close

Enter

Log in using OpenID

systematic review and meta-analysis

embedDownload
Hindawi Publishing Corporation
International Journal of Endocrinology
Volume 2014, Article ID 904573, 8 pages
http://dx.doi.org/10.1155/2014/904573
Review Article
Selenium Supplementation for Autoimmune Thyroiditis:
A Systematic Review and Meta-Analysis
Yaofu Fan, Shuhang Xu, Huifeng Zhang, Wen Cao, Kun Wang, Guofang Chen,
Hongjie Di, Meng Cao, and Chao Liu
Endocrine and Diabetes Center, Jiangsu Province Hospital on Integration of Chinese and Western Medicine,
Nanjing University of Chinese Medicine, Nanjing 210000, China
Correspondence should be addressed to Chao Liu; liuchao@nfmcn.com
Received 5 August 2014; Revised 12 November 2014; Accepted 25 November 2014; Published 11 December 2014
Academic Editor: Ajai K. Srivastav
Copyright © 2014 Yaofu Fan et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Many studies have reported that selenium (Se) has a close relationship with autoimmune thyroiditis (AIT). The therapeutic effect
of Se supplementation in AIT treatment remains unclear. The objective of the present study was to determine the efficacy of Se
supplementation for the treatment of AIT. A structured literature search was undertaken to identify all randomized controlled
trials conducted in patients with AIT receiving Se supplementation or placebo. Nine studies enrolling a total of 787 patients were
included. The results showed that Se supplementation with duration 6 months significantly dropped the TPOAb titers but did not
decrease the TgAb titers. Patients assigned to Se supplementation for 12-month duration showed significantly lower TPOAb titers
and TgAb titers. Patients after Se supplementation had a higher chance to improve the mood or well-being compared with controls.
Se supplementation is associated with a significant decrease in TPOAb titers at 6 and 12 months; meanwhile, the TgAb titers can be
dropped at 12 months. After Se supplementation treatment, patients had a higher chance to improve the mood without significant
adverse events.
1. Introduction
The thyroid is the organ with the highest selenium (Se)
concentrations per gram among all tissue [1, 2]. Se is the
only trace element to be specified in the genetic code and
the main structure of it is selenoproteins, including glutathione peroxidase (GPXs), thioredoxin reductases (TRs),
and iodothyronine deiodinases (DIO) [3, 4], which have
been functionally characterized as having reduction of DNA
damage, antioxidant processes, and hormone metabolism
[5]. Se deficiency has been associated with many conditions,
such as increased thyrocytes damage, infections, and the
incidence of cancer [6]. Some studies have reported that Se
deficiency causes a decline in GPXs and DIO enzymes activity
and the concentrations of hydrogen peroxide (H2 O2 ), which
will eternally result in impairing the synthesis of thyroid
hormones [7].
Autoimmune thyroiditis (AIT) is the most common
human organ-specific autoimmune disease. Hashimoto’s thyroiditis (HT) accounts for more than 90% of all patients. The
incidence of this disease is approximately 1% in the general
population, and women are ten times more often affected
than men. The tendency is even more obvious at the postmenopausal period [8, 9]. Thyroglobulin antibody (TgAb)
and thyroid peroxidase autoantibody (TPOAb) are the main
antibodies detected in AIT. TgAb is present in high titers in
sera of patients with AIT (40%–70%) [10], and TPOAb is
present in the majority of AIT (>80%) [11]. Currently, several
factors were reported to be associated with AIT including
gene, environment, diet, and diseases. Se deficiency could
induce the damage of thyroid cell and the tissue. However,
it is still unknown whether Se deficiency was an important
condition for AIT or marker for increased AIT incidence.
Se supplementation to improve autoimmune process has
been explored. There are some inconsistent conclusions on
effects of Se supplementation for treating AIT. Several papers
have maintained that it had no evidences on the effects of
Se supplementation, while the others suggested that there
was beneficial evidence for Se supplementation, including the
decrease of TPOAb and TgAb titers [12–14].
