Dr Robert Legg and Dr Jaya Sujatha Gopal-Kothandapani

In part 2 of our discussion of the late endocrine effects of chemotherapy, we continue to consider the cases of Jan and Emma (both 12 years old, with ALL, receiving cyclophosphamide and TBI in preparation for bone marrow transplant), and Bethany (7 years old, with craniopharyngioma, receiving cranial radiotherapy).

This time we look at bone health, metabolic syndrome and thyroid function.

If you haven’t seen Part 1 yet, here it is

Bone Health

Children acquire peak bone mass at the end of their sexual maturity and so the effects of treatment will be most significant during their adolescence and young adulthood.  Chemotherapy (particularly methotrexate), steroids, cranial radiotherapy, bone marrow transplant and secondary endocrine disorders all increase risk of reduced bone mass/osteoporosis.  This can be compounded by the disease itself, as well as suboptimal nutrition and physical activity.

Ahmed is 13 and has received intensive chemotherapy and craniospinal radiotherapy for medulloblastoma.  Since he has at least one of the risk factors listed above, he should have assessment of his bone density 2 years post treatment, typically with a dual energy x-ray absorptiometry (DXA) scan.  Jan/Emma (bone marrow transplant), and Bethany (cranial radiotherapy) should also have their bone density assessed.

Reduced bone mineral density (BMD) in children is defined when the age and gender adjusted lumbar spine BMD z score is <-2.5.  If there is evidence of low BMD in his DXA scan, he should be managed with optimisation of his calcium and vitamin D status and lifestyle modification.  Bisphosphonate therapy is indicated only when there are vertebral crush fractures even in the absence of low BMD or 2 or more long bone fractures +/- reduced BMD and not just based on reduced BMD.

If Ahmed’s bone density is normal, it does not need to be re-checked unless his clinical status changes.

Metabolic Syndrome

This trio of central obesity (often with insulin resistance), dyslipidaemia, and hypertension is associated with the significant increase in morbidity in survivors of some types of paediatric cancer through its impact on cardiovascular health.  

It is particularly linked with ALL survivors (Jan and Emma), and those with brain tumours who receive irradiation (Bethany and Ahmed), as part of the hypothalamic syndrome. 

All of our cases so far are at risk of developing metabolic syndrome, and screening should be part of their regular review. Their blood pressure and BMI should be checked annually, though patients may have metabolic syndrome in the presence of a normal BMI. Their fasting glucose, HbA1C, insulin levels and lipid profile should also be checked: every 2 years if overweight, every 5 years otherwise.  Treatment is via lifestyle and risk factor modification.

Thyroid Function

Impaired thyroid function can be either primary (due to effects on the thyroid itself from treatment) or secondary (from effects on the hypothalamic-pituitary axis).  Chemotherapy and direct radiation treatment (e.g. in Hodgkin’s lymphoma, or primary thyroid cancer) can cause the former, whereas typically direct cranial radiotherapy is responsible for the latter.

In either instance, cancer survivors with risk factors will need annual thyroid function testing, with replacement if needed. They should also be encouraged to self-examine for nodules and goitres, which may indicate thyroid disease, or more rarely, a subsequent primary thyroid cancer. Such surveillance should be lifelong. 

Summary

Fertility/Puberty:

  • Patients/families should be counselled about the risks to fertility, and referred for gonadal shielding or gamete cryopreservation where appropriate
  • Regularly check pubertal status for delay or precocious puberty in those that received treatment affecting hypothalamic-pituitary-gonadal axis.
  • Offer access to fertility testing later in life

Growth

  • Check height (sitting and standing) regularly in patients at risk of GH deficiency
  • Refer to paediatric endocrinology if GH treatment may be required

Bone Health

  • In at risk patients, perform a DXA scan at 2 years post-treatment and monitor for fractures
  • Adjust lifestyle and risk factors

Metabolic syndrome:

  • Annually check height, weight, BMI and blood pressure 
  • Check fasting glucose, HbA1c, insulin and lipid profile every 2 years if overweight, or 5 years if not

Thyroid disorders

  • Annual thyroid function tests, and regular self-examine for nodules, lumps and goitres

Key learning points

Patients and their families should be aware of the need for long-term monitoring
  • The late endocrine effects of cancer are often determined more by treatment than the original disease.
  • Patients should receive a comprehensive summary of their treatment – this can be used to guide subsequent follow up, which is often in primary and secondary care settings.
  • At risk patients should receive regular assessment of growth, weight, puberty, metabolic status, and thyroid status. Bone health should be assessed 2 years after treatment finishes.

Please note, ‘Jan’, ‘Emma’, ‘Bethany’, and ‘Ahmed’ are fictional patients and any similarities to real life cases are purely coincidental.

Further reading

Children’s Cancer and Leukaemia Group

Cancer research UK

SurvivorNet

Teenage Cancer Trust

Authors: Dr Robert Legg and Dr Jaya Sujatha Gopal-Kothandapani

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