European Journal of Endocrinology (2000) 143 639±647 ...
640 T Bjùro and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000)...
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Thyroid disease, dysfunction an...
642 T Bjùro and others EUROPEAN JOURNA...
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Thyroid disease, dysfunction and ...
644 T Bjùro and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (...
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Thyroid disease, dysfunction and autoimmunity ...
646 T Bjùro and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (20...
EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Thyroid disease, dysfunction an...
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Prevalence of thyroid disease, thyroid dysfunction and thyroid

Published on: Mar 4, 2016
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Transcripts - Prevalence of thyroid disease, thyroid dysfunction and thyroid

  • 1. European Journal of Endocrinology (2000) 143 639±647 ISSN 0804-4643 CLINICAL STUDY Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trùndelag (HUNT) T Bjùro1, J Holmen3,4, é Kruger3,4, K Midthjell3, K Hunstad5, T Schreiner2, L Sandnes1 and H Brochmann6 È 1 Hormone Laboratory and 2Department of Endocrinology, Aker University Hospital, Oslo, 3National Institute of Public Health, Community Medicine Research Unit, Verdal, 4Institute of Community Medicine, Norwegian University of Technology and Science, 5Stjùrdal Health Centre, Stjùrdal, and 6 Nñrùy Health Centre, Kolvereid, Norway (Correspondence should be addressed to T Bjùro, Hormone Laboratory, Aker University Hospital, N-0514 Oslo, Norway; Email: trine.bjoro@ioks.uio.no) Abstract Objective: To examine the prevalence of thyroid disease and dysfunction including thyroid autoimmu- nity in Norway. Materials and methods: All inhabitants 20 years and older (94 009) in Nord-Trùndelag were invited to participate in a health survey with a questionnaire and blood samples. Results: The prevalence of former diagnosed hyperthyroidism was 2.5% in females and 0.6% in males, hypothyroidism 4.8% and 0.9%, and goitre 2.9% and 0.4% respectively. In both sexes the prevalence increased with age. In individuals without a history of thyroid disease the median, 2.5 and 97.5 percentiles for TSH (mU/l) were 1.80 and 0.49±5.70 for females and 1.50 and 0.56±4.60 for males. The TSH values increased with age. When excluding individuals with positive thyroid peroxidase antibodies (TPOAb) (> 200 U/ml), the 97.5 percentiles dropped to 3.60 mU/l and 3.40 mU/l respectively. The prevalence of pathological TSH values in females and males were TSH $10 mU/l 0.90% and 0.37%; TSH 4.1±9.9 mU/l 5.1% and 3.7%; and TSH # 0.05 mU/l 0.45% and 0.20% respectively. The prevalence of positive TPOAb (> 200U/ml) was 13.9% in females and 2.8% in males. In females the lowest percentage (7.9%) of positive TPOAb was seen with TSH 0.2± 1.9 mU/l and increased both with lower and higher levels of TSH. The percentage of males with positive TPOAb was lower than in females in all TSH groups except for those with TSH > 10 mU/l (85% TPOAb positive). Conclusions: In spite of a high prevalence of recognised thyroid disease in the population a considerable number of inhabitants have undiagnosed thyroid dysfunction and also positive TPOAb. European Journal of Endocrinology 143 639±647 Introduction unrecognised hypothyroidism was 1% in females over 70 years (attendance rate 71%) (11). Thyroid abnormalities affect a considerable portion of Most prevalence studies of thyroid diseases are small the population (1±3). However, the prevalence and the and performed in selected groups of the populations (5, pattern of thyroid disorders depend on ethnic and 10, 12, 13). In 1995±1997, a large health study was geographical factors and especially on iodine intake performed in Nord-Trùndelag County, Norway. A (4±6). Norway is generally considered to have suf®cient questionnaire included enquiries about thyroid diseases, iodine-intake (7, 8). Norman (9) reported differences in and blood samples for TSH measurements were drawn incidences of hypo- and hyperthyroidism in southern from 35 576 persons. and northern parts of Norway. Brochmann et al. (10) In this paper we report the prevalence of earlier reported prevalences of earlier diagnosed and unrecog- diagnosed hyperthyroidism, hypothyroidism and goitre, nised hypothyroidism of 3.6% and 1.8% respectively, in the treatment given and the prevalence of undiagnosed females over 70 in a small community (Nñrùy) in Nord- thyroid dysfunction in persons without known thyroid Trùndelag (attendance rate 99%). In Oslo the preva- disease. We also report the prevalence of positive thyroid lence of earlier diagnosed hypothyroidism was 4.5% and peroxidase antibodies (TPOAb). q 2000 Society of the European Journal of Endocrinology Online version via http://www.eje.org