2
International Journal of Endocrinology
Studies identified through the main search
(n = 61)
Articles identified full-text review
(n = 21)
Articles excluded (n = 40):
Reviews (n = 12)
Irrelevant studies (n = 13)
Case reporteds (n = 7)
Redundant publications (n = 4)
Letters (n = 4)
Articles excluded (n = 12):
No RCT (n = 2)
Meta-analysis (n = 3)
Sequence treatment strategy (n = 2)
No intervention (n = 1)
No controlled group (n = 4)
9 RCTs were included in final analysis
Figure 1: Study selection process. RCTs: randomized controlled trials.
Therefore, we performed this systematic review and
meta-analysis of all currently available randomized controlled trials (RCTs) to determine whether Se supplementation is an effective treatment for AIT.
2. Materials and Methods
2.1. Search Strategy. Medline, Embase, the Cochrane Central
Register of Controlled Trial, Chinese Biomedical Literature
Database, National Knowledge Infrastructure, WANFANG,
and VIP Database were searched until 31 March 2014. The
following search terms were used individually or combined: “selenium,” “sodium selenite,” “thyroid,” “thyroiditis,”
“AITD,” “autoimmune thyroiditis,” and “Hashimoto thyroiditis,” with no language restriction. Two investigators (Yaofu
Fan and Huifeng Zhang) independently screened all titles and
abstracts to identify articles for full review. Any discrepancy
was solved by discussion and consensus reached through a
third author (Shuhang Xu). Only published studies with fulltext articles were included in our meta-analysis.
2.2. Inclusion Criteria. Only the studies that met the following criteria were included: (1) RCT study sign; (2) all
participants were AIT patients; (3) one group was treated
with Se supplementation compared with the other groups
receiving only placebo or no treatment; (4) the main outcome
measures were TPOAb titers and TgAb titers.
2.3. Quality Assessment of Primary Studies. Two authors
(Yaofu Fan and Huifeng Zhang) independently evaluated
the quality of all included RCTs by Jadad scale in the
following domains: randomization, blinding, and description
of withdrawals and dropouts [22]. A cut score of 3 was used
to indicate high quality studies as it has been reported to
be sufficient to determine high quality versus low quality in
previous studies.
2.4. Data Extraction. Two authors (Yaofu Fan and Huifeng
Zhang) independently extracted data based on a predesigned
data extraction form. Information was extracted on baseline
characteristics (the first author, publication date, sample size,
age range, and sex), therapeutic interventions, and results
(TPOAb and TgAb titers at baseline and at endpoint). If the
extracted data had any divergences, these could be assessed
by a third author (Shuhang Xu). We contacted authors of
included studies for missing or unclear information.
2.5. Data Analysis. All meta-analyses were performed using
Stata statistical software (STATA version SE-10.1; Stata Corporation, College Station, TX). For each eligible study, the
continuous data were presented as standardized mean difference (SMD) and 95% confidence intervals (CI). We assessed
the statistical heterogeneity between trials by 2 statistic [23].
When heterogeneity was confirmed ( < 0.10, 2 > 50%),
the random-effect method was used; otherwise, the fix-effect
model was adopted [24]. Subgroup analyses were performed
by stratifying the available data according to trial duration.
A sensitivity analysis was performed to identify potential
outliers. Funnel plots, Egger’s test, and Begg’s test were used
to evaluate publication bias.
3. Results
3.1. Characteristic and Quality of Studies. A flow diagram
of our search strategy and results is listed in Figure 1.
The main search strategy identified 61 articles. By scanning
titles or abstracts, 40 articles were discarded, because they
were reviews, case reports, redundant publications, letters, or
irrelevant studies. The full texts of the remaining 21 articles
were reviewed; only 9 RCTs were eligible, and 12 articles were
excluded due to two studies were non-RCT, four studies didn’t
have a placebo-control group or a treatment control group,
three studies were meta-analyses, two studies did not state the
treatment strategy, one study was not intervention study.
