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Association of Tobacco Smoking With Goiter in a Low-Iodine-Intake Area
Nils Knudsen, MD, PhD;
Inge Bülow, MD;
Peter Laurberg, MD, MDSci;
Lars Ovesen, MD;
Hans Perrild, MD;
Torben Jørgensen, MD, MDSci
Arch Intern Med. 2002;162:439-443.
ABSTRACT
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Background Goiter development depends on genetic and environmental factors. The
major environmental factor is iodine intake, whereas diverging results have
been published concerning the association between smoking and goiter.
Methods A comparable, cross-sectional study was performed of patients from 2
areas in Denmark with mild and moderate iodine deficiency. A random sample
of women and men in selected age groups from the general community was investigated;
4649 subjects participated. Smoking habits were investigated with questionnaires
and interviews. Ultrasonography and clinical examination of the thyroid were
performed, serum thyroglobulin was measured, and iodine concentration in spot
urine samples was analyzed. Data were analyzed in linear models and logistic
regression analyses.
Results Serum thyroglobulin level and thyroid volume at ultrasonography were
positively associated with smoking habits (P<.001);
the association was stronger in the area with the lowest iodine intake (interaction: P<.001 for thyroglobulin, P
= .04 for thyroid volume). A positive association with smoking was also found
for thyroid enlargement (odds ratio, 2.9; 95% confidence interval, 2.2-3.7)
and palpable goiter (odds ratio, 3.1; 95% confidence interval, 1.6-5.8). Ex-smokers
had a goiter prevalence close to that of never smokers. The fraction of goiter
cases attributable to smoking was 49% (95% confidence interval, 29%-65%).
Conclusions Thyroid volume and goiter prevalence were closely associated with smoking
habits, with the strongest association being found in the area with the most
pronounced iodine deficiency. This may have implications for future goiter
prevalences in Third World countries, with their increasing use of tobacco.
Half of goiter cases in this population could be ascribed to smoking.
INTRODUCTION
GOITER IS A common disorder in all populations. In an English study,
palpable and visible goiter was found in 12.3% of women in the general population.1 The goiter prevalence is even higher in iodine-deficient
areas, and more than 1.5 billion people live in such areas, including many
regions in Europe.2 The annual costs for treatment
of goiter was estimated at $1 billion (US) in 1992 in Germans with mild iodine
deficiency.3
Risk factors for goiter include genetic as well as environmental factors,4 although evidence of these environmental factors is
scarce except for the important impact of iodine deficiency. Iodine deficiency
undoubtedly represents the most important risk factor for the development
of goiter in the world today.5
Thiocyanate is abundant in cigarette smoke and exerts goitrogenic effects
through competitive inhibition of iodine transport and organification.6 The possible impact of smoking on goiter prevalence
has been investigated in a few previous studies, but these were hampered by
either inaccurate methods of estimating goiter prevalence7-9
or the inclusion of small or highly selected groups of subjects.10-15
The association between tobacco smoking and goiter in these studies was contradictory,
possibly because of differences in study design; however, another confounding
factor might be iodine status of the populations, as the strongest association
was found in iodine-deficient populations.10, 12
The purpose of our study was to determine the association between smoking,
goiter, and iodine intake. This was done in a large population sample from
2 areas with different iodine intake by means of precise epidemiologic methods
and high-resolution ultrasonography.
SUBJECTS AND METHODS
PARTICIPANTS
From the Danish Civil Registration System, in which all inhabitants
in Denmark are registered by a unique number, a record of all subjects of
Danish origin from the northern part of Copenhagen and the central part of
Aalborg (a city in the western part of Denmark) was made within the following
groups: women aged 18 to 22 years, 25 to 30 years, 40 to 45 years, or 60 to
65 years and men aged 60 to 65 years. These age groups were chosen to include
women before, in, and after childbearing age, and postmenopausal women. A
group of men were chosen in the age group with the supposed highest occurrence
of thyroid abnormalities for comparison between the sexes. The 2 regions were
chosen as previous studies have indicated that iodine deficiency is more severe
in Aalborg than in Copenhagen.16 Of 40 233
subjects, a random selection of 9274 subjects were invited and 4649 participated
(50.1%). The cohort has previously been described in detail.17
THYROID INVESTIGATIONS
Thyroid volume was evaluated by ultrasound according to standardized
criteria and was reproducible in this setup.18
The volumes were determined as the sum of  /6 x length x width
x depth of each lobe, and thyroid enlargement was defined as a volume
exceeding 18 mL for women and 25 mL for men.19
The ultrasonographers were blinded to the smoking status of the participants.