  • 2. 640 T Bjùro and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Table 1 Questions about thyroid illness in the questionnaire. fT4 with DELFIA free T4 (total analytical variation < 7%) and total T3 with AutoDELFIA T3 (total analytical Have you ever been diagnosed with hyperthyroidism? Have you ever been diagnosed with hypothyroidism? variation < 5%), all from Wallac Oy, Turku, Finland. Have you ever been told that you have or have had goitre? TPOAb were measured with a luminoimmunoassay and Have you ever had a disease in the thyroid gland? TRAb with a radioreceptor assay (bovine TSH receptor), Are you or have you been on thyroxine medication? both from B.R.A.H.M.S, Diagnostica GmbH, Berlin, Are you or have you been on Neo-Mercazole medication*? Germany. The sera were stored at À 20 8C. Have you ever had an operation on your thyroid gland? Have you ever been treated with radioactive iodine? The laboratory's reference values were TSH 0.2± 4.5 mU/l, fT4 8±20 pmol/l, T3 1.2±2.7 nmol/l, TPOAb < * Neo-Mercazole ˆ carbimazole. 200 U/ml and TRAb < 10 U/l. Data analysis Materials and methods The data analysis was performed with SPSS (version The study was approved by the regional committee for 8.0). For continuous variables, non-parametric tests ethics in medical research and by the Norwegian Data (2-tailed Mann-Whitney U tests) were used. Group inspectorate. differences between the number of subjects were Nord-Trùndelag is a county in Mid-Norway with analysed using Chi-squared test. P values < 0.05 were 127 000 inhabitants. The population is stable with low considered statistically signi®cant. in- and out-migration. During the period August 1995± June 1997 all inhabitants 20-years-old and above (total 94 009) were invited to participate in the Nord- Results Trùndelag Health Study (HUNT). This study was carried out by the National Health Screening service in Population studied cooperation with the National Institute of Public Of the 94 009 persons invited to participate in the study, Health, Unit for Health Services Research, Nord- 46 855 (49.8%) were males and 47 254 (50.2%) were Trùndelag county and the Norwegian University of females. In all, 30 557 (65.3%) of the invited males and Science and Technology (NTNU). 34 803 (73.7%) of the invited females participated in In addition to clinical measurements, the participants the study. The youngest and oldest age groups had the were asked to complete a three-page self-assessment lowest attendance rate (20±29 years 42% and 55%, questionnaire that included eight thyroid-related ques- and above 80 years, 48% and 53% respectively, for tions (Table 1). The questionnaire was distributed by males and females). In persons under 30, a substantial mail and returned on arrival at the screening site. number were resident outside the county because of Height, weight, blood pressure and hearing were studies or work but they were still registered as living in measured in all participants, and spirometry, osteoden- Nord-Trùndelag. In the oldest age group, a large simetry and vision were measured in selected sub- number were not able to attend the screening owing groups. Venous blood samples were drawn from all to illness or reduced mobility. In the age group 35±75 participants and analysed for glucose, creatinine and years, the attendance rates were 75.0% for males and lipids. Thyroid blood tests were carried out in all 83.3% for females respectively. females, 50% of males over 40, and in 5% of both females and males 20±40 years of age. Answers to the questionnaire Five hundred and sixty-four males (1.8%) and 3126 Thyroid function tests females (8.9%) (sex ratio females : males 4.9) answered Blood samples were drawn without any restriction yes to at least one of the thyroid-related questions in the regarding eating or time of medication. The thyrotropin questionnaire (Table 1), indicating a history of thyroid (TSH) levels of serum samples were analysed at the disease or dysfunction; the majority answered yes to Hormone Laboratory, Aker University Hospital. If TSH more than one of these questions. was < 0.2 mU/l, free thyroxine (fT4) and total triio- dothyronine (T3) were measured in the same sample. If Hyperthyroidism In all, 0.6% of males and 2.5% of TSH > 4.0 mU/l, fT4 and TPOAb were measured. TPOAb females reported to have hyperthyroidism (sex ratio were also measured in randomly selected subgroups. females : males 4.2). The prevalence increased by age up The age and TSH values of the subgroups did not differ to the age of 80 (Table 2). For males aged 50±79 years, from the values of the whole group. TSH receptor the prevalence was about 1%, compared with females antibodies (TRAb) were measured in a small subgroup who had a prevalence between 3.1% and 3.6%. of samples with TSH < 0.05 mU/l. The numbers of persons who had either been treated TSH was measured with DELFIA hTSH Ultra (sensi- with carbimazole, radioactive iodine or thyroid surgery tivity 0.03 mU/l and total analytical variation < 5%), are shown in Table 2. No participants answered no to all www.eje.org