419 AIT patients were included in the Se supplementation
group and 368 AIT patients in the placebo or no treatment
group. The characteristics of the retained RCTs and the Jadad
scores are shown in Table 1. The quality scores ranged from
47.8 (22–61)
39.2 ± 14.4
40 ± 12
43.4 ± 12.9
39.3 ± 13.1
40.3 ± 11.2
40.8 ± 12.5
39 ± 12
42.1 ± 13.6
36.3 ± 11.1
43.8 ± 12.7
NM
34/31
48/40
48/46
50/46
46/20
59/55
46/50
Duntas et al. [16]
Turker et al. [14]
Deng et al. [17]
Zhu et al. [18]
Zhang et al. [19]
Yan et al. [20]
Shou et al. [21]
NM
8/51
4/41
9/41
7/41
0/48
9/56
NM
6/49
1/19
7/39
6/40
0/40
0/18
1/61
Sex (M/F)
Control
3 months
6 months
12 months
3 months
3 months
6 months
TPOAb, TgAb, TSH,
FT4, FT3, serum Se
TPOAb, TgAb, TSH,
FT4, FT3
TPOAb, TgAb, TSH,
FT4, FT3
TPOAb, TgAb, TRAb
TSH, FT4, FT3
TPOAb, TgAb, TSH,
FT4, FT3
TPOAb, TgAb, TSH,
FT4, FT3
TPOAb, TgAb, TSH,
FT4, FT3
L-Thyroxine plus
placebo
No medication
L-Thyroxine
L-Thyroxine
Methimazole
Placebo
Placebo
L-Thyroxine plus
placebo
Sodium selenite
200 g/d
L-Thyroxine plus
selenomethionine
200 g/d
L-Thyroxine plus
L-selenomethionine
200 g/d
Selenious yeast tablet
200 g/d
Methimazole plus
selenious yeast
capsule
200 g/d
L-Thyroxine plus
selenious yeast tablet
200 g/d
L-Thyroxine plus
selenomethionine
200 g/d
Sodium selenite
200 g/d
3, 6 months
3 months
12 months
Levothyroxine
L-Seleno-methionine
200 g/d
Therapy
period
Main outcome
measures
TPOAb, TgAb, TSH,
FT4, FT3, urinary
iodine
TPOAb, TSH, FT4,
FT3, plasma Se
Control
Intervention
Case
TPOAb, thyroid peroxidase autoantibody; TgAb, thyroglobulin antibody; TSH, thyroid-stimulating hormone; FT3, free triiodothyronine; FT4, free thyroxine.
NM
47 (19–85)
18/18
Karanikas et al. [12]
0/18
2/68
41.4 ± 9.5
70/62
42.7 ± 8.3
Case
Median (range) age (years)
Case
Control
Table 1: Characteristics of included randomized controlled trials.
Bal´azs [15]
Study
Sample size
Case/control
2
2
2
2
2
2
2
2
4
Jadad
scores
International Journal of Endocrinology
3
4
International Journal of Endocrinology
Study
ID
SMD (95% CI)
Weight (%)
Karanikas G (2008)
−0.05 (−0.71, 0.60)
16.08
Duntas LH (2003)
−0.83 (−1.34, −0.32)
19.64
Zhang W (2013)
0.45 (−0.08, 0.98)
19.05
Yan MZ (2008)
−0.26 (−0.63, 0.11)
23.37
Turker O (2006)
−0.44 (−0.86, −0.02)
21.8
−0.24 (−0.63, 0.14)
100.00
Duntas LH (2003)
−1.34 (−1.89, −0.80)
33.12
Deng SY (2013)
−2.75 (−3.32, −2.19)
32.93
Shou L (2013)
−0.48 (−0.89, −0.08))
33.95
−1.52 (−2.82, −0.21)
100.00
−4.45 (−5.21, −3.70)
49.80
3 months
Subtotal (I2 = 68.8%, P = 0.012)
6 months
2
Subtotal (I = 95.1% , P = 0.000)
12 months
Zhu CY (2012)
́ C (2008)
Balazs
Subtotal (I2 = 68.9% , P = 0.073)
−5.42 (−6.16, −4.68))
50.20
−4.94 (−5.89, −3.99)
100.00
Note: weights are from random effects analysis
−6.16
0
6.16
Figure 2: Forest plot showing the effects of Se supplementation on TPOAb titers in patients of AIT.
