Endocrine Abstracts

Late effects of therapy can only become a meaningful concern, when the cure rate of the primary disorder is high enough to provide sufficient survivors. This happened for childhood cancer survivors around 50 years ago. The primary treatment modalities were surgery, radiotherapy, and combination chemotherapy. Amongst the most common treatment complications were dysfunction of the pituitary, thyroid, and gonad. The observation of gonadal damage and subsequent infertility led to studies exploring the timing between the damaging insults and future fertility potential, as well as the possibility of hormonal protection to preserve fertility

The pituitary dysfunction, seen classically in brain tumour survivors, was a consequence of radiotherapy (XRT) and consisted of various degrees of anterior hypopituitarism. The first hormone to be affected was always growth hormone (GH). These children grew poorly due to a number of factors, including impaired spinal growth (XRT) and early puberty, but GH deficiency (GHD) was a key contributor to the growth failure. Early studies investigated the relationship between the radiotherapy dose and the timing and degree of GHD, then moved on to search for the optimal biochemical method of diagnosing GHD with the increasing knowledge that the pathological insult was primarily hypothalamic rather than pituitary. Treatment with GH replacement began in the mid-1970s without, at that time, any safety data. Subsequently the efficacy of GH replacement in normalising linear growth was established, and the gradually acquired safety data reassuringly revealed no increase in tumour recurrence. Studies of the physiological profiles of GH secretion excluded any major prevalence of GH neurosecretory dysfunction, implying that pharmacological testing provided meaningful results. With the advent of DNA-derived GH, defining severe GHD in adolescence and various stages of adult life became important as well as determining response to GH therapy in adult life.