Paeds · endocrinology-diabetes-and-growth
Endocrine late effects of cancer treatment
Also known as Endocrine late effects of childhood cancer · Cancer survivor endocrinopathy · Radiation-induced hypopituitarism · Chemotherapy-induced gonadal failure · Cranial irradiation endocrinopathy · Childhood cancer survivor endocrine surveillance · Radiation-induced growth hormone deficiency · Treatment-related central hypothyroidism · Secondary thyroid cancer after neck radiation · Paediatric oncology long-term follow-up
A fellowship approach to the endocrine late effects of childhood cancer treatment: recognise that the survivor who slows on the growth chart, develops central hypothyroidism, adrenal insufficiency, gonadotropin deficiency or paradoxical precocious puberty after cranial irradiation, or primary thyroid dysfunction, gonadal failure, metabolic syndrome and reduced bone density after neck radiation and alkylating chemotherapy, is showing the most common and earliest complications of cure — then risk-stratify by exposure, screen the vulnerable axes with a structured long-term follow-up programme, and replace each deficiency in the correct order with hydrocortisone before thyroxine and sex steroids and recombinant growth hormone only after magnetic resonance imaging excludes recurrence.
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- A childhood cancer survivor whose growth velocity slows or whose height crosses centiles downward months to years after cranial irradiation — growth hormone deficiency is the earliest and most common endocrine late effect, with a dose-dependent threshold near 18 Gy
- A survivor who develops fatigue, cold intolerance, weight gain and bradycardia after hypothalamic-pituitary radiation — central hypothyroidism from TSH deficiency
- A survivor who presents with hypotension, hyponatraemia, vomiting or collapse during an intercurrent infection — undiagnosed adrenocorticotropic hormone and cortisol deficiency that can become a fatal adrenal crisis
- A girl treated with alkylating agents or total-body irradiation who has primary amenorrhoea or arrested puberty, or a boy with absent testicular growth — primary gonadal failure and future infertility
- A survivor exposed to neck or craniospinal radiation who develops a palpable thyroid nodule — secondary differentiated thyroid cancer that demands fine-needle aspiration
- A survivor with rapid pubertal progression after lower-dose cranial radiation — paradoxical central precocious puberty that will compromise final adult height if untreated
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- Recognising growth failure after cranial irradiation as growth hormone deficiency
- The exposure-based surveillance framework for the childhood cancer survivor
- Principles of hormone replacement in panhypopituitarism
- Dose-dependent hierarchy of radiation-induced hypothalamic-pituitary damage
- Paradoxical precocious puberty at lower cranial doses versus gonadotropin deficiency at higher doses
- Surveillance and replacement of primary thyroid and gonadal failure after alkylators and neck radiation
- Recognising the survivor with endocrine late effects across the growth, thyroid, adrenal and gonadal axes
- Building a risk-stratified long-term follow-up plan including stress-dose hydrocortisone counselling
- Counselling on fertility preservation and the transition to adult survivorship care
- Long case of a childhood cancer survivor with multiple endocrine late effects on replacement
- Short case of a survivor with growth failure after cranial radiation
- Long-term follow-up of the childhood cancer survivor
- Endocrine consequences of cancer therapy
- Growth and puberty after cancer treatment
- Pathophysiology of radiation-induced hypothalamic-pituitary damage
- Diagnosis and surveillance of endocrine late effects
- Replacement therapy and its monitoring in survivors
- Growth chart interpretation in the cancer survivor
- Communicating a long-term surveillance and hormone replacement plan to a family
- Growth hormone deficiency after cranial irradiation
- Primary gonadal failure and thyroid dysfunction after cancer therapy
- Endocrine surveillance of the childhood cancer survivor
- Endocrine late effects of cancer treatment
- Risk-stratified long-term follow-up after childhood cancer
- Multidisciplinary management of the survivorship endocrinopathy
- Radiation-induced hypopituitarism and the dose hierarchy
- Gonadal and thyroid late effects of cancer therapy
- Transition of care from paediatric oncology to adult survivorship
