| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
Department of Endocrinology and Internal Medicine (P.L., K.M.P., E.I.), Aalborg Hospital, DK-9000 Aalborg, Denmark; Department of Radiology (P.R.K.), Randers Hospital, Denmark; Department of Internal Medicine (A.H.), Landspitalinn; and The Heart Preventive Clinic (N.S.), Reykjavik, Iceland
Address all correspondence and requests for reprints to: Peter Laurberg, M.D., Department of Internal Medicine and Endocrinology, Aalborg Hospital, DK-9000 Aalborg, Denmark.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Random samples of elderly subjects (68 yr) were selected from the central person registers in Jutland, Denmark, with low (n = 423) and, in Iceland, with longstanding relatively high (n = 100) iodine intake.
Females from Jutland had a high prevalence of goiter or previous goiter surgery (12.2%), compared with males from Jutland (3.2%) and females (1.9%) and males (2.2%) from Iceland. Abnormal thyroid function was very common in both areas, with serum TSH outside the reference range in 13.5% of subjects from Jutland and 19% of those from Iceland. In Jutland, it was mainly thyroid hyperfunction (9.7% had low, 3.8% had high serum TSH), whereas in Iceland, it was impaired thyroid function (1% had low, 18% had high serum TSH). All subjects with serum TSH more than 10 mU/L had autoantibodies in serum, but antibodies were, in general, more common in Jutland than in Iceland.
Thus, thyroid abnormalities in populations with low iodine intake and those with high iodine intake develop in opposite directions: goiter and thyroid hyperfunction when iodine intake is relatively low, and impaired thyroid function when iodine intake is relatively high. Probably, mild iodine deficiency partly protects against autoimmune thyroid disease. Thyroid autoantibodies may be markers of an autoimmune process in the thyroid or secondary to the development of goiter.
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The other major thyroid abnormality is autonomous nodular growth and function of the gland. The exact mechanism leading to this often multifocal process is unknown (5), but it is facilitated by a low iodine intake or an intake of goitrogens, which inhibit the thyroidal use of iodine. In iodine-deficient populations, goiter may affect more than half of the population, and autonomous function of thyroid nodules is the major cause for hyperthyroidism (6). It may take many years before a major change in the iodine intake is followed by a new steady pattern of thyroid disease (7, 8).
We performed comparative studies of thyroid abnormalities in Iceland and in Jutland, Denmark, to evaluate the effect of differences in population iodine intake on the prevalence rate of various thyroid disorders in the elderly. These areas have similar levels of medical care and socioeconomic development and a similar genetic background (9). The levels of iodine intake (low in Jutland, high in Iceland) have been relatively stable during the lifetime of the inhabitants (10, 11). A previous study showed profound differences in the pattern of diseases causing hyperthyroidism and the ages at manifestation (12). Now, major differences were demonstrated in the prevalence rate of abnormalities in thyroid function. The results suggest that, even in areas without goiter endemia, the population iodine intake level is a major determinant of which types of thyroid abnormalities are common.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The populations studied were elderly subjects living in Iceland (Reykjavik and surroundings) and Jutland, Denmark (Randers and surroundings). Randers is a city of 56,000 inhabitants in East Jutland. Selection took place from the central person registers. For practical reasons, the investigation in Iceland included a random sample of 66- to 70-yr-old subjects (n = 100, males/females = 46/54, mean age 68 yr) also invited to participate in a population survey of heart diseases (n = 3,000), whereas in Jutland (n = 423, males/females = 185/238), it was all subjects in the municipality being 68 yr. In both areas, approximately 70% of the subjects invited to participate accepted the invitation. Hence, both groups were random population samples, with no special selection, apart from the necessary acceptance of participation. The investigation involved an interview on previous or present thyroid disease, past and actual smoking habits, pregnancies, health state and medication, possible sources of extra iodine intake, duration of habitation in the areas, goiter evaluation, and sampling of blood and urine. The majority had lived in the areas for more than 30 yr (Iceland 82%, Jutland 77%), and a large part of the remaining group had lived in other areas of Iceland and Jutland with similar levels of iodine intake. All were Caucasian. The number of smokers or previous smokers (Iceland males/females = 74/59%), Jutland males/females 48/43%), and the number of child births in women (Iceland 3, Jutland 2, medians) were moderately higher in Iceland than in Jutland.
