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Fluoride and thyroid function in children in two villages in China

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Eighty two children, aged 8 -13 years old, from Wamiao village (severe endemic fluorosis area), from Xinhuai village (nonendemic fluorosis area) were 88 (as a control group), were recruited in this study. The prevalence of dental fluorosis (DF) were 85.37% (Wamiao) and 6.82% (Xinhuai) in two village's children respectively; drinking water fluoride (F -) in children's household shallow well from 0.62 -4.00 mg/L in Wamiao and 0.23 -0.76 mg/L in Xinhuai; serum total triiodothyronine (TT3), total thyronine (TT4), thyroid-stimulating hormone (TSH) were 1.47 ± ± ± ± 0.28 and 1.47 ± ± ± ± 0.33 ng/mL, 9.67 ± ± ± ± 1.76 and 9.22 ± ± ± ± 2.54 µ µ µ µg/dL, 3.88 ± ± ± ± 2.15 and 2.54 ± ± ± ± 2.07 µ µ µ µIU/mL in two villages children respectively. The prevalence of DF, drinking water F -, serum TSH in Wamiao village was significantly higher than that in Xinhuai village. As the children in Wamiao village were divided into different subgroups according to their severity of DF, serum TT3 and TSH showed significant difference in different groups. The results in this study confirmed that the high F -exposure can caused functional abnormalities of thyroid, and the different severity degree of DF may be relation to significant deviation in the serum levels of thyroid hormone.
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Journal of Toxicology and Environmental Health Sciences Vol. 1(3) pp. 054-059, August, 2009
Available online at http://www.academicjournals.org/JTEHS
© 2009 Academic Journals
Full Length Research Paper
Fluoride and thyroid function in children in two villages
in China
Quanyong Xiang
1
*, Liansheng Chen
1
, Youxin Liang
2
, Ming Wu
1
and Bingheng Chen
2
1
Jiangsu Province Center for Disease Control and Prevention, 172 Jiangsu Road, Nanjing 21009, P. R. China.
2
School of Public Health, Fudan University (formerly Shanghai Medical University), 138 Yixueyuan Rd., Shanghai
(200032), China.
Accepted 1 September, 2009
Eighty two children, aged 8 - 13 years old, from Wamiao village (severe endemic fluorosis area), from
Xinhuai village (nonendemic fluorosis area) were 88 (as a control group), were recruited in this study.
The prevalence of dental fluorosis (DF) were 85.37% (Wamiao) and 6.82% (Xinhuai) in two village’s
children respectively; drinking water fluoride (F
-
) in children’s household shallow well from 0.62 - 4.00
mg/L in Wamiao and 0.23 - 0.76 mg/L in Xinhuai; serum total triiodothyronine (TT3), total thyronine
(TT4), thyroid-stimulating hormone (TSH) were 1.47 ±
±±
± 0.28 and 1.47 ±
±±
± 0.33 ng/mL, 9.67 ±
±±
± 1.76 and 9.22 ±
±±
±
2.54 µ
µµ
µg/dL, 3.88 ±
±±
± 2.15 and 2.54 ±
±±
± 2.07 µ
µµ
µIU/mL in two villages children respectively. The prevalence of
DF, drinking water F
-
, serum TSH in Wamiao village was significantly higher than that in Xinhuai village.
As the children in Wamiao village were divided into different subgroups according to their severity of
DF, serum TT3 and TSH showed significant difference in different groups. The results in this study
confirmed that the high F
-
exposure can caused functional abnormalities of thyroid, and the different
severity degree of DF may be relation to significant deviation in the serum levels of thyroid hormone.
Key words: Thyroid function, fluoride, dental fluorosis.
INTRODUCTION
Professor John Grevers had sent specimens of mottled
teeth, found the identical condition in the teeth of people
with goiter in Utrecht; Grevers also obtained laboratory
evidence that there was a clear association of his clinical
cases of goiter with mottled enamel; Goldemberg even
became convinced that the goiters were, in fact, caused
by excessive intake of fluoride (F
-
) (Schuld, 2005).
Some animal studies indicated that the rats had
thyromegaly, increasing or reducing of thyroid weight,
reducing of follicle and atrophy of follicular epithelium of
thyroid when the rats were exposed to F
-
for 6 ~ 12
months (Editorial, 1976). The research results also
*Corresponding author. E-mail: quanyongxiang@yahoo.com.cn.
Tel: 86-25-83759469. Fax: 86-25-83759411.
Abbreviations: DF, Dental fluorosis; F
-
, fluoride; T3, 3,5,3’-
triiodothyronine; TT3, total 3,5,3’- triiodothyronine; FT3, free
3,5,3’- triiodothyronine; T4, thyronine; TT4, total thyronine; FT4,
free thyronine; TSH, thyroid-stimulating hormone; IDD, iodine
deficiency disorder.
indicated that F
-
can affect the hormone secretion of the
thyroid (Chuanhua et al., 1998; Desun et al., 1994; Fuzun
et al., 2001; H Wang et al., 2009; Hu Aiwu et al., 2007;
Juvenal et al., 1978; Liu Guoyan et al., 2008; Xiuan Z et
al., 2006). Yaming et al. gave the results that excessive
long-term intake of F
-
, with or without adequate intake,
are a significant risk factor for the development of thyroid
dysfunction (Yaming et al., 2005). A few future studies on
human showed different results. Xiaoli et al. (1999)
reported that serum thyronine (T4) reduced significantly,
but the triiodothyronine (T3); thyroid-stimulating hormone
(TSH) increased significantly, in the 8 - 12 years old
children in endemic fluorosis areas in China. T3 and T4
concentrations in the serum of the patients with endemic
fluorosis were significantly below the Normal reference
value (Guimin et al., 2001). Whereas the study by
Mingyin F (Mingyin et al., 1994) and other researchers
(Baum et al., 1981; Eichner et al., 1981) indicated that
the high F
-
intake does not have effects on thyroid-
function. In order to get a better understanding between
the F
-
intake and the children’s thyroid function, this study
investigated the TT3 (total T3), TT4 (total T4), and TSH in
the serum of the children in endemic fluorosis and
Xiang et al. 055
Table 1. F
-
in drinking water in children’s household shallow well in two
villages.