The mark goes to the candidate who reasons along three axes at once. The first is the exposure history: the radiation dose to the hypothalamic-pituitary axis, the radiation field to the neck and spine, and the cumulative dose of alkylating chemotherapy. The second is the axis physiology: which hormone is lost depends on which neurone population is most vulnerable to fractionated radiation, and the growth-hormone axis is the most radiosensitive. The third is the whole survivor: endocrine late effects accumulate over decades, they interact with other late effects (cardiac, neurocognitive, second malignancy), and they are entirely treatable when caught early — which is why surveillance fidelity, not clever rescue, is what determines outcome. [1] [3]
Overview & Definition
Endocrine late effects are the structural and functional disorders of the endocrine system that appear months to decades after successful treatment of childhood cancer. They arise from direct damage to the hypothalamic-pituitary axis by cranial or craniospinal radiation and surgery, and from direct damage to the peripheral glands by neck radiation, by gonadotoxic chemotherapy, and by stem cell transplantation conditioning. They are the single most common group of late complications of childhood cancer therapy, affecting roughly forty to fifty percent of long-term survivors, and they are the earliest to declare themselves — growth failure from growth hormone deficiency can appear within the first year after cranial irradiation. Because cure of childhood cancer is now the expected outcome in the majority of patients, the population of survivors at risk is large and growing, and endocrine late effects have moved from a curiosity to the central clinical problem of survivorship. [1] [4]
The endocrine system is vulnerable for two reasons. First, the hypothalamic-pituitary axis sits in the central nervous system where it receives the full dose of cranial radiation given for brain tumours, leukaemia prophylaxis and transplant conditioning. Its neurone populations are exquisitely sensitive to fractionated radiation in a dose-dependent hierarchy. Second, the peripheral glands — thyroid and gonads especially — sit in or near radiation fields used for head and neck, mediastinal, craniospinal, and total-body irradiation, and the gonads are additionally damaged by alkylating chemotherapy that targets rapidly dividing cells. The bone and the metabolic system are injured more indirectly, through growth hormone deficiency, glucocorticoid exposure, and the inflammatory and nutritional consequences of cancer and its treatment. [2] [7]
References11ShowHide
- [1]Chemaitilly W, Sklar CA. Childhood Cancer Treatments and Associated Endocrine Late Effects: A Concise Guide for the Pediatric Endocrinologist. Horm Res Paediatr, 2019.PMID 30404091
- [2]Sklar CA, Antal Z, Chemaitilly W, et al. Hypothalamic-Pituitary and Growth Disorders in Survivors of Childhood Cancer: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2018.PMID 29982476
- [3]Chemaitilly W, Cohen LE, Mostoufi-Moab S, Patterson BC. Endocrine Late Effects in Childhood Cancer Survivors. J Clin Oncol, 2018.PMID 29874130
- [4]Mostoufi-Moab S, Seidel K, Leisenring WM, et al. Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol, 2016.PMID 27382091
- [5]Armstrong GT, Kawashima T, Leisenring W, et al. Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study. J Clin Oncol, 2014.PMID 24638000
- [6]van Iersel L, Mulder RL, Denzer C, et al. Hypothalamic-Pituitary and Other Endocrine Surveillance Among Childhood Cancer Survivors. Endocr Rev, 2022.PMID 34962573
- [7]Cohen LE. Endocrine late effects of cancer treatment. Endocrinol Metab Clin North Am, 2005.PMID 16085170
- [8]van Iersel L, Li Z, Srivastava DK, Brinkman TM, Wilson CL, Robison LL, et al. Hypothalamic-Pituitary Disorders in Childhood Cancer Survivors: Prevalence, Risk Factors and Long-Term Health Outcomes. J Clin Endocrinol Metab, 2019.PMID 31373627
- [9]Clement SC, Kremer LCM, Verburg FA, et al. Balancing the benefits and harms of thyroid cancer surveillance in survivors of Childhood, adolescent and young adult cancer: Recommendations from the international Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium. Cancer Treat Rev, 2018.PMID 29202445
- [10]Goodenough CG, Baedke JL, Delaney AM, et al. Attributable Risk and Consequences of Bone Mineral Density Deficits in Childhood Cancer Survivors. JAMA Netw Open, 2025.PMID 39792384
- [11]Vatanen A, Wilhelmsson M, Borgström B, Gustafsson B. Ovarian function after allogeneic hematopoietic stem cell transplantation in childhood and adolescence. Eur J Endocrinol, 2014.PMID 24179099