Goiter evaluation
A clinical examination was performed for the presence of goiter,
using a simplified score, where 0 was no goiter, I was an enlarged
thyroid visible with extended neck or as judged from palpation, II was
an easily depictable and clearly enlarged thyroid with the head in
normal position, and III was a large goiter visible at a distance. The
relevance of the distinction between grades 0 and I was tested in a
control study. A random sample of participants from Jutland (n =
106) subsequently had thyroid volume measured by ultrasound (13) by a
trained radiologist unaware of the initial score. Many had a relatively
large thyroid volume without clinical goiter, but thyroid volume was
not different in subjects with score 0 vs. score I (Fig. 1
). Hence, only subjects with score II or
III were considered to have goiter.
|
Iodine was measured in morning spot urine samples in all subjects, to evaluate the possibility of excessive iodine intake as the cause for an elevated serum TSH. The concentrations were as expected: higher in Iceland [150 µg/L (33–703), median, range, n = 89] than in Jutland [38 µg/L (6–770), n = 197] in subjects with no extra iodine intake, as judged from history (P < 0.01). Subjects with intake of iodine containing medication or supplements of any kind and subjects with recent radiographic investigations involving iodine containing contrast media were excluded for this calculation. It reflects the basic iodine intake of the elderly population from the two areas. Iodine measurements were performed in duplicate as previously described (14). The recovery rate was more than 95%. Intra- and interassay coefficients of variation were 2.1 and 2.7%, respectively, and the detection limit in the setup used was 3 µg/L.
Blood samples were obtained during the time interval 0900–1600 h. Serum was stored at -20 C until analyses. Reagents for measurements of total T4 (RIA, reference range 60–140 nmol/L) and T3 (RIA, 1.2–2.7 nmol/L), and T3 uptake test (0.8–1.2) were supplied by Farmos (Turko, Finland). T3 Uptake test results were used to test for abnormalities in thyroid hormone binding proteins giving misleading T4 and T3 values (outside the reference range in euthyroid subjects or normal in hypo- or hyperthyroid subjects). No such abnormalities were found. TSH was measured by an immunoluminometric assay (Behring Werke, Marburg, Germany; detection limit 0.01 mU/L; reference range 0.40–4.0 mU/L). Characteristics of the assay have been given previously (15). Thyroid peroxidase antibodies (TPO-Ab) were measured by a very sensitive enzyme-linked immunosorbent assay [detection limit 4 U/L (reference standard code 66/387 NIBSC, London, UK)] using purified human TPO as antigen (4), thyroglobulin antibodies (Tg-Ab) by a very sensitive radioimmunoprecipitation assay (detection limit 20 U/L, reference standard code A 65193) (3), and Tg by an immunoluminometric assay (Behring Werke; detection limit <1 µg/L) including recovery measurements. Because Tg-Ab may influence Tg values (16), only samples with Tg-Ab values less than 200 U/L were used. No difference was found in subjects without Tg-Ab and with Tg-Ab [20–200 U/L; median Tg 13.1 (n = 390) vs. 14.3 µg/L (n = 50)]. During sampling, handling, transport, and storage of samples and during all analyses, special care was taken to avoid bias which could lead to spurious systematic differences between areas. For this purpose, all single runs of all assays included shifting groups of samples from both areas.
The Medstat program version 2.12 (Astra Albertslund, Denmark) was
employed for calculation of medians and for statistical analyses
(
2-test).
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The prevalence rate of goiter or previous goiter surgery was high
in Jutland (23 subjects had undergone thyroid operations, 19 for
nontoxic goiter; and 12, nonoperated, had goiter), compared with
Iceland (1 had undergone thyroid surgery for goiter and 1, in addition,
had goiter). The difference was because of a high prevalence rate in
females from Jutland (Fig. 2)
[statistically significant in females (P < 0.05) with
no difference in males]. In addition, there were few cases of treated
hyperthyroidism and hypothyroidism (Jutland: 6 cases of previously
treated hyperthyroidism, 6 patients receiving T4
supplementation at the time of investigation; Iceland: none with
hyperthyroidism and 1 receiving T4).
|
Low TSH levels were common in Jutland (Fig. 3A), with 9.7% of values less than 0.40
mU/L [11 males, 31 females (5 of the females received T4;
2 of the males and 5 of the females had goiter)], whereas this was
seen only in one subject from Iceland (a male receiving T4
supplementation). The distribution of TSH values in elderly subjects
from Jutland was very similar to that of young subjects from this
area, except for the high prevalence rate of values less than 0.4
mU/L in the elderly (Fig. 3A). The low serum TSH values were
distributed over the range from <0.01 to 0.40 mU/L.