2 to 4 points out of a theoretical maximum of 5 points. All
articles adopted random assignment of patients, and 7 RCTs
did not state the detailed randomized method [12, 14, 16–
18, 20, 21]. The double-blinded study was performed in only
1 RCT [15]. All RCTs had defined inclusion and exclusion
criteria for patients and provided clear definitions of the
treatment responses.
3.2. The Effects of Se Supplementation on TPOAb Titers.
Six studies reported serum TPOAb titers at 3 months of
treatment [12, 14, 16, 19, 20]. Patients who received Se supplementation showed no change in TPOAb titers compared with
controls (SMD, −0.243; 95% CI −0.630 to 0.144;  = 0.218).
But three studies after 6 months of treatment [16, 17, 21] and
two studies after 12 months of treatment [15, 18] had different
result, which showed significant lower TPOAb titers when
compared with controls (6 months, SMD, −1.516; 95% CI
−2.823 to −0.210;  = 0.023; and 12 months, SMD, −4.940;
95% CI −5.887 to −3.992;  < 0.001) (Figure 2).
3.3. The Effects of Se Supplementation on TgAb Titers. No
significant difference in TgAb titers after 3 months or 6
months of treatment was detected (four studies, 3 months,
SMD, −0.310; 95% CI −0.938 to 0.319;  = 0.334; and
three studies, 6 months, SMD, −2.068; 95% CI −4.218 to
0.081;  = 0.059). As compared with the control group,
Se supplementation after 12 months of treatment showed
significant effects on declining the TgAb titers (two studies,
12 months, SMD, −2.210; 95% CI −2.956 to −1.464;  < 0.001)
(Figure 3).
3.4. The Effects of Se Supplementation on Mood. Only two
studies reported the effects of Se supplementation on mood.
Patients after Se supplementation had a higher chance in
improving the mood or well-being compared with controls
(39/52 versus 18/49, RR = 1.61; 95% CI 1.01 to 2.57;  = 0.045)
(Figure 4).
3.5. Adverse Events. Only two studies reported the side
effects. One study reported that no adverse events happened
[16]. Another reported that one patient suffered from gastric
discomfort during Se therapy [14].
3.6. Publication Bias. No evidence of publication bias was
found on TPOAb and TgAb titers after Se supplementation
treatment, but the funnel plots for TPOAb and TgAb titers
at different course of treatment were performed including a
small subset of RCTs. Therefore, it is difficult to assess the
results of publication bias.
International Journal of Endocrinology
5
Study
ID
SMD (95% CI)
Weight (%)
Duntas LH (2003)
0.06 (−0.43, 0.54)
24.60
Zhang W (2013)
0.21 (−0.31, 0.74)
24.00
Yan MZ (2008)
−1.16 (−1.56, −0.77)
25.87
Turker O (2006)
−0.29 (−0.71, 0.13)
25.54
−0.31 (−0.94, 0.32)
100.00
Duntas LH (2003)
−0.14 (−0.63, 0.34)
33.60
Deng SY (2013)
−4.62 (−5.40, −3.84)
32.72
Shou L (2013)
−1.51 (−1.97, −1.06)
33.68
−2.07 (−4.22, 0.08)
100.00
Zhu CY (2012)
−1.83 (−2.31, −1.35)
49.71
́ C (2008)
Balazs
−2.59 (−3.05, −2.12)
50.29
−2.21 (−2.96, −1.46)
100.00
3 months
Subtotal (I2 = 86.9%, P = 0.000)
6 months
2
Subtotal (I = 97.8%, P = 0.000)
12 months
2
Subtotal (I = 80.0%, P = 0.025)
Note: weights are from random effects analysis
−5.4
0
5.4
Figure 3: Forest plot showing the effects of Se supplementation on TgAb titers in patients of AIT.
