An increased incidence of overt hypothyroidism after iodine fortification of salt in Denmark: a prospective population study

CONTEXT: Iodine fortification (IF) of salt was introduced in Denmark in 1998. Little is known about the effect of a minor increase in iodine intake on the incidence of hypothyroidism. We prospectively identified all new cases of overt hypothyroidism in two areas of Denmark before and for the first 7 yr after IF had been introduced. METHODS: A computer-based register was used to identify continuously all new cases of overt hypothyroidism in two subcohorts with previous moderate and mild iodine deficiency (ID), respectively (Aalborg, n = 310,124, urinary iodine = 45 microg/liter; and Copenhagen, n = 225,707, urinary iodine = 61 microg/liter). Data were obtained 1) before IF (1997-1998), 2) during voluntary IF (1999-2000), 3) during early (2001-2002) and 4) during late (2003-2005) period with mandatory IF. RESULTS: The overall incidence rate of hypothyroidism increased during the study period: baseline, 38.3/100,000.yr; voluntary IF, 43.7 (not significant vs. baseline); early mandatory IF, 48.7 [vs. baseline, rate ratio (RR) = 1.27; 95% confidence interval (CI) = 1.10-1.47]; and late mandatory IF, 47.2 (vs. baseline, RR = 1.23; 95% CI = 1.07-1.42). There was a geographic difference because hypothyroidism increased only in the area with previous moderate ID: Aalborg, late mandatory IF vs. baseline, 40.3/29.7 (RR = 1.11; 95% CI = 1.11-1.66); Copenhagen, 56.7/51.6 (RR = 1.10; 95% CI = 0.90-1.34). The increase occurred in young and middle-aged adults. CONCLUSION: Even a cautious iodization of salt was accompanied by a moderate increase in the incidence rate of overt hypothyroidism. This occurred primarily in young and middle-aged subjects with previous moderate ID.     

The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives

OBJECTIVE: Denmark was an area of iodine deficiency, and mandatory iodine fortification of table salt and salt in bread (13 p.p.m. iodine) was initiated in 2000/2001. The Danish investigation on iodine intake and thyroid disease (DanThyr) is the monitoring of the iodine fortification program. DESIGN AND METHODS: DanThyr consists of three main parts: a study of population cohorts initialized before (n=4649) and after (n=3570) iodization of salt, a prospective identification of incident cases of overt hyper- and hypothyroidism in a population of around 550,000 people since 1997, and compilation of data from the national registers on the use of thyroid medication, thyroid surgery, and radioiodine therapy. Studies were carried-out in parallel in subcohorts living in areas with differences in iodine content of ground water. RESULTS: The study showed profound effects of even small differences in iodine intake level on the prevalence of goiter, nodules, and thyroid dysfunction. Mild and moderate iodine deficiency was associated with a decrease in serum TSH with age. Other environmental factors were also important for goiter development (increase in risk, smoking and pregnancy; decrease in risk, oral contraception and alcohol consumption), and the individual risk depended on the genetic background. Environmental factors had only a minor influence on the prevalence of thyroid autoantibodies in the population. There were more cases of overt hypothyroidism in mild than in moderate iodine deficiency caused by a 53% higher incidence of spontaneous (presumably autoimmune) hypothyroidism. On the other hand, there were 49% more cases of overt hyperthyroidism in the area with moderate iodine deficiency. The cautious iodine fortification program, aiming at an average increase in iodine intake of 50 mug/day has been associated with a 50% increase in incidence of hyperthyroidism in the area with the most severe iodine deficiency. The incidence is expected to decrease in the future, but there may be more cases of Graves' hyperthyroidism in young people. CONCLUSION: A number of environmental factors influence the epidemiology of thyroid disorders, and even relatively small abnormalities and differences in the level of iodine intake of a population have profound effects on the occurrence of thyroid abnormalities. Monitoring and adjustment of iodine intake in the population is an important part of preventive medicine.     

