Growth hormone (GH) deficiency can occur secondary to hypothalamic-pituitary injury12 and is the most common endocrinopathy seen in childhood cancer survivors.
It is often the first and only pituitary hormone deficiency to arise after cranial radiation therapy (RT).
GH deficiency can be caused by:
- Tumours in the hypothalamic and pituitary regions
- RT induced hypothalamic-pituitary injury15,16
- Commonest cause
- Risk depends on total dose of RT given and fraction size
- The higher the dose of RT, the greater the risk
- Cranial RT with doses greater than 24 Gy result in long term GH deficiency in at least two thirds of patients
- 100% of patients treated with 30 Gy or more will have blunted GH responses to insulin tolerance tests
- Younger children have a lower tolerance to RT and are more likely to develop GH deficiency
- Lower doses of RT (18 Gy) can cause GH deficiency in young children
Incidence of GH deficiency also increases with time from therapy.
GH replacement therapy in childhood cancer survivors has been shown to increase final adult height in these individuals, particularly if GH is given at an earlier age and in higher doses.17
However, many factors may contribute towards short stature in childhood cancer survivors:5,12-13
- Direct radiation therapy (RT) induced injury to the skeleton
- RT causes reduced growth of the bones and soft tissues within the treatment field
- Precocious puberty caused by damage the hypothalamic-pituitary axis
- GH deficiency
Those patients most at risk of GH deficiency:
- Received cranial RT
- Diagnosed with a brain tumour
- Diagnosed with leukemia
Radiation Induced GH neurosecretory dysfunction:
- Described after RT to the hypothalamic-pituitary axis
- Diminished spontaneous (physiological) GH secretion in the presence of preserved peak GH responses to provocative testing
- Normally GH is secreted in a "pulsatile" pattern with secretory bursts during sleep and this pattern becomes severely disturbed after cranial RT
Pediatric Brain Tumor Survivors (PBTS):
Data from the Childhood Cancer Survivor Study has shown that 13% of PBTS had an adult height two or more standard deviations below population norms.8
PBTS that did not receive RT had adult heights similar to the general population.
PBTS treated with cranial or craniospinal RT were at a significantly increased risk of short stature compared to non-irradiated survivors.8
In one prospective study, all of the 21 children treated with a dose of over 45 Gy for optic pathway glioma developed GH deficiency and significant slowing of growth within 2 years of RT.
Shorter stature was most prevalent in PBTS in those patients who were:
- Diagnosed before 10 years of age
- Female patients
- Treated with higher doses of RT8
Acute Lymphoblastic Leukemia (ALL) survivors:
The Childhood Cancer Survivor Study showed that 9% of ALL survivors had adult heights two or more standard deviations below the population norms.14
Cranial RT is a risk factor for short stature in ALL survivors, with the risk increasing in a dose-dependent manner.14
Low dose prophylactic cranial RT (18 - 24 Gy) often leads to isolated GH deficiency.
A higher prevalence of short stature has also been found in ALL survivors treated with spinal RT prior to puberty, as well as survivors treated with chemotherapy only.14
RT doses of only 12 - 14 Gy total body irradiation (TBI) combined with intensive chemotherapy as part of a bone marrow transplant regime have a high risk of causing GH deficiency.