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Thyroid and the environment: Exposure to excessive nutritional iodine increases the prevalence of thyroid disorders in Sao Paulo, Brazil

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To evaluate the prevalence of chronic autoimmune thyroiditis (CAT) and iodine-induced hypothyroidism, hyperthyroidism (overt and subclinical), and goiter in a population exposed to excessive iodine intake for 5 years (table salt iodine concentrations: 40-100 mg/kg salt). Design This was a population-based, cross-sectional study with 1085 participants randomly selected from a metropolitan area in São Paulo, Brazil, and conducted during the first semester of 2004. Thyroid ultrasound examination was performed in all participants and samples of urine and blood were collected from each subject. Serum levels of thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase (TPO) antibodies, urinary iodine concentration, thyroid volume, and thyroid echogenicity were evaluated. We also analyzed table salt iodine concentrations. At the time the study was conducted, table salt iodine concentrations were within the new official limits (20-60 mg/kg salt). Nevertheless, in 45.6% of the participants, urinary iodine excretion was excessive (above 300 microg/l) and, in 14.1%, it was higher than 400 microg/l. The prevalence of CAT (including atrophic thyroiditis) was 16.9% (183/1085), women were more affected than men (21.5 vs 9.1% respectively, P=0.02). Hypothyroidism was detected in 8.0% (87/1085) of the population with CAT. Hyperthyroidism was diagnosed in 3.3% of the individuals (36/1085) and goiter was identified in 3.1% (34/1085). Five years of excessive iodine intake by the Brazilian population may have increased the prevalence of CAT and hypothyroidism in subjects genetically predisposed to thyroid autoimmune diseases. Appropriate screening for early detection of thyroid dysfunction may be considered during excessive nutritional iodine intake.
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Thyroid and the environment: exposure to excessive nutritional
iodine increases the prevalence of thyroid disorders in Sa
Paulo, Brazil
Rosalinda Y A Camargo, Eduardo K Tomimori, Solange C Neves, Ileana G S Rubio, Ana Luiza Galra˜o, Meyer Knobel
and Geraldo Medeiros-Neto
Thyroid Unit (LIM-25), Division of Endocrinology, Department of Clinical Medicine, University of Sa
o Paulo Medical School, Avenue Dr Arnaldo,
455 - 4A, 01246-000 Sa
o Paulo, SP, Brazil
(Correspondence should be addressed to G Medeiros-Neto; Email:
Objective: To evaluate the prevalence of chronic autoimmune thyroiditis (CAT) and iodine-induced
hypothyroidism, hyperthyroidism (overt and subclinical), and goiter in a population exposed to
excessive iodine intake for 5 years (table salt iodine concentrations: 40–100 mg/kg salt).
Design: This was a population-based, cross-sectional study with 1085 participants randomly selected
from a metropolitan area in Sa˜o Paulo, Brazil, and conducted during the rst semester of 2004.
Methods: Thyroid ultrasound examination was performed in all participants and samples of urine and
blood were collected from each subject. Serum levels of thyroid-stimulating hormone, free thyroxine,
and anti-thyroid peroxidase (TPO) antibodies, urinary iodine concentration, thyroid volume, and
thyroid echogenicity were evaluated. We also analyzed table salt iodine concentrations.
Results: At the time the study was conducted, table salt iodine concentrations were within the new
official limits (20–60 mg/kg salt). Nevertheless, in 45.6% of the participants, urinary iodine excretion
was excessive (above 300 mg/l) and, in 14.1%, it was higher than 400 mg/l. The prevalence of CAT
(including atrophic thyroiditis) was 16.9% (183/1085), women were more affected than men (21.5 vs
9.1% respectively, PZ0.02). Hypothyroidism was detected in 8.0% (87/1085) of the population with
CAT. Hyperthyroidism was diagnosed in 3.3% of the individuals (36/1085) and goiter was identified in
3.1% (34/1085).
Conclusions: Five years of excessive iodine intake by the Brazilian population may have increased the
prevalence of CAT and hypothyroidism in subjects genetically predisposed to thyroid autoimmune
diseases. Appropriate screening for early detection of thyroid dysfunction may be considered during
excessive nutritional iodine intake.
European Journal of Endocrinology 159 293–299
Prevalence rates of thyroid dysfunction vary around the
world according to the studies from different countries
(1–6). These differences may be due to variations in
disease definition, heterogeneity of the studied popu-
lations, relative insensitivity of thyroid function measure-
ments, and absence of ultrasound imaging of the thyroid
gland (2–5). In the Whickham survey, 7.5% of women
and 2.8% of men of all ages had hypothyroidism as defined
by serum thyroid-stimulating hormone (TSH) level above
6mU/l(2). After reviewing their data 20 years later and
comparing with 12 similar studies from different
countries, Vanderpump et al. (3) concluded that primary
thyroid failure has a prevalence of about 5% in multiple
populations. In a very large population-based study
(nZ25 862), Canaris et al. (4) observed elevated serum
TSH levels in 9.5% of the participants. Virtually all
studies report higher prevalence rates of hypothyroidism
in women and in advanced age (4–8).
Nutritional iodine status is an important factor
associated with thyroid dysfunction and thyroid auto-
immunity (9). As indicated by the World Health
Organization, more than two-thirds of the 5 billion
people living in countries affected by iodine deficiency
now have access to iodized salt (10). In South America,
iodine nutrition has improved considerably over the last
decade; however, excessive iodine intake has been
confirmed in Brazil and Chile, where urinary iodine
excretion concentrations above 300 and 500 mg/l
respectively have been demonstrated (11). Excessive
dietary iodine is associated with increased risk for
chronic autoimmune thyroiditis (CAT), hypothyroidism
(mostly in women), and hyperthyroidism (mostly in
elderly individuals) (12–17). Some studies have indi-
cated that excessive iodine intake may increase thyroid
European Journal of Endocrinology (2008) 159 293–299 ISSN 0804-4643
q 2008 European Society of Endocrinology DOI: 10.1530/EJE-08-0192
Online version via
volume in children (18) and increase the risk of post
partum thyroiditis (19).
In Brazil, a national survey conducted in 1994
detected a relatively low iodine intake (median urinary
iodine excretion !100 mg/l) in more than 50% of
20 000 schoolchildren evaluated (20, 21).Asa
consequence, the Brazilian health authorities increased
the iodination of table salt from 40–60 mg iodine per
kilogram of salt to 40–100 mg/kg in 1998. Two
population studies conducted after the iodine fortifica-
tion (11, 22) documented that more than 60% of the
examined subjects had elevated median urinary iodine
excretion (O300 mg/l), indicating that the Brazilian
population became exposed to excessive iodine from
1998 to 2003, after which iodination of table salt was
lowered to 20–60 mg/kg of salt.
In this study, we aimed to evaluate the consequences
to the thyroid gland of 5 years of excessive nutritional
iodine intake in Brazil (1998–2003) in a cohort of
randomly selected individuals from the metropolitan
region of Sa˜o Paulo. We examined all participants with
thyroid ultrasound, serum-free thyroxine (T
) and TSH,
presence of anti-TPO antibodies, and urinary iodine
excretion, as well as tested the iodine content of the
table salt being used by the participants at the time the
evaluation was conducted.
