Department of Paediatric Diabetes and Endocrinology, Bristol Royal Hospital for Children, Bristol, UK.
Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHSFT, Birmingham, UK.
Lancet Diabetes Endocrinol. 2015 Jul;3(7):568-76. doi: 10.1016/S2213-8587(15)00008-X. Epub 2015 Apr 12.
The past 30 years have seen a great improvement in survival of children and young adults treated for cancer. Cancer treatment can put patients at risk of health problems that can develop many years later, most commonly affecting the endocrine system. Patients treated with cranial radiotherapy often develop dysfunction of the hypothalamic-pituitary axis. A characteristic pattern of hormone deficiencies develops over several years. Growth hormone is disrupted most often, followed by gonadal, adrenal, and thyroid hormones, leading to abnormal growth and puberty in children, and affecting general wellbeing and fertility in adults. The severity and rate of development of hypopituitarism is determined by the dose of radiotherapy delivered to the hypothalamic-pituitary axis. Individual growth hormone deficiencies can develop after a dose as low as 10 Gy, whereas multiple hormone deficiencies are common after 60 Gy. New techniques in radiotherapy aim to reduce the effect on the hypothalamic-pituitary axis by minimising the dose received. Patients taking cytotoxic drugs do not often develop overt hypopituitarism, although the effect of radiotherapy might be enhanced. The exception is adrenal insufficiency caused by glucocorticosteroids which, although transient, can be life-threatening. New biological drugs to treat cancer can cause autoimmune hypophysitis and hypopituitarism; therefore, oncologists and endocrinologists should be vigilant and work together to optimise patient outcomes.
过去 30 年来,接受癌症治疗的儿童和青年的存活率有了显著提高。癌症治疗可能会使患者面临健康问题的风险,这些问题可能在多年后才会出现,最常见的是影响内分泌系统。接受颅放疗的患者通常会出现下丘脑-垂体轴功能障碍。这种激素缺乏的特征模式会在几年内逐渐发展。生长激素最常受到干扰,其次是性腺、肾上腺和甲状腺激素,导致儿童生长异常和青春期提前,以及影响成年后的整体健康和生育能力。垂体功能减退症的严重程度和发展速度取决于下丘脑-垂体轴接受的放射剂量。即使剂量低至 10Gy,也可能会出现个别生长激素缺乏症,而接受 60Gy 后则常见多种激素缺乏症。放射治疗的新技术旨在通过最小化所接受的剂量来降低对下丘脑-垂体轴的影响。接受细胞毒性药物治疗的患者通常不会出现明显的垂体功能减退症,尽管放疗的效果可能会增强。例外情况是由糖皮质激素引起的肾上腺功能不全,尽管是暂时的,但可能危及生命。用于治疗癌症的新型生物药物可引起自身免疫性垂体炎和垂体功能减退症;因此,肿瘤学家和内分泌学家应保持警惕并共同努力,以优化患者的治疗效果。