Serum samples were analyzed for thyroglobulin (Tg) by a commercial test (LUMItest;
BRAHMS Diagnostica GmbH, Berlin, Germany) with an effective working range
of 1 to 500 µg/L and within-run and between-run coefficients of variation
of less than 8% for Tg values above 5 µg/L.20
Antibodies to Tg were measured with a radioimmunoassay (DYNOtest; BRAHMS Diagnostica
GmbH) with a functional assay sensitivity below 20 kU/L, and samples with
Tg antibodies above 20 kU/L were excluded from statistical analyses involving
serum Tg level to avoid possible analytical interference. Apart from this,
Tg antibody status was not used in the analyses, as this status was not associated
with thyroid volume (P = .53).
A clinical examination of the thyroid was performed by a physician (N.K.
or I.B.) without knowledge of the result of the ultrasonography, and thyroid
size at the clinical examination was recorded according to World Health Organization
criteria5 as 0 (no enlarged thyroid), 1a (palpable
and enlarged, but not visible thyroid), 1b (palpable and enlarged thyroid,
visible with extended neck), and 2 and 3 (visible goiter). In the analyses,
subjects with grades 2 and 3 goiter were included in group 1b.
DEFINITION OF SMOKING STATUS
Smoking was evaluated from questionnaires and, in case of ambiguous
or missing answers, also from the subsequent interviews. Participants were
asked about present or previous smoking, daily or occasional smoking, amount
of tobacco consumed, type of smoking (cigarettes, cheroots, cigars, or pipe
tobacco), years of smoking, years since cessation of smoking, inhalation,
and exposure to passive smoking. Most of the smokers were solely cigarette
smokers, and as no significant differences were found for the association
of smoking with thyroid disease between smokers of cigarettes (33.1% of participants),
cheroots (1.0%), cigars (0.2%), and pipe tobacco (2.6%), the different types
of smoking were combined in the further analyses. To combine the different
types of tobacco, cigarettes were regarded as 1 g of tobacco, cheroots as
2 g, and cigars as 5 g. Participants were classified as never smokers (never
daily use of tobacco), ex-smokers (previous daily use of tobacco), moderate
smokers (1-19 g/d), and heavy smokers ( 20 g/d), or simply as smokers or
nonsmokers, depending on the context. Familial occurrence of thyroid disease
among first-degree relatives and consumption of alcohol were also reported
in the questionnaires.
IODINE STATUS
Iodine excretion was measured in casual urine samples with a ceric-arsenite
method as previously described.21-22
Median iodine excretion was 68 µg/L in Copenhagen and 53 µg/L
in Aalborg; after exclusion of subjects taking individual iodine supplementation
in the form of iodine-containing vitamin tablets, the excretion was 61 µg/L
and 45 µg/L, respectively. According to World Health Organization criteria,5 the Copenhagen area is mildly iodine deficient and
the Aalborg area, moderately iodine deficient.
ETHICS
The study was approved by the regional ethics committee in Copenhagen
and Northern Jutland, and all participants gave written informed consent.
STATISTICS
All data processing was done with SPSS 8.0 software (SPSS Inc, Chicago,
Ill). For the association of serum Tg level and thyroid volume to smoking,
linear models were applied after logarithmic transformation, as the distribution
of these variables was skewed toward higher values. For thyroid enlargement
and clinical goiter, a logistic regression model was applied.
The frequency of smoking was significantly different in the 2 regions
and in the different age and sex groups (Table 1). Consequently, region of inhabitance and age and sex group
were included in all regression models. Thus, with the use of multivariate
statistics, possible differences in thyroid volume owing to different distribution
on age and sex of the different smoking groups were adjusted for. Alcohol
consumption and familial occurrence of thyroid disease were also tested in
the models but could be excluded, as they had no influence on the estimates
for the association of smoking with serum Tg level, thyroid volume, or goiter.