|
A low serum TSH in subjects not receiving T4 may
indicate thyroid hyperactivity or be caused by medication or severe
nonthyroidal disease. None received medication suppressing serum TSH,
except for T4 substitution, and all were ambulatory without
signs of severe disease. Figure 3B
demonstrates the frequency of
finding different grades of thyroid hyperactivity. This was very common
in Jutland, especially in the females (females and males from Jutland
compared with Iceland, and in Jutland females compared with males,
P < 0.01, subjects receiving T4 excluded).
One of 30 of the elderly females from Jutland had unrecognized
hyperthyroidism with suppressed serum TSH and elevated serum
T4 and or serum T3.
Thyroid hypofunction
In Iceland, TSH values were not low; on the contrary, they were
high, compared with values from Jutland (Fig. 3C) [Iceland: 18% had a
TSH value >4.0 mU/L, this was 3.8% in Jutland (P <
0.01 in both males and females, and in both areas females
vs. males)]. Some subjects had relatively high TSH values,
more than 10 mU/L (4.0% in Iceland, 0.9% in Jutland), up to 50 mU/L,
but none had a subnormal serum T4. None of the subjects
with high serum TSH had excessive amounts of iodine in urine, and none
received medications with antithyroid action.
Thyroid Antibodies
All sera containing more than 10 mU/L TSH also had high
concentrations of TPO-Ab and/or Tg-Ab. Antibodies were also common in
subjects with normal serum TSH. The prevalence rates of detectable
Tg-Ab and TPO-Ab were nearly similar (Fig. 4A), although many subjects had only one
type measurable (89 subjects had TPO-Ab > 10 U/L, 50 of these had
measurable Tg-Ab; 83 had Tg-Ab > 200 U/L, 44 of these had
measurable TPO-Ab). Antibodies were nearly twice as common in females
as in males (P < 0.05 in both areas). Both types of
antibodies were approximately twice as common in Jutland as in Iceland
(P < 0.01) (Fig. 4A).
|
Serum Tg concentrations usually ranged between 5 and 15 µg/L in
both populations (Fig. 4B). In Jutland, however, many values were much
higher: among the females, 35.3% had Tg values above 30 µg/L,
whereas this was seen in 20.5% of the males (Iceland females 6.3%,
males 0%, P < 0.01 for both sexes).
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In Jutland, the iodine intake has been stable (low) for many years, being in the order of 40–60 µg/day (12). Because studies of school children have shown no excessive goiter frequency (17), and newborns had normal thyroid function independent of iodine supplements (13), an iodine supplementation program has not been initiated. Apparently the group at risk at this low level of iodine intake is not children and young subjects but elderly females. In the present study, they had a high prevalence rate of clinical goiter and of various degrees of undiagnosed hyperthyroidism. In a previous comparative study, the incidence of diagnosed hyperthyroidism caused by multinodular toxic goiter was also excessive in this group (12). The dangers of such a condition are predominantly atrial fibrillation (18) (with a risk of impaired cardiac function and embolism) and osteoporosis (19).
In Iceland, several studies, over the years, have shown a high iodine intake (up to 300–350 µg/day) (10). Values from the present study were somewhat lower but still much higher than in Jutland. The change towards lower values could be caused by differences in eating habits between age groups or to changes, over time, in eating habits.
A major source of iodine intake in Iceland may be iodine in dairy
products caused by feeding of cattle with fish meal. The iodine
contents of two dairy milk samples from Reykjavik, measured as part
of the current study, were 270 and 229 µg/L, whereas tap water
contained less than 1 µg/L. Hence, an age-associated change from high
intake of milk to water or coffee or to tea could be a reason for the
iodine intake in elderly subjects in Iceland being lower than found in
previous studies of young subjects. However, no special history on milk
vs. coffee and tea intake was obtained in the subjects
investigated. In Iceland, none had a low serum TSH (except for one
subject receiving T4). This corresponds to the very low
incidence of diagnosed hyperthyroidism in elderly subjects from Iceland
(12). On the other hand, subclinical hypothyroidism was very common
(
4 times the prevalence rate in Jutland). The risks of such a
condition may be an increase in lipid abnormalities with
atherosclerosis and also in other abnormalities (20).
