Littley M D, Shalet S M, Beardwell C G, Ahmed S R, Applegate G, Sutton M L
Department of Endocrinology, Christie Hospital and Holt Radium Institute, Withington, Manchester.
Q J Med. 1989 Feb;70(262):145-60.
The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis.
对165例因垂体或与其紧密相关解剖部位肿瘤接受外照射放疗且已观察长达10年的患者，研究了垂体前叶激素缺乏症的发生情况。其中140例患者在放疗前接受过垂体手术。所有患者均采用三野技术进行外照射放疗，在20 - 22天内分15或16次给予3750 - 4250 cGy。放疗前采用胰岛素低血糖或胰高血糖素刺激联合促甲状腺素和促性腺激素释放激素试验以及催乳素、甲状腺激素和睾酮或雌二醇的基础测定对垂体前叶功能进行联合检测。放疗后6个月、12个月及随后每年重复此项检测。放疗前，18%的患者生长激素分泌正常，21%的患者促性腺激素分泌正常，57%的患者促肾上腺皮质激素储备正常，80%的患者促甲状腺素分泌正常。寿命表分析显示，随着时间推移，所有垂体前叶激素缺乏症的发生率均增加：至5年时所有患者均出现生长激素缺乏，91%的患者促性腺激素缺乏，77%的患者促肾上腺皮质激素缺乏，42%的患者促甲状腺素缺乏。8年时，相应的缺乏发生率分别为100%、96%、84%和49%。73例患者出现放疗诱导的高催乳素血症；血清催乳素平均浓度在2年时从227±11 mU/l升至峰值369±60 mU/l，随后朝基础值下降。对可能影响垂体前叶激素缺乏症发生速率的变量，如初始诊断、患者年龄、性别、照射组织体积和既往手术情况进行了检查，但这些因素均无显著影响。然而，放疗诱导的高催乳素血症在女性患者中更为明显。尽管垂体前叶激素缺乏症最常见的发生顺序是生长激素、促性腺激素、促肾上腺皮质激素、促甲状腺素（61%的患者），但也有其他顺序。最值得注意的是促肾上腺皮质激素缺乏发生在促性腺激素缺乏之前。接受垂体肿瘤手术治疗的患者垂体前叶激素缺乏症发生率较高，外照射放疗后发生率增加。缺乏症可能按不可预测的顺序发生，建议每年进行内分泌检测。