Likewise, iodine concentration in the spot urine samples was not different
in the 4 smoking groups (P = .98) and iodine excretion
could be excluded from the regression models.
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Table 1. Frequency of Daily Smoking Among 4644 Unselected Subjects
From a Danish Cohort From 2 Areas of Denmark*
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Interactions between region of inhabitance and smoking were investigated
in all models to describe a possible difference in the impact of smoking on
goiter prevalence between the regions; where significant interactions were
found, a new variable was constructed with all combinations of region and
smoking to provide separate estimates. Generally, smoking as a continuous
covariate showed a linear relation to the different estimates of thyroid volume
and goiter, but data are presented for the grouped variable with 4 levels
of smoking to include nonsmokers and ex-smokers in a comprehensive view.
The population attributable fraction (AF) was computed as follows: AF
= [p(RR - 1)]/[p(RR - 1) + 1], where p is the fraction of smokers
in the cohort and RR is the relative risk.23
Relative risks were replaced by odds ratios from the logistic regression analysis
to obtain adjusted estimates.
RESULTS
There was a strong association between smoking and serum Tg level (P for trend <.001) (Figure 1). The association was strongest in the area with the lowest
iodine intake (P for interaction <.001).
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Figure 1. The association between smoking
and serum thyroglobulin level in 2 regions of Denmark with different degrees
of iodine deficiency (ID). Data are from 3764 unselected subjects, as subjects
with thyroglobulin antibodies or previous thyroid disease were excluded. The
curves represent mean serum thyroglobulin levels after correction for age
and sex in a linear model with logarithmic transformation of thyroglobulin
values. Vertical bars are 95% confidence intervals for the mean. Differences
are as follows: a, P = .24 vs never smokers; b, P = .20 vs never smokers; c, P
= .004 vs ex-smokers and P<.001 vs never smokers;
d, P<.001 vs ex-smokers and P = .001 vs never smokers; e, P<.001 vs
all other groups; and f, P = .008 vs moderate smokers
and P<.001 vs other groups.
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A similar association was found between smoking and thyroid volume (P for trend <.001) (Figure 2). The overall interaction term for region and smoking was
not significant (P = .15), but a significant interaction
was found between region and never smoking vs heavy smoking (P = .04), indicating that the influence of at least heavy smoking on
thyroid volume is more pronounced in moderate than in mild iodine deficiency.
A similar interaction was found if participants were divided according to
iodine concentration in spot urine samples. The association between smoking
and thyroid volume tended to be stronger in participants with a urinary iodine
concentration less than 50 µg/L (P for interaction
= .07).
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Figure 2. Association between thyroid volume
and smoking in 2 regions of Denmark with different degrees of iodine deficiency
(ID). Data are from 4412 subjects, as subjects previously treated for thyroid
disease were excluded. The curves represent mean thyroid volume determined
with ultrasound after correction for age and sex in a linear model with logarithmic
transformation of thyroid volume. Vertical bars are 95% confidence intervals
for the mean. Differences are as follows: a, P =
.51 vs never smokers; b, P = .03 vs never smokers;
c, P<.001 vs ex-smokers and never smokers; d, P = .003 vs ex-smokers and P<.001
vs never smokers; e, P = .06 vs moderate smokers
and P<.001 vs other groups; and f, P = .006 vs moderate smokers and P<.001
vs other groups.
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For thyroid enlargement and clinically detectable goiter, no significant
differences between the 2 regions were found for the effect of smoking. Consequently,
the results are given only as a common value for the 2 regions in Figure 3. A strong association was found
between smoking and thyroid enlargement on ultrasonography and at the clinical
examination.
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Figure 3. Association between smoking and
goiter in a Danish population study. Figures are odds ratios adjusted for
age, sex, and region of inhabitance in a logistic regression analysis with
95% confidence intervals. Never smokers constitute the reference group. Thyroid
enlargement was defined as a thyroid volume on ultrasound exceeding 18 mL
for women and 25 mL for men.19 Odds ratios
are significantly different from the reference if the 95% confidence interval
does not include 1.