  • 3. EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Thyroid disease, dysfunction and autoimmunity 641 Table 2 Self-reported previously diagnosed thyroid disease and treatment. Diagnosis Treatment Thyroid Thyroid Radioactive Hyperthyroid Hypothyroid Goitre diseases** Carbimazole surgery iodine Thyroxine Age Total (years) number* n % n % n % n % n % n % n % n % Males 20±29 4325 7 0.16 14 0.32 2 0.05 4 0.09 2 0.05 2 0.05 3 0.07 10 0.23 30±39 5503 12 0.22 25 0.45 9 0.16 5 0.09 0 0.00 5 0.09 3 0.05 21 0.38 40±49 6581 28 0.43 51 0.77 19 0.29 12 0.18 7 0.11 16 0.24 19 0.29 44 0.67 50±59 5143 44 0.86 34 0.66 24 0.47 27 0.52 2 0.04 26 0.51 20 0.39 49 0.95 60±69 4340 44 1.01 70 1.61 27 0.62 20 0.46 7 0.16 34 0.78 27 0.62 86 1.98 70±79 3537 37 1.05 56 1.58 23 0.65 12 0.34 1 0.03 27 0.76 18 0.51 73 2.06 $ 80 1090 6 0.55 21 1.93 8 0.73 1 0.09 1 0.09 10 0.92 4 0.37 20 1.83 All 30 519 178 0.58 271 0.89 112 0.37 81 0.27 20 0.07 120 0.39 94 0.31 303 0.99 Females 20±29 5188 51 0.98 80 1.54 30 0.58 11 0.21 8 0.15 6 0.12 11 0.21 48 0.93 30±39 6251 93 1.49 175 2.80 110 1.76 39 0.62 21 0.34 32 0.51 32 0.51 128 2.05 40±49 7089 160 2.26 313 4.42 184 2.60 77 1.09 22 0.31 105 1.48 75 1.06 300 4.23 50±59 5538 170 3.07 373 6.74 183 3.30 86 1.55 18 0.33 151 2.73 99 1.79 395 7.13 60±69 4708 171 3.63 354 7.52 206 4.38 63 1.34 10 0.21 143 3.04 92 1.95 398 8.45 70±79 4282 155 3.62 281 6.56 214 5.00 42 0.98 10 0.23 132 3.08 61 1.42 356 8.31 $ 80 1688 56 3.32 90 5.33 76 4.50 10 0.59 3 0.18 46 2.73 24 1.42 115 6.81 All 34 744 856 2.46 1666 4.80 1003 2.89 328 0.94 92 0.26 615 1.77 394 1.13 1740 5.01 Percentages of males and females who answered yes to the questions in Table 1. * Total number who attended the health survey and returned the questionnaire. ** Thyroid diseases including thyroid cancer, thyroiditis but also other thyroid disorders (see text). three questions regarding treatment; however, 47 males Thyroid function tests in persons without (26%) and 172 females (20%) did not answer yes to any former or present thyroid disease of these questions. Reference range for TSH In calculating the reference ranges for TSH, the results from persons (9754 males Hypothyroidism The prevalence of hypothyroidism and 19 327 females) answering no to all questions was 0.9% and 4.8% for males and females about thyroid disease (Table 1) and diabetes mellitus respectively (sex ratio females : males 5.4). Only 1.5% were included. of females under 30 were, or had been, hypothyroidic, Table 3 shows the median, 2.5 and 97.5 percentiles compared with 7.5% of those in their seventh decade. for TSH, all increasing with age. Regardless of age, the However in the oldest group (females over 80) the 2.5 and 97.5 percentiles were 0.56±4.60 mU/l for prevalence decreased. In males, the prevalence of males and 0.49±5.70 mU/l for females. The TSH value hypothyroidism increased by age also in the oldest was signi®cantly lower in males than in females (Table 2). (P < 0.001) and increased with age. The number of participants on current or former TPOAb was measured in samples with TSH > 4.0 mU/l thyroxine medication is shown in Table 2. However, (1082 females and 370 males) and in randomly 219 out of the 271 hypothyroid males (81%) reported selected samples from females (n ˆ 582) and males current or former thyroxine medication and 1349 of (n ˆ 360) without a history of thyroid disease (see 1666 females (81%). below). The median, 2.5 and 97.5 percentiles for TSH were recalculated after excluding persons Goitre The prevalence of self-reported goitre was 2.9% known to have TPOAb > 200 U/ml even though in females. In the youngest group, the prevalence was TPOAb was measured only in a small percentage only 0.6% compared with almost 5% in the oldest age (2.5%) of the samples with TSH < 4.0 mU/l. In groups. In males, the prevalence was only 0.4%, and males, the median and 2.5 percentile for TSH did increased with age (Table 2). not change, while the 97.5 percentile dropped from 4.60 to 3.40 mU/l. The TSH values in males without Thyroid diseases A total of 328 females (1.0%) and 81 positive TPOAb were signi®cantly lower than in (0.3%) males answered yes to this question, but only males regardless of TPOAb value in all age groups 176 females (0.5%) and 48 males (0.2%) also answered except for those below 40 years (P < 0.001 for those no to the questions about goitre, hypo- and hyperthy- over 40 years and P ˆ 0.085 for those below 40 roidism. This group included persons treated for years). In females the median and 2.5 percentile nodules, cancer or thyroiditis. marginally decreased, whereas the 97.5 percentile www.eje.org