Subjects and methods
This was a population-based, cross-sectional study with
participants randomly selected from a metropolitan
area in Sa˜o Paulo, Brazil and conducted during the first
semester of 2004. To select the target districts to be
assessed, a detailed map of two urban areas with single-
family homes was obtained and blocks were selected by
chance. From these, streets were arbitrarily chosen and
houses within the streets were randomly selected. Each
home was visited by two medical students and one or
more residents were randomly chosen and questioned
whether he/she would be willing to participate in the
study. The interviews were conducted by the medical
students and the visits took place on Fridays and
Saturdays. As expected, the sample included more
women, since men are less likely to be home during
workdays. Also, most men enrolled were older than 30
years, since young men are less likely to be home on
Saturdays. As a consequence, women outnumbered
men in the age groups below 50 years (Table 1).
During the visit, an oral questionnaire was adminis-
tered to each participant eliciting personal information
and data on the economic status of the family, eating
habits, brand name of the table salt used, and estimation of
the amount of salt ingested per day. Eight patients were on
LT4 treatment for more than 5 years, all of them with the
diagnosis of atrophic autoimmune thyroiditis. For the
remaining eight patients with atrophic thyroiditis, the
information obtained was that they were on and off LT4
substitutive therapy for more than 5 years. All these
patients had elevated serum TSH concentrations (meanG
S.D.11.73G7.8 mU/l). Pregnant and lactating women
were not included in the study. Sixteen patients with overt
(nZ7) and subclinical hypothyroidism (nZ9) were
excluded because in the past they have been submitted
to either thyroid surgery (nZ5) or radioiodine therapy
(nZ9). All participants were evaluated with thyroid
B-mode ultrasound by the same observers (RAYC and
EKT) using a portable General Electric (GE) apparatus
with a 7.5 mHz probe. The samples of urine and blood
were obtained from each subject and kept refrigerated
until analysis.
The Cochran formula (nZpq/(d/t)
) (23) was used to
determine the sample size based on the estimated
population of Sa˜o Paulo City (11 million inhabitants).
The application of this formula yielded nZ385, whereas
data were collected on 1085 subjects (Table 1).
All participants signed a detailed consent form. The
study was approved by the Ethical Committee for
Research Projects of the Hospital das Clinicas,
University of Sa˜o Paulo Medical School.
Serum levels of TSH, free T
, and anti-TPO antibodies
(normal !35 U/ml) were assayed by chemiluminescence
(Elecsys, Roche Diagnostics). The reference range for
normal TSH and free T
values was derived from 320
subjects from the study. These individuals had no history
Table 1 Distribution of subjects by gender and age groups.
Female (F) Male (M)
Age group (years) n (%) Mean age (years) n (%) Mean age (years) Ratio M:F
!30 113 (16.7) 24.7 16 (3.9) 24.1 1:7.0
30–39 122 (18.0) 34.8 27 (6.6) 35.4 1:4.5
40–49 184 (27.1) 44.5 68 (16.7) 46.1 1:2.7
50–59 138 (20.4) 53.6 129 (31.7) 54.4 1:1.0
60–69 88 (13.0) 64.0 109 (26.8) 63.8 1:0.8
70–79 28 (4.1) 72.7 51 (12.5) 72.5 1:0.5
O80 5 (0.7) 81.0 7 (1.7) 82.0 1:0.7
Total 678 45.3 407 55.8 1:1.67
294 R Y A Camargo and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2008) 159
of thyroid disease, negative antithyroid antibodies, normal
thyroid gland on ultrasound (normal volume, echogeni-
city, and absence of cysts and nodules), and urinary iodine
excretion between 100 and 299 mg/l. Results were
considered to be within the normal range if situated
between the 2.5th and 97.5th percentile of this normal
population. In this reference cohort, serum TSH levels
ranged from 0.6 to 3.7 mU/l and serum free T
from 0.87
to 1.6 ng/dl. Thyroid volume ranged from 6 to 14.2 ml
(women) and from 7 to 14.9 ml (men) and was consistent
with normal range for the city of Sa˜o Paulo, as previously
described (8, 22).
Urinary iodine excretion was determined by the
colorimetric ceric arsenite method, based on the
Sandell–Kolthoff reaction, as previously described (21).
Normal reference range was considered 100–299 mg/l,
according to the World Health Organization (10).
On ultrasound evaluation, the echogenicity of the
thyroid was graded by comparison with the echogenicity
of the neck muscles and defined as normal (grade 1),
mildly hypoechoic (grade 2), moderately hypoechoic
(grade 3), and markedly hypoechoic (grade 4). Thyroid
volume was estimated by ultrasound in all participants.
The volume of each lobe was calculated by the formula
longitudinal diameter!transversal axis!anteroposter-
ior axis multiplied by 0.52. The total volume of the thyroid
was the sum of both lobes plus the volume of the isthmus,
calculated as width!height!length!0.52 (8, 22).
Goiter was defined by ultrasound as a thyroid volume
greater than 16.0 ml for women and 18.1 ml for men.
Samples of the table salt in use by the family at the
time of the visit were collected in plastic bags and
analyzed for iodine content at the Public Health
Reference Laboratory, Sa˜o Paulo, Brazil.
Diagnostic criteria for thyroid disease
CAT was diagnosed when anti-TPO antibodies were
positive (O35 U/ml) and grade 3 or 4 thyroid
hypoechogenicity was concurred by both observers on
ultrasound evaluation. The presence of low titer of anti-
TPO antibodies (between 36 and 100 U/ml) without
ultrasound documented hypoechogenicity may be
found in healthy subjects without evidence of thyroid
disease (1, 26). Therefore, these individuals were not
included as affected by CAT. The diagnosis of atrophic
autoimmune thyroiditis was established in patients with
reduced thyroid volume on ultrasound (! 5 ml) regard-
less of anti-TPO antibody status. These patients were
then included in the CAT group and considered as the
end stage of the autoimmune process with destruction
of the affected thyroid gland (1). Overt hypothyroidism
was diagnosed in subjects with serum TSH above
4.1 mU/l and free T
levels below 0.9 ng/dl; subclinical
hypothyroidism was determined to be present when
TSH levels were above 4.1 mU/l but free T
levels were
within the normal range. Both modalities of decreased
thyroid function were within the group of CAT.
Overt hyperthyroidism (low or undetectable TSH and
high free T
levels) and subclinical hyperthyroidism (low
or undetectable TSH and normal free T
levels) were
diagnosed irrespective of thyroid ultrasound features.
Statistical analysis
Pearson’s c
- and Fisher’s exact tests were used to
compare categorical values. For some analyses, the
fitting linear models and characteristics (slope, R
, and
P value) were applied. The parametric Student’s t-test
was used to compare different levels of urinary iodine
excretion with gender. The locally weighted polynomial
regression (Lowess, no parametric) was applied to
evaluate the association between thyroid volume and
age; the absence of association between these two
variables was later confirmed by log transformation. All
statistical analyses were performed at a significance
level of 0.05 with R software, version 2.5.0 (24).
Table 1 summarizes the main characteristics of the
population analyzed. A total of 1085 individuals between
the ages of 20 and 87 years were evaluated. From these,
678 were women (62.5%, mean ageG
years) and 407 were men (37.5%, 55.8G12.0 years;
ratio men/women 1:1.67).