Radioiodine treatment of hyperthyroidism-prognostic factors for outcome

There is little consensus regarding the most appropriate dose regimen for radioiodine (131I) in the treatment of hyperthyroidism. We audited 813 consecutive hyperthyroid patients treated with radioiodine to compare the efficacy of 2 fixed-dose regimens used within our center (185 megabequerels, 370 megabequerels) and to explore factors that may predict outcome. Patients were categorized into 3 diagnostic groups: Graves' disease, toxic nodular goiter, and hyperthyroidism of indeterminate etiology. Cure after a single dose of 131I was investigated and defined as euthyroid off all treatment for 6 months or T4 replacement for biochemical hypothyroidism in all groups. As expected, patients given a single dose of 370 megabequerels had a higher cure rate than those given 185 megabequerels, (84.6% vs. 66.6%, P < 0.0001) but an increase in hypothyroidism incidence at 1 yr (60.8% vs. 41.3%, P < 0.0001). There was no difference in cure rate between the groups with Graves' disease and those with toxic nodular goiter (69.5% vs. 71.4%; P, not significant), but Graves' patients had a higher incidence of hypothyroidism (54.5% vs. 31.7%, P < 0.0001). Males had a lower cure rate than females (67.6% vs. 76.7%, P = 0.02), whereas younger patients (<40 yr) had a lower cure rate than patients over 40 yr old (68.9% vs. 79.3%, P < 0.001). Patients with more severe hyperthyroidism (P < 0.0001) and with goiters of medium or large size (P < 0.0001) were less likely to be cured after a single dose of 131I. The use of antithyroid drugs, during a period 2 wk before or after 131I, resulted in a significant reduction in cure rate in patients given 185 megabequerels 131I (P < 0.01) but not 370 megabequerels. Logistic regression analysis showed dose, gender, goiters of medium or large size, and severity of hyperthyroidism to be significant independent prognostic factors for cure after a single dose of 131I. We have demonstrated that a single fixed dose of 370 megabequerels 131I is highly effective in curing toxic nodular hyperthyroidism as well as Graves' hyperthyroidism. Because male patients and those with more severe hyperthyroidism and medium or large-sized goiters are less likely to respond to a single dose of radioiodine, we suggest that the value of higher fixed initial doses of radioiodine should be evaluated in these patient categories with lower cure rates.     

Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients

To determine the clinical impact of endogenous subclinical hyperthyroidism, specific symptoms and signs of thyroid hormone excess and quality of life were assessed in 23 patients (3 males and 20 females; mean age, 43 +/- 9 yr) and 23 age-, sex-, and lifestyle-matched normal subjects by using the Symptoms Rating Scale and the Short Form 36 Health Survey questionnaires. Because the heart is one of the main target organs of the thyroid hormone, cardiac morphology and function were also investigated by means of standard 12-lead electrocardiogram (ECG), 24-h Holter ECG, and complete Doppler echocardiography. Stable endogenous subclinical hyperthyroidism had been diagnosed in all patients at least 6 months before the study (TSH, 0.15 +/- 0.1 mU/L; free T(3), 6.9 +/- 1.1, pmol/L; free T(4), 17.2 +/- 2.3, pmol/L). Fifteen patients were affected by multinodular goiter, and eight patients by autonomously functioning thyroid nodule. The mean Symptoms Rating Scale score (9. 8 +/- 5.5 vs. 4.3 +/- 2.2, P: < 0.001) and both the mental (36.1 +/- 9.5 vs. 50.0 +/- 8.5, P: < 0.001) and physical (42.6 +/- 8.0 vs. 55. 6 +/- 4.1, P: < 0.001) component scores of Short Form 36 Health Survey documented a significant prevalence of specific symptoms and signs of thyroid hormone excess and notable impairment of quality of life in patients. Holter ECG showed a higher prevalence of atrial premature beats in endogenous subclinical hyperthyroid patients than in the controls, but the difference was not statistically significant, although the average heart rate was significantly increased in the patients (P: < 0.001). An increase of left ventricular mass (162 +/- 24 vs. 132 +/- 22 g, P: < 0.001) due to the increase of septal (P: = 0.025) and posterior wall (P: = 0.004) thickness was observed in patients. Systolic function was enhanced in patients as shown by the significant increase of both fractional shortening (P: = 0.005) and mean velocity of heart rate-adjusted circumferential fiber shortening (P: = 0.036). The Doppler parameters of diastolic function were significantly impaired in the patients as documented by the reduced early to late ratio of the transmitral flow velocities (P: < 0.001) and the prolonged isovolumic relaxation time (P: = 0.006). These data indicate that endogenous subclinical hyperthyroidism has a relevant clinical impact and that it affects cardiac morphology and function. Moreover, they suggest that treatment of persistent endogenous subclinical hyperthyroidism should be considered also in young and middle-aged patients to attenuate specific symptoms and signs of thyroid hormone excess, ameliorate the quality of life, and avoid the consequences to the heart of long exposure to a mild excess of thyroid hormone.     