Village No. of samples F
-
(mg/L) (M±S) Range (mg/L)
Wamiao 82 2.36 ± 0.70 0.62 ~ 4.00
Xinhuai 88 0.36 ± 0.10 0.23 ~ 0.76
Note: t = -26.47, p = 0.000.
Table 2. Prevalence of DF in children in two villages.
Village No. of samples No. of DF Prevalence of DF (%)
Wamiao 82 70 85.37
Xinhuai 88 6 6.82
Note: χ
2
= 105.94, p = 0.000.
Table 3. TT3 concentration in serum in the children in two
villages (ng/mL).
Village No. of samples TT3 (M±S) Range
Wamiao 62 1.47 ± 0.28 1.01 ~ 2.10
Xinhuai 68 1.47 ± 0.33 0.66 ~ 2.20
Note: t = 0.855, p = 0.394.
Table 4. TT4 concentration in serum in the children in two
villages (µg/dL).
Village No. of samples TT4 (M ± S) Range
Wamiao 58 9.67 ± 1.76 5.98 ~ 15.09
Xinhuai 61 9.22 ± 2.54 5.22 ~ 15.41
Note: t = 1.111, p = 0.269.
non-endemic fluorosis areas, the dental fluorosis (DF)
and the drinking water F
-
concentration in children’s
household shallow well were also analyzed.
MATERIALS AND METHODS
The investigation of age, gender, and DF was conducted from
February, 2003 - June, 2003 in Wamiao village (a severe endemic
fluorosis area) and Xinhuai village (a non-endemic fluorosis), and
the samples of water and blood were also collected during this time.
The basic information of these two villages was formerly reported
(QY Xiang et al., 2004).
Fasting venous blood samples (2 - 2.5 mL) were collected and
preserved in clean plastic centrifuge tubes, which were immediately
centrifuged for 10 min at 3000 rpm. Serum was quickly removed to
other clean plastic tubes and kept in a refrigerator at -40°C. The
TT3, TT4 and TSH were measured at the time of September, 2006,
with the Test Kit, which were bought from Hainan Huamei Medicine
Co. LTD, manufactured by BioCheck, Inc. (Foster City, CA94404,
USA).
The drinking water samples, which were collected from the
household shallow wells in each child’s family, were kept in clean
plastic bottles and analyzed within two week. F
-
in drinking water
was measured with an F
-
ion selective electrode according to the
National Standard of China (National Standard of P.R. China, 1999).
A dentist and a specialist in endemic fluorosis control and
prevention examined the children for dental fluorosis with a mouth
mirror, forceps, and a probe under natural light. Dean’s
classification was used for diagnosing dental fluorosis. The six
grades of Dean’s classification scale for dental fluorosis are: none
(normal enamel) (the score marked for 0), suspected or
questionable (0.5), very mild (1), mild (2), moderate (3), and severe
(4) (Chinese Ministry of Health 1991). Statistical analysis of the
prevalence of dental fluorosis was made according to the rates of
DF%.
Data were analyzed using SPSS Software. Before the
investigation, the informed consent must be signed by the children’s
parents. We have complied with all requirements of International
Regulations for the human investigation.
RESULTS
There were 170 children in this study, 82 in Wamiao
village (46 male and 36 female), 88 in Xinhuai village (52
male and 36 female). The average age was 11.00 ± 1.44
in Wamiao village and 10.84 ± 1.67 in Xinhuai village.
The F
-
concentration in drinking water and the
prevalence of DF in two villages were shown in Table 1 -
2. The results indicated that the drinking water F
-
and the
prevalence of DF in children in Wamiao village were
significantly higher than that in Xinhuai village.
The TT3 and TT4 concentrations in children’s serum in
two villages were not have significant difference. But the
TSH concentration in the children’s serum in Wamiao
village was higher than that in Xinhuai village, there was
a significant difference between two villages. The details
were shown in Table 3 - 5.
The means of TSH/TT3 and TSH/TT4 in Wamiao
village were significant higher than that in Xinhuai village,
but the means of TT3/TT4 in Wamiao village was
056 J. Toxicol. Environ. Health Sci.
Table 5. TSH concentration in serum in the children in two
villages (µIU/mL).
Village No. of samples TSH (M±S) Range
Wamiao
Xinhuai
62
67
3.88 ± 2.15
2.54 ± 2.07
0.19 ~ 8.82
0.71 ~ 9.37
Note: t = 3.604, p = 0.000.
Table 6. Compared the difference in the values of TT3/TT4, TSH/TT3, TSH/TT4
between the two villages.
TT3/TT4 TSH/TT3 TSH/TT4 Village
No.
*
Mean ± S No.
Mean ± S No.
Mean ± S
Wamiao
Xinhuai
40
41
0.151± 0.037
0.170 ± 0.044
#
55
66
2.735 ± 1.485
1.932 ± 1.813
#
41
42
0.416 ± 0.218
0.284 ± 0.191
#
Note: * the number of subjects. # compared with Wamiao village.TT3/TT4: t = 2.028 p = 0.046;
TSH/TT3: t = 2.628 p = 0.010 ; TSH/TT4: t = 2.925 p = 0.004.
Table 7. The correlation between the serum TT3, TT4, TSH in
the children’s serum and drinking water F
-
in two villages.
TT3 and F
-
TT4 and F
-
TSH and F
-
Village
PC p PC p PC p
Wamiao
Xinhuai
0.087
0.108
0.502
0.381
0.057
-0.167
0.672
0.198
0.023
-0.112
0.858
0.381
Note: F
-
(drinking water fluoride). PC (Pearson correlation).
Table 8. The relationship between the DF score and the serum TT3, TT4, TSH in the children in Wamiao village.