Urinar y iodine excretion
The distribution of urinary iodine excretion in the
studied population is shown in Fig. 1. Fasting urine
Figure 1 Distribution of urinary iodine excretion in the studied
population. Note that 7.8% of all subjects had low urinary iodine
excretion (%100 mg/l), whereas an elevated excretion (O300 mg/l)
was observed in 45.1% of the samples. Moreover, 11% of the
women and 17% of the men had values above 400 mg/l. Men had a
significantly higher excretion of median urinary iodine
(womenZ270 mg/l and menZ290 mg/l; PZ0.028, Fisher’s exact
test). Vertical lines indicate the normal range.
Excessive iodine intake and thyroid disorders
specimens suitable for iodine content analysis were
obtained in 1022 participants and kept refrigerated
until assayed. The total cohort median urinary iodine
excretion was 273 mg/l (womenZ 270 mg/l and
menZ290 mg/l). Men had a significant higher
excretion of iodine when compared with women
(PZ0.028, Fisher’s exact test). Normal urinary iodine
excretion (100–299 mg/l) was present in 49.6% of the
women and 43.0% of the men. A relatively low urinary
iodine excretion (!100 mg/l) was detected in 8.11% of
the women and 7.3% of the men, whereas an elevated
excretion was observed in 461 (45.1%) subjects
(womenZ42.3% and menZ49.6%; PZ0.02). Five
participants excreted more than 1000 m g/l and were
considered to have possible exogenous iodine
Table salt iodine content
Samples of the table salt being consumed in the home at
the moment of the visit had a meanG
S.D. concentration
of iodine of 35.6G8.9 mg/kg of salt (range 23.8–
81.2 mg/kg). Three samples were above the legal limit
of 60 mg/kg and none had less than 20 mg/kg.
Thyroid ultrasound
Twenty-three women (3.4%) and three men (0.73%)
had atrophic thyroid gland (PZ0.004, Fisher’s exact
test); 14 women and 2 men had an atrophic thyroid
associated with positive anti-TPO antibodies. An
enlarged and frequently nodular goiter was present in
34 patients (Table 2); from these, 24 were women
(3.54%) and 10 were men (2.46%). A significant
increase in thyroid volume with advancing age was
not observed in both genders.
Prevalence of CAT
The prevalence of thyroid disease in the studied
population is presented in Table 2 and the prevalence
distribution of CAT by age group in women and men is
shown in Fig. 2. Ten subjects (eight women and two men)
had low (36–100 U/ml) positive anti-TPO antibodies but
normal thyroid ultrasound (echogenicity and volume),
so were not considered to have CAT. The overall
prevalence of CAT (including atrophic thyroiditis) was
16.87%; it significantly affected more women (21.53%)
than men (9.09%; PZ0.02). Women younger than 30
years had a lower prevalence of CAT when compared
with women between 60 and 69 years (16.81 and
28.41% respectively), whereas older men (between 50
and 59 years) had a higher prevalence (11.64%) when
compared with younger men (between 30 and 39 years,
7.40%). There was a significant increase in the
prevalence of CAT with advanced age in both genders
Z0.745, PZ0.0269).
Most of the subjects with CAT were euthyroid
(women 51.3% and men 56.7%). Women had a higher
prevalence of CAT associated with overt hypothyroidism
when compared with men (women 39/146 (26.7%)
and men 6/37 (16.2%); P!0.01). CAT associated with
subclinical hypothyroidism was detected in 18/146
(12.3%) of the women and in 8/37 (21.6%) of the men.
Atrophic thyroiditis was identified in 14/183 (9.6%) of
women and in 2/37 (5.4%) of men with CAT, being
considered as the end stage of the destructive auto-
immune process.
Prevalence of hyperthyroidism
population in relation to gender and age is shown in
Fig. 3. Hyperthyroidism was detected in 3.32% of
subjects. From these, 1.66% had overt hyperthyroidism
and 1.66% had subclinical hyperthyroidism. Subclinical
hyperthyroidism was more prevalent in women (2.06%)
than men (0.98%), although it did not attain statistical
significance (Table 2). In women (but not in men), both
subclinical and overt hyperthyroidism were more
prevalent with advancing age. The high relative
prevalence of hyperthyroidism in men aged 70–79
years old may be related to the low number of patients
included in this group (Fig. 3).
Table 2 Prevalence of thyroid disease in the studied population.
Total population (1085) Women (678) Men (407)
Thyroid disease n (%) n (%) n (%) P
Chronic autoimmune thyroiditis
183 (16.87) 146 (21.53) 37 (9.09) !0.001
Euthyroidism 96 (8.85) 75 (11.10) 21 (5.16) !0.001
Overt hypothyroidism 45 (4.15) 39 (5.75) 6 (1.47) !0.001
Sub-clinical hypothyroidism 26 (2.39) 18 (2.65) 8 (1.96) NS
Atrophic thyroiditis 16 (1.47) 14 (2.06) 2 (0.49) !0.01
Hyperthyroidism 36 (3.32) 26 (3.83) 10 (2.46) NS
Overt 18 (1.66) 12 (1.77) 6 (1.47) NS
Sub-clinical 18 (1.66) 14 (2.06) 4 (0.98) NS
Goiter 34 (3.13) 24 (3.54) 10 (2.46) NS
Including patients with atrophic thyroiditis.
296 R Y A Camargo and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2008) 159
The influence of dietary iodine on thyroid function has
been clearly shown in several studies with experimental
autoimmune thyroiditis (1). This association may be
due to an iodine-induced increase in the immunogenicity
of the thyroglobulin molecule (and possibly other
thyroid antigens as well) attracting antithyroid
antibodies and culminating in thyroid injury (9, 25).
High iodine intake has been shown to initiate and
exacerbate thyroid infiltration by lymphocytes in
genetically susceptible BB/W rats (26). In humans,
susceptibility to autoimmune thyroid disease (AITD)
clearly increases with age, as a result of extended
exposure to environmental factors (such as excessive
nutritional iodine intake) and changes in immunoregu-
lation. The identification of genes placing individuals at
an increased risk for development of AITD has been a
slow process. However, as recently reviewed by Zeitlin
et al. (27), novel insights have been made. AITD runs in
families and more than 50% of patients with AITD have a
familiar history suggesting that genetically predisposed
individuals under a specific environment condition
(iodine excess) may develop AITD.
In many countries, the introduction of iodine
prophylaxis has increased the prevalence of CAT and
induced a surge in thyroid antibodies positivity (12, 16).
Zois et al. (28) have reported the impact of increased
nutritional iodine in 3000 schoolchildren in Northern
Greece. After 7 years of iodine prophylaxis, 10% of the
children had ultrasonographic features of CAT associ-
ated with positive anti-TPO antibodies, whereas 2.5%
had laboratory evidence of subclinical hypothyroidism.
