Endocrine Abstracts

Some 10-15% of the 1:1000 young adults who are cancer survivors, has survived a brain tumour. Increasing treatment efficacy and decreasing long-term disability are important human and economic aims.

The growth failure of children with brain tumours is multifactorial. Cranial irradiation, blamed for late neurotoxicity, is increasingly substituted by chemotherapy, but the disease itself, surgery and adjuvant chemotherapy must contribute. Evolving irradiation-induced panhypopituitarism after pituitary tumours in adults was not confirmed in children after tumours distant from the HPA in whom isolated GH deficits were observed, despite similar pituitary doses.

Children with centrally positioned optic, pineal or HPA tumours remain at risk of life threatening endocrinopathies even if irradiation is replaced by chemotherapy. Surgery escalates this risk as seen in craniopharyngiomas and conservative strategies are advocated to reduce the otherwise high incidence of HPA morbidity and late mortality.

Irradiation-induced growth hormone (GH) deficiency is dose, fractionation and time-dependent, occurring early and completely after the highest (>30Gy), and evolving more slowly after lower cranial doses. Its diagnosis is complicated by discrepancies between growth rates, provocation tests and 24h GH profiles, reflecting neuroregulatory disturbance. This may, in subtle form, be present before irradiation and compounded by it, with independent and additive toxic effects of chemotherapy at pituitary, gonadal, thyroid and skeletal levels.

Determining aetiology is important for targeting therapeutic options. Fertility induction with GnRH is limited by significant pituitary or gonadal disease. GH therapeutic responses are diminished in those with lesser degrees of GH deficiency or skeletal lesions induced by irradiation or cytotoxic inhibition of bone turnover. Elevations in TSH, attributed to primary hypothyroidism from the scattered spinal irradiation beam, require separating from higher irradiation-induced hypothalamic hypothyroidism.

Early r-hGH therapy appears safe but does not fully restore pubertal growth in the irradiated spine, nor prevent weight gain. An early spontaneous puberty may further limit growth potential. Final height within the normal range is nevertheless an achievable target if treatment delays are avoided, particularly in the smallest and most intensively treated patients. Given their recognised long-term psychosocial morbidity, it is important not to add to microcephaly, alopecia, obesity, osteopaenia and subfertility, by delaying hormone replacement, although educational and psychotherapeutic support are inevitably required to improve rehabilitation.