Study
ID
RR (95% CI)
Weight (%)
Karanikas G (2008)
3.06 (1.00, 9.38)
33.18
Duntas LH (2003)
1.30 (0.78, 2.17)
66.82
Overall (I2 = 48.6%, P = 0.163)
1.73 (0.77, 3.87)
100.00
Note: weights are from random effects analysis
.107
1
9.38
Figure 4: Forest plot showing the effects of Se supplementation on mood in patients of AIT.
3.7. Sensitivity Analysis. The sensitivity analysis showed that
the association between the TPOAb titers and Se supplementation treatment of 10 studies (including all cases and
controls) was vulnerable: when someone study was omitted at
a time, the 95% CI of the model would include −1.0 (Figure 5).
Further, the sensitivity analysis showed that the association
between the TgAb titers and Se supplementation treatment
was also vulnerable (Figure 6).
6
International Journal of Endocrinology
Meta-analysis random-effects estimates (linear form)
study omitted
Karanikas G
Duntas LH
Zhang W
Yan MZ
Turker O
Duntas LH
Deng SY
Shou L
Zhu CY
́ C
Balazs
−2.79 −2.51
−1.54
−0.56 −0.31
Figure 5: Sensitivity analysis: examining the influence of individual
studies of ten studies (TPOAb titers and Se supplementation
treatment). This figure shows the influence of each study on the
meta-analysis, in which the meta-analysis estimates are computed
by omitting one study at a time. By default, random-effects analyses
are displayed.
Meta-analysis random-effects estimates (linear form)
study omitted
Duntas LH
Zhang W
Yan MZ
Turker O
Duntas LH
Deng SY
Shou L
Zhu CY
́ C
Balazs
−2.33 −2.11
−1.30
−0.49 −0.23
Figure 6: Sensitivity analysis: examining the influence of individual studies of nine studies (TgAb titers and Se supplementation
treatment). This figure shows the influence of each study on the
meta-analysis, in which the meta-analysis estimates are computed
by omitting one study at a time. By default, random-effects analyses
are displayed.
4. Discussion
AIT is characterized by autoimmune destruction of the
thyroid [25]. Se may catalyze the extrathyroid production of
T3 from T4 , and Se deficiency can increase thyroid necrosis
and reduce compensatory epithelial regeneration. A lot of
studies have reported that Se is important for antioxidant
defense and adjuvant supplementation with Se may be beneficial to AIT patients’ inflammatory and immune responses
[12]. Huang et al. [26] reported that Se status could affect
T cell differentiation and Se deficiency is associated with
Th2 cells/markers. Some articles suggested that increased Se
intake may compound in AIT patients, and adequate Se status
can prevent postpartum thyroiditis development [1, 27, 28]. It
is well known that the pregnant women with AIT have more
risk of miscarriage, preterm delivery, and development of
postpartum thyroid dysfunction [29]. Some studies showed
that the pregnant women taking 200 g Se during and after
pregnancy were less possible of emerging some diseases when
compared with untreated group [1]. However, Karanikas et al.
found no immunological changes in peripheral T cells after
a short period of Se supplementation [12]; this discrepancy
is probably due to the immunological processes occurring in
the thyroid gland in AIT.
