Vanderpump M P, Tunbridge W M, French J M, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan D M, Rodgers H, Tunbridge F
Department of Medicine, Newcastle General Hospital, UK.
Clin Endocrinol (Oxf). 1995 Jul;43(1):55-68. doi: 10.1111/j.1365-2265.1995.tb01894.x.
The original Whickham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the incidence and natural history of thyroid disease in this cohort.
DESIGN, PATIENTS AND MEASUREMENTS: Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, in addition to death certificates, two-thirds had information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91% were tested for clinical, biochemical and immunological evidence of thyroid dysfunction.
Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5-1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an increase with age in hypothyroidism but no age relation in hyperthyroidism. The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially. The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors identified at first survey. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A logit model indicated that increasing values of serum TSH above 2mU/l at first survey increased the probability of developing hypothyroidism which was further increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism in women.
This historical cohort study has provided incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease identified twenty years earlier.
最初的维克姆调查记录了从2779名成年人中随机抽取的样本中甲状腺疾病的患病率,该样本在年龄、性别和社会阶层方面与英国人口相匹配。这项为期20年的随访调查的目的是确定该队列中甲状腺疾病的发病率和自然病史。
设计、研究对象与测量方法:通过选民登记册、全科医生登记册、盖茨黑德家庭健康服务管理局登记册以及人口普查与调查办公室对研究对象进行随访追踪。825名研究对象(占样本的30%)已经死亡,除死亡证明外,三分之二的人有来自医院/全科医生记录或尸检报告的信息,以记录死亡前的发病情况。在1877名已知的幸存者中,96%参与了随访研究,91%接受了甲状腺功能障碍的临床、生化和免疫学检测。
针对原样本中超过97%的研究对象确定了发病和死亡情况。女性自发性甲状腺功能减退的平均发病率(95%置信区间)为3.5/1000幸存者/年(2.8 - 4.5),所有原因导致的甲状腺功能减退发病率升至4.1/1000幸存者/年(3.3 - 5.0),男性为0.6/1000幸存者/年(0.3 - 1.2)。女性甲状腺功能亢进的平均发病率为0.8/1000幸存者/年(0.5 - 1.4),男性可忽略不计。对已故研究对象计算出的发病率相似。特定时间甲状腺功能减退和甲状腺功能亢进发生概率的估计值,即风险率,显示甲状腺功能减退的风险率随年龄增加,而甲状腺功能亢进则与年龄无关。甲状腺肿的发生率随年龄下降,随访时10%的女性和2%的男性有甲状腺肿,而在首次调查时,相同研究对象中这一比例分别为23%和5%。两次调查中甲状腺肿的存在均与甲状腺功能障碍的任何临床或生化证据无关。在女性中,随访时发现甲状腺肿的发生与甲状腺抗体状态有关,但最初并无关联。根据首次调查确定的风险因素,对随访时发生甲状腺功能减退的风险进行了检查。发生甲状腺功能减退的比值比(95%置信区间)为:(a)仅血清促甲状腺激素(TSH)升高,女性为8(3 - 20),男性为44(19 - 104);(b)仅抗甲状腺抗体阳性,女性为8(5 - 15),男性为25(10 - 63);(c)血清TSH升高且抗甲状腺抗体阳性,女性为38(22 - 65),男性为173(81 - 370)。一个逻辑模型表明,首次调查时血清TSH值高于2mU/l会增加发生甲状腺功能减退的概率,抗甲状腺抗体的存在会进一步增加该概率。首次调查时任何形式的甲状腺疾病家族史阳性以及女性的生育情况均与发生甲状腺功能减退的风险增加无关。首次调查时校正年龄后的空腹胆固醇和甘油三酯水平与女性甲状腺功能减退的发生无关。
这项历史性队列研究为具有代表性的横断面人群样本提供了20年间甲状腺疾病的发病率数据,并确定了20年前所识别的甲状腺疾病预后风险因素的重要性。