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As demonstrated in Table 2,
the increased risk of thyroid enlargement associated with smoking was most
pronounced among women aged 40 to 45 years (P for
interaction = .003). The trend was increased risk associated with smoking
in all groups, however. The overall observed prevalence of thyroid enlargement
was 10.8% among nonsmokers and 28.4% among heavy smokers, and the prevalence
of palpable and visible goiter was 1.1% among nonsmokers and 4.0% among heavy
smokers.
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Table 2. Odds Ratios for Thyroid Enlargement in the Different Age Strata
of the Cohort Comprising 4412 Subjects With No Known Thyroid Disease*
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For ex-smokers, years since cessation of smoking was an insignificant
factor. Correspondingly, only a slight association was found between years
of smoking and serum Tg level (P = .04), and no association
was found with the other variables. Occasional smoking, exposure to passive
smoking, and inhalation or no inhalation showed no significant relationship
to any of the measures of thyroid volume.
The public health implications of smoking regarding goiter were assessed
through the population attributable fraction. This figure gives an estimate
of the fraction of goiter cases in the population that can be ascribed to
smoking, given the existence of a causal relation. The population attributable
fraction for thyroid enlargement when smokers were compared with nonsmokers
was 36% (95% confidence interval, 28%-44%). The population attributable fraction
regarding clinically detected goiter (minimum grade, 1b) was 49% (29%-65%).
COMMENT
In this study of a large cohort representing an unselected part of the
population from 2 regions of Denmark, we demonstrate a highly significant
positive association between smoking and goiter. Both thyroid enlargement
on ultrasonography and clinically detected goiter were included, as ultrasonography
represents a reproducible and precise estimate of thyroid size, whereas goiter
at the clinical examination may be regarded as clinically more relevant. Furthermore,
serum Tg level was included as a sensitive but nonspecific marker of thyroid
abnormalities. All of these different expressions gave concordant positive
associations with smoking.
The modest participation rate may introduce bias in the analyses; the
nonresponder problem has previously been discussed.17
The bias is, however, more important in descriptive statistics, whereas estimates
of relative risks or odds ratios as in these analyses are less affected by
selection. However, given a higher proportion of tobacco smoking among nonparticipants,
the population attributable fraction in this study is slightly underestimated
for the participants compared with the entire cohort.
Contradictory reports have been published on the relationship of smoking
to goiter and thyroid enlargement in the few previous studies. Of 3 Swedish
epidemiologic studies using palpation to evaluate goiter in iodine-sufficient
areas, 2 found a positive association with smoking7-8
and 1 did not.9 In an Italian study investigating
highly selected subjects with no indication of iodine status, no association
between goiter and smoking was detected.15
This discrepancy may be due to the inaccuracy of palpation of the thyroid.24 Four studies have used ultrasonic thyroid volume
measurements to determine the association with smoking; in 2 studies from
mildly iodine-deficient areas, a marked association was found,10, 12
whereas no association was found in a small study from an iodine-sufficient
area.13 A small Greek study with no indication
of iodine status found a small impact of smoking on thyroid volume, but only
among subjects with familial predisposition to goiter.14
In our study, familial occurrence of goiter had no influence on the relationship
between smoking and thyroid volume. In a recent twin study from an area with
mild iodine deficiency, an insignificant association between smoking and nontoxic
goiter was found, but the power of the study was limited.11
The different effects of smoking reported from areas with different
iodine intake is in accordance with our finding of an interaction between
smoking and inhabitance of regions with different iodine intake. This interaction,
indicating a more profound association between smoking and thyroid enlargement
in more severe iodine deficiency, was significant, even though there was only
a relatively small difference in iodine excretion between the regions. This
difference supports the hypothesis that thiocyanate is the important goitrogen
in cigarette smoke.25 Thiocyanate is a competitive
inhibitor of iodine transport and organification, and a more severe effect
in iodine deficiency could be anticipated.
We have previously shown that the major increase in goiter prevalence
takes place between the ages of 30 and 40 years in areas of mild and moderate
iodine deficiency.17 The major impact of smoking
was also seen in this vulnerable period, possibly by accelerating iodine deficiency–induced
thyroid enlargement.