Optimization of iodine intake in Belgium

Mild iodine deficiency (MID) is a long-standing problem in Belgium and was recognized only recently as public health issue by the Ministry of Health (MOH). The main MID-related health problems in Belgium are a high prevalence of thyroid nodules and multinodular goiter. The economic cost of thyroid nodular disease only in Belgium was estimated at about € 40 millions per year. The Belgian health authorities adopted a selective strategy to optimize iodine intake through the fortification of bread with iodized salt. A progressive, step-by-step increase of the iodine content of salt was chosen in order to minimize the incidence of hyperthyroidism. MOH monitors this strategy by assessing periodically the urinary iodine concentration in school-aged children and pregnant women, as well as by a yearly follow-up of TSH concentrations in all Belgian newborns. Although the implementation of this strategy was an important step, the main drawback of the current situation is the absence of a legal framework to support the strategy. The utilization of iodized salt in bread on a voluntary basis was endorsed by the bakery industry and MOH. However a legal framework is required to assure the effectiveness and continuity of the program and to avoid a higher than optimal iodine intake in the population.     

Comparative study of thyroid function and types of thyroid dysfunction in two areas in Denmark with slightly different iodine status

OBJECTIVE: The pattern of thyroid dysfunction seems to depend on the iodine status of the population. Prevalence of thyroid dysfunction could be a parameter to consider when evaluating iodine deficiency disorders in a population. DESIGN: Comparative cross-sectional investigation in two regions in Denmark with marginally different iodine excretion. METHODS: A random selection of 4649 participants from the Civil Registration System in Denmark in age groups between 18 and 65 years were examined. Thyroid dysfunction was evaluated from blood samples and questionnaires, and compared with results from ultrasonography. RESULTS: Median iodine excretion was 53 microg/l in Aalborg and 68 microg/l in Copenhagen. Previously diagnosed thyroid dysfunction was found with the same prevalence in the regions. Serum TSH was lower in Aalborg than in Copenhagen (P=0. 003) and declined with age in Aalborg, but not in Copenhagen. Not previously diagnosed hyperthyroidism was found with the same overall prevalence in the regions, but in age >40 years hyperthyroidism was more prevalent in Aalborg (1.3 vs 0.5%, P=0.017). Not previously diagnosed hypothyroidism was found more frequently in Aalborg (0.6 vs 0.2%, P=0.03). Hyperthyroidism was more often associated with macronodular thyroid structure at ultrasound in Aalborg and hypothyroidism was more often associated with patchy thyroid structure in Copenhagen. CONCLUSIONS: Significant differences in thyroid dysfunction were found between the regions with a minor difference in iodine excretion. The findings are in agreement with a higher prevalence of thyroid autonomy among the elderly in the most iodine-deficient region.     

A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population

Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (Tg‐Ab) as the most common can often be demonstrated in serum. The effect of public iodization programmes on antibody prevalence is uncertain. Aim To measure the concentrations of thyroid autoantibodies in the Danish population before and after mandatory iodization of salt. Methods Two identical cross‐sectional population studies were performed before (Cohort 1 (C1), year 1997–1998, n = 4649, median urinary iodine 61 μg/l) and 4–5 years after (Cohort 2 (C2), year 2004–2005, n = 3570, median urinary iodine 101 μg/l) mandatory iodine fortification of salt was implemented in Denmark. Blood tests were analysed for TPO‐Ab and Tg‐Ab using sensitive assays. Results Antibodies were more frequent in C2 than in C1: TPO‐Ab > 30 U/ml, C1 vs C2: 14·3 vs 23·8% (P < 0·001) and Tg‐Ab > 20 U/ml, C1 vs C2: 13·7 vs 19·9% (P < 0·001). The C2 vs C1 effect was confirmed in multivariate regression models (C1 reference): TPO‐Ab: OR (95% CI): 1·80 (1·59–2·04) and Tg‐Ab: 1·49 (1·31–1·69). The increase in the frequency of thyroid antibodies was most pronounced in young women and especially observed at low concentrations of antibodies. Conclusion The prevalence of both TPO‐Ab and Tg‐Ab was higher 4–5 years after a cautious iodine fortification of salt was introduced in Denmark. The increase was most pronounced in young women and in the low concentrations of antibody. Further studies are needed to evaluate the long‐term effects of increased iodine intake on thyroid autoimmunity in the population.     

Use of adjunctive potassium iodide after radioactive iodine (131I) treatment of Graves' hyperthyroidism