In a recent study by Teng et al. (29) conducted in three
areas of China with different levels of iodine intake (low,
median urinary iodine excretionZ84 mg/l; more than
adequate, 243 mg/l; and excessive, 651 mg/l), the
authors demonstrated that patients from the area with
excessive iodine intake had 5.6 times more CAT and 6.6
times more hypothyroidism (subclinical and overt)
when compared with patients from the area with low
iodine intake. The authors concluded that excessive
iodine intake may lead to autoimmune thyroiditis and
In the same year of the Brazilian population-based
survey of 1994 that found a relatively low iodine intake
in a large number of examined schoolchildren (20),
Tomimori et al. (8) examined 547 healthy overweight
subjects in Sa˜o Paulo, Brazil, with thyroid ultrasound,
thyroid function tests, and anti-TPO antibody measure-
ments. The authors found in this largely urban
population, a prevalence of CAT of 9.4% and clinical
and laboratory evidence of hypothyroidism in 4.9%. The
median urinary iodine excretion in this population was
106 mg/l.
In 1995, following the approval of a legislation that
regulated iodine in a concentration of 40–100 mg/kg of
salt for human use, it was believed that iodine deficiency
and its consequences would be abolished in Brazil.
When our group launched the Thyromobil Project in
2001 (11), examining 2013 schoolchildren in 21
villages of 8 Brazilian states, the initial conclusion was
that goiter had been practically eliminated. However,
67% of the schoolchildren were found to have a urinary
iodine excretion O300 mg/l and 35% of them excreted
Figure 2 Prevalence distribution of chronic autoimmune thyroiditis
by age in women and men. Bars indicate the percentile of chronic
autoimmune thyroiditis. Black bars indicate the percentile of
patients with chronic autoimmune thyroiditis associated with
overt or subclinical hypothyroidism in women (upper panel)
and men (lower panel). Note that there was a significant increase
of hypothyroidism in both genders with advancing age
Z0.745, PZ0.02).
Figure 3 Prevalence of hyperthyroidism in the studied population in
relation to gender and age. Note that hyperthyroidism was more
frequent in women (white bars) with advancing age (but not in men,
black bars). The high relative prevalence of hyperthyroidism in men
aged 70–79 years may be related to the low number of patients
respectively included in this group.
Excessive iodine intake and thyroid disorders
more than 500 mg iodine per liter of urine, compatible
with excessive iodine intake mainly, if not exclusively,
from iodized table salt. Therefore, the recommended
table salt iodination was reduced to 20–60 mg/kg salt
in 2004.
In any event, it became clear that for almost 5 years
the Brazilian population had been exposed to excessive
iodine intake. As a consequence, and as observed in
the present study, there was a significant increase in
the prevalence of CAT from 9.4 (8) to 16.9% in the
metropolitan area of Sa˜o Paulo. Although the pre-
valence of 9.4% found by Tomimori et al. (8) among
healthy overweight individuals may not represent the
general population, the prevalence of CAT virtually
doubled after 5 years of excessive iodine nutrition. Based
on these observations, we strongly believe that the
increase in prevalence of CAT (diagnosed by both
positive anti-TPO antibodies and thyroid hypoechogeni-
city) presented in this study is associated with the
increased iodination of table salt observed between
1998 and 2003.
Excessive iodine intake, as indicated by urine iodine
excretion higher than 500 mg/l, has been also associ-
ated with increased thyroid volume (18).Inour
patients, thyroid volume was considered to be within
the normal range for both genders, with an acceptable
prevalence of nodular goiters of about 3% of the
A number of recent studies (30–32) have indicated
that thyroid hypoechogenicity associated with positive
anti-TPO antibodies is highly indicative of the presence
of CAT. Raber et al. (30), using an arbitrary scale to
define hypoechogenicity, have concluded that a mark-
edly hypoechogenic thyroid gland has a positive
predictive value for detecting autoimmune thyroiditis
of 94% independent of the degree of hypothyroidism.
Others (31) have introduced a quantitative gray-scale
analysis of thyroid echogenicity for patients with
Hashimoto’s thyroiditis, showing that hypoechogenicity
is significantly correlated with high serum TSH value
and with the presence of anti-TPO antibodies. In this
study regarding the thyroid hormone state, 96/183
(52.5%) of the subjects with CAT were euthyroid,
whereas as expected overt hypothyroidism was signi-
ficantly more frequent in women than in men.
It has been reported that a sudden increase in iodine
supplementation increases the prevalence of hyperthy-
roidism (33). Our findings did not confirm this
observation; however, it is possible that iodine-induced
hyperthyroidism may have peaked in the years of
excessive salt iodination (between 1998 and 2003).
The absolute and relative prevalence rates of hyper-
thyroidism that we found in this study were higher than
those observed in population studies conducted in other
countries (4, 6, 7), but similar to the prevalence of
hyperthyroidism (both overt and subclinical) in the
‘more than adequate’ and ‘excessive’ intake cohorts in
China (29, 34). Therefore, we could not reach a
conclusion if there were a relationship between
excessive iodine intake and increased prevalence of
(overt and subclinical) hyperthyroidism.
In conclusion, there is no doubt that iodine
supplementation should be instituted in countries like
Brazil with history of chronic iodine deficiency dating
back to the 19th century (21, 22). Nutritional iodine,
however, should be maintained at safe levels. Excessive
iodine intake (urinary iodine excretion O300 mg/l) does
not appear to be safe, especially for individuals with
genetic potential to develop autoimmune disorders.
Prolonged excessive iodine intake could eventually lead
to a steep increase in CAT prevalence with resulting
(subclinical and overt) hypothyroidism that could be not
detected and treated accordingly. As demonstrated in
this study, a large proportion of the Brazilian population
may have unknowingly developed thyroid dysfunction
when exposed to iodine excess. This evidence strongly
supports appropriate screening for early detection of
thyroid dysfunction in the presence of excessive iodine
This study was made possible through a Research Grant
(FAPESP 03/00827-0) from the State of Sa˜o Paulo
Research Foundation and a partial nancial grant
from Instituto da Tiroide. We gratefully acknowledge
the major contribution in the field studies that was
made by Thiago Ueda and Ana Carulina Lassa Moreno,
both medical students from the University of Sa˜o Paulo
Medical School. We also acknowledge the laboratorial
work of Maria Silvia Cardia and the statistical analysis
by Elier Broche Cristo. We are grateful to the Health
Authorities, nurses and social workers of the urban
areas of Sa˜o Paulo that were screened for thyroid
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Received 10 June 2008
Accepted 14 June 2008
Excessive iodine intake and thyroid disorders
... In addition to regional and ethnic factors, it is also related to factors such as gender, age, and thyroid autoantibodies. It is generally believed that the prevalence of abnormal thyroid function in women was higher than that in men [1][2][3][4][5][6][7][8][9]. In terms of TSH alone, many studies have reported that the average serum TSH level of women was higher than that of men of the same age [4,10]. ...
... Except for the age group ≥70 years, the prevalence of thyroid disease in women in all age groups was significantly higher than that in men. Camargo et al. conducted an epidemiological survey of thyroid diseases in São Paulo, Brazil, and found that the prevalence of women increased with age [9]. Especially in the two age groups 40∼49 and 50∼59 years of age, the gender difference in thyroid prevalence was particularly obvious. ...
