old woman complains of tiredness over the past few weeks. She had a total 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 30 mU/L (reference range 0.4-4.5 mU/L).

Some hypothyroid patients continue to have symptoms or biochemical evidence of hypothyroidism (serum TSH above the upper laboratory reference range) despite standard thyroid replacement therapy. The prevalence of treatment-refractory hypothyroidism is not established. Studies in different populations report about a third of patients taking thyroid medications have TSH levels above the reference range, suggesting inadequate thyroid hormone replacement.12

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 …

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