One hundred and nineteen patients with Graves' hyperthyroidism who were treated with 131I alone or 131I followed by potassium iodide (131I + KI) were studied retrospectively. Patients in both groups who required only a single dose of 131I for successful treatment of hyperthyroidism had similar age, gland size, 24-h radioactive iodine uptake, pretreatment serum T4 concentrations, and radioactive iodine treatment dose. Seven weeks after 131I, mean serum T4 concentrations were 12.3 +/- 6.1 micrograms/dl (mean +/- SD) in patients who received 131I alone and 8.0 +/- 3.9 micrograms/dl in patients who received 131I + KI (p less than 0.001). Sixty percent of the patients who received 131I + KI and remained euthyroid 1 yr after 131I treatment developed documented transient hypothyroidism while receiving KI (serum T4, 1.4 +/- 0.9 micrograms/dl). Patients with transient hypothyroidism receiving KI had larger estimated thyroid gland weights when hypothyroid than patients whose hypothyroidism was permanent (32 +/- 6 vs. 16 +/- 11 g; P less than 0.001). The overall incidence of hypothyroidism 1 yr after treatment with 131I was 58% in each of the two groups. Sixteen percent of each group were not successfully treated by a single dose of 131I and required further therapy. Adjunctive KI effectively treated thyrotoxicosis more rapidly than 131I alone without adversely affecting outcome at 1 yr; however, patients taking KI more often develop transient hypothyroidism.     

Iron status in Danish women, 1984-1994: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload

BACKGROUND AND OBJECTIVES: From 1954 to 1986, flour in Denmark was fortified with 30 mg carbonyl iron per kilogram. This mandatory enrichment of cereal products was abolished in 1987. The aim was to evaluate iron status in the Danish female population before and after abolishment of iron fortification. METHODS: Iron status, serum ferritin and haemoglobin, was assessed in population surveys in 1983-1984 comprising 1221 Caucasian women (1089 non-blood-donors, 130 donors) and in 1993-1994 comprising 1261 women (1155 non-blood-donors, 104 donors) equally distributed in age cohorts of 40, 50, 60 and 70 yr. RESULTS: In the 1984 survey, median ferritin values in the four age cohorts in non-blood-donors were 44, 57, 84 and 80 microg/L, and in the 1994 survey 40, 67, 97 and 95 microg/L, respectively. In 1984, premenopausal women had median ferritin of 43 microg/L and in 1994 of 39 microg/L (NS). In 1984, postmenopausal women had median ferritin of 75 microg/L and in 1994 of 93 microg/L (P < 0.0001). The prevalence of depleted iron stores (ferritin < 16 microg/L) was not significantly different in 1984 and 1994 either in premenopausal or in postmenopausal women. The prevalence of small + depleted iron stores (ferritin 300 microg/L) was unchanged in premenopausal women and had increased from 2.4% to 5.5% in postmenopausal women (P = 0.003). During the study period there was an increase in body mass index both in premenopausal and postmenopausal women (P = 0.06 and P = 0.008). Postmenopausal women displayed an increase in alcohol consumption (P < 0.0001) and a decrease in tobacco smoking (P < 0.001). In premenopausal women, there was a marked increase in the use of non-steroid anti-inflammatory drugs (P < 0.0001) in the study period, while this was unchanged in postmenopausal women. In premenopausal blood donors, median ferritin decreased from 1984 to 1994 (36 microg/L vs. 24 microg/L, P < 0.06). In postmenopausal blood donors, ferritin was not significantly different from 1984 to 1994 (50 microg/L vs. 41 microg/L, P = 0.15). CONCLUSION: Abolition of iron fortification reduced the median dietary iron intake in Danish women from 12 to 9 mg/d. Despite the absence of food iron fortification, from 1984 to 1994, body iron stores were unchanged in premenopausal women, whereas iron stores and the prevalence of iron overload in postmenopausal women had increased significantly. The reason appears to be the changes in dietary habits with a lower consumption of dairy products and eggs, which inhibit iron absorption, and a higher consumption of alcohol, meat and poultry, containing heme iron and enhancing iron absorption.     

Iron status in Danish men 1984-94: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload

BACKGROUND AND OBJECTIVES: From 1954 to 1987, flour in Denmark was fortified with 30 mg carbonyl iron per kg. This mandatory fortification was abolished in 1987. The aim of this study was to compare iron status in Danish men before and after abolition of iron fortification. METHODS: Iron status (serum ferritin, haemoglobin), was assessed in population surveys in Copenhagen County during 1983-84 comprising 1324 Caucasian men (1024 non-blood-donors, 300 blood donors) and in 1993-94 comprising 1288 Caucasian men (1103 non-blood-donors, 185 donors), equally distributed in age cohorts of 40, 50, 60 and 70 yr. RESULTS: In the 1984 survey median serum ferritin values in the four age cohorts in non-blood-donors were 136, 141, 133 and 111 microg/L, and in the 1994 survey 177, 173, 186 and 148 microg L(-1), respectively. The difference was significant in all age groups (P<0.001). There was no significant difference between the two surveys concerning the prevalence of small iron stores (ferritin 16-32 micro g L(-1)), depleted iron stores (ferritin <16 microg L(-1)) or iron-deficiency anaemia (ferritin <13 microg L(-1) and Hb <5th percentile for iron-replete men). However, from 1984 to 1994, the prevalence of iron overload (ferritin >300 microg L(-1)) increased from 11.3% to 18.9% (P<0.0001). During the study period there was an increase in body mass index (P<0.0001), alcohol consumption (P<0.03) and use of non-steroid anti-inflammatory drugs (NSAID) (P<0.0001), and a decrease in the use of vitamin-mineral supplements (P<0.04) and in the prevalence of tobacco smoking (P<0.0001). In contrast, median ferritin in blood donors showed a significant fall from 1984 to 1994 (103 vs. 74 micro g L(-1), P<0.02). CONCLUSION: Abolition of iron fortification reduced the iron content of the Danish diet by an average of 0.24 mg MJ(-1), and the median dietary iron intake in men from 17 to 12 mg d(-1). From 1984 to 1994, body iron stores and the prevalence of iron overload in Danish men increased significantly, despite the abolition of food iron fortification. The reason appears to be changes in dietary habits, with a lower consumption of dairy products and eggs, which inhibit iron absorption, and a higher consumption of alcohol, meat, and poultry, containing haem iron and enhancing iron absorption. The high prevalence of iron overload in men may constitute a health risk.     

