Treatment

‘Block and replace’ regimen for 36 months.

• Carbimazole is commenced in a total daily dose of 0.75 mg/kg/day,(5mg and 20mg tablets).
• Initial Dose should not exceed 40mg per day. The intention is to completely prevent endogenous thyroxine production. Thyroxine is then added in a replacement dose as the patient becomes euthyroid and then hypothyroid.
• If thyroxine values remain elevated (> 2SD, i.e. outside the lab ref range) at 2 months into treatment or beyond with a suppressed TSH then consider increasing the dose to 1 mg/kg. However, it is unlikely that a child will require more than 40mg daily of Carbimazole, so consider compliance issues if larger doses appear necessary.
• When Free thyroid hormone levels are <15 pmol/l, start thyroxine in a low replacement dose ~ 75 micrograms / m².
• If the TSH is suppressed and the free thyroxine is low or in the bottom part of the normal range in the initial phase of treatment (the first 4 months) then thyroxine should still be commenced. (A delay in the rise of TSH after treatment has commenced is common).
• The treatment regimen may not require adjustment if the free thyroxine is relatively high but the TSH is normal.
• If compliance is not a concern and if the dose of thyroxine is not greater than 75micrograms/m² then a suppressed TSH beyond the first 4 months of therapy should be managed by increasing the dose of carbimazole in the first instance.
• If the patient becomes thyrotoxic with a suppressed TSH when the biochemistry has been normal at an earlier stage of therapy – check compliance and consider increasing the dose of carbimazole by 5 mg/day. It is unlikely that a child will require more than 40mg daily of Carbimazole, so consider compliance issues if larger doses appear necessary.
• If the patient subsequently develops a high TSH then increase the dose of thyroxine up to 100 micrograms/m² /day or by 12.5 to 25 microgram increments (12.5 micrograms under 30 kg, 25 micrograms for those over 30kg)

Dose titration for 36 months with carbimazole alone. 

• Carbimazole is commenced in a total daily dose of 0.75 mg/kg/day until the child is euthyroid (the initial dose should not exceed 40mg per day).
• The dose is then reduced to 0.25 mg/kg/day with the intention of maintaining a euthyroid state.
• The primary objective of treatment is to maintain free T4 concentrations in the normal laboratory range with a TSH that is also within the normal laboratory range (neither elevated nor suppressed):
  
  • The dose of carbimazole will be adjusted up or down depending on the thyroid function. It is unlikely that a child will require more than 40mg daily of Carbimazole, so consider compliance issues if larger doses appear necessary.
  • If the patient is hypothyroid then the carbimazole dose will be reduced by 5mg/day for those patients under 30 kg and 10 mg for those over 30kg.
• If the patient is hyperthyroid then it will be increased by 5mg for those patients under 30 kg and 10 mg for those over 30kg.
• Be primarily guided by the thyroid hormone value (not the TSH) in the first 4 months after diagnosis.
• Be guided by both the TSH and free T4 thereafter; if the TSH is suppressed in the presence of normal free T4 values then consider reducing the dose of carbimazole as detailed above.
• The treatment regimen may not, therefore, need to be adjusted if the TSH is suppressed and the free thyroxine is normal in the initial phase of treatment (the first 4 months).
• The treatment regimen may not need to be adjusted if the free thyroxine is relatively high but the TSH is normal (analogous to the congenital hypothyroid patient who may have a normal TSH but a relatively high free T4 when on T4 replacement).

Propylthiouracil

Most paediatricians in the UK commence thyrotoxic children on carbimazole rather than propylthiouracil although either drug can be taken once a day and they have similar side effects. The guidelines detailed here can be used in the knowledge that 1mg of carbimazole is approximately equivalent to 10 mg of propylthiouracil.

Propranolol

Propranolol or other beta-blockers can be used to give relief from symptoms such as anxiety, tremor and palpitations in the first few weeks of treatment.

Propranolol can be given orally at a dose of 250–750 µg/kg/dose three times per day.

It can be weaned and stopped as the patient becomes euthyroid.

Side effects of carbimazole and propylthiouracil (Thionamides)

Minor side effects such as rashes, nausea, and headaches occur in 2–15% of patients and usually develop during the first weeks of therapy.

Agranulocytosis is reported to occur in 0.1-0.5% of patients on either carbimazole or propylthiouracil in equal numbers. It most often occurs in the first 3 months after starting treatment, but occasionally a long time afterwards. It also occurs suddenly, so routine monitoring of full blood count is of little use.

Alternatives to Carbimazole and Propylthiouracil

Iodide blocks thyroid hormone synthesis and release and can be administered in addition to ß blockade. Its action tends to diminish over time so it cannot be used in the long term. Lithium also has antithyroid properties by blocking thyroxine release and has been used occasionally in adults before surgery and radioiodine treatment.

Radioiodine therapy and Surgery are definitive treatment options for thyrotoxicosis. They will ultimately render the child permanently euthyroid, or hypothyroid (requiring long-term thyroxine replacement). Although drug based treatments are currently the favoured treatment option outlined here, there are several reasons that a definitive treatment option may be sought:

• Treatment failure – for compliance reasons, medical treatment may fail to allow the child to reach a euthyroid state for any reasonable time.
• ‘Relapse’ – After 36 months a trial off drug therapy may result in a recurrence of thyrotoxicosis. The patient may choose to continue drug therapy in the long term or may wish definitive treatment.

Patient choice

As outlined above, there are pros and cons of each treatment option in thyrotoxicosis. Before embarking on a particular treatment plan, the child and their parents should be equipped to make an informed choice by meeting to discuss the options with their paediatric endocrinologist, the radiologist and the surgeon. Referrals for this may need to be made across NHS trusts depending preferences and availability of these services.

Radioiodine Therapy

The aim of radioiodine therapy is to ablate the thyroid and render the patient hypothyroid.

Antithyroid medication should be stopped 3–7 days prior to RI therapy and be recommenced, if necessary, one week afterwards. It should be restarted earlier in the patient thought to be at risk of a thyroid storm, although this may also compromise the efficacy of RI therapy.

Titrating the RI dose according to gland size requires a tracer dose of 131 I, and recent reports have used a predetermined amount between 300 and 550 MBq during adolescence.

Patients should be reviewed within the first few days after RI therapy because of the small possibility of a thyroid "crisis", and then every six weeks so that thyroxine replacement can be initiated before the patient becomes profoundly hypothyroid.

Some patients will require a second dose of RI (more likely if lower doses are used). Children and adolescents receiving RI in an average dose of 14.7 mCi ( 540 MBq), hypothyroidism developed between 40 and 90 days in 75% of patients.¹⁴

Surgery

Subtotal thyroidectomy has the potential to render the patient euthyroid off therapy although the likelihood of recurrence or of hypothyroidism has resulted in many surgeons recommending total thyroidectomy