Abnormalities of thyroid gland structure and function may occur following treatment for childhood cancer.¹⁹³ This may be due to primary damage to the thyroid gland itself, particularly from neck irradiation, or may be secondary to damage to the hypothalamic-pituitary axis. Chemotherapy is an independent risk factor for thyroid dysfunction.

Thyroid cancer as a second primary cancer is a rare but highly significant potential long term problem following successful treatment for childhood cancer.

6.1 Special groups at risk of thyroid dysfunction

6.1.1 SURVIVORS WHO RECEIVED HIGH-DOSE RADIATION TO THE NECK

This small subgroup of survivors includes children treated for thyroid cancer and survivors of neuroblastoma who have received treatment with 131I-MIBG (meta-iodo benzyl guanidine).¹⁹⁴ These children will all require thyroid hormone replacement. Evidence level 2++,2+

Children with Hodgkin’s disease, treated with radiotherapy to the neck, have a significantly increased risk of thyroid function abnormalities, thyroid nodules and thyroid cancer, when compared with those treated with chemotherapy alone.^{32, 195, 196, 197} Estimates of the prevalence of abnormal thyroid function in this group are very variable. Transient abnormalities of thyroid function tests are common in the first 1-2 years after treatment, and may resolve spontaneously.¹⁹⁵ A significant minority, with persistently increased thyroid stimulating hormone levels, will require thyroid hormone replacement.^{32, 196} Hypothyroidism may develop decades after treatment.³² Estimates of the prevalence of thyroid nodules in this group depend upon the methods used to detect them, and at present it is not possible to give an accurate figure, or to comment on their significance. The risk of second primary thyroid cancer is significant, about 1% over a lifetime.^{32, 196, 198, 199} Evidence level 2++,2+

6.1.2 SURVIVORS WHO RECEIVED CRANIOSPINAL RADIATION

Children with brain tumours, particularly medulloblastoma, treated with craniospinal radiotherapy, have a similar increased risk of thyroid function abnormalities.^{200, 201} This risk may be less with hyperfractionated rather than conventional radiotherapy regimens.²⁰⁰ Cranial radiotherapy does not seem to confer additional risk of direct thyroid damage, but may increase risk of damage to the hypothalamic-pituitary axis. Evidence level 2++,2+

6.1.3 ADULTS WHO WERE TREATED WITH LOW-DOSE RADIOTHERAPY IN CHILDHOOD

Although there is no evidence from studies of cancer patients, in the past large numbers of children were treated with low-dose radiotherapy for non-malignant conditions, including lymphoid hyperplasia and various skin conditions. These cohorts have been followed for up to 35 years, and have a significant risk of thyroid nodules (up to 27%) and of thyroid cancer (up to 10% over 35 years).^{202, 203} Evidence level 2++

6.1.4 SURVIVORS WHO HAVE BEEN TREATED WITH TOTAL BODY IRRADIATION PRIOR TO BONE MARROW TRANSPLANTATION

Estimates of the prevalence of abnormal thyroid function tests in this group range from 10-90%.^{204, 205, 206} These are more likely in the first 1-2 years, and may be transient. Long term data are not available. Effects on hypothalamic and pituitary function are also possible following treatment. Evidence level 2+

6.1.5 SURVIVORS WHO HAVE BEEN TREATED WITH CRANIAL RADIOTHERAPY

This subgroup includes children with pituitary or hypothalamic tumours, other brain tumours and leukaemias. The effects depend on the dose of radiation used and other treatment factors, including surgery and chemotherapy.^{31, 201, 207} Evidence level 2+

Survivors of childhood cancer who received radiotherapy to the neck, spine or brain should have thyroid function checked after completion of treatment and regularly thereafter. Survivors are likely to require lifetime surveillance.

6.2 Screening for thyroid nodules or second primary thyroid cancers

There are no good quality clinical trials or cohort studies which address this question. There are preliminary studies comparing ultrasound scan with clinical examination, which suggest that the former will detect more abnormalities.^{208, 209, 210} The clinical significance of this is unclear.

At present there is insufficient evidence on which to base recommendations for screening.

Survivors who are at risk of thyroid nodules or second primary thyroid cancers should be advised of the risk of thyroid cancer and to seek urgent medical attention if they notice palpable neck masses.

6.3 Treatment options

Thyroid hormone replacement therapy is generally safe and effective. Thyroxine may need to be introduced gradually in people with potential cardiac dysfunction (eg in patients who have received anthracycline). There is no evidence to support or refute the use of thyroid hormone supplementation in cases of compensated hypothyroidism in this patient group.

Annual thyroid function tests are recommended for survivors at risk of thyroid dysfunction.

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