... In summary, the prevalence of thyroid diseases, the positive rate of thyroid autoantibodies, the level of TSH, and their respective gender and age distribution characteristics are not the same in different studies. is may be caused by the selected population's regional selection [2,4,9,38], ethnic inheritance, sample size [3][4][5]7], age-sex ratio of research subjects [39,40], iodine intake level [40], and the establishment of different detection methods and diagnostic criteria [40]. However, this study and many of the abovementioned research results showed that the prevalence of thyroid dysfunction was highly correlated with gender, age, and positive thyroid autoantibodies. ...
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Background: In recent years, the incidence of thyroid diseases has increased significantly, which has seriously affected people's work and life. The purpose of this study was to explore the epidemiological characteristics of thyroid diseases and autoantibodies. Method: According to the principle of overall sampling, resident residents ≥18 years and who will not move within 5 years are randomly selected. A total of 2136 eligible individuals were divided into case and control groups according to whether they have thyroid disease. Finally, the impact of potential risk factors on thyroid diseases was evaluated. Results: The overall prevalence of thyroid disease was 58.3%, and there was a significant difference in the prevalence of thyroid disease between women and men (p = 0.004). Except for the age group ≥70 years, with the increase in age, the prevalence gradually increased (p < 0.05). Participants with positive thyroid autoantibodies (TPOAb or TgAb) had a higher prevalence than participants with negative autoantibodies. The positive rate of autoantibodies in women was higher than that in men (p < 0.05). UIC (p = 0.004) and free thyroid hormone (FT4) (p = 0.001) levels of men were higher than those of women, and the TSH level of women was higher than that of men (p = 0.002). The regression analysis showed that women, older age, and family history of thyroid disease were independent risk factors for thyroid disease. Conclusion: The prevalence of thyroid diseases in Hainan was high. Women are more susceptible to thyroid disease than men, and the prevalence increased with age.
... High intake of iodine and increased occurrence of autoimmune thyroiditis have been studied in various epidemiological studies [28][29][30][31][32][33]. Decreased occurrence of autoimmune thyroiditis resulted when the iodine intake was optimized [34]. ...
Background: Thyroid hormones play a vital role in regulating our body's metabolism. Two important thyroid hormones released from the thyroid gland are- tri-iodothyronine (T3) and tetra-iodothyronine (T4). Thyroid stimulating hormone and thyroid regulating hormone control the T3 and T4 levels in our body. Increased TSH levels indicate hypothyroidism and decreased TSH levels indicate hyperthyroidism. Iodine is a crucial nutrient for the synthesis of thyroid hormones and is mostly obtained from our diet. Other essential nutrients for the thyroid hormones formation include selenium, iron, vitamin D, vitamin B12, etc. Dietary changes in these nutrients can result in alterations in thyroid function and structure. Although, normally the hormonal diseases cannot be cured but we can improve their signs and symptoms using suitable dietary supplements. Objective: To thoroughly analyze the various benefits and risks associated with the use of dietary supplements for the prevention and treatment of various thyroid disorders, like hypothyroidism, as seen in hashimoto's thyroiditis; hyperthyroidism, as seen in grave's disease, sick euthyroidism and subclinical hypothyroidism. Methods: Literature was searched using the search terms; "dietary supplements+ thyroid diseases" on pub med, google scholar, scopus, cochrane library and other search engines and data was collected from 1967- November 2021 including research inputs from the authors. The literature was thoroughly read and deep knowledge was acquired on this topic, which was then sequentially organized and summarized using suitable tables and figures. Conclusion: After analyzing the various studies on this topic we arrived at the conclusion that although, there are various claimed and observed health benefits of dietary supplements in prevention and treatment of various thyroid disorders; but still several studies have shown that, there are many risks associated too with the use of dietary supplements, and people using these products should be aware of these risks in order to use them very judiciously for the improvement of their thyroid status.
... This finding was similar to those of previous studies. Some studies have shown that subclinical hypothyroidism and autoimmune thyroid disease are likely prevalent in people in high water iodine areas [20][21][22][23][24]. However, the median iodine concentrations of high water iodine areas in this study are less than those in previous studies; the median iodine concentration of high water iodine areas of previous studies is at least 201.8 μg/L [5,25]. ...
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The aim of this study was to assess the population’s iodine nutrition and thyroid diseases in different water iodine areas and to offer suggestions to the governments of different countries to adjust the present policy in different water iodine areas. A cross-sectional survey was conducted in different water iodine areas in China. Urinary iodine, water iodine, salt iodine and thyroid function were determined. The thyroid volumes and nodules were measured by ultrasound. Upon categorization by water iodine level for the 10.0 ~ 39.9 μg/L, 40.0 ~ 100.0 μg/L and 100.1 ~ 150.0 μg/L areas, in adults, the prevalence of subclinical hypothyroidism was 9.28%, 5.35% and 11.07%, and the median urinary iodine (MUI) was 153.7 μg/L, 189.8 μg/L and 317.0 μg/L; in children of the three areas, the prevalence of goitre was 3.83%, 4.47% and 16.02%, and the MUI was 164.1 μg/L, 221.0 μg/L and 323.3 μg/L; in pregnant women of those areas, the MUI was 148.6 μg/L, 176.9 μg/L and 324.9 μg/L. Logistic regression results indicated that low iodine intake was a risk factor for developing hypothyroxinaemia in pregnant women. The iodine status of pregnant women is insufficient in areas with a median water iodine level of 10.0 ~ 39.9 μg/L. Low iodine intake increases the risk of developing hypothyroxinaemia in pregnant women. The iodine status of adults and children is excessive, and the iodine status of pregnant women is above the requirements in areas with a median water iodine concentration of 100.1 ~ 150.0 μg/L. Iodized salt, especially for pregnant women, should be supplied in areas with a median water iodine concentration of 10.0 ~ 39.9 μg/L to improve the iodine status of pregnant women. Supplying non-iodized salt is not enough to protect local residents from the harm from excess iodine in areas with a median water iodine concentration above 100.0 μg/L.
... Hyperthyroidism prevalence varies widely worldwide, from 0.34%-1.66% (17)(18)(19)(20)(21).The differences in prevalence among countries are related to various factors including iodine status, thyroid autoimmune antibodies, gender, age, and ethnicity. ...
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Background Universal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination. Methods Data were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015–2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured. Results After two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves’ disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% vs . 0.64%, P<0.001; GD: 0.65% vs . 0.37%, P<0.001).Prevalence was significantly decreased after 60 years-of-age compared with 30–39 years-of-age (OH:0.61% vs . 0.81%, P<0.001; GD: 0.38% vs . 0.57%, P<0.001).Excessive iodine(EI) and deficient iodine(DI) were both related to increased prevalence of OH (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.68–2.59; OR1.35, 95%CI 1.07–1.72, respectively); however, only deficient iodine was associated with increased prevalence of GD (OR1.67, 95%CI 1.30–2.15). Increased thyroid peroxidase antibody and thyroglobulin antibody levels were significantly associated with prevalence of OH and GD, but not severe SCH and mild SCH. Although hyperthyroidism was more prevalent in women, the association disappeared after adjusting for other factors such as antibody levels. Conclusion OH and GD prevalences in mainland China are stable after two decades of USI. Iodine deficiency, elevated thyroid antibody levels, and middle age are the main risk factors for OH and GD. The severe SCH population, rather than the mild SCH population, shows similar characteristics to the OH population.