TT3 (ng/mL) TT4 (µg/dL) TSH (µIU/mL) DF (group)
No. of samples TT3 (M ± S) No. of samples TT4 (M ± S) No. of samples TSH (M ± S)
1
2
3
4
5
11
14
22
12
3
1.19 ± 0.18
1.38 ± 0.28
1.54 ± 0.21
1.49 ± 0.34
1.40 ± 0.38
7
15
19
12
5
9.33 ± 1.92
9.20 ± 1.00
10.24 ± 2.18
9.46 ± 1.88
9.86 ± 1.04
8
14
25
12
3
3.31 ± 1.26
5.15 ± 2.68
3.50 ± 1.71
3.61 ± 2.50
3.74 ± 2.06
Note: TT3: 1 and 3, t = -4.680 p < 0.000; 1 and 4, t = -2.57 p = 0.018. TSH: 1 and 2, t = -2.183 p = 0.041.
significant lower than that in Xinhuai village. The details
were shown in Table 6.
Each child’s serum concentration of TT3, TT4, and TSH
was compared with the drinking water F
-
concentration in
their household shallow well in two villages, there were
not significant relationships between the TT3, TT4, TSH
and the drinking water F
-
. See Table 7.
As shown in Table 8, In Wamiao village, there were not
significant trend between the dental fluorosis score
(severity of DF) and the serum TT3, TT4, TSH
concentration (the children with 0 and 0.5 DF score were
divided into group 1, 1 score was group 2, 2 score was
group 3, 3 score was group 4, 4 score was group 5). But
the results of the comparison between each group
indicated that the TT3 concentration has a significant
difference between group 1 and group 3, group 1 and
group 4; there were also significant differences between
the group 1 and 2 in the TSH concentration. In Xinhuai
Xiang et al. 057
Table 9. The relationship between the DF score and the serum TT3, TT4, TSH in the children in Xinhuai village.
TT3 (ng/mL) TT4 (µg/dL) TSH (µIU/mL) DF (score)
No. of samples TT3 (M ± S) No. of samples TT4 (M ± S) No. of samples TSH (M ± S)
1
2
63
5
1.48 ± 0.33
1.30 ± 0.21
56
5
9.34 ± 2.58
7.82 ± 1.55
62
5
2.53 ± 2.09
2.72 ± 1.98
Table 10. The TT3, TT4, and TSH results by age and gender in Wamiao village.
TT3 TT4 TSH Age
No. High Normal low No. High Normal Low No. High Normal Low
Male
8
9
10
11
12
13
2
4
5
5
10
10
0
0
0
1
0
0
2
4
5
4
10
10
0
0
0
0
0
0
1
3
4
6
11
10
0
0
1
0
1
0
1
3
3
6
10
10
0
0
0
0
0
0
2
4
5
4
9
10
1
0
0
2
2
2
1
4
5
2
7
8
0
0
0
0
0
0
Total
36 1 35 0 35 2 33 0 34 7 27 0
Female
8
9
10
11
12
13
0
2
4
8
9
3
0
0
0
0
0
0
0
2
4
8
9
3
0
0
0
0
0
0
2
2
3
8
6
2
1
0
0
1
0
0
1
2
3
7
6
2
0
0
0
0
0
0
2
2
5
10
7
2
0
1
1
2
1
0
2
1
4
8
6
2
0
0
0
0
0
0
Total
26 0 26 0 23 2 21 0 28 5 23 0
village there was not a significant difference between the
two groups in TT3, TT4, and TSH (see Table 9).
In China as clinical diagnosis biomarkers, the reference
normal values of TT3, TT4, TSH were 0.80 ~ 2.00 ng/mL,
5.00 ~ 13.00 µg/dL, 0.34 ~ 5.60 µIU/mL. As shown in
Tables 10 - 11, there was 1 subject with high serum TT3
concentration in each village; and 4 in Wamiao, 5 in
Xinhuai with high serum TT4; and 12 in Wamiao, 9 in
Xinhuai with high serum TSH. There was not significant
difference between the gender and total in the ratio of
high TT3, TT4, and TSH in two villages indicated by the
results of Chi-Square Tests.
DISCUSSION
In Wamiao and Xinhuai village primary school, the less
economic development conditions are not allowed the
school to provide food and drinking water for students
and teachers; they must back to home to have meals for
breakfast, lunch, and dinner; a few students may be bring
boiling water in plastic or glass bottle from family to
school. In our formerly investigation, the daily total intake
of drinking water in two villages’ children was: 156.0 ml
crude water and 1085.1 ml boiled water included average
2 mL/child/day tea. The rate of crude water was only
14.38% for the total daily intake of drinking water. Each
family has a household shallow well in the yard; the
average use age of the shallow well was 5.16 ±3.12
years in Xinhuai village and 8.27 ±3.02 years in Wamiao
village. Students in these two villages hardly ever move
from one residential site to another, and hardly drink the
market sell water. So the F
-
exposure history of the
subjects was relatively clear and the F
-
in drinking water
was the main source of the F
-
intake (QY Xiang, et al
2004; QY Xiang et al. 2005). Therefore, it was relatively
easy to explore the exact relationships between the
drinking water F
-
and the serum concentration of TT3,
TT4, and TSH.
In 1990, the Government of China has an official
commitment to the world that the hazard of IDD (iodine
deficiency disorder) will be removed in China before
2000. So, in China, all the countrymen will eat the
qualified iodize salt from 1994. In Wamiao and Xinhuai
village the mean levels of iodine in children’s urinary were
over 280.70±87.16 µg/L and 300.96 ± 92.88 µg/L, and
there was not significant difference in childrens’ urinary
iodine concentration in two villages (Q Xiang et al., 2003).
Neither village was identified as being in an area of
endemic iodine deficiency area according to The Manual
of Prevention and Treatment of Endemic Iodine
Deficiency published by Chinese Ministry of Health
058 J. Toxicol. Environ. Health Sci.
Table 11. The TT3, TT4, and TSH results by age and gender in Xinhuai village.
