1 Department of Endocrinology and Medicine, Aalborg University Hospital , Aalborg, Denmark .
Thyroid. 2013 Dec;23(12):1518-24. doi: 10.1089/thy.2013.0074. Epub 2013 Sep 3.
Hospital-based studies may be hampered by referral bias. We investigated how the phenomenon may influence studies of hyperthyroid patients.
By means of a computer-based linkage to the laboratory database and subsequent detailed evaluation of subjects with abnormal test results, we prospectively identified all 1148 patients diagnosed with overt hyperthyroidism in a four-year period in and around Aalborg City, Denmark. Each patient was classified according to nosological type of hyperthyroidism. We studied the referral pattern of patients to local hospital units, and analyzed how referral depended on subtype of disease, sex, age, and degree of biochemical hyperthyroidism.
In a 4-year period, 1032 hyperthyroid patients were diagnosed at primary care offices, and 435 of these (42.2%) were referred to specialized units, 92 patients had hyperthyroidism diagnosed in other hospital departments (referral: 43, 46.7%), and 24 patients had hyperthyroidism diagnosed at the specialized unit after referral for other diseases. Patients suffering from Graves' disease (GD; n=474, median age=65.8 years) were referred more often (odds ratio=1.7 [95% confidence interval 1.3-2.2]) than those diagnosed with multinodular toxic goiter (MNTG; n=525, median age=74.6 years). Higher age was associated with less referral of patients suffering from MNTG (referred vs. nonreferred patients, 64.0 vs. 77.4 years, p<0.001) and GD (43.9 vs. 56.4 years, p<0.001), whereas GD patients referred to a hospital had more severe biochemical hyperthyroidism (serum total triiodothyronine, 4.86 vs. 3.79 nmol/L; serum total thyroxine, 204 vs. 180 nmol/L; both p<0.001). Findings were confirmed in multivariate models reporting age as a significant predictor for referral in both GD and MNTG patients (both p<0.001). Among referred hyperthyroid patients (all combined), those aged up to 40 years (referral rate, 66.8%) were represented 11.6 (6.6-20.6) times more often than those aged 80 years and above (referral rate, 14.8%).
Hyperthyroid patients referred to a specialized hospital unit were younger (GD+MNTG) and had more severe biochemical hyperthyroidism (GD) compared to nonreferred patients. Thus, referral bias may influence hospital-based studies of hyperthyroid patients, and may hamper external generalization of such studies. Whether the referral bias of hyperthyroid patients in Denmark can be generalized to other countries or cultures remains unknown.
基于医院的研究可能受到转诊偏倚的影响。我们调查了这种现象如何影响甲状腺功能亢进症患者的研究。
通过计算机与实验室数据库的链接，并对检测结果异常的患者进行详细评估，前瞻性地确定了丹麦奥尔堡市及其周边地区四年内诊断为显性甲状腺功能亢进症的 1148 名患者。根据甲状腺功能亢进症的分类，对每位患者进行分类。我们研究了患者向当地医院科室转诊的模式，并分析了转诊如何取决于疾病亚型、性别、年龄和生化甲状腺功能亢进的程度。
在四年期间，有 1032 名甲状腺功能亢进症患者在初级保健办公室就诊，其中 435 名（42.2%）被转诊至专科科室，92 名患者在其他医院科室被诊断为甲状腺功能亢进症（转诊率为 43.7%），24 名患者因其他疾病转诊后在专科科室被诊断为甲状腺功能亢进症。患有格雷夫斯病（GD）的患者（n=474，中位年龄=65.8 岁）比患有多结节毒性甲状腺肿（MNTG）的患者（n=525，中位年龄=74.6 岁）更常被转诊（比值比=1.7[95%置信区间 1.3-2.2]）。年龄较大与 MNTG（转诊患者 vs. 未转诊患者，64.0 岁 vs. 77.4 岁，p<0.001）和 GD（43.9 岁 vs. 56.4 岁，p<0.001）患者转诊率降低有关，而转诊至医院的 GD 患者的生化甲状腺功能亢进症更严重（血清总三碘甲状腺原氨酸，4.86 vs. 3.79 nmol/L；血清总甲状腺素，204 vs. 180 nmol/L；均 p<0.001）。在多变量模型中报告年龄为 GD 和 MNTG 患者转诊的显著预测因子，结果得到证实（均 p<0.001）。在所有转诊的甲状腺功能亢进症患者（所有组合）中，年龄在 40 岁以下（转诊率为 66.8%）的患者比年龄在 80 岁及以上（转诊率为 14.8%）的患者多 11.6（6.6-20.6）倍。
与未转诊的患者相比，被转诊至专科科室的甲状腺功能亢进症患者更年轻（GD+MNTG），且生化甲状腺功能亢进症更严重（GD）。因此，转诊偏倚可能会影响基于医院的甲状腺功能亢进症患者的研究，并可能阻碍此类研究的外部推广。丹麦甲状腺功能亢进症患者的转诊偏倚是否可以推广到其他国家或文化，尚不清楚。
