Aron D C, Howlett T A
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Endocrinol Metab Clin North Am. 2000 Mar;29(1):205-21. doi: 10.1016/s0889-8529(05)70124-9.
The optimal strategy for hormonal screening of a patient with any incidentally discovered pituitary mass is unknown. The authors' review of the endocrinologic literature supports the view that such patients are at slightly increased risk for morbidity and mortality. This risk implies a benefit of early diagnosis for at least for some of the disorders, suggesting the importance of case finding. Nevertheless, the data in Table 1 illustrate that clinically diagnosed hormone-secreting pituitary tumors are far less common than incidentalomas. Clinically, one cannot accurately determine the approximately 0.5% of patients with incidentaloma who are at increased risk among the vast majority who are not. Given the limitations of diagnostic tests, effective hormonal screening requires a sufficiently high pretest probability to limit the number of false-positive results. This condition is met to varying degrees in the patient with a small incidentally discovered pituitary mass but no signs or symptoms of hormone excess. Even the more common lesions, such as prolactinoma, are relatively rare. [table: see text] Subjecting patients to unnecessary testing and treatment is associated with risk. In addition to its initial cost, testing may result in further expense and harm as false-positive results are pursued, producing the "cascade effect" described by Mold and Stein as a "chain of events (which) tends to proceed with increasing momentum, so that the further it progresses the more difficult it is to stop." The extensive evaluations performed for some patients with incidentally discovered masses may reflect the unwillingness of many physicians to accept uncertainty, even in the case of an extremely unlikely diagnosis. This unwillingness may be driven, in part, by fear of potential malpractice liability, the failure to appreciate the influence of prevalence data on the interpretation of diagnostic testing, or other factors. The major justification for further evaluation of these patients is not so much to avoid morbidity and mortality for the rare patient who truly is at increased risk but to reassure patients in whom further testing is negative and the physician. Physicians must take care not to create inappropriate anxiety in patients by overemphasizing the importance of an incidental finding unless it is associated with a realistic clinical risk. The authors' recommendations are based on currently available information to minimize the untoward effects of the cascade. As evidence accumulates, these recommendations may need to be revised. The benefit of the diagnosis of an adrenal or pituitary disorder must be considered in the context of the patient's overall condition. Additional studies are needed to analyze the clinical utility of hormonal screening for these common radiologic findings. Data from these studies can be used to identify critical gaps in knowledge and to adopt the epidemiologic methods of evaluation of evidence that have been applied to preventive measures. One must be careful to recognize lead-time bias, in which survival can appear to be lengthened when screening simply advances the time of diagnosis, lengthening the period of time between diagnosis and death without any true prolongation of life; and length bias, which refers to the tendency of screening to detect a disproportionate number of cases of slowly progressive disease and to miss aggressive cases that, by virtue of rapid progression, are present in the population only briefly. Physicians must avoid the pitfalls of overestimation of disease prevalence and of the benefits of therapy resulting from advances in diagnostic imaging. Clinical judgment based on the best available evidence should be complemented and not replaced by laboratory data.
对于任何偶然发现垂体肿块的患者,激素筛查的最佳策略尚不清楚。作者对内分泌学文献的回顾支持这样一种观点,即此类患者的发病和死亡风险略有增加。这种风险意味着至少对某些疾病进行早期诊断是有益的,这表明病例发现的重要性。然而,表1中的数据表明,临床诊断的分泌激素的垂体肿瘤远比意外瘤少见。临床上,在绝大多数没有风险增加的患者中,无法准确确定约0.5%有意外瘤且风险增加的患者。鉴于诊断测试的局限性,有效的激素筛查需要足够高的预测试概率,以限制假阳性结果的数量。对于偶然发现垂体小肿块但无激素过多体征或症状的患者,这种情况在不同程度上是满足的。即使是更常见的病变,如催乳素瘤,也相对罕见。[表格:见正文]让患者接受不必要的检查和治疗会带来风险。除了初始成本外,检查可能会因追求假阳性结果而导致进一步的费用和伤害,产生Mold和Stein所描述的“级联效应”,即“一系列事件(往往)会以越来越大的势头发展,因此进展得越远就越难停止”。对一些偶然发现肿块的患者进行的广泛评估可能反映了许多医生不愿意接受不确定性,即使在诊断极不可能的情况下也是如此。这种不愿意可能部分是由对潜在医疗事故责任的恐惧、未能认识到患病率数据对诊断测试解释的影响或其他因素驱动的。对这些患者进行进一步评估的主要理由与其说是为了避免极少数真正风险增加的患者的发病和死亡,不如说是为了让进一步检查为阴性的患者和医生放心。医生必须注意,除非偶然发现与实际临床风险相关,否则不要通过过度强调其重要性来给患者造成不适当的焦虑。作者的建议基于目前可用的信息,以尽量减少级联效应的不良影响。随着证据的积累,这些建议可能需要修订。肾上腺或垂体疾病诊断的益处必须在患者整体状况的背景下考虑。需要进行更多研究来分析激素筛查对这些常见放射学发现的临床效用。这些研究的数据可用于识别知识上的关键差距,并采用已应用于预防措施的评估证据的流行病学方法。必须小心识别提前期偏倚,即当筛查仅仅提前诊断时间时,生存时间似乎会延长,从而延长诊断和死亡之间的时间,而没有真正延长生命;以及长度偏倚,这是指筛查倾向于检测出不成比例数量的缓慢进展疾病病例,并遗漏那些由于进展迅速而在人群中仅短暂存在的侵袭性病例。医生必须避免高估疾病患病率和诊断成像进展带来的治疗益处的陷阱。基于现有最佳证据的临床判断应得到实验室数据的补充,而不是被其取代。