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monitoring thyroxine (levothyroxine) therapy

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Response to thyroxine (levothyroxine sodium) is best monitored biochemically.

Thyroid function should be assessed every 6-8 weeks until the patient is euthyroid and then rechecked annunally, aiming to maintain T4 and TSH within the normal range (1).

Elevated T4 with TSH suppression may suggest overtreatment

  • suppression of TSH with serum T4 at the upper end of the normal range or even slightly elevated is sometimes observed in those taking standard doses. These biochemical findings are indicative of over-treatment and indicate a need for dose reduction; there is evidence for long-term cardiovascular risk associated with mild over-treatment (2)

In the community, undertreatment is more likely and annual measurements of serum TSH may be valuable in assessing the adequacy of therapy and compliance

  • evidence that up to 25% of patients in the community receiving T4 for hypothyroidism are under-treated, so the adequacy of therapy and compliance should be checked by annual serum TSH measurement. In non-compliant patients who take T4 for a few days before the clinic, thyroid function tests typically reveal normal or even elevated T4 with paradoxically raised TSH (2)

In patients with persistent fatigue, somnolence, or subtle cognitive problems (forgetfulness, befuddlement) the dose can be increased by 25 μg daily, or on alternate days (3).

If the original diagnosis of hypothyroidism is in doubt once thyroxine (levothyroxine sodium) therapy has been initiated, then consider stopping treatment for 6 weeks and measure serum TSH and T4 in the non-treated patient.

NICE have stated guidance relating to monitoring of primary hypothyroidism - with different guidance with respect to adults, children and young people older than 2 years, and children less than 2 years old (4):

  • Follow-up and monitoring of primary hypothyroidism
  • Tests for follow-up and monitoring of primary hypothyroidism
    • Aim to maintain TSH levels within the reference range when treating primary hypothyroidism with levothyroxine. If symptoms persist, consider adjusting the dose of levothyroxine further to achieve optimal wellbeing, but avoid using doses that cause TSH suppression or thyrotoxicosis.
    • Be aware that the TSH level can take up to 6 months to return to the reference range for people who had a very high TSH level before starting treatment with levothyroxine or a prolonged period of untreated hypothyroidism. Take this into account when adjusting the dose of levothyroxine

  • Adults
    • For adults who are taking levothyroxine for primary hypothyroidism, consider measuring TSH every 3 months until the level has stabilised (2 similar measurements within the reference range 3 months apart), and then once a year.
    • Consider measuring FT4 as well as TSH for adults who continue to have symptoms of hypothyroidism after starting levothyroxine

  • Children and young people aged 2 years and over
    • For children aged 2 years and over and young people taking levothyroxine for primary hypothyroidism, consider measuring FT4 and TSH:
    • every 6 to 12 weeks until the TSH level has stabilised (2 similar measurements within the reference range 3 months apart),
    • then every 4 to 6 months until after puberty,
    • then once a year

  • Children under 2 years
    • For children aged between 28 days and 2 years who are taking levothyroxine for primary hypothyroidism, consider measuring FT4 and TSH:
    • every 4 to 8 weeks until the TSH level has stabilised (2 similar measurements within the reference range 2 months apart),
    • then every 2 to 3 months during the first year of life,
    • and every 3 to 4 months during the second year of life

Notes:

  • in the majority of patients, dose requirements for T4 do not change
    • however pregnancy often necessitates a dose increase to maintain serum TSH within the normal range. Therapy with some drugs also alters T4 dose requirements, because of effects on T4 absorption or metabolism
      • rifampicin, phenytoin, carbamazepine (increased clearance of thyroxine)
      • cholestyramine, sucralfate, aluminium hydroxide, ferrous sulphate (reduced absorption of thyroxine)

Reference:

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