TT3 TT4 TSH
Age
No. High Normal Low No. High Normal Low No. High Normal Low
Male
8
9
10
11
12
13
6
3
5
9
11
4
0
0
0
0
1
0
6
3
5
9
10
4
0
0
0
0
0
0
5
3
3
10
11
5
1
1
0
1
1
1
4
2
3
9
10
4
0
0
0
0
0
0
6
3
5
8
11
5
2
0
1
0
0
0
4
3
4
8
11
5
0
0
0
0
0
0
Total
38 1 37 0 37 5 32 0 38 3 35 0
Female
8
9
10
11
12
13
4
4
5
1
9
7
0
0
0
0
0
0
4
4
5
1
9
7
0
0
0
0
0
0
0
1
3
1
10
9
0
0
0
0
0
0
0
1
3
1
10
9
0
0
0
0
0
0
4
4
4
1
9
7
2
2
0
1
1
0
1
2
4
0
8
7
1
0
0
0
0
0
Total
30 0 30 0 24 0 24 0 29 6 22 1
(Chinese Ministry of Health, 1989). Thus urinary iodine
levels do not appear to affect the differences in TT3, TT4,
and TSH in children between the two villages.
In this study, there were not significant relationships
between the drinking water F- and the serum concen-
tration of TT3, TT4, and TSH. There was significant
difference between the two villages in serum TSH,
TT3/TT4, TSH/TT3, and TSH/TT4; the serum TSH,
TSH/TT3, and TSH/TT4 were significantly higher in
Wamiao village than that in Xinhuai village, but the values
of TT3/TT4 was on the contrary which was founded in the
study of H Wang in rats (H Wang et al., 2009). In the
study of Susheela AK (Susheela et al., 2005) and his co-
worker, the results indicated that in Two-thirds of the
sample children have elevated TSH in the sample group
with high drinking water fluoride, but none are below
normal; in this study, as shown in Tables 10 - 11, there
were 19.35% in Wamiao and 13.42% in Xinhuai with
higher serum TSH than normal, and none are below
normal. Serum TSH level in children in endemic fluorosis
area was significant higher than that in non endemic
fluorosis area in the study of (Xiaoli et al., 1999). With the
increasing F
-
in the diet, the serum TSH level was
correspondingly increased in the young pigs and rats (Liu
Guoyan et al. 2008; Xiuan et al. 2006). Those results
were consistent with this study. But there were opposed
results in the study of (Xiaowei et al., 1994). There were
not significant differences between the residents of
endemic fluorosis areas and non-endemic fluorosis areas
in serum TSH in the study of Mingyin et al (Mingyin et al.,
1994).
The results in this study indicated that there were not
significant difference between two villages in serum TT3
and TT4 in the children. But in the study of Xiaowei
(Xiaowei et al. 1994) indicated that serum TT3 and FT3
(free T3) were significant increased, serum FT4 (free T4)
was significant reduced in adults in the higher F
-
drinking
water area compared with the control area. Serum T4
was significant lower, T3 was significant higher in the
children in the endemic fluorosis area compared with the
non endemic fluorosis area in the report of Xiaoli (Xiaoli
et al., 1999).
It has long been suggested that DF is associated with
IDD and thyroid dysfunction (Susheela et al. 2005).
The
results reported in Table 7 revealed significant deviations
in the serum levels in TT3 and TSH in the children in
Wamiao village between the different DF groups. The
serum TT3 in Group 3 (with mild dental fluorosis) and 4
(with moderate dental fluorosis) were significant higher
compared with group 1 (with normal and suspected
dental fluorosis). The serum TSH in group 2 (with very
mild dental fluorosis) was significant higher than that in
group 1.
F
-
and iodine are belong to chlorine group element, and
F
-
is more active than iodine. The mechanism of F
-
causing the functional disorder of appendix cerebri -
thyroid may be: 1. F
-
can compete with iodine and
influence the absorption and condensing of iodine in
thyroid; 2. F
-
can influence the biologic activity of func-
tional enzyme system in thyroid; 3. F
-
can influence the
feedback mechanism of hypothalamus and adenohypo-
physis of appendix cerebri and control the secretion of
thyroid directly (Xiaowei et al., 1994).
The statement in the guest editorial of Andreas Schuld
said that: “In fact, DF is a developmental disorder-
originating from aberrant thyroid hormone metabolism. It
is well established that DF can only occur as a result of
excessive fluoride exposure during crucial times of
development Thyroid hormone (TH) deficiency leads to
delayed tooth eruption. The more F
-
ingested, the longer
it takes for the tooth to erupt. The later in life maturation
of enamel is completed, the greater is the severity of DF.
At the same time, other risk factors known to influence
DF are identical to those observed in thyroid dysfunction.
Thus, while DF gets more severe at higher altitudes, the
same is generally true for iodine deficiency” (Schuld,
2005).
The results in this study indicated or suggested that the
high F
-
exposure can caused the thyroid functional
abnormalities, and the different severity degree of DF
may be relation to deviation in the serum levels of thyroid
hormone. There were different results in the past reports
about these. So the exact relationship among fluoride,
DF, and appendix cerebri-thyroid function need to further
study.
ACKNOWLEDGEMENTS
This work was supported by Jiangsu Province
Association for Endemic Disease Control and Prevention
(X200327). We thank Prof BH Chen (School of Public
Health, Fudan University for her valuable suggestions.
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... In contradiction to our results, studies by Wilson, [27] Murray et al., [28] Steyn and Reinach, [29] Obel, [30] Jooste, [31] Rathee et al., [32] Susheela et al., [5] Xiang et al., [33] Peckham et al., [34] and Sachdeva et al. [35] found evidence of at least one or more thyroid hormone derangements among those deemed as having "high" fluoride exposure (defined in various ways). Lin et al. [36] found that individuals residing in high fluoride areas (defined as areas with an average fluoride concentration of 0.88 ppm in drinking water) had significantly higher TSH levels than those residing in low fluoride areas (average fluoride concentration of 0.34 ppm in drinking water) (P < 0.01). ...