  • 4. 642 T Bjùro and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Table 3 TSH ± median, 2.5 and 97.5 percentiles in persons without known thyroid disease or diabetes. Regardless of TPOAb value Without positive TPOAb Age Number Median* 2.5% 97.5% Number Median* 2.5% 97.5% Males < 40 459 1.40 0.50 4.05 441 1.40 0.50 3.40 40±49 3049 1.40 0.54 3.90 2899 1.40 0.54 3.30 50±59 2398 1.50 0.56 4.10 2257 1.50 0.56 3.30 60±69 1986 1.60 0.59 4.73 1849 1.50 0.59 3.50 70±79 1454 1.70 0.58 5.56 1322 1.60 0.58 3.50 $ 80 388 1.90 0.60 6.70 349 1.80 0.59 3.80 All 9754 1.50 0.56 4.60 9130 1.50 0.56 3.40 Females < 40 540 1.40 0.37 5.09 514 1.30 0.37 3.30 40±49 6241 1.50 0.52 4.90 5845 1.40 0.53 3.40 50±59 4591 1.60 0.51 5.30 4256 1.50 0.50 3.60 60±69 3712 1.70 0.51 6.92 3380 1.60 0.49 3.60 70±79 3158 1.70 0.42 6.60 2857 1.70 0.39 3.70 $ 80 1019 1.80 0.37 6.40 916 1.70 0.36 3.80 All 19 327 1.60 0.49 5.70 17 824 1.50 0.48 3.60 * TSH values above 1.0 mU/l were reported with only one decimal. decreased from 5.70 to 3.60 mU/l. In all age groups, fT4 values). In females the highest prevalence of TSH was signi®cantly lower in females without biochemical hypothyroidism was in those aged 60±69 positive TPOAb (P < 0.001). years (1.24%) and lowest in those aged 40±49 years (0.63%). Biochemical hypothyroidism The prevalence of A TSH value between 4.0 and 10 mU/l was present in TSH $ 10 mU/l was 0.37% in males and 0.90% in 3.7% of the males and 5.1% of the females, and 2.2% females without former or present thyroid disease (Table and 5.1% respectively (or 0.08% and 0.26% of the total) 4). Only 37% of males and 56% of females with simultaneously had fT4 values below 8.0 pmol/l, TSH $ 10 mU/l also had fT4 below 8.0 pmol/l (i.e. below whereas 63% of males and 76% of females with TSH the reference range); however, up to 92% and 97% levels between 4.0 and 10 mU/l had fT4 values below respectively, had fT4 < 12 pmol/l (i.e. low or low normal 12.0 pmol/l (Table 4). Table 4 Prevalence of biochemical hypothyroidism in persons without former or present thyroid disease. A) De®ned as TSH $ 10 mU/l and B) de®ned as TSH > 4 and < 10 mU/l. A) TSH $ 10 mU/l B) TSH > 4 and < 10 mU/l & TPOAb > & TPOAb > All & FT4 < 8.0 & FT4 < 12.0 200 All & FT4 < 8.0 & FT4 < 12.0 200 Total Age number n %1 n %2 n %2 n %2 n %1 n %3 n %3 n %3 Males < 40 460 1 0.22 1 100 1 100 1 100 11 2.4 0 0.0 5 46 2 18 40±49 3096 14 0.45 5 36 13 93 14 100 60 1.9 1 1.7 37 62 19 32 50±59 2474 8 0.32 2 25 7 88 5 63 60 2.4 2 3.3 38 63 24 40 60±69 2094 5 0.24 2 40 5 100 4 80 93 4.4 4 4.3 63 68 24 26 70±79 1588 8 0.50 3 38 7 88 8 100 97 6.1 1 1.0 67 69 20 21 $ 80 453 2 0.44 1 50 2 100 1 50 51 11.3 0.0 23 45 8 16 All 10 165 38 0.37 14 37 35 92 33 87 372 3.7 8 2.2 233 63 97 26 Females < 40 542 5 0.92 4 80 5 100 4 80 13 2.4 2 15.4 13 100 7 54 40±49 6309 40 0.63 18 45 40 100 35 88 231 3.7 10 4.3 176 76 137 59 50±59 4697 37 0.79 21 57 36 97 31 84 218 4.6 11 5.0 175 80 110 51 60±69 3881 48 1.24 33 69 47 98 41 85 229 5.9 19 8.3 177 77 101 44 70±79 3479 38 1.09 20 53 36 95 32 84 227 6.5 9 4.0 161 71 98 43 $ 80 1224 14 1.14 6 43 13 93 11 79 101 8.3 1 1.0 71 70 34 34 All 20 132 182 0.90 102 56 177 97 154 85 1019 5.1 52 5.1 773 76 487 48 1 % of total number; 2 % of number with TSH $ 10 mU/l; 3 % of number with TSH $ 4 and < 10 mU/l. www.eje.org
  • 5. EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Thyroid disease, dysfunction and autoimmunity 643 Table 5 Prevalence of biochemical hyperthyroidism in persons without former or present thyroid diseases. A) De®ned as TSH # 0.05 mU/l and B) de®ned as TSH > 0.05 and < 0.2 mU/l. A) TSH # 0.05 mU/l B) TSH > 0.05 and < 0.2 mU/l & FT4 > 20 or T3 > 2.8 & FT4 > 20 or T3 > 2.8 Total Age number n %1 n %2 n %1 n %3 Males < 40 460 0 0.00 0 0 1 0.22 0 0 40±49 3096 1 0.03 1 100 1 0.03 0 0 50±59 2474 2 0.08 1 50 1 0.04 0 0 60±69 2094 1 0.05 0 0 4 0.19 2 50 70±79 1588 3 0.19 1 33 4 0.25 1 25 $ 80 453 2 0.44 1 50 0 0.00 0 0 All 10 165 9 0.09 4 44 11 0.11 3 27 Females < 40 542 3 0.55 1 33 3 0.55 1 33 40±49 6309 26 0.41 17 65 13 0.21 1 8 50±59 4697 21 0.45 11 52 4 0.09 0 0 60±69 3881 14 0.36 7 50 15 0.39 2 13 70±79 3479 19 0.55 12 63 23 0.66 4 17 $ 80 1224 10 0.82 7 70 8 0.65 1 13 All 20 132 93 0.46 55 59 66 0.33 9 14 1 % of total number; 2 % of number with TSH # 0.05 mU/l; 3 % of number with TSH > 0.05 and < 0.2 mU/l. Biochemical hyperthyroidism The prevalence of group with TSH $ 0.2 mU/l but # 2.0 mU/l, whereas suppressed TSH (# 0.05 mU/l) was 0.09% in males only 7.6% of the females and none of the 197 males and 0.46% in females (Table 5). Four of nine males with measured TPOAb had positive antibodies. A small (44%) and 55 of 93 females (59%) with suppressed TSH increase in TSH values (> 2.0 mU/l but # 4.0 mU/l) also had elevated fT4 (> 20 pmol/l) and/or elevated T3 more than doubled the percentage of positive TPOAb, (> 2.8 nmol/l) values. 19.7% in females and 6.9% in males. The percentage TSH values between 0.05 and 0.2 mU/l were found in with positive TPOAb increased with TSH both in females 0.11% of males and 0.33% of females respectively. and males. Up to 85.6% of the females and 87% of males However, 3 of 11 males (27%) and 9 of 66 females with TSH > 10 mU/l had positive TPOAb. (14%) also had elevated fT4 and/or T3. The prevalence The percentage of positive TPOAb also increased with of low TSH (> 0.05 mU/l but < 0.2 mU/l) in combina- low TSH; 16.7% of males and 34.7% of females with tion with elevated fT4 and/or T3 was 0.03% in males TSH < 0.2 mU/l were TPOAb positive. and 0.05% in females. The percentage of males with positive TPOAb was lower than in females in all age groups except for those Thyroid antibodies The prevalence of positive TPOAb with TSH > 10 mU/l (Fig. 1). (> 200 U/ml) in a randomly selected subgroup of females About 70% (males 68.6% and females 74.4%) of the (n ˆ 582) and males (n ˆ 360) aged over 40 without persons with positive TPOAb had values > 1000 U/ml current or former thyroid diseases was 13.9% and 2.8% and approximately 10% (males 11.7% and respectively (females compared with males, P < 0.001). females 8.5%) had TPOAb values between 200 and The prevalence of positive TPOAb did not change 400 U/ml. This tendency was independent of age (40± signi®cantly with age in these individuals (P ˆ 0.55). 