Ex-smokers had only a slightly increased risk of thyroid enlargement
and goiter compared with never smokers and much less than present smokers.
The impact of smoking thus seems to be reversible to a large extent, emphasizing
the importance and benefits of smoking cessation for goitrous subjects. Two
studies have investigated goiter prevalence among ex-smokers and found prevalences
comparable with those of never smokers,7-8
but goiter was evaluated only by palpation.
The public health consequences of smoking were addressed by the population
attributable fraction. A prerequisite for the estimation of a population attributable
fraction is a causal relationship. For serum Tg level, thyroid volume, thyroid
enlargement, and goiter, a dose-response relationship was demonstrated, supporting
a causal relationship. Furthermore, the concordance with previous investigations
from iodine-deficient areas, a plausible experimental basis for the association,
and little confounding from other factors in the analyses support a causal
relation. We estimated that 49% of clinically detectable goiters were related
to smoking, and as goiter is common in areas of low iodine intake, smoking
may be causing large numbers of goiters. Many European countries are exposed
to some degree of iodine deficiency, and the cost of goiter treatment is considerable;
hence, this is a problem not only for the individual but also for the health
care system. With an ongoing increase in smoking prevalence in the developing
countries, which are in many cases iodine deficient,5
goiter prevalence may be increasing substantially in the coming years, along
with the expected increase in cardiovascular diseases, lung diseases, and
cancer.
AUTHOR INFORMATION
Accepted for publication June 4, 2001.
This study was supported by grants from the Tømmerhandler Vilhelm
Bang Foundation, Copenhagen Hospital Corporation Research Foundation, 1991
Pharmacy Foundation, Danish Medical Foundation, and Health Insurance Foundation,
Copenhagen, and the North Jutland County Research Foundation, Aalborg, Denmark.
We thank technicians Inge-Lise Legaard and Rene Fiege, who carefully
performed the ultrasonography.
Corresponding author and reprints: Nils Knudsen, MD, PhD, Medical
Clinic I, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark (e-mail: nijak{at}herlevhosp.kbhamt.dk).
From the Danish Centre for Prevention of Thyroid Diseases (DanThyr)
(Drs Knudsen, Bülow, Laurberg, Ovesen, Perrild, and Jørgensen)
and Centre for Preventive Medicine (Drs Knudsen and Jørgensen), Glostrup
University Hospital, and Department of Internal Medicine I, Bispebjerg Hospital
(Drs Knudsen and Perrild), University of Copenhagen, Copenhagen; Department
of Endocrinology, Aalborg Hospital, Aalborg (Drs Bülow and Laurberg);
and Institute of Food Research and Nutrition, The Danish Veterinary and Food
Administration, Soeborg (Dr Ovesen), Denmark.
REFERENCES
| |
1. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977;7:481-493.
PUBMED
2. Delange F. Correction of iodine deficiency: benefits and possible side effects. Eur J Endocrinol. 1995;132:542-543.
ISI
| PUBMED
3. Pfannenstiel P. Schilddrüsenreport. Darmstadt, Germany: Merck KGaA; 1997.
4. Brix TH, Kyvik KO, Hegedus L. Major role of genes in the etiology of simple goiter in females: a
population-based twin study. J Clin Endocrinol Metab. 1999;84:3071-3075.
FREE FULL TEXT
5. Delange F. The disorders induced by iodine deficiency. Thyroid. 1994;4:107-128.
ISI
| PUBMED
6. Colzani R, Fang SL, Alex S, Braverman LE. The effect of nicotine on thyroid function in rats. Metabolism. 1998;47:154-157.
FULL TEXT
|
ISI
| PUBMED
7. Ericsson UB, Lindgarde F. Effects of cigarette smoking on thyroid function and the prevalence
of goitre, thyrotoxicosis and autoimmune thyroiditis. J Intern Med. 1991;229:67-71.
ISI
| PUBMED
8. Christensen SB, Ericsson UB, Janzon L, Tibblin S, Melander A. Influence of cigarette smoking on goiter formation, thyroglobulin,
and thyroid hormone levels in women. J Clin Endocrinol Metab. 1984;58:615-618.