... Although early or incidental detection of smaller tumors due to more advanced and frequent use of imaging technology may partially explain this increase [2], research has highlighted the potential contribution of exposure to environmental pollutants to this phenomenon [3]. Several studies have suggested that exposure to certain endocrine disruptive chemicals (EDCs) alter thyroid function and is associated with increased risk of numerous adverse health outcomes including developmental abnormalities, thyroid disorders and various types of cancer [4][5][6][7]. In 2002, the World Health Organization (WHO) and the International Programme on Chemical Safety (IPCS) defined an EDC as "an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny or (sub-) populations" [8]. ...
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Endocrine disruptive chemicals (EDC) are known to alter thyroid function and have been associated with increased risk of certain cancers. The present study aims to provide a comprehensive overview of available studies on the association between EDC exposure and thyroid cancer. Relevant studies were identified via a literature search in the National Library of Medicine and National Institutes of Health PubMed as well as a review of reference lists of all retrieved articles and of previously published relevant reviews. Overall, the current literature suggests that exposure to certain congeners of flame retardants, polychlorinated biphenyls (PCBs), and phthalates as well as certain pesticides may potentially be associated with an increased risk of thyroid cancer. However, future research is urgently needed to evaluate the different EDCs and their potential carcinogenic effect on the thyroid gland in humans as most EDCs have been studied sporadically and results are not consistent.
... A lesser level of excess iodine intake than described above, or a rise in intake following iodine fortification of an iodine-deficient population, is known to increase the risk of thyroid autoimmunity, as attested by studies in many countries [24][25][26][27][28][29][30][31][32][33][34][35]. This is partly because highly iodinated thyroglobulin SARS-CoV-2 [1]. ...
Iodine excess (IE) can cause thyroid dysfunction, thyroid diseases can adversely affect cardiovascular function. Accordingly, this study was to explore the direct and indirect effects of IE on endothelial function. Nthy‐ori 3‐1 and HUVECs cells were treated with potassium iodide (KI). CCK‐8, LDH leakage, Elisa, RT‐PCR and Western blotting were used to detect relevant indicators. Results showed that a certain level of KI can directly and indirectly reduce the viability of HUVECs and increase cytotoxicity. KI decreased the expression of ET‐1 and VWF in HUVECs, inhibited the secretion of ET‐1 in culture medium, and increased the expression of IL‐6 and TNFα in HUVECs or Nthy‐ori 3‐1 cells alone. In the co‐culture system, KI decreased the expression of ET‐1 and THBD and increased the expression of TNFα and IL‐6. Collectively, IE can directly and indirectly inhibit endothelial function of endothelial cells, which may be related to its induced inflammatory response.
Iodine is an integral component of thyroid hormones. Relationship between the level of iodine intake and the risk of occurrence of thyroid diseases is ‘U’ shaped, that indicates there is an increasing risk with both low and high iodine intake. There are studies to evaluate thyroid functions in iodine deficient regions on humans and animals. To prevent iodine deficiency iodized salt has been introduced through universal salt iodization programme and enormous benefits have been achieved. However, improper monitoring of iodine content in edible salt at consumer level have increased the risk of excessive iodine intake leading serious health consequences to thyroid as iodine induced hypothyroidism, hyperthyroidism, goitre, thyroid gland disruption, thyrocyte apoptosis, thyroiditis, etc. Further, excess iodine induces marked alteration in the morphology and histology of testis along with male accessory sex organs including functional characteristics of sperm which are associated with the antifertility potential; in female cyclic ovarian function changes leading to decreased fertility potential that prevents pregnancy. Hypothyroidism caused by excess iodine impairs glial cell structure causing functional as well as morphological impairment of the major areas of brain developing neurological disorders interrupting connectivity of neural networks that signals early cognitive impairments triggering cognitive weakening, memory impairment and depression. Iodine in excess has the immunomodulatory effect in thyroid developing autoimmunity. Prolonged exposure of excess iodine impairs carbohydrate and lipid metabolic pattern and the histoarchitecture of the pancreas, liver, kidney, as well as skeletal and cardiac muscles. All these show the emergence of several health consequences in post-salt iodization.
Backgroud: Epigenetic disorders play an important role in the pathogenesis of autoimmune thyroiditis (AIT). Therefore, to explore the possible role of DNA methylation in AIT is of great significance to explore the pathogenesis of AIT. Methods: From May 2019 to June 2019, whole blood samples were collected from 176 AIT patients and 176 controls from different water iodine levels in Shandong Province, China. According to the Illumina Methylation of 850K BeadChip results of this research group in the early stage, HLA-DPB1 and PDCD1LG2 genes related to cell adhesion molecule pathway with significant differences were selected, and MethylTargetTM assay was used to verify the methylation level in 176 cases and 176 controls. The relative mRNA levels of HLA-DPB1 and PDCD1LG2 genes were detected by QRT-PCR. Results: There were multiple differential methylation sites (DMS) of HLA-DPB1 and PDCD1LG2 genes in the total case and control population and the case and health control population with different water iodine levels. Some target regions of HLA-DPB1 and PDCD1LG2 genes were negatively correlated with relative mRNA expression in the total case and control populations and in the case and control population with different water iodine levels. Conclusions: There was indeed a change in genomic DNA methylation status in patients with AIT. The methylation patterns of HLA-DPB1 and PDCD1LG2 genes related to cell adhesion molecule pathway may be different under different areas with different water iodine levels. HLA-DPB1 and PDCD1LG2 genes related to the cell adhesion molecules pathway may play a role in the occurrence and development of AIT.
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When a pharmaceutical company first markets a new drug, it is usually under a patent. All the manufacturers pay patent royalty to the patentee company to get share of the sole right of manufacturing the innovated drug during its patent period. After the patent period is completed, drug manufacturers do not require paying royalty thereafter. Patent royalty is the major stake of the price. Even after completion of the patent period, the prices of some branded medicines are still high. Generic medicines contain the same active ingredient with same quantity whose patent is expired, and hence cost cheaper than the branded medicine. As the gap in prices of generic and branded medicine is high, false notions like “generics do not comply to the quality standards” is circulating among the public. To eradicate that notion, an attempt was made taking three regular usage drugs – telmisartan, glimepiride and atorvastatin – to compare their quality standards both in branded and generic formulations. The outcome has proved that generics are no way inferior to the branded formulations. Moreover, generic formulations proved to be quite close to the stipulated standards in all the three drugs. Wide publicity is required about generic drugs to swipe off false notions
SUMMARYA survey has been conducted in Whickham, County Durham, to determine the prevalence of thyroid disorders in the community. Two thousand seven hundred and seventy-nine people (82.4% of the available sample) were seen in the survey. The prevalence of overt hyperthyroidism was 19/1000 females rising to 27/1000 females when possible cases were included, compared with 1.6–2.3/1000 males. The prevalence of overt hyothyroidism was 14/1000 females rising to 19/1000 females when possible cases were included, compared with less than 1/1000 males. The prevalence of spontaneous overt hypothyroidism (excluding iatrogenic cases) was 10/1000 females or 15/1000 females including unconfirmed cases. Minor degrees of hypothyroidism were defined on the basis of elevated serum thyrotrophin (TSH) levels in the absence of obvious clinical features of hypothyroidism. TSH levels did not vary with age in males but increased markedly in females after the age of 45 years. The rise of TSH with age in females was virtually abolished when persons with thyroid antibodies were excluded from the sample. TSH levels above 6 mu/1 were shown to reflect a significant lowering of circulating thyroxine levels and showed a strong association with thyroid antibodies in both sexes, independent of age. Elevated TSH levels (>6mu/l) were recorded in 7.5% of females and 2.8% of males of all ages. Thyroglobulin antibodies were present in 2% of the sample. Thyroid cytoplasmic antibodies were present in 6.8% of the sample (females 10.3%, males 2.7%) and their frequency did not vary significantly with age in males but increased markedly in females over 45 years of age. 3% of the sample (females 5.1%, males 1.1%) had thyroid antibodies and elevated TSH levels and the relative risk of a high TSH level in subjects with antibodies was 20:1 for males and 13:1 for females, independent of age. Small goitres (palpable but not visible) were found in 8.6% of the sample and obvious goitres (palpable and visible) in 6.9%. Goitres were four times more common in females than in males and were most commonly found in younger rather than older females. TSH levels were slightly but not significantly lower in those with goitre than in those without goitre. There was a weak association between goitre and antibodies in females but not males.