79 years). The TSH values were signi®cantly higher in patients TRAb and TPOAb were measured in a subgroup of with positive TPOAb than in those with negative females with TSH < 0.05 mU/ml and 27% had both antibodies. Median TSH for TPOAb negative females positive TRAb and TPOAb. A few had only positive was 1.5 mU/l and 2.5 mU/l for those with positive TPOAb (1.2%) and none of the patients were only TRAb TPOAb (P < 0.001) and 1.5 mU/l and 3.5 mU/l respec- positive. tively for males (P < 0.001). The percentage of elevated TSH (> 4 mU/l) in TPOAb positive females was 24.0% and 2.4% in TPOAb negative females (P < 0.001), and Discussion 6.0% in the total group. In TPOAb positive males, TSH Nearly 9% of females and 2% of males over the age of 20 was elevated in 40.0% whereas it was only increased in had a previously diagnosed thyroid disorder. Hypothy- 3.5% in TPOAb negative males (P < 0.001). roidism had been diagnosed in 4.8% of females and 0.9% The prevalence of positive TPOAb changed with TSH of the males. The TSH screening revealed unrecognised values (Fig. 1). The lowest prevalence was seen in the biochemical hypothyroidism (TSH $ 10 mU/l) in 0.9% www.eje.org
  • 6. 644 T Bjùro and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Hypothyroidism The prevalence of previously diagnosed hypothyroidism was higher in males (0.9%) and lower in females (4.8%) than reported by Vandepump et al. (14) (0.5% and 7.1% respectively). The prevalence of unrecognised hypothy- roidism was higher in both females and males compared with the reports from Sweden and the UK. However, most of the unrecognised hypothyroidism was mild to moderate. Compared with the data reported by Broch- mann et al. (10), the prevalence of former diagnosed hypothyroidism in females over 70 years of age in Nñrùy had increased (3.5% vs. 6.2% reported in this study). Comparing the prevalence of undiagnosed hypothyroidism is dif®cult owing to the different diagnostic criteria used. Brochmann et al. (10) reported a prevalence of TSH > 6 mU/l of 5.2% in females and Figure 1 Percentage positive TPOAb at different TSH values in 3.5% in males over 70 in Nñrùy. The prevalence of males (shaded bars) and females (solid bars) without known thyroid TSH > 6 mU/l was exactly the same in our study (data disease. TPOAb was measured in all blood samples with not shown). TSH > 4 mU/l and in randomly selected subgroups with TSH < 4 mU/l. The number of samples with measured TPOAb was A recent report from Colorado stated a prevalence of TSH < 0.2 mU/l, males n ˆ 30, females n ˆ 49; TSH 0.2±2.0 mU/l, elevated TSH (> 5.1 mU/l) of 9.5% in the adult males n ˆ 197, females n ˆ 315; TSH 2.1±4.0 mU/l, males n ˆ 72, population increasing with age from 3 to 16% in females n ˆ 117; TSH 4.1±5.0 mU/l, males n ˆ 183, females males and from 4 to 21% in females (3). The prevalence n ˆ 446; TSH 5.1±10.0 mU/l, males n ˆ 161, females n ˆ 493; of elevated TSH in the Colorado study was almost twice TSH > 10 mU/l, males n ˆ 38, females n ˆ 180. the prevalence we observed (5.3% of the total popula- tion in our study) even though we used a lower cut-off value (TSH > 4.0 mU/l vs. > 5.1 mU/l). Also in the of females and 0.4% of males, and moderately elevated Rotterdam study (15), the prevalence of elevated TSH TSH (4.0±9.9 mU/l) in 5.1% of females and 3.7% of was higher (11% of elderly females over 55 years of age males. Hyperthyroidism had been diagnosed in 2.5% had subclinical hypothyroidism). The classic study of of females and in 0.6% of males. The TSH Sawin et al. (2) reported a higher prevalence of elevated screening revealed unrecognised biochemical hyper- TSH (13% of the females over 60 years of age); however, thyroidism (TSH # 0.05 mU/l) in 0.5% of females and there is no information regarding former diagnosed in 0.1% of males and moderately suppressed TSH thyroid disorders in this report. In our study, the (0.05±0.19 mU/l) in 0.3% and 0.1% respectively. prevalence data of abnormal TSH values is from subjects Goitre was reported in 2.9% of females and 0.4% in without former thyroid disorders or use of thyroxine. males. From Italy, Rivolta et al. (16) recently reported a similar The strength of our study was the very large prevalence of subclinical hypothyroidism to the present number of participants from an unselected popu- study. lation, the large age range, with no upper age limits, The prevalence of moderately elevated TSH (4.1± and the high attendance rate, especially in the age 9.9 mU/l) was substantially higher in both males and group aged 35±80. In those over 80, the attendance females over 80 compared with the younger age groups, rate was lower, which might explain the lower