The high prevalence rate of subclinical hypothyroidism in Iceland could be caused by the high iodine intake. Iodine inhibits the thyroid (21), but when given to normal young subjects during short periods of time, the amount has to be considerably higher to induce an increase in serum TSH (22). Thyroids affected by autoimmunity are more sensitive to the inhibitory effect of iodine (23), and possibly, the subjects in Iceland with high TSH were those who, for other reasons, had autoimmune thyroiditis. Another possibility is that the high iodine intake in Iceland by itself worsens autoimmune thyroiditis in subjects who are genetically predisposed to develop thyroid autoimmunity. Such a mechanism is supported by series of animal experiments (24). Also, lymphocytic infiltrations of the thyroid in humans may be more common after an increase in iodine intake (25, 26). This relation between iodine intake level and autoimmune thyroid disease is in accordance with our previous finding that Graves’ disease manifests at a considerably younger age in Iceland than in Jutland (12).
The comparative design of our study makes evident the difference between the areas with relatively low, and those with high, iodine intake levels. The results, however, are in line with those obtained in other epidemiological studies. In the United States, with relatively high iodine intake, the Framingham study showed that 4.4% of subjects 60–87 yr old had serum TSH more than 10 mU/L (27) (similar to the level found in Iceland). On the other hand, studies from European countries with relatively low iodine intake have shown a low prevalence rate of subclinical hypothyroidism and more hyperthyroidism, similar to Jutland [serum TSH >10 mU/L; Italy: 0.9% (28); Germany: 1.5% (29)]. Another example of the dominant effect of the iodine intake level on the type of thyroid disease is seen in patients receiving the iodine-containing drug, amiodarone. In the United States, the drug induced predominantly hypothyroidism; in Italy, hyperthyroidism (30).
All subjects, from both areas, with high serum TSH (>10 mU/L), had thyroid antibodies in serum; but in subjects with normal or low serum TSH, antibodies were more common in Jutland than in Iceland. Hence, thyroid antibodies did correlate to impaired thyroid function, as evaluated by high serum TSH, but the population with the highest prevalence rate of antibodies was not characterized, in general, by high TSH levels. It had a high prevalence rate of goiter. A correlation between goiter and thyroid antibodies in serum has also been found in some other epidemiological studies. In the 20-yr follow-up study in Wickham, UK, subjects who had developed goiter had also developed thyroid antibodies (31). In Italy, Fenzi et al. (32) noted that thyroid antibodies were common in subjects with goiter and suggested that this was caused by long-standing goiter and that thyroid antibodies did not cause the goiter. Previously, thyroid antibodies and goiter were found to be more common in Scotland than in Iceland (33, 34).
A possible explanation for these findings is that TPO-Ab and Tg-Ab in serum are mainly markers and not inducers of disease and can result from different abnormalities. A common cause would be an autoimmune process in the thyroid (tending to inhibit thyroid function). This is the clinical pattern of autoimmune thyroiditis with circulation thyroid antibodies and impaired thyroid function (the insufficiency not being caused by the circulating antibodies but by the cellular autoimmunity in the gland). Antibodies might also be the result of goiter formation with exposure in the thyroid or release from the thyroid of antigens leading to autoantibody formation inside or outside the thyroid. Excessive Tg release from the thyroid was common in Jutland, and TPO may also be released from the thyroid (35). This is the clinical pattern of multinodular goiter with circulation thyroid antibodies but with no tendency to impair thyroid function. Formation of TPO-Ab and Tg-Ab may be induced easily in many subjects by one or another abnormality in the thyroid gland. This is not incompatible with the finding in animal studies of an enhancing effect of a high iodine diet on thyroid autoimmunity. The major event in this would be lymphocytic infiltration of the gland, and thyroid antibody formation would be a secondary phenomenon.
In conclusion, the study has demonstrated that both low and high iodine intake levels correlate to a high prevalence rate of thyroid abnormalities (although the types of abnormalities are different). It remains to be evaluated whether a window in iodine intake levels exists where thyroid disorders are less common. Probably mild iodine deficiency partly protects against autoimmune thyroid disease, as known from several animal strains (24). Knowledge of the iodine intake level of an area is valuable for the understanding of the pattern of thyroid abnormalities and for the planning of care of thyroid disorders.
Received July 7, 1997.
Revised October 2, 1997.
Revised November 21, 1997.