... Michael et al. [37] found significant increases in T4 level in population with high fluoride exposure. Xiang et al. [33] reported that the high fluoride exposure can cause thyroid functional abnormalities. The reason for this contradiction may be the higher water fluoride levels of the study location (2.36-14 ppm) in comparison to ours (1.4 ppm). ...
... Relating dental fluorosis to thyroid dysfunction, Schuld [42] reported that tooth and thyroid gland develop almost at the same age, so fluorosis and thyroid dysfunction may be correlated. Supporting the above hypothesis, a study by Xiang et al. [33] reported that the different severity degrees of dental fluorosis may be related to significant deviation in the serum levels of thyroid hormone. In contradiction, the present study results show a nonsignificant association between dental fluorosis and thyroid function. ...
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Background: Literature shows association between systemic fluorides and endocrine disorders especially related to thyroid, with lack of clarity. Aims and objectives: The aim and objective of this study was to estimate serum triiodothyronine (T3), thyroxin, thyroid-stimulating hormone (TSH), fluoride, calcium, phosphate, and alkaline phosphatase levels among children with normal nutritional status and optimal iodine intake residing in three different ranges of drinking water fluoride levels. Materials and methods: The present double-blinded, observational trial comprised of 293 children aged between 9 and 13 years consuming naturally fluoridated water of three different ranges: Group I: 0.01-0.6 parts per million (ppm), Group II: 0.7-1.2 ppm, and Group III: 1.3-1.8 ppm. For each child's demographic data, body mass index and Clinical Fluorosis Index were recorded along with serum T3, T4, TSH, fluoride, calcium, phosphate, and serum alkaline phosphatase levels. Data were analyzed using Chi-square test, Kruskal-Wallis test, and repeated measures ANOVA with SPSS 23. Results: For serum TSH levels, 40% of children in Group I had deranged levels followed by Group III (20%) and Group II (16%). For serum T4 levels, 24% of children of both Groups I and III had deranged levels followed by Group II (20%). Intergroup correlation of drinking water fluoride levels to the number of deranged serum T3, T4, and TSH of the children showed nonsignificant association. Serum T3, calcium, phosphate, and alkaline phosphatase levels in all children showed values falling within normal range. Conclusion: According to the present study results, long-term intake of fluoridated drinking water (0.02-1.4 ppm) did not show effect on the thyroid function in children with normal nutritional status and optimal iodine intake.
... In this area (RM) this phenomena is so pronounced that it is causing 90.5% D.F with 66.4% children suffering from mild to severe degree of fluorosis ( Figure 4). 94.63% and 85.37% teeth fluorosis was also found in Dadanpur and Wamiao respectively, the two endemic fluorosis villages in India and China [44,48] thereby confirming this relationship. D.F is also an indication of abnormal thyroid metabolism [49]. ...
... Therefore TSH is the first hormone getting disturbed by excess fluoride intake. Similar outcomes were reported by Xiang in children from an endemic fluorosis village compared to a non-fluorosis village in China [48]. ...
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In the present study 134 children were studied for comparison and correlation between an endemic fluorotic village Rukh Mudke (RM), n = 74 , and a non-fluorotic village Ottawa (OTW), n = 60 . The children were aged between 7-18 years and selected for the estimation of fluoride in their household water, body fluids (urine-serum), dental fluorosis and thyroid hormones (Free tri-iodothyronine (FT 3 ) free tetra iodothyronine (FT 4 ) and thyroid stimulating hormone (TSH) respectively . Mean concentration of water fluoride in subjects of RM was 4.6 ×10 ⁶ ng/L, urine fluoride 2.59 ×10 ⁶ ng/L, serum fluoride 6.0 ×10 ⁴ and dental fluorosis 90.5% respectively. Significant elevation ( P = 0.000) in the concentration of three out of these four variables ( P < 0.01) was observed (except in serum fluoride) in subjects of RM compared to those in the control group (OTW). Mean FT 4 , FT 3 and TSH concentrations in RM subjects was 18.3 pmol/L, 5.06 pmol/L and 3.2 mlU/L respectively. No marked difference in FT 4 and FT 3 ( P = 0.17 and P = 0.7) was found compared to the control (OTW) group, while significant elevation in TSH ( P < 0.05) was found in. 22% of the children in the RM group, portrayed well defined thyroid hormonal aberrations. A negative correlation between water fluoride - FT 4 (r = - 0.24); a strong positive between water, urine, serum, dental fluorosis and TSH (r = 0.94, 0.87, 0.88, 0.74 and 0.8) and moderate correlation between water fluoride - FT 3 (r = 0.52) was observed. Results of this study indicate that the fluoride intoxication through drinking water is not only increasing fluoride level in body fluids and deteriorating teeth but also destroying thyroid function in a large number of children.
... There is significant relationship between serum fluoride and TSH, serum fluoride and FT 3 /FT 4 , TSH and FT 3 /FT 4 [11]. High fluoride exposure can cause functional abnormalities of thyroid and different degrees of dental fluorosis could be observed with significant deviation in the serum thyroid hormone levels [12]. ...
... According to the authors, the results undermine the validity of fluoridation of drinking water and food products. A similar study conducted by Xiang et al. [73] came to the same conclusions. However, in a study by Hosur et al. [74], no significant changes in the levels of FT3, FT4 and TSH thyroid hormones were observed in people with dental fluorosis from endemic fluorosis populations compared to controls (10 subjects without dental fluorosis). ...