whereas the prevalence of markedly elevated TSH prevalence of all types of thyroid disorders in this ($ 10 mU/l) was higher in the younger age groups. group. However, when comparing results from different This might be explained by the more frequent need of areas, the results might be in¯uenced by various medical care with increased age, including more treatment traditions and diagnostic criteria. frequent TSH measurements. Our results demonstrate that thyroid dysfunction may develop gradually. Using the established reference Hyperthyroidism values for fT4 only a small fraction had fT4 values below The prevalence of previously diagnosed hyperthyroid- the normal range; however, the majority had fT4 in the ism in the present study was lower than previously lower normal range. This ®nding corresponds well to reported from Great Britain (14) for females (2.5% vs. what Bauer & Brown (17) reported in outpatients. The 3.7%). However, the prevalence of unknown hyperthyr- negative correlation between fT4 and TSH is well known oidism is similar to that reported from the UK (14) but and the reported results also focus on the dif®culties in somewhat higher than in Sweden (13), and lower than establishing `reference values'. A considerable portion of in Denmark (5). those with low TSH had fT4 and T3 values within the www.eje.org
  • 7. EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Thyroid disease, dysfunction and autoimmunity 645 normal range, but this could also be due to a non- estimated to be 0.1±0.125 mg. Assuming the number thyroid-related illness. of persons under 20 on thyroxine medication is negligible, then between 2.6% (if the daily dosage is 0.125 mg) and 3.3% (if the daily dosage is 0.1 mg) of the Goitre total population over 20 years used thyroxine. This is in The prevalence of goitre in those aged 60±69 was 4.4% accordance with the 3% of the population reporting in females and 0.6% in males, compared with 12.2% former or current T4 medication. and 3.2% respectively in Jutland and 1.9% and 2.2% in Nearly 80% of those with a history of hyperthyroid- Iceland (5). ism answered yes to one or more of three questions on This age group in our study showed a higher treatment of hyperthyroidism. Few patients reported prevalence of undiagnosed hyperthyroidism than in carbimazole treatment but nearly 20% had not Iceland, but far lower than in Jutland (5). Ten per cent of answered all the treatment questions. females in Jutland had TSH below 0.4 mU/l whereas this Both overt hyper- and hypothyroidism have a variety was less than 2.5% in Nord-Trùndelag. The prevalence of adverse effects and should be treated. However, of elevated TSH was high in Iceland, and approximately diagnosing and treatment of subclinical or biochemical 18% of females in their sixties had TSH above 4 mU/l, thyroid dysfunction remains controversial. Subclinical but only 7.1% in Norway and 3.8% in Jutland. Both the hyperthyroidism is a risk factor for atrial ®brillation at goitre data and the TSH values indicate that the pattern least in older persons (19) and approximately 10±15% of thyroid disorders is between those found in Iceland of patients with overt hyperthyroidism, who have atrial (high iodine intake area) and Jutland (low iodine intake ®brillation will have an atrial embolic event (20, 21). At area). We do not have recent data for iodine intake in least older persons with low TSH should be monitored Nord-Trùndelag; however, Kapelrud et al. (8) reported regarding overt hyperthyroidism and/or atrial ®brilla- an iodine intake of about 200 mg/24 h in six different tion. In persons with subclinical hypothyroidism the communities in Norway. Laurberg et al. (5) concluded lipid pro®les did not differ from the control groups for that both high and low iodine intake levels correlated to those with moderately elevated TSH values, but when high prevalence rate of thyroid abnormalities (although analysed according to the severity of the subclinical the pattern of abnormalities differ). They speculate that hypothyroidism (TSH $ 10mU/l), the data showed a window in iodine intake level might exist where increases in serum total- and LDL-cholesterol and thyroid disorders are less common. Mild iodine de®- decreases in serum HDL-cholesterol (22, 23). The ciency may partly protect against autoimmune thyroid unfavourable lipid pro®le can be reversed by thyroxine disease, as reported for several animal strains (18). therapy (24±27). Whether thyroxine treatment of The prevalence of spontaneous hypothyroidism subclinical hypothyroidism reduces the risk of coronary (TSH $ 10 mU/l) of 0.9% in females and 0.4% in heart disease has not been demonstrated. males in our cross-sectional study is somewhat higher A recent report from The Netherlands demonstrates than expected from the mean incident rate for that subclinical hypothyroidism is a strong indicator of hypothyroidism in females of 0.35% per year and risk for atherosclerosis and myocardial infarction in 0.06% per year in males reported by Vanderpump et elderly females (15). al. (14). Also, our reported prevalence of undiagnosed