Accepted December 1, 1997.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  H. Volzke, D. M. Robinson, T. Spielhagen, M. Nauck, A. Obst, R. Ewert, B. Wolff, H. Wallaschofski, S. B. Felix, and M. Dorr Are serum thyrotropin levels within the reference range associated with endothelial function? Eur. Heart J., November 13, 2008; (2008) ehn508v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dorr, K. Empen, D. M Robinson, H. Wallaschofski, S. B Felix, and H. Volzke The association of thyroid function with carotid artery plaque burden and strokes in a population-based sample from a previously iodine-deficient area Eur. J. Endocrinol., August 1, 2008; 159(2): 145 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, D. Teng, Z. Shan, X. Teng, H. Guan, X. Yu, C. Fan, W. Chong, F. Yang, H. Dai, et al. Antithyroperoxidase and Antithyroglobulin Antibodies in a Five-Year Follow-Up Survey of Populations with Different Iodine Intakes J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1751 - 1757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. B. Pedersen, P. Laurberg, N. Knudsen, T. Jorgensen, H. Perrild, L. Ovesen, and L. B. Rasmussen Smoking is negatively associated with the presence of thyroglobulin autoantibody and to a lesser degree with thyroid peroxidase autoantibody in serum: a population study Eur. J. Endocrinol., March 1, 2008; 158(3): 367 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Biondi and D. S. Cooper The Clinical Significance of Subclinical Thyroid Dysfunction Endocr. Rev., February 1, 2008; 29(1): 76 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bulow Pedersen, P. Laurberg, N. Knudsen, T. Jorgensen, H. Perrild, L. Ovesen, and L. B. Rasmussen An Increased Incidence of Overt Hypothyroidism after Iodine Fortification of Salt in Denmark: A Prospective Population Study J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3122 - 3127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Li and G. Carayanniotis Induction of Goitrous Hypothyroidism by Dietary Iodide in SJL Mice Endocrinology, June 1, 2007; 148(6): 2747 - 2752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O.E. Okosieme, R.C. Taylor, A.E. Ohwovoriole, A.B. Parkes, and J.H. Lazarus Prevalence of thyroid antibodies in Nigerian patients QJM, February 1, 2007; 100(2): 107 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Cooper Approach to the Patient with Subclinical Hyperthyroidism J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 3 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bulow Pedersen, P. Laurberg, N. Knudsen, T. Jorgensen, H. Perrild, L. Ovesen, and L. B. Rasmussen Increase in Incidence of Hyperthyroidism Predominantly Occurs in Young People after Iodine Fortification of Salt in Denmark J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3830 - 3834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O E Okosieme Impact of iodination on thyroid pathology in Africa. J R Soc Med, August 1, 2006; 99(8): 396 - 401. [Full Text] [PDF]
|
|
|
|
 |
|
 W. Teng, Z. Shan, X. Teng, H. Guan, Y. Li, D. Teng, Y. Jin, X. Yu, C. Fan, W. Chong, et al. Effect of iodine intake on thyroid diseases in China. N. Engl. J. Med., June 29, 2006; 354(26): 2783 - 2793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S Hansen, T. H Brix, I. Iachine, K. O Kyvik, and L. Hegedus The relative importance of genetic and environmental effects for the early stages of thyroid autoimmunity: a study of healthy Danish twins Eur. J. Endocrinol., January 1, 2006; 154(1): 29 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Hoogendoorn, A. R. Hermus, F. de Vegt, H. A. Ross, A. L.M. Verbeek, L. A.L.M. Kiemeney, D. W. Swinkels, F. C.G.J. Sweep, and M. den Heijer Thyroid Function and Prevalence of Anti-Thyroperoxidase Antibodies in a Population with Borderline Sufficient Iodine Intake: Influences of Age and Sex Clin. Chem., January 1, 2006; 52(1): 104 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Diez Goiter in Adult Patients Aged 55 Years and Older: Etiology and Clinical Features in 634 Patients J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2005; 60(7): 920 - 923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Belin, B. C. Astor, N. R. Powe, and P. W. Ladenson Smoke Exposure Is Associated with a Lower Prevalence of Serum Thyroid Autoantibodies and Thyrotropin Concentration Elevation and a Higher Prevalence of Mild Thyrotropin Concentration Suppression in the Third National Health and Nutrition Examination Survey (NHANES III) J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6077 - 6086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. V. Flynn, T. M. MacDonald, A. D. Morris, R. T. Jung, and G. P. Leese The Thyroid Epidemiology, Audit, and Research Study: Thyroid Dysfunction in the General Population J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3879 - 3884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. N. Pearce, A. P. Farwell, and L. E. Braverman Thyroiditis N. Engl. J. Med., June 26, 2003; 348(26): 2646 - 2655. [Full Text] [PDF]