OBJECTIVE The importance of iodine intake and thyroiditis in the pathogenesis of thyroid cancer remains controversial. We have investigated the natural history of thyroid cancer and thyroiditis in a goitrous region before and after iodine prophylaxis over a 31-year period. DESIGN For the analysis of thyroid cancer the material was divided in two periods. The first 15 years (59 cases), including 5 years before prophylaxis, was compared with the second 16 years (85 cases), a period well after iodine supplementation of salt. Histological diagnosis of the tumours was based on the WHO system. Moderate to severe thyroiditis in the non-tumoral surrounding thyroid from female patients was recorded. For this, the material was analysed in the two periods In relation to the introduction of iodine prophylaxis in 1963, taking account of the age of the patients. RESULTS Papillary carcinomas formed the largest group of tumours in both periods, with nearly twice as many in the second period as the first, while the numbers of follicular and medullary carcinomas remained about the same. The ratio of papillary to follicular carcinoma rose from 1.7:1 in the first period to 3.1:1 in the second. All three thyroid lymphomas were of the non-Hodgkin's type, and all occurred in the second period in females aged over 50. A severe lymphoid thyroiditis was present in the two cases with assessable background thyroid tissue. The frequency of lymphoid infiltrate in females rose from 8% 11/12) before 1963 to 25% (18172) after prophylaxis in the whole series. After salt prophylaxis, thyroiditis was more frequent in patients with papillary carcinoma in general (31%), and clinically significant papillary carcinomas in particular (35%), than in those with non-papillary tumours (6%) (X2, P < 0.05 and P < 0.025, respectively). CONCLUSIONS Our observations indicate that a high dietary intake of iodine may be associated with a high frequency of papillary carcinoma and thyroiditis, and that thyroiditis is more commonly associated with papillary carcinoma than with other thyroid tumours. The occurrence of non-Hodgkin's lymphomas only in the post-prophylaxis period may be linked to an increase in thyroiditis.
The prevalence of thyroid dysfunction was determined in a healthy urban population over the age of 55 years. A highly sensitive serum thyrotropin assay was used initially to screen 968 subjects. Elevated values (greater than 6 mU/L) were found in 7.3%, while suppressed values (less than 0.1 mU/L) were present in 2.5% subjects. Protirelin stimulation testing demonstrated exaggerated responses in 95% of the subjects with elevated thyrotropin levels and subnormal responses in 81% of the subjects with suppressed thyrotropin levels. Thyroid dysfunction, as defined by abnormalities of both serum thyrotropin level and protirelin response, was calculated to be present in 8.9% of the population. The prevalence was greater in whites (vs blacks), in women, and in subjects older than 75 years as compared with the 55- to 64-year age group. Hypothyroidism was calculated to be present in 6.9% subjects. Despite an increased prevalence of thyroid autoantibodies in these subjects, only 8.5% of them had subnormal serum thyroxine concentrations. Hyperthyroidism was calculated to be present in 2.0% of the population, two thirds of whom were taking thyroid hormone preparations. These results suggest a significant prevalence of thyroid dysfunction in the elderly, with important sex and racial differences.
It has been suggested that the incidence of Hashimoto's thyroiditis is increased in the presence of high iodide intake. The diabetes-prone BB/W rat develops spontaneous histological autoimmune lymphocytic thyroiditis (LT) without functional hypothyroidism between 60 and 120 days of age. Studies were carried out to determine whether iodine administration to BB/W rats would affect the incidence and severity of LT and induce hypothyroidism. Iodide (0.05% in water) or tap water (C) was administered ad libitum to 42 10-month-old BB/W rats and 71 30-day-old BB/W rats for 8 weeks. For control purposes, 0.05% iodide or tap water (C) was also administered ad libitum to 42 30-day-old nondiabetic and non-LT-prone BB/W genetically equivalent rats (W-line) for 12 weeks and 41 21-day-old Wistar rats for 7 weeks. In a separate experiment, weanling BB/W rats were fed a low iodine diet, a control iodine-sufficient (C) diet, or Purina chow (P) and tap water ad libitum for 8 weeks. In each experiment, blood was obtained at the time of death for the measurement of serum T4, T3, TSH, and antithyroglobulin antibody (anti-Tg Ab), and the thyroids were removed for histological evaluation (0 = no LT; 1-4 = LT). Iodide administration (0.05%) induced a significant increase in the incidence of LT in 30-day-old BB/W rats (I, 77%; C, 30%, P less than .001). Thyroid weight and serum T4, T3, and anti-Tg Ab concentrations were not affected by iodide administration. However, the presence of LT was associated with a significant increase in thyroid weight and anti-Tg Ab concentrations. BB/W rats subjected to a low iodine diet exhibited a significantly decreased incidence of LT (low I, 8.6%; C, 47.3%; P less than 0.01), but no statistically significant difference in anti-Tg Ab levels. Increased iodide intake did not significantly affect the incidence of LT in adult BB/W rats and did not induce LT or affect thyroid function in W-line or Wistar rats. These data show that iodine intake significantly affects the incidence of spontaneous LT in young, genetically predisposed rats.
An ultrasonographic survey of thyroid abnormalities was conducted in 547 consecutive apparently normal overweight subjects (380 females and 167 males), aged 27-58 years in an urban area with relatively low iodine intake (mean daily urinary iodine excretion: 10.6 micrograms/dL). Individuals with any previous thyroid disease or familial thyroid pathology were excluded. In 240 subjects (44%) high resolution ultrasonography of the thyroid was considered normal. In 307 individuals (56%) abnormalities of the echo structure (39%) or thyroid nodular disease (17%) were detected by ultrasonography. Marked heterogeneity of the echo structure that was considered suggestive of chronic autoimmune thyroiditis was present in 81 subjects (15%). In 72 of these patients the serum anti-TPO levels were positive by a sensitive RIA. Thyroid nodules either solid or predominantly cystic were present in 90 subjects (17%). Eighteen patients had a relatively large nodule (diameter 15-18 mm). Eleven of these nodules were missed at clinical examination. Fine needle aspiration cytology was performed in 14 patients and 7 individuals underwent thyroid surgery. In 6 subjects the pathologic diagnosis was benign adenomatous goiter and one patient had a follicular carcinoma. Thyroid function studies confirmed subclinical hypothyroidism in 27 patients (4.9%), all of them with elevated serum anti-TPO autoantibodies levels. It was concluded that the overall occurrence of thyroid disease is more common than suspected by clinical examination.