Effect of iodine supplementation on a pediatric population with mild iodine deficiency.

A cross-sectional study in two stages consisted of healthy children to assess the effect of iodine supplementation on a pediatric population with mild iodine deficiency in an ongoing program in the Province of Pontevedra, northwestern Spain. In the first survey (1984), 1565 schoolchildren and in the second survey (1995) 907 schoolchildren were randomly selected from the population. In January 1985, a mandatory consumption of iodized salt in our region was begun. In both surveys we studied prevalence of goiter, urinary iodine excretion, and prevalence of thyroid dysfunction. Similar prevalences of goiter were observed in both surveys, 3.7% versus 3.9%; however, significantly lower prevalence of Ib and II degree goiters were observed in the second survey. The mean iodine excretion was 88.6 +/- 73 microg/L (median 66.3) and 146.4 +/- 99 microg/L (median 115.7), p < 0.01 for the first and second surveys, respectively. Finally, the overall prevalence of thyroid dysfunction was similar in both surveys, 9.2% versus 7.0%; however, significantly lower prevalence of suppressed serum thyrotropin (TSH), considered as a marker of subclinical hyperthyroidism, was observed in the second survey when compared to the first, 0.1% versus 2%, p < 0.01. Our results are in agreement with the recent data from Denmark, where the prevention of subclinical hyperthyroidism occurring in the elderly as a consequence of longstanding mild iodine deficiency is the reason that the Danish finally started iodine supplementation on a national basis. In conclusion, long-term correction of mild iodine deficiency in a pediatric population has beneficial effects on the prevalence of high-degree goiters, and this correction reduces significantly the prevalence of subclinical hyperthyroidism. The present observation constitutes a strong argument for correcting even mild iodine deficiency.     

Age and gender predict the outcome of treatment for Graves' hyperthyroidism

The response to treatment in Graves' hyperthyroidism is unpredictable, and factors postulated to predict outcome have not generally proved clinically useful or been widely adopted in clinical practice. We audited outcome in 536 patients with Graves' hyperthyroidism presenting consecutively to determine whether simple clinical features predict disease presentation and response to treatment. At presentation males had slightly more severe biochemical hyperthyroidism [free T4: males, 64.3 +/- 3.0 pmol/L (mean +/- SE); females, 61.3 +/- 1.7 (P = 0.45); free T3: males, 24.3 +/- 1.5 pmol/L; females, 21.0 +/- 0.6, (P = 0.04)]. Patients less than 40 yr at diagnosis had more severe hyperthyroidism than patients more than 40 yr old [free T4: <40 yr, 64.3 +/- 2.0; >40 yr, 56.7 +/- 2.3 (P = 0.02); free T3: <40 yr, 22.8 +/- 0.8; >40 yr, 19.0 +/- 0.9 (P = 0.003)]. Males had a lower remission rate than females after a course of antithyroid medication [19.6% vs. 40%; odds ratio, 0.37; 95% confidence interval (CI), 0.17-0.79; P < 0.01]. Similarly, patients aged less than 40 yr had a lower remission rate than older patients (32.6% vs. 47.8%; odds ratio, 0.53; 95% CI, 0.32-0.87; P = 0.01). One dose of radioiodine cured hyperthyroidism in fewer males than females (47% vs. 74%; P < 0.0001). Logistic regression analysis demonstrated male sex (odds ratio, 2.80; 95% CI, 1.31-5.98; P = 0.008), serum free T4 concentration at diagnosis (odds ratio, 1.02; 95% CI, 1.0-1.04; P = 0.01), and dose of radioiodine administered (odds ratio, 0.99; 95% CI, 0.99-1.00; P = 0.001) were contributing factors associated with failure to respond to a single dose of radioiodine. As males and younger patients are more likely to fail to respond to medical treatment, and male patients are likewise less likely to respond to a single dose of radioiodine, we suggest that those groups with low remission rates should be offered definitive treatment with radioiodine or surgery soon after presentation and that the value of higher initial doses of radioiodine in males be evaluated.     