|
|
|
|
|
|
L. Hegedus, S. J. Bonnema, and F. N. Bennedbaek Management of Simple Nodular Goiter: Current Status and Future Perspectives Endocr. Rev., February 1, 2003; 24(1): 102 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B Rasmussen, L. Ovesen, I. Bulow, T. Jorgensen, N. Knudsen, P. Laurberg, and H. Perrild Relations between various measures of iodine intake and thyroid volume, thyroid nodularity, and serum thyroglobulin Am. J. Clinical Nutrition, November 1, 2002; 76(5): 1069 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bulow Pedersen, N. Knudsen, T. Jorgensen, H. Perrild, L. Ovesen, and P. Laurberg Large Differences in Incidences of Overt Hyper- and Hypothyroidism Associated with a Small Difference in Iodine Intake: A Prospective Comparative Register-Based Population Survey J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4462 - 4469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Boltze, G. Brabant, H. Dralle, R. Gerlach, A. Roessner, and C. Hoang-Vu Radiation-Induced Thyroid Carcinogenesis as a Function of Time and Dietary Iodine Supply: An in Vivo Model of Tumorigenesis in the Rat Endocrinology, July 1, 2002; 143(7): 2584 - 2592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Dunn Guarding our Nation's Thyroid Health J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 486 - 488. [Full Text] [PDF]
|
|
|
|
|
|
J. G. Hollowell, N. W. Staehling, W. D. Flanders, W. H. Hannon, E. W. Gunter, C. A. Spencer, and L. E. Braverman Serum TSH, T4, and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III) J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 489 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Knudsen, I. Bulow, T. Jorgensen, H. Perrild, L. Ovesen, and P. Laurberg Serum Tg--A Sensitive Marker of Thyroid Abnormalities and Iodine Deficiency in Epidemiological Studies J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3599 - 3603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Nøhr, A. Jørgensen, K. M. Pedersen, and P. Laurberg Postpartum Thyroid Dysfunction in Pregnant Thyroid Peroxidase Antibody-Positive Women Living in an Area with Mild to Moderate Iodine Deficiency: Is Iodine Supplementation Safe? J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3191 - 3198. [Abstract] [Full Text]
|
|
|
|
|
|
M. Tonacchera, P. Agretti, L. Chiovato, V. Rosellini, G. Ceccarini, A. Perri, P. Viacava, A. G. Naccarato, P. Miccoli, A. Pinchera, et al. Activating Thyrotropin Receptor Mutations Are Present in Nonadenomatous Hyperfunctioning Nodules of Toxic or Autonomous Multinodular Goiter J. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2270 - 2274. [Abstract] [Full Text]
|
|
|
|
 |
|
 U. Leutgeb Ambient iodine and lithium-associated clinical hypothyroidism The British Journal of Psychiatry, May 1, 2000; 176 (5): 495a - 496a. [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Brix, P. S. Hansen, K. O. Kyvik, and L. Hegedus Cigarette Smoking and Risk of Clinically Overt Thyroid Disease: A Population-Based Twin Case-Control Study Arch Intern Med, March 13, 2000; 160(5): 661 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Nøhr and P. Laurberg Opposite Variations in Maternal and Neonatal Thyroid Function Induced by Iodine Supplementation during Pregnancy J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 623 - 627. [Abstract] [Full Text]
|
|
|
|
|
|
T. W. Furlanetto, L. Q. Nguyen, and J. L. Jameson Estradiol Increases Proliferation and Down-Regulates the Sodium/Iodide Symporter Gene in FRTL-5 Cells Endocrinology, December 1, 1999; 140(12): 5705 - 5711. [Abstract] [Full Text]
|
|
|
|
|
|
F. Aghini-Lombardi, L. Antonangeli, E. Martino, P. Vitti, D. Maccherini, F. Leoli, T. Rago, L. Grasso, R. Valeriano, A. Balestrieri, et al. The Spectrum of Thyroid Disorders in an Iodine-Deficient Community: The Pescopagano Survey J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 561 - 566. [Abstract] [Full Text]< |
