Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Endocrine care following childhood malignancy (#43)

Margaret Zacharin 1
  1. Royal Children's Hospital, Parkville, VIC, Australia

Survival after childhood cancer treatment has increased significantly over 30 years, with overall >70-80% survival now recorded.  It is estimated that within 25 years of primary diagnosis  4% of survivors will develop a second tumour with risks from 8 – 380 times expected population risk, thyroid cancer 18 times expected population rate, 50% risk of hypothyroidism and 20% risk of thyroid nodules at 20 years. Endocrine late effects of irradiation and chemotherapy can be direct, resulting in endocrine gland hypofunction or indirect via metaplasia and malignant transformation of normal exposed tissues and via altered bone growth. Increasing recognition of evolution of loss of endocrine function underlines a need for surveillance and planning strategies to anticipate loss and to provide solutions.Recognition of major global effects on learning, short term memory impairment and memory processing is necessary, to understand complex management needs. Beliefs related to survival and need for care may be unusual, along with risk taking behaviours.Hypothalamic pituitary axis deficits occur after radiation exposure in a dose related fashion. Low dose XRT (12Gy) with total body irradiation and chemotherapy alone have also been associated with deficits. Growth hormone deficiency is the most frequent loss, occurring 1-4 years after exposure to XRT, followed by gonadotrophin deficiency, TSH then ACTH deficiency. Evolution of losses may take up to 20+ years.  Altered timing and tempo of puberty after CXRT or total body irradiation requires in depth understanding, to provide treatment appropriate to current status. Specific losses of gonadal function vary depending on age at exposure to toxins and type of intervention.  Testicular radiation of 4Gy causes loss of germinal epithelium. 20Gy before puberty and 30Gy after puberty causes loss of Leydig cell function. The prepubertal testis is not protected from damage by chemotherapy. Complete germ cell loss occurs after puberty, making semen collection imperative prior to treatment. Spermatogonial cell line salvage before puberty is no e being undertaken as a standard procedure. Although it is currently considered experimental in humans it is of proven success in murine species and primates.  Ova are lost with either treatment modality throughout life. Recovery of the female ovary after chemotherapy varies but premature menopause is likely. Ovum salvage is now offered to all children and adolescents prior to gonadotoxic treatments.Puberty can occur in up to 50% of males and females after TBI but ongoing losses ad hypogonadism remain risks long term.Acquisition of optimal peak bone mass and maintenance of bone quality in adulthood is compromised by alterations in pubertal and growth cascades.Thyroid nodularity and differentiated carcinoma is common after scatter or direct radiation, with multifocal papillary lesions and local invasion. Risk continues for 40 years. Surveillance with ultrasound every second year is mandatory for detection.Future planning should involve risk-based screening and surveillance, targeted education for risk reduction and healthcare delivered by clinicians familiar with issues and risks.