Effect of a mandatory iodization program on thyroid gland volume based on individuals' age, gender, and preceding severity of dietary iodine deficiency: a prospective, population-based study

OBJECTIVE: We aimed to evaluate prospectively the effect of 4 yr of mandatory iodization of salt (13 ppm iodine) on thyroid volume in two regional areas with respectively mild and moderate iodine deficiency. METHODS: Two separate cross-sectional studies were performed before (n=4649) and after (n=3570) the iodization in year 2000 in two areas with mild and moderate iodine deficiency. Women aged 18-22, 25-30, 40-45, and 60-65 yr and men aged 60-65 yr were examined. Thyroid ultrasonography was performed. RESULTS: A lower median thyroid volume was seen in all age groups after iodization. The largest relative decline was found among the younger females from the area with previous, moderate iodine deficiency. Only a minor decrease was seen among the youngest participants in the area with previous, mild iodine deficiency. After iodization, there were no regional differences in median thyroid volume in the age groups younger than 45 yr. When adjusted for confounders, a lower mean volume was seen among those with multiple nodules in both areas and in the group with diffuse structure in the area with moderate iodine deficiency. Before the iodization, 17.6% of the total cross-section had thyroid enlargement; after the iodization, 10.9% of the cross-section had thyroid enlargement. CONCLUSION: In this prospective study, we demonstrated a lower thyroid volume in all age groups after iodization of salt. The decline was largest in the area with former, moderate iodine deficiency. The equal volumes in the regions among the younger age groups indicate approximation to an optimal iodine intake.     

轻度碘缺乏城市食盐加碘后甲状腺疾病流行病学调查研究

 目的 评价轻度碘缺乏城市贵阳食盐加碘25年后的碘营养状态及各种甲状腺疾病的患病情况。
方法 采用分层整群抽样方法,抽取贵阳市云岩区宅吉社区20岁及以上居民1509人,测定其血清促甲状腺素（TSH）、游离T₃、游离T₄、甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TgAb）水平、尿碘水平及甲状腺B超检查;同时抽取8~10岁学龄儿童80名,测定其尿碘水平。
结果 8~10岁儿童尿碘中位数为228.7 μg/L。成人临床甲状腺功能减退症（甲减）、亚临床甲减、临床甲状腺功能亢进症（甲亢）及亚临床甲亢的患病率分别为1.79%、14.12%、1.52%及1.06%,亚临床甲减的患病率显著高于临床甲减（P < 0.05）;TPOAb及TgAb的阳性率分别为14.38%及 13.59%,自身免疫性甲状腺炎的患病率为4.44%。甲状腺肿大患病率为1.06%,其中,弥漫性甲状腺肿（0.86%）较结节性甲状腺肿（0.20%）多见（P < 0.05）。
结论 食盐加碘25年后,贵阳市处于碘超足量状态,成人临床甲减、亚临床甲减、甲状腺自身抗体阳性及自身免疫性甲状腺炎的患病率均较高。     

Simple electrocardiographic markers for the prediction of paroxysmal atrial fibrillation in hyperthyroidism

BACKGROUND: Hyperthyroidism is a major cause of paroxysmal atrial fibrillation (AF). The purpose of this study was to evaluate the predictors of AF in the patients with clinical and subclinical hyperthyroidism. METHODS AND RESULTS: The study population consisted of four groups: group I (57 euthyroid healthy persons), group II (33 patients with subclinical hyperthyroidism), group III (69 patients with overt hyperthyroidism) and group IV (31 patients with overt hyperthyroidism and documented paroxysmal AF). The maximum P wave duration (P maximum) in group IV (114 +/- 8 ms) was significantly higher than group I (102 +/- 7 ms, p < 0.001), group II (106 +/- 7 ms, p < 0.001) and group III (108 +/- 9 ms, p0.005). The P wave dispersion (PWD) was measured as 46 +/- 9 ms in group IV and this was significantly higher than group I (29 +/- 8 ms, p < 0.001), group II (36 +/- 9 ms, p < 0.001) and grup III (38 +/- 8 ms, p = 0.001). The P maximum and PWD were higher in the patients with subclinical hyperthyroidism compared to healthy individuals. Univariate regression analysis revealed that age, P maximum and PWD, multivariate analysis showed that P maximum and PWD were significant predictors of paroxysmal AF. A PWD value of 37.5 ms separated group IV from others with a sensitivity of 90%, specificity of 85%, and positive predictive accuracy of 77%. CONCLUSION: Simply measuring P maximum and PWD values, we could identify the patients with high risk for the development of AF and these simple ECG parameters may help in clinical judgement to determine the requirement for treatment in the patients with subclinical hyperthyroidism.     