ABSTRACT
9. Petersen K, Lindstedt G, Lundberg PA, Bengtsson C, Lapidus L, Nystrom E. Thyroid disease in middle-aged and elderly Swedish women: thyroid-related
hormones, thyroid dysfunction and goiter in relation to age and smoking. J Intern Med. 1991;229:407-413.
ISI
| PUBMED
10. Hegedus L, Karstrup S, Veiergang D, Jacobsen B, Skovsted L, Feldt-Rasmussen U. High frequency of goitre in cigarette smokers. Clin Endocrinol (Oxf). 1985;22:287-292.
PUBMED
11. Brix TH, Hansen PS, Kyvik KO, Hegedus L. Cigarette smoking and risk of clinically overt thyroid disease: a population-based
twin case-control study. Arch Intern Med. 2000;160:661-666.
FREE FULL TEXT
12. Nygaard B, Gideon P, Dige-Petersen H, Jespersen N, Solling K, Veje A. Thyroid volume and morphology and urinary iodine excretion in a Danish
municipality. Acta Endocrinol (Copenh). 1993;129:505-510.
13. Berghout A, Wiersinga WM, Smits NJ, Touber JL. Determinants of thyroid volume as measured by ultrasonography in healthy
adults in a non-iodine deficient area. Clin Endocrinol (Oxf). 1987;26:273-280.
PUBMED
14. Georgiadis E, Papapostolou C, Korakis T, Evagelopoulou K, Mantzoros C, Batrinos M. The influence of smoking habits on thyroid gland volume: an ultrasonic
approach. J R Soc Health. 1997;117:355-358.
ISI
| PUBMED
15. Bartalena L, Martino E, Marcocci C, et al. More on smoking habits and Graves' ophthalmopathy. J Endocrinol Invest. 1989;12:733-737.
ISI
| PUBMED
16. Pedersen KM, Nohr SB, Laurberg P. Iodine intake in Denmark. Ugeskr Laeger. 1997;159:2201-2206.
PUBMED
17. Knudsen N, Bulow I, Jorgensen T, Laurberg P, Ovesen L, Perrild H. Goitre prevalence and thyroid abnormalities at ultrasonography: a comparative
epidemiological study in two regions with slightly different iodine status. Clin Endocrinol (Oxf). 2000;53:479-485.
FULL TEXT
| PUBMED
18. Knudsen N, Bols B, Bulow I, et al. Validation of ultrasonography of the thyroid gland for epidemiological
purposes. Thyroid. 1999;9:1069-1074.
ISI
| PUBMED
19. Gutekunst R, Becker W, Hehrmann R, Olbricht T, Pfannenstiel P. Ultraschalldiagnostik der Schilddruse. Dtsch Med Wochenschr. 1988;113:1109-1112.
PUBMED
20. Schlumberger M, Fragu P, Gardet P, Lumbroso J, Violot D, Parmentier C. A new immunoradiometric assay (IRMA) system for thyroglobulin measurement
in the follow-up of thyroid cancer patients. Eur J Nucl Med. 1991;18:153-157.
FULL TEXT
|
ISI
| PUBMED
21. Wilson B, Van Zyl A. The estimation of iodine in thyroidal amino acids by alkaline ashing. S Afr J Med Sci. 1967;32:70-82.
PUBMED
22. Laurberg P. Thyroxine and 3,5,3'-triiodothyronine content of thyroglobulin
in thyroid needle aspirates in hyperthyroidism and hypothyroidism. J Clin Endocrinol Metab. 1987;64:969-974.
ABSTRACT
23. Greenland S. Applications of stratified analysis methods. In: Rothman J, Greenland S, eds. Modern Epidemiology. 2nd ed. Philadelphia, Pa: Lippincott-Raven Publishers; 1998:281-300.
24. Jarlov AE, Hegedus L, Gjorup T, Hansen JM. Observer variation in the clinical assessment of the thyroid gland. J Intern Med. 1991;229:159-161.
ISI
| PUBMED
25. Fukayama H, Nasu M, Murakami S, Sugawara M. Examination of antithyroid effects of smoking products in cultured
thyroid follicles: only thiocyanate is a potent antithyroid agent. Acta Endocrinol (Copenh). 1992;127:520-525.
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