Inadequate response to thyroxine replacement therapy for hypothyroidism in adults
Inadequate response to levothyroxine refers to persistence of high serum TSH or low serum T4 concentrations, despite continuous uptitration of levothyroxine (eg higher than 300 micrograms daily).
Check that the patient is adhering to the dosage regimen. If adherence to a daily dose is not feasible, a single weekly dose of levothyroxine, equal to the total weekly dose, can safely be used for maintenance therapy. If the appropriate total weekly dose is unclear because the patient has not been taking their dose regularly, start with 11.2 micrograms/kg/week (ie 1.6 micrograms/kg/day) to the nearest 100 micrograms. Check thyroid function before starting weekly dosing, and again after 4 to 8 weeks of stable dosing.
Also consider factors that impair levothyroxine absorption, such as concomitant drug therapy (see Drugs that influence thyroid hormones), incorrect storage of levothyroxine1 and coeliac disease. The absorption of levothyroxine can also be impaired by food—advise patients to take levothyroxine consistently in relation to food.
Persistently high serum TSH but normal or elevated serum T4 concentrations can be due to intermittent poor adherence, but this should also prompt consideration of laboratory error (eg heterophile antibody interference). Consider contacting the laboratory to confirm the result.
Although less common, inadequate response to treatment can also refer to a patient who reports continued symptoms despite normalised thyroid function tests. The most commonly reported symptoms are fatigue, neurocognitive symptoms and weight gain. Consider the presence of coexisting medical disorders (eg autoimmune or psychological disorders).
If other contributing factors are excluded and the response to treatment is still inadequate, seek specialist advice.