Tomlinson J W, Holden N, Hills R K, Wheatley K, Clayton R N, Bates A S, Sheppard M C, Stewart P M
Division of Medical Sciences, Queen Elizabeth Hospital, University of Birmingham, UK.
Lancet. 2001 Feb 10;357(9254):425-31. doi: 10.1016/s0140-6736(00)04006-x.
Four retrospective studies have reported premature mortality in patients with hypopituitarism with standard mortality ratios (SMRs) varying between 1.20 and 2.17. Patients with hypopituitarism have complex endocrine deficiencies, and the mechanisms underpinning any excess mortality are unknown. Furthermore, the suggestion has emerged that endogenous growth-hormone deficiency might account for any excess mortality. We aimed to clarify these issues by doing a large prospective study of total and specific-cause mortality in patients with hypopituitarism.
We followed up 1014 UK patients (514 men, 500 women) with hypopituitarism from January, 1992, to January, 2000. 573 (57%) patients had non-functioning adenomas, 118 (12%) craniopharyngiomas, and 93 (9%) prolactinomas. SMRs were calculated as the ratio of observed deaths to the number of deaths in an age-matched and sex-matched UK population.
The number of observed deaths was 181 compared with the 96.7 expected (SMR 1.87 [99% CI 1.62-2.16], p<0.0001). Univariate analysis indicated that mortality was higher in women (2.29 [1.86-2.82]) than men (1.57 [1.28-1.93], p=0.002), in younger patients, in patients with an underlying diagnosis of craniopharyngioma (9.28 [5.84-14.75] vs 1.61 [1.30-1.99], p<0.0001), and in the 353 patients treated with radiotherapy (2.32 [1.71-3.14] vs 1.66 [1.30-2.13], p=0.004). Excess mortality was attributed to cardiovascular (1.82 [1.30-2.54], p<0.0001), respiratory (2.66 [1.72-4.11], p<0.0001), and cerebrovascular (2.44 [1.58-4.18], p<0.0001) causes. There was no effect of hormonal deficiency on mortality, except for gonadotropin deficiency, which, if untreated was associated with excess mortality (untreated 2.97 [2.13-4.13] vs treated 1.42 [0.97-2.07], p<0.0001). Multiple regression analyses identified age at diagnosis, sex, a diagnosis of craniopharyngioma, and untreated gonadotropin deficiency as independent significant factors affecting mortality.
Patients with hypopituitarism have excess mortality, predominantly from vascular and respiratory disease. Age at diagnosis, female sex, and above all, craniopharyngioma were significant independent risk factors. Specific endocrine-axis deficiency, with the exception of untreated gonadotropin deficiency, does not seem to have a role.
四项回顾性研究报告了垂体功能减退患者的过早死亡情况，其标准化死亡比（SMR）在1.20至2.17之间。垂体功能减退患者存在复杂的内分泌缺陷，导致任何额外死亡的机制尚不清楚。此外，有观点认为内源性生长激素缺乏可能是导致额外死亡的原因。我们旨在通过对垂体功能减退患者的全因和特定病因死亡率进行大型前瞻性研究来阐明这些问题。
我们对1992年1月至2000年1月期间英国的1014例垂体功能减退患者（514例男性，500例女性）进行了随访。573例（57%）患者患有无功能性腺瘤，118例（12%）患有颅咽管瘤，93例（9%）患有泌乳素瘤。SMR计算为观察到的死亡人数与年龄和性别匹配的英国人群中的死亡人数之比。
观察到的死亡人数为181例，而预期为96.7例（SMR 1.87 [99% CI 1.62 - 2.16]，p<0.0001）。单因素分析表明，女性（2.29 [1.86 - 2.82]）的死亡率高于男性（1.57 [1.28 - 1.93]，p = 0.002）；年轻患者、潜在诊断为颅咽管瘤的患者（9.28 [5.84 - 14.75] 对比 1.61 [1.30 - 1.99]，p<0.0001）以及接受放疗的353例患者（2.32 [1.71 - 3.14] 对比 1.66 [1.30 - 2.13]，p = 0.004）的死亡率更高。额外死亡归因于心脑血管（1.82 [1.30 - 2.54]，p<0.0001）、呼吸（2.66 [1.72 - 4.11]，p<0.0001）和脑血管（2.44 [1.58 - 4.18]，p<0.0001）病因。除促性腺激素缺乏外，激素缺乏对死亡率无影响，促性腺激素缺乏若未治疗与额外死亡相关（未治疗2.97 [2.13 - 4.13] 对比 治疗后1.42 [0.97 - 2.07]，p<0.0001）。多元回归分析确定诊断时的年龄、性别、颅咽管瘤诊断以及未治疗的促性腺激素缺乏是影响死亡率的独立显著因素。
垂体功能减退患者存在额外死亡，主要源于血管和呼吸系统疾病。诊断时的年龄、女性性别，尤其是颅咽管瘤是显著的独立危险因素。除未治疗的促性腺激素缺乏外，特定内分泌轴缺乏似乎不起作用。