Observation suggests that subclinical hypothyroidism hyperthyroidism (0.5% in females and 0.1% in males) is lowers the threshold for the development of major higher than expected from the mean incident rate for depressive disorders and modi®es its clinical features hyperthyroidism in females of 0.08% per year and the (28±30). Still, controlled studies of thyroxine treatment negligible incident rate in males (14). are lacking. The prevalence data of former diagnosed thyroid Nystro et al. (31) reported that 25% of middle-aged Èm disease is based on questionnaires. Similar questions and old women with subclinical hypothyroidism would were used in the Nñrùy study (10) and the answers bene®t from thyroxine medication. The threshold for were then compared with the medical records and measuring TSH, at least in these females, should be low showed a good correlation. Furthermore, the percen- because the prevalence of thyroid dysfunction is high. tage of patients answering yes to questions about We have no de®nitive information on the nature of treatment corresponds to the prevalence of thyroid hyperfunction of the thyroid gland except in a subgroup disease. Surprisingly, only 81% of those who reported revealing 27% of the females with TSH # 0.05 as TRAb former or present hypothyroidism also con®rmed positive. We also report that about 17% of males and 35% present or former thyroxine medication. However, of females without former diagnosed thyroid diseases and none of those who answered yes to present or former with TSH < 0.2 were TPOAb positive. Our study demon- hypothyroidism also answered no to former or present strates that the large majority of females and males with thyroxine medication. hypothyroidism were TPOAb positive. This indicates that In 1997 1.16 million dosages of 0.1 mg thyroxine autoimmunity is an important factor in both hyper- and were sold in Nord-Trùndelag (information from Norsk hypothyroidism in Norway. Nord-Trùndelag is fairly Medisinaldepot A/S). The average daily dosage is representative of Norway as a whole (32, 33). www.eje.org
  • 8. 646 T Bjùro and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Positive TPOAb were found in 2.8% of males and positive TPOAb, whereas the female : male ratio of 13.9% of females over 40 years of age and no difference unrecognised hypothyroidism was surprisingly low between the age groups was observed. The prevalence (approximately 2). Thyroid dysfunction is known to be was also lower in both sexes compared with that more common in females than in males, and females reported in Norwegian blood donors (34). In the present generally use the health care system more than males. study we have prevalence data only for TPOAb in It is important to recognise that thyroid disorders may persons over 40 years of age. We reported a higher be responsible for dysfunctions or illnesses also in males. prevalence of positive thyroid antibodies in females over The clinical signi®cance of positive TPOAb and/or 45 years compared with those under 45 years (34). This subclinical hypo- or hyperfunction of the thyroid gland might indicate that TPOAb appears in the circulation is not conclusive from the present study. The ongoing long before the change of thyroid function can be follow-up study in Nord-Trùndelag may hopefully observed by changes in the TSH values. provide answers. It is interesting to note that both the sex and age differences in median TSH, and 97.5 percentile dis- appeared when the TPOAb positive persons were Acknowledgements excluded. The higher prevalence of TPOAb in females We acknowledge the valuable ®nancial support from than in males explains the higher TSH values in Nycomed Pharma, Wallac and B.R.A.H.M.S. and also a females. However, we did not ®nd an increased scienti®c grant from Glaxo. The authors are grateful to prevalence of positive TPOAb with age, whereas there Inger Gustafsson and the staff at the Hormone is a marked increase in prevalence of elevated TSH Laboratory, Aker University Hospital for their skilful values with age. These observations support the technical assistance. hypothesis that the autoimmune process starts at an earlier age, whereas the thyroid dysfunction is observed several years after the appearance of TPOAb. Mariotti References et al. (35) have reported that thyroid function appears to 1 Tunbridge WM, Evered DC, Hall R, Appelton D, Brewis M, Clark F be well preserved until the eighth decade of life in et al. The spectrum of thyroid disease in a community: the healthy subjects without changes in the TSH values, Wickham survey. Clinical Endocrinology 1977 7 481±493. and they did not report differences in the prevalence of 2 Sawin CT, Castelli WP, Hershman JM, McNamara, P & Bacharach P. The aging thyroid. Thyroid de®ciency in the Framingham study. the presence of TPOAb with age. Archives of Internal Medicine 1985 145 1386±1388. The prevalence of positive TPOAb reported by 3 Canaris GJ, Manowitx NR, Mayor G & Ridgway EC. The Colorado different groups is dif®cult to compare because of the thyroid disease prevalence study. Archives of Internal Medicine different assays used, no international standardisation 2000 160 526±534. 