Lower prevalence of mild hyperthyroidism related to a higher iodine intake in the population: prospective study of a mandatory iodization programme

Objective  Marked differences in pattern of thyroid dysfunction are seen in populations with different iodine intakes. We evaluated the influence of a higher iodine intake on thyroid hormone levels and the prevalence of thyroid dysfunction in the Danish population.
Design  Two cross-sectional studies matched on a group level according to sex and age.
Participants  In all, 8219 individuals were examined before ( n  = 4649) or after ( n  = 3570) the introduction of a mandatory iodization programme in 2000 in two regions with established mild and moderate iodine deficiency. Serum TSH, fT₄ and fT₃ were measured. An ultrasonography of the thyroid was performed.
Results  We found a higher median serum TSH after the introduction of mandatory iodization of salt: 1·51 mU/l (10–90th percentiles: 0·72–3·00) vs. 1·30 mU/l (10–90th percentiles: 0·59–2·66) before iodization. The difference was found in both regions and across age groups. There was a lower prevalence of mild hyperthyroidism and a tendency towards a lower prevalence of overt hyperthyroidism. The prevalence of mild hypothyroidism increased, most pronounced among young women after iodization. Conversely, there was a lower prevalence of undiagnosed overt hypothyroidism. However, when currently treated participants were included, the prevalence of hypothyroidism increased after iodization in the area with formerly mild iodine deficiency.
Conclusion  A change in pattern of thyroid dysfunction was seen in relation to mandatory iodization of salt. There was no rise in the prevalence of hyperthyroidism and the prevalence of mild hyperthyroidism was halved. Conversely, prevalence of hypothyroidism increased.     

Reappraisal of the risk of iodine-induced hyperthyroidism: an epidemiological population survey

The occurrence of iodine-induced hyperthyroidism (IIH) has been reported after iodine supplementation from clinics and hospitals, but not following an epidemiologic survey. We studied the prevalence of thyroid derangement in a population following iodine supplementation. One yr after more than 75% of the population had been consuming 40 ppm iodized salt; information regarding history of endemic goiter and iodized salt production, distribution, consumption and monitoring were collected in four cities of the Islamic Republic of Iran. A total of 6048 subjects were randomly selected. All subjects were assessed for size of goiter, and urinary iodine and serum T4, T3, TSH, anti-thyroglobulin and anti-thyroperoxide were measured. Before iodine supplementation, all four cities were areas of endemic goiter. The rate of household consumption of iodized salt was 50, 75 and 90% in 1994, 1995 and 1996, respectively. Ninety-one percent of the salt samples contained 15-55 ppm iodide. Total goiter rate was 57, 62 and 68%; median urinary iodine was 188, 197 and 190 microg/l in the age groups of 6-18, 19-40 and >40 yr, respectively. Prevalence of clinical and subclinical hyperthyroidism was 0.34 and 0.41 and those of clinical and subclinical hypothyroidism were 0.51 and 1.07%, respectively. Nine point eight and 18% in the 19-40 yr age group and 17.6 and 25.6% in >40 yr old subjects had positive anti-thyroperoxidase and anti-thyroglobulin, respectively. This systemic epidemiologic study in an iodine deficient population showed that, following a well-executed iodine supplementation program, the occurrence of IIH is rare.     

Early pituitary-gonadal activation before clinical signs of puberty in 5- to 8-year-old adopted girls: a study of 99 foreign adopted girls and 93 controls