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Thyroid hormones are known for controlling metabolism of lipids, carbohydrates, proteins, minerals, and electrolytes and for regulating body temperature. Normal thyroid status depends on the chemical/elemental composition of body fluids and tissues, which changes depending on physiological state, lifestyle and environment. A deficiency or excess of certain essential chemical elements (selenium, zinc, copper, iron or fluorine) or exposure to toxic (cadmium or lead) or potentially toxic elements (manganese or chromium) interacts with thyroid hormone synthesis and may disturb thyroid homeostasis. In our review, accessible databases (Scopus, PubMed and Web of Science) were searched for articles from 2001–2021 on the influence of selected chemical elements on the development of hypothyroidism. Our review adopted some of the strengths of a systematic review. After non-eligible reports were rejected, 29 remaining articles were reviewed. The review found that disruption of the physiological levels of elements in the body adversely affects the functioning of cells and tissues, which can lead to the development of disease.
... A similar insignificant correlation with the values of FT3 and FT4 was observed by Singh et al. 12 Previous evidence suggests that intake of the high level of fluoride can interfere with thyroid gland function with derangements of thyroid hormone levels. 12,13 Excess of fluoride in drinking water, especially groundwater has been shown to demonstrate a linear correlation with raised TSH levels, most of which are subclinical. Also, fluorosis is known to compound its detrimental effects in areas previously deficient in their iodine status. ...
... Consistent with this, several in vitro studies have shown a synergistic effect of F − and TSH on adenylate cyclase activity resulting in increased cAMP production [253,254]. Evidence from human studies also show that F − induces TSH production [140,[255][256][257][258][259][260][261][262][263][264][265][266][267][268][269]. In this scenario, a positive feedback loop exists that may amplify the effects of TSH and F − on cAMP activity, which may explain the synergistic effect of F − and TSH on cAMP production. ...
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In this study, several lines of evidence are provided to show that Na + , K + -ATPase activity exerts vital roles in normal brain development and function and that loss of enzyme activity is implicated in neurodevelopmental, neuropsychiatric and neurodegenerative disorders, as well as increased risk of cancer, metabolic, pulmonary and cardiovascular disease. Evidence is presented to show that fluoride (F) inhibits Na + , K + -ATPase activity by altering biological pathways through modifying the expression of genes and the activity of glycolytic enzymes, metalloenzymes, hormones, proteins, neuropeptides and cytokines, as well as biological interface interactions that rely on the bioavailability of chemical elements magnesium and manganese to modulate ATP and Na + , K + -ATPase enzyme activity. Taken together, the findings of this study provide unprecedented insights into the molecular mechanisms and biological pathways by which F inhibits Na + , K + -ATPase activity and contributes to the etiology and pathophysiology of diseases associated with impairment of this essential enzyme. Moreover, the findings of this study further suggest that there are windows of susceptibility over the life course where chronic F exposure in pregnancy and early infancy may impair Na + , K + -ATPase activity with both short- and long-term implications for disease and inequalities in health. These findings would warrant considerable attention and potential intervention, not to mention additional research on the potential effects of F intake in contributing to chronic disease.
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190 children aged 7-18 years from an endemic fluorotic village "Talab Sarai (n = 130) and a non-fluorotic, control, village "Ottawa" (n = 60) were selected for comparison. Children were examined for fluoride (F-) concentration in drinking water, urine, and serum as well as Dental fluorosis (DF) and thyroid hormone levels. The mean concentration of water fluoride (WF) in the sample group was 6.23 mg/L, urine fluoride (UF) 3.38 mg/L, and serum fluoride (SF) 0.21 mg/L, while DF was 93.07%. Significant elevations (P = 0.000) in the concentration of all these four variables were observed in sample group children as compared to control. Mean Free Tetra-iodothyronine (FT4), Free Tri-iodothyronine (FT3) and Thyroid Stimulating Hormone (TSH) concentrations in the sample group were 16.64pmol/L, 5.57 pmol /L and 4.41 mlU/L, respectively. No marked difference in FT4 (P = 0.1) was noted, while significant elevations in FT3 and TSH (P = 0.000) were found in the sample relative to the control group. 80% of the children displayed clear thyroid hormonal derangements, with 36.92% having high TSH and 43.07% with FT3 and FT4 disorders. A moderate to strong correlation among WF, UF, SF and DF (r = 0.94, 0.60, 0.60, 0.72) and a very strong correlation between WF and TSH (r = 0.9) were observed. Our results suggest that excess F-level that is four times greater than the "safe limit" is not only increasing fluoride concentration in body fluids but is also affecting thyroid hormones in 4 out of 5 children which could lead to abnormal physical and mental growth in later developmental stages.
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Background: Literature shows association between systemic fluorides with water fluoride level above 3ppm and endocrine disorders especially related to thyroid. Aim & Objectives: To estimate serum T3, T4, TSH, Fluoride levels among children with normal nutritional status and optimal iodine intake, residing in three different ranges of drinking water fluoride levels below 3ppm. Material and methods: Present double blinded observational trial comprised of 293 children aged between 9-13 years consuming naturally fluoridated water of 3 different ranges: Group I: 0.01 - 0.6ppm, Group II: 0.7-1.2ppm and Group III: 1.3-1.8ppm. For each child demographic data, BMI and Clinical Fluorosis Index were recorded along with serum T3, T4, TSH, Fluoride levels. Data was analyzed using Chi Square, Kruskal Wallis test and Repeated measures of ANOVA with SPSS 23. Results: For serum TSH levels 40% of children of group I had deranged levels followed by group III (20%) and Group II (16%). For serum T4 levels 24% of children of both groups I and III had deranged levels followed by group II (20%). Inter group correlation of drinking water fluoride levels to number of deranged serum T3, T4, and TSH of the children showed non-significant association. Conclusions: According to the present study results long term intake of fluoridated drinking water (0.02 -1.4 ppm) did not showed effect on the thyroid function in the children with normal nutritional status and optimal iodine intake. Key words:Iodine, nutrition, serum fluoride, systemic fluoride, thyroid function test.