4 Laurberg P, Pedersen KM, Vestergaard H & Sigurdsson G. High of the assays and different cut-off values (36, 37). In this incidence of multinodular toxic goitre in the elderly population study we used a well documented assay system but set in low iodine intake area vs. high incidence of Graves' disease the cut-off value to 200 U/ml instead of 100 U/ml to be in the young in a high iodine intake area: comparative surveys sure not to include those with weakly positive anti- of thyrotoxicosis epidemiology in East-Jutland Denmark and bodies. Positive TPOAb were strongly correlated to Iceland. Journal of Internal Medicine 1991 229 415±420. 5 Laurberg P, Pedersen KM, Hreidarsson A, Sigfusson N, Iversen E & thyroid dysfunction, and in our study even those with Knudsen PR. Iodine intake and the pattern of thyroid disorders: a TSH values between 2 and 4 mU/l had a markedly comparative epidemiological study of thyroid abnormalities in the increased percentage of positive TPOAb. The prevalence elderly in Iceland and in Jutland, Denmark. Journal of Clinical of elevated TSH was nearly 10-fold higher both in Endocrinlogy and Metabolism 1998 83 765±769. 6 Delang F. Disorders induced by iodine de®ciency. Thyroid 1994 4 females and males with positive TPOAb compared with 107±128. subjects with negative TPOAb. Vanderpump et al. (14) 7 Frey H, Rosenlund B & Storli U. Urinary secretion of iodine in reported that, independent of age, the higher the serum Norwegian population groups 1971±72. Tidsskrift for Den norske level of TSH is above 2 mU/l, the greater the prognostic lñgeforening 1974 94 982±987. signi®cance for development of overt hypothyroidism in 8 Kapelrud H, Frey HM & Theodorsen L. Urine iodine secretion. Tidsskrift for Den norske lñgeforening 1987 115 1320±1321. both TPOAb positive and negative subjects. 9 Norman N. The incidence of hyperthyroidism, hypothyroidism Both environmental and genetic factors are involved and diabetes in northern and southern Norway, a comparative in the development of thyroid disorders. Except for study. Acta Medica Scandinavica 1955 151. iodine, the environmental determinants remain 10 Brochmann H, Bjùro T, Gaarder PI, Hanson F & Frey HM. Prevalence of thyroid dysfunction in elderly subjects. Acta unknown. Evidence for genetic factors in the develop- Endocrinologica 1989 117 7±12. ment of autoimmune thyroid disease has been demon- 11 Bjùro T, Frey HM, Larsen IF, Brochmann H, Hanson F & Gaarder strated by clustering within families and in studies with PI. Prevalence of thyroid dysfunction and thyroid antibodies in twins (38, 39). Susceptibility genes or loci for auto- elderly subjects. Tidsskrift for Den norske lñgeforening 1989 10 immune thyroid disease have not yet been identi®ed 1048±1051. 12 Sundbeck G, Lundberg P-A, Lindstedt G, Jagenburg R & Eden S. Â (40). Incidence and prevalence of thyroid disease in elderly women: The female : male ratios for previously diagnosed results from the longitudinal population study of elderly people in thyroid diseases were between 4.2 and 7.1, and 5.0 for Gothenburg, Sweden. Age and Ageing 1991 20 291±298. www.eje.org
  • 9. EUROPEAN JOURNAL OF ENDOCRINOLOGY (2000) 143 Thyroid disease, dysfunction and autoimmunity 647 13 Petersen K, Lindstedt G, Lundberg P-A, Bengtson C, Lapidus L & of patients referred for dyslilpidemia. Archives of Internal Medicine Nystrom E. Thyroid disease in middle-aged and elderly Swedish È 1995 155 1490±1495. women: thyroid-related hormones, thyroid dysfunction and goitre 28 Haggerty JJ Jr & Prange AR Jr. Borderline hypothyroidism and in relation to age and smoking. Journal of Internal Medicine 1991 depression. Annual Review of Medicine 1995 46 37±46. 229 407±414. 29 Custro N, Sca®di V, LoBaido R, Nastri L, Abbate G, Gallo S et al. 14 Vanderpump MPJ, Tunbridge WMG, French JM, Appleton D, Bates Subclinical hypothyroidism resulting from autoimmune thyroi- D, Clark F et al. The incidence of thyroid disorders in the ditis in female patients with endogenous depression. Journal of community: a twenty-year follow-up of the Wickham Survey. 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A Archives of Internal Medicine 1990 150 2097±2100. population-based study of Graves' disease in Danish twins. Clinical 25 Caron Ph, Calazei G, Parra HJ, Hoff M & Louvet JP. Decreased HDL Endocrinology 1998 48 397±400. cholesterol in subclinical hypothyroidism; the effect of L-thyroxine 40 Allahabadia A & Gough SCI. The different approaches to the therapy. Clinical Endocrinology 1990 33 519±523. genetic analysis of autoimmune thyroid disease. Journal of 26 Bogner U, Arbtz H-R, Peters H & Schleusener H. Subclinical Endocrinology 1999 163 7±13. hypothyroidism and hyperlipoproteinaemia: indiscriminate L- thyroxine treatment not justi®ed. Acta Endocrinologica 1993 128 202±206. 27 Diekman T, Lansberg PJ, Kastelein JJ & Wiersienga WW. Received 13 April 2000 Prevelance and correction of hypothyroidism in a large cohort Accepted 19 June 2000 www.eje.org

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