CONTEXT: Recent studies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Clinical studies including a contemporary control group are lacking. OBJECTIVE: The objective was to study clinical, biochemical, and ultrasonographic markers of pituitary-gonadal activation in prepubertal adopted girls and a control group in the same age categories. SETTING: The study took place at University Hospital, Copenhagen, Denmark. DESIGN AND PARTICIPANTS: The study included randomly selected internationally adopted girls [(n = 99; mean age, 6.9 (5.1-8.5) yr] and controls of Danish origin [n = 93; mean age, 6.8 (5.2-8.5) yr] who were studied cross-sectionally. METHODS: Height, weight, and pubertal stage were assessed with serum levels of reproductive hormones. Size and morphology of internal genitals were evaluated by ultrasonography. Bone age was evaluated by x-ray of the left hand. RESULTS: Serum values of FSH were significantly higher in prepubertal adopted girls compared with controls [median, 1.4 (95% confidence interval, 0.4-3.6) vs. 1.0 (0.4-2.4) IU/liter; P <0.001]. Serum estradiol was above detection limit (>18 pmol/liter) in 46.5% of prepubertal adopted girls and 20.7% of controls (P = 0.001). In prepubertal adopted girls, the proportion of measurable samples increased significantly with age [odds ratio, 2.5 (95% confidence interval, 1.3-5.0; P = 0.009]. In controls, the odds ratio was 1.0 (0.6-1.7) (P = 0.9). Serum SHBG levels were significantly lower in prepubertal adopted girls compared with controls [99.0 (50.4-153.0) vs. 115.0 (53.1-202.1); P < 0.001]. CONCLUSION: Five- to 8-yr-old adopted girls showed signs of increased pituitary as well as gonadal activity despite prepubertal phenotype in the majority of girls. Our findings suggest that early onset of puberty in adopted girls is centrally driven.     

Alterations in nocturnal serum melatonin levels in humans with growth and aging

The available data on potential alterations in serum melatonin (MLT) levels during a human lifetime are fragmentary and inconsistent. We, therefore, measured day- and nighttime serum MLT concentrations in 367 subjects (210 males and 157 females), aged 3 days to 90 yr. Blood samples were collected between 0730 and 1000 h and between 2300 and 0100 h. Serum MLT levels were measured by RIA. The mean nighttime serum MLT concentration was low during the first 6 months of life, i.e. 27.3 +/- 5.4 (+/- SE) pg/mL (0.12 +/- 0.02 nmol/L). It then increased to a peak value at 1-3 yr of age [329.5 +/- 42.0 pg/mL; (1.43 +/- 0.18 nmol/L)], and it was considerably lower [62.5 +/- 9.0 pg/mL; (0.27 +/- 0.04 nmol/L)] in individuals aged 15-20 yr. During the following decades serum MLT declined moderately until old age (70-90 yr of age), i.e. 29.2 +/- 6.1 pg/mL (0.13 +/- 0.03 nmol/L). This biphasic MLT decline follows 2 exponential functions with different slopes (from age 1-20 yr: r = -0.56; P less than 0.001; y = 278.7 X e -0.09x; from age 20-90 yr: r = -0.44; P less than 0.001; y = 84.8 X e -0.017x). The decrease in nocturnal serum MLT in children and adolescents (1-20 yr) correlated with the increase in body weight (r = -0.54; P less than 0.001) and body surface area (r = -0.71; P less than 0.001). At a later age (20-90 yr) there was no correlation among these variables. Daytime serum MLT levels were low and no age-related alterations were found. This study revealed major age-related alterations in nocturnal serum MLT levels. The negative correlation between serum MLT and body weight in childhood and adolescence is evidence that expansion of body size is responsible for the huge MLT decrease during that period. The moderate decline at older ages must derive from other factors.     

Prematurity may be a risk factor for thyroid dysfunction in childhood

CONTEXT: Children born prematurely and/or small for gestational age (SGA) frequently show disturbances in thyroid function. OBJECTIVE: The objective of the study was to determine the role played either by size or gestational age on subsequent thyroid function. DESIGN AND SETTING: This cross-sectional study was conducted at a tertiary referral hospital. PATIENTS: A total of 117 children, 88 of whom were SGA (mean age 7.8 +/- 2.5 yr) and 29 appropriate for gestational age (AGA) (mean age 8.1 +/- 1.9 yr), were selected for the study. MAIN OUTCOME MEASURES: We evaluated TSH, free T(4), free T(3), urinary iodine, and antithyroid antibodies, and all patients underwent a thyroid ultrasound. Insulin sensitivity was assessed with the quantitative insulin sensitivity check index. RESULTS: TSH and free T3 were not significantly different in the two groups, whereas free T4 was higher in the AGA group (P < 0.005). Interestingly, four AGA (13.8%) and 17 SGA (19.3%) patients had TSH levels above the upper limit of normality. Thyroid volume was normal and thyroid autoimmunity was excluded. Urinary iodine was also similar in the two groups (115 +/- 66 vs. 143 +/- 87); however, in both groups there were some children [15 AGA (51%) and 13 SGA (14.7%) (P < 0.001)] with a mild to moderate iodine deficiency. By multiple regression analysis, gestational age was found to be the only determinant of TSH serum levels. Insulin sensitivity was the same in both groups of children and similar to controls. CONCLUSIONS: Some children born prematurely, independently from their birth size, frequently have disturbances of the hypothalamus-pituitary-thyroid axis later in life.