The original Whickham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the incidence and natural history of thyroid disease in this cohort. Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, in addition to death certificates, two-thirds had information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91% were tested for clinical, biochemical and immunological evidence of thyroid dysfunction. Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5-1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an increase with age in hypothyroidism but no age relation in hyperthyroidism. The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially. The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors identified at first survey. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A logit model indicated that increasing values of serum TSH above 2mU/l at first survey increased the probability of developing hypothyroidism which was further increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism in women. This historical cohort study has provided incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease identified twenty years earlier.
The revolution in molecular techniques has allowed dissection of the autoimmune response in a way impossible to imagine 10 yr ago. There have been spectacular advances in our understanding of self-tolerance mechanisms and how these may fail, combined with a detailed comprehension of antigen presentation, functional T cell subsets, and TCR utilization in autoimmunity, albeit usually in animal models that resemble, but do not exactly duplicate, human diseases. More gradually, these findings are being translated to thyroid autoimmunity, where the major achievement of the last decade has been the molecular characterization of the three main thyroid autoantigens. This in turn has allowed epitope identification, although again the only clear data so far have come from animal models of EAT. Another advance has been the recognition that the thyrocyte is not a helpless target of autoaggression, being capable of expressing a wide array of immunologically active molecules, which may exacerbate or diminish the autoimmune response. In 1983, there was considerable excitement at the discovery of the first of these phenomena, namely MHC class II expression, but its possible role in autoantigen presentation remains to be defined. By analogy with pancreatic beta-cells, and based on our own data, we believe that class II-expressing thyrocytes have little, if any, such role and suspect that instead this may be a mechanism for inducing peripheral tolerance. Defining the contribution of thyrocytes to the intrathyroidal autoimmune response, whether from released cytokines or surface-bound molecules, will be crucial to our future understanding, as well as holding the promise that these thyroid-derived products might be therapeutic targets. Despite molecular developments in HLA analysis, there have been no really major improvements in our understanding of the immunogenetics of thyroid autoimmunity, equivalent to those made in type 1 diabetes mellitus. The available data suggest strongly that non-MHC genes play an important role in susceptibility, and novel approaches will be required to identify these. On the other hand, we know more about the importance of environmental and endogenous (most probably hormonal) factors in thyroid autoimmunity. Understanding the basic immunological changes in the postpartum period is still poor, however, as most studies to date have concentrated on epidemiology and clinical delineation. As PPTD undergoes spontaneous remission, elucidation of these mechanisms has clear implications for treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
To investigate the effect of varying amounts of iodine intake on the prevalence of thyroid dysfunction, autoimmunity and goitre in old age. The first screening study where elderly subjects with varying amounts of iodine supply but from the same geographical and ethnographical region (Carpathian basin) were compared, and all hormone measurements and ultrasonography were performed by the same laboratory or person. Nursing home residents were screened for thyroid disorders from: (A) an iodine-deficient area, Northern Hungary (n = 119; median age 81 years; median iodine excretion (MIE) 0.065 mumol/mmol creatinine (equivalent to 72 micrograms/g creatinine); (B) an area of obligatory iodinated salt prophylaxis since the 1950s, Slovakia (n = 135; median age 81 years, MIE 0.090 mumol/mmol creatinine (equivalent to 100 micrograms/g creatinine)) and (C) an abundant iodine intake area, Eastern Hungary (n = 92; median age 78 years; MIE 0.462 mumol/mmol creatinine (equivalent to 513 micrograms/g creatinine)). TSH, T4, free T4, T3, thyroglobulin (Tg), antibodies to Tg (AbTg) and to thyroid peroxidase (AbTPO), iodine excretion, ultrasonography of the thyroid gland. In regions A, B, and C, the prevalence of unsuspected clinical hypothyroidism was 0.8%, 1.5% and 7.6% (P = 0.006), with all cases except one being antibody positive (Ab+). The occurrence of subclinical hypothyroidism was 4.2% in region A, 10.4% in region B and 23.9% in region C (P < 0.001), but only 3 of 22 cases with subclinical hypothyroidism from region C were Ab+. The overall prevalence of Ab positivity (either antiTg+ or antiTPO+) was similar in the three regions (A, 19.3%; B, 24.4%; C, 22.8%). The occurrence of hyperthyroidism (clinical plus subclinical) was 3.4% in region A, 3.0% in region B and 0% in region C (not significant). The rate of elevated Tg levels was similar in the three regions. The prevalence of goitre was 39.4%, 16.4% and 12.2% (P < 0.001), respectively in regions A, B and C. In euthyroid subjects the mean ultrasonographically determined thyroid volume was 21.9 ml in region A, 13.6 ml in region B and 15.1 ml in region C (ANOVA F = 5.76; P = 0.0038). There was no significant difference in the occurrence of cases with hypoechogenic echotexture of the thyroid gland. The screening for hypothyroidism in nursing home residents living in iodine-rich regions is justified by the high prevalence of unsuspected clinical hypothyroidism. The high prevalence of antibody positivity in old age is independent of the iodine supply, but iodine supply has a determining role in the development of autoimmune hypothyroidism in the aged. Most cases of subclinical hypothyroidism in iodine-rich regions are not of autoimmune origin. In old age, hypoechogenic texture of the thyroid gland is not predictive of thyroid dysfunction.
We have critically reviewed the available information on iodine-induced hyperthyroidism (IIH) from published sources and other reports as well as the experience of the authors in Tasmania, Zaire, Zimbabwe, and Brazil. Administration of iodine in almost any chemical form may induce an episode of thyrotoxicosis (IIH). This has been observed in epidemic incidence in several countries when iodine has been given as prophylaxis in a variety of vehicles, but the attack rate as recorded has been low. IIH is most commonly encountered in older persons with long standing nodular goiter and in regions of chronic iodine deficiency, but instances in the young have been recorded. It customarily occurs after an incremental rise in mean iodine intake in the course of programs for the prevention of iodine deficiency, or when iodine-containing drugs such as radiocontrast media or amiodarone are administered. The biological basis for IIH appears most often to be mutational events in thyroid cells that lead to autonomy of function. When the mass of cells with such an event becomes sufficient and iodine supply is increased, the subject may become thyrotoxic. These changes may occur in localized foci within the gland or in the process of nodule formation. IIH may also occur with an increase in iodine intake in those whose hyperthyroidism (Graves' disease) is not expressed because of iodine deficiency. The risks of IIH are principally to the elderly who may have heart disease, and to those who live in regions where there is limited access to medical care. More information is needed on the long-term health impact of IIH or "subclinical" IIH, especially in the course of prophylaxis programs with iodized salt or iodinated oil in regions where access to health care is limited.