METHODS: We conducted a prospective, longitudinal study of 598 acromegaly (309 men, 289 women) and 292 clinically nonfunctioning pituitary adenoma (CNFPA)(140 women, 152 men) patients from the same underlying population. GH and IGF-1 levels were measured longitudinally and outcomes were observed during long-term follow-up. Cumulative exposure to IGF-1 excess was tested as a predictor of cancer. We compared cancer prevalence in acromegaly and CNFPA cohorts and incidence in each to that expected from SEER data.
RESULTS: Cancer prevalence by last follow up was 22.6% in acromegaly and 12.7% in CNFPAs (OR = 1.99 (95% CI, 1.34, 2.97)(P=0.0005). Overall SIR for cancer was 1.78 (1.51, 1.81) in the acromegaly and 1.26 (0.89, 1.70) in the CNFPA cohorts. Cumulative exposure to IGF-1 excess, OR=1.278 (1.060, 1.541)(P = 0.01), years from acromegaly diagnosis to cancer or last follow up, OR= 1.03 (1.004, 1.057)(P=0.024), and age at follow up, OR =1.064 (1.047, 1.082)(P<0.001), were predictors of cancer.
CONCLUSIONS: Cancer risk is increased in acromegaly, but not in CNFPA patients. Cumulative exposure to IGF-1 excess is a predictor of cancer in acromegaly. Our data suggest that cancer risk in acromegaly relates to the degree and duration of IGF-1 excess and that full appreciation of this risk requires long-term follow up.
方法:我们进行了前瞻性,598例肢端肥大症的纵向研究(309名男性,289名妇女)和292名临床无功能垂体腺瘤(CNFPA)(140名妇女,152名男性)来自同一基础人群的患者。纵向测量GH和IGF-1水平,并在长期随访中观察结果。对过量IGF-1的累积暴露作为癌症的预测因子进行测试。我们比较了肢端肥大症和CNFPA队列中的癌症患病率以及每个队列中的发病率与根据SEER数据预期的发病率。
结果:末次随访时肢端肥大症的癌症患病率为22.6%,CNFPA为12.7%(OR=1.99(95%CI,1.34,2.97)(P=0.0005)。在肢端肥大症中,癌症的总SIR为1.78(1.51,1.81),在CNFPA队列中为1.26(0.89,1.70)。累积暴露于过量的IGF-1,OR=1.278(1.060,1.541)(P=0.01),从肢端肥大症诊断到癌症或最后一次随访,OR=1.03(1.004,1.057)(P=0.024),和随访时的年龄,OR=1.064(1.047,1.082)(P<0.001),是癌症的预测因子。
结论:肢端肥大症的癌症风险增加,但在CNFPA患者中没有。过量IGF-1的累积暴露是肢端肥大症中癌症的预测因子。我们的数据表明,肢端肥大症的癌症风险与IGF-1过量的程度和持续时间有关,并且完全了解这种风险需要长期随访。