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The sodium iodide symporter (NIS) is the plasma membrane glycoprotein that mediates active iodide transport in the thyroid and other tissues, such as the salivary, gastric mucosa, rectal mucosa, bronchial mucosa, placenta and mammary glands. In the thyroid, NIS mediates the uptake and accumulation of iodine and its activity is crucial for the development of the central nervous system and disease prevention. Since the discovery of NIS in 1996, research has further shown that NIS functionality and iodine transport is dependent on the activity of the sodium potassium activated adenosine 5′-triphosphatase pump (Na+, K+-ATPase). In this article, I review the molecular mechanisms by which F inhibits NIS expression and functionality which in turn contributes to impaired iodide absorption, diminished iodide-concentrating ability and iodine deficiency disorders. I discuss how NIS expression and activity is inhibited by thyroglobulin (Tg), tumour necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β), interferon-γ (IFN-γ), insulin like growth factor 1 (IGF-1) and phosphoinositide 3-kinase (PI3K) and how fluoride upregulates expression and activity of these biomarkers. I further describe the crucial role of prolactin and megalin in regulation of NIS expression and iodine homeostasis and the effect of fluoride in down regulating prolactin and megalin expression. Among many other issues, I discuss the potential conflict between public health policies such as water fluoridation and its contribution to iodine deficiency, neurodevelopmental and pathological disorders. Further studies are warranted to examine these associations.
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Although it has been known since 1917 that mottled dental enamel (later recognized as dental fluorosis-DF) is identical with that observed in thyroid dysfunction, disturbances of thyroid hormone metabolism during crucial periods of tooth development as the primary cause of DF have received very little consideration by dental researchers. New findings indicate that thyroid hormone metabolism is disturbed in peripheral tissue of children with DF, thereby helping to account for timing of events observed in DF and the delayed eruption of teeth in fluoridated areas and further suggesting the use of DF as a marker and diagnostic aid for iodine deficiency disorders.
Article
: An epidemiological investigation was conducted to determine the relationship between dental fluorosis and serum fluoride (measured by a minitype fluoride ion selective electrode) in the children aged 8-13 years in the Jiangsu Province villages of Wamiao (water fluoride: 2.45±0.80 mg/L; range: 0.57–4.50 mg/L) and Xinhuai (water fluoride: 0.36±0.15 mg/L; range: 0.18–0.76 mg/L). When divided into five groupings, higher serum fluoride levels were significantly associated with higher prevalences of dental fluorosis and the more severe defect dental fluorosis, which included significant dose-response relationships between serum fluoride levels and these two degrees of dental fluorosis (regression equations: Y = 1025.512X – 20.005, R 2 = 0.830; and Y = 614.656X – 16.922, R 2 = 0.920). Gender related differences in serum fluoride levels and the prevalence of dental fluorosis were found in both village, but not age related differences. There was also a significant positive relationship between the levels of fluoride in drinking water and the levels of fluoride in serum (Pearson correlation coefficient = 0.860, p<0.001). The survey findings indicated that drinking water is the main source of fluoride intake in Wamiao and Xinhuai, along with a significant positive dose-response relationship between serum fluoride and dental fluorosis.
Article
Thirty-two one-month-old Wistar albino rats were divided randomly into four equal groups of eight (female:male = 3:1). To assess damage to DNA in their thyroid gland cells, the first group (1) of rats served as the untreated control, the second group (2) was administered a high concentration of fluoride (HiF, 100 mg NaF/L [45 mg F-/L] in their drinking water), the third group (3) was placed on a low iodine intake (Ll, 0.0855 mg l/kg diet), and the fourth group (4) was exposed to the high fluoride and low iodine treatment combined (HiF+Ll). At 20 months of age, the rats were sacrificed for experimental purpose and their thyroid gland cells were removed for single cell gel electrophoresis (SCGE = comet assay). In comparison with DNA damage in the thyroid gland cells of the control group 1 (10.74 ± 12.59%), such DNA damage in the Ll, HIF, and HiF+Ll groups 2, 3, and 4, was 83.50 ± 10.20%, 83.03 ± 12.11 %, and 89.32 ± 8.21 %, respectively. Moreover, the proportion of grade III thyroid gland cell damage increased by 32.26% in group 2,47.83% in group 3, and 69.23% in group 4, as compared to the control group 1. These findings indicate that excessive long-term intake of fluoride, with or without adequate I intake, is a significant risk factor for the development of thyroid dysfunction.
Article
This study was undertaken to investigate the effects of fluoride on growth and thyroid function in young pigs. Three groups of eight crossbred barrows were exposed to 100, 250, and 400 mg F-/kg (from NaF) in their diets for 50 days. Compared to a control group of eight pigs, the average daily gain in weight was significantly reduced, and serum thyroxine (T4) and free thyroxine (FT4) levels also decreased significantly. On the other hand, the level of serum thyroid-stimulating hormone (TSH) was significantly increased, but no significant differences were observed in serum triiodothyronine (T3) and free triiodothyronine (FT3). The activity of Na/K-ATPase in the thyroid was significantly inhibited as well as thyroid peroxidase (TPO). The results suggest that excessive fluoride in the diet can cause growth depression and hypothyroxinemia in pigs. Accompanying thyroid lesions were attributed to fluoride acting as a TSH analogue in concert with elevated TSH levels.
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The Intelligence Quotient (IQ) was measured in 512 children, aged 8-13 years, living in two villages in Sihong County, Jiangsu Province, China, differing in the level of fluoride in their drinking water. In the high- fluoride village of Wamiao (water fluoride: 2.47±0.79 mg/L; range: 0.57-4.50 mg/L), the mean IQ of 222 children was significantly lower (92.02±13.00; range: 54-126) than in the low-fluoride village of Xinhuai (water fluoride: 0.36±0.15 mg/L; range: 0.18-0.76 mg/L), where the mean IQ of 290 children was higher (100.41±13.21; range: 60-128). The children's IQs were not related to urinary iodine, family income, or parent's education level. Higher drinking water fluoride levels were significantly associated with higher rates of mental retardation (IQ
Article
: Serum fluoride in relation to the prevalence of skeletal fluorosis was investigated in two villages in Jiangsu Province, China. In the high-fluoride village of Wamiao, 132 adults (average age 52.36 years; water fluoride 2.18±0.86mg/L; range 0.85–4.50mg/L) were surveyed. In the low-fluoride village of Xinhuai, 35 adults (average age 48.11 years; water fluoride 0.37±0.09 mg/L; range 0.21–0.55mg/L) were surveyed. Subjects were recruited by sampling according to the fluoride content of the drinking water in their household wells. When the subjects were divided into five subgroups according to their serum fluoride concentration, higher serum fluoride concentration was strongly associated with a higher prevalence of skeletal fluorosis in the form of a significant positive dose-response relationship (regression equation: Y = –27.29+890.42X–223.20X 2). In Wamiao village a significant difference was also found between serum fluoride concentrations in 41 subjects with X-ray detectable skeletal fluorosis and in 91 subjects without X-ray detectable skeletal fluorosis. Gender related differences in serum fluoride concentration, household well water fluoride, and the prevalence of skeletal fluorosis were not found in the subjects in Wamiao village. These findings indicate that serum fluoride concentrations have a significant positive dose-response relationship with the prevalence of skeletal fluorosis in an endemic fluorosis area associated with high-fluoride drinking water.
Article
: Ninety children with dental fluorosis, aged 7–18, living in fluoride endemic, non-iodine deficient areas of the National Capital Territory of Delhi, India, where iodized salt has been promoted for over a decade, were investigated, along with 21 children in two control groups without dental fluorosis living in non-endemic areas, to determine their levels of free T 4 (FT 4), free T 3 (FT 3), and thyroid stimulating hormone (TSH). The drinking water fluoride of the 90 children in the sample group ranged from 1.1 to 14.3 mg F – /L (mean 4.37 mg F – /L); their serum ranged from 0.02 to 0.41 mg F – /L (mean 0.14 mg F – /L); their urine ranged from 0.41 to 12.8 mg F – /L (mean 3.96 mg F – /L). The drinking water fluoride of the control I group (n = 10) ranged from 0.14 to 0.81 mg F – /L (mean 0.23 mg F – /L) and that of the control II group (n = 11) ranged from 0.14 to 0.73 mg F – /L (mean 0.41 mg F – /L). In control I, only 3 children had serum fluoride below the normal upper limit of 0.02 mg F – /L. The remaining 7 children, even though they were consuming "safe" water, had elevated serum fluoride. In control II, only one child had serum fluoride below the normal upper limit. The remaining 8 children who were tested also had elevated serum fluoride. In control I, only 3 children had urine fluoride samples in the normal range (0.09–0.10 mg F – /L); in the remaining 7 children they were above normal. In control II, only one child had urinary and serum fluoride within the normal range. In the remaining 8 children who were tested it was high, suggesting they had excess F – exposure from sources other than drinking water. The hormonal status of the 90 sample children indicated that 49 (54.4%) had well-defined hormonal derangements. In the remaining 41 children the findings were borderline. The hormonal deviations among the affected 49 children fall into the following five categories: (1) high TSH with normal FT 4 and FT 3 (46.9%); (2) normal TSH and FT 4 with low FT 3 (32.7%); (3) high TSH and FT 3 with normal FT 4 (14.3%); (4) high TSH with normal FT 3 but low FT 4 (4.1%); and (5) high TSH with normal FT 4 but low FT 3 (2.0%). In control I and control II, similar hormonal deviations were detected in as many as 50% and 45.4% of the children, respectively.
Article
To assess the roles of dietary protein (Pr) and calcium (Ca) level associated with excessive fluoride (F) intake and the impact of dietary Pr, Ca, and F on thyroid function, 144 30-day-old Wistar albino rats were randomly allotted to six groups of 24 (female:male = 1:1). The six groups were fed (1) a normal control (NC) diet (17.92% Pr, 0.85% Ca = NC group); (2) the NC diet and high F (338 mg NaF [=150 mg F ion]/L in their drinking water = NC+F group); (3) low Pr and low Ca diet (10.01% Pr, 0.24% Ca = LPrLCa group); (4) low Pr and low Ca diet plus high F = LPrLCa+F group; (5) high Pr and low Ca diet plus high F (25.52% Pr, 0.25% Ca = HPrLCa+F group); and (6) low Pr and high Ca diet plus high F (10.60% Pr, 1.93% Ca = LPrHCa+F group). The areas of thyroid follicles were determined by Image-Proplus 5.1, and triiodothyronine (T3), free T3 (FT3), thyroxine (T4), and free T4 (FT4) levels in serum were measured by radioimmunoassay. The histopathological study revealed obviously flatted follicular epithelia cells and hyperplastic nodules, consisting of thyroid parafollicular cells that appeared by excessive F ingestion, on the 120th day. Pr or Ca supplementation reverses the F-induced damage in malnutrition. The serum T3, FT3, T4, and FT4 levels in the NC+F group were significantly decreased and significantly increased in the LPrLCa+F group. Thus, excessive F administration induces thyroid dysfunction in rats; dietary Pr and Ca level play key roles in F-induced thyroid dysfunction.
Article
The present studies were performed in order to investigate the role of neurotransmitters, prostaglandins and glucose on [3H] uridine incorporation into total RNA in beef thyroid slices. Carbamylcholine strongly stimulated RNA labelling from [3H uridine; atropine abolished this effect. NaF, at 1 and 5 mM, progressively increased this parameter while norepinephrine caused a similar effect at 10(-3) but not at 10(-6) M. Phentolamine (1 mM) blocked the stimulatory action of TSH; propranolol and atropine did not. Glucose at concentrations between 4 and 24 mM caused a progressive increase in RNA labelling from [3H] uridine. This effect was inhibited by dinitrophenol. Prostaglandins (E1, A1, F1alpha and F2alpha) assayed in concentrations between 5 and 25 microgram/ml, with or without caffeine, had no effect on RNA labelling. Moreover, neither aspirin nor indomethacin inhibited TSH stimulation. Under similar experimental conditions, PGE1 did simulate PB125I formation.