However, the efficacy of Se supplementation for AIT
patients has shown conflicting results. Our meta-analysis
found that Se supplementation with duration of 6 months
or 12 months significantly reduced the TPOAb titers in
patients with AIT; meanwhile, Se supplementation with
duration of 12 months could decrease the TgAb titers in
AIT individuals. After treatment, mood improvement was
found in Se supplementation group when compared with the
controls. No serious adverse effects were recorded after Se
supplementation, except mild gastric discomfort.
Comparing with other systematic reviews, we updated
some studies about Se supplementation for AIT from 2007 to
2013 [17–21]. Our result is consistent with some meta-analysis
supporting Se supplementation for AIT. Jin et al. conducted
a review including 7 RCTs and had a general conclusion
that Se therapy for AIT is effective and safe, though there
was no change in TgAb titers [30]. However, the quantitative
systematic review and meta-analysis performed by Toulis
et al. reported that Se supplementation is associated with a
significant decrease in TPOAb titers at 3 months (WMD:
−271.09; 95% CI −421.98 to −120.19;  < 0.0001) [27], and
this result is different from our conclusion. G¨artner et al. [31]
reported that the mean TPOAb titers were significantly lower
in the Se supplementation group than those in the control
group after 3 months ( = 0.013). When the authors followed
up some of the patients for 6 months, the results have no
change ( = 0.004), but nine patients ceased this treatment
and found a significant increase in their TPOAb titers [13].
The experiment carried out by Karanikas et al. in 2008 found
no statistical decrease in TPOAb titers after 3 months [12].
It is possible that longer follow-up periods are needed for
revealing better endpoints.
There are some limitations of our meta-analysis. Firstly,
because of our strict inclusion criteria, only nine RCTs were
included. These RCTs were limited by the small sample size
and some studies were not double-blinded, so the results
would have more bias. Secondly, we tried our best to search
complete RCTs of Se supplementation for AIT, but it was
affected by many uncertain factors, such as language barrier,
limited retrieving resources, and publication bias. Thirdly,
all studies included did not discuss the disease-process, the
degree of AIT, and the forms of Se. With the aggravation of
the disease, the degree of thyroid injury was getting worse
steadily, and this aspect would reduce the absorption rate and
the effect of Se. Meanwhile, the absorption in different forms
varied. So it may lead to high heterogeneity. Last but not least,
only one study has discussed the TPOAb titers. Due to their
correlation with T-lymphocyte cytokine production patterns,
the different TPOAb titers reflect different immunological
states. It was closely associated with the immunomodulatory
International Journal of Endocrinology
effects of Se on cellular immune response. So we assume that
the different TPOAb titers were one of the reasons of the
high heterogeneity and we will pay close attention to them.
We tried to acquire data about two RCTs for all antibodies
values [31, 32], but we were not able to do so. In this review,
we tried to analyze the efficacy after the different follow-up
time points. There were only five studies that were followed
up for 3 months, three studies for 6 months, and two studies
for 12 months, so it was difficult to interpret the results of
publication bias due to a smaller subset of studies. Only two
studies reported the adverse events after Se supplementation
and two studies included the effects of Se supplementation
on mood, so the definite conclusions were not possible and it
should be studied in the future by higher RCTs with different
follow-up time points.
In conclusion, this systematic review found the positive
evidence that Se supplementation is associated with a significant decrease in TPOAb titers at 6 and 12 months; meanwhile,
the TgAb titers can be dropped at 12 months. Patients after
Se supplementation had a higher chance in improving the
mood or well-being. Se supplementation should be one of
the effective complementary treatments for AIT. More highquality, well-designed, long term, randomized controlled,
multicenter trials that are adequately powered are still needed
to evaluate the real beneficial effects of the Se supplementation in AIT patients.
Conflict of Interests
The authors declare that they have no conflict of interests.
Authors’ Contribution
Yaofu Fan and Shuhang Xu contributed equally to the paper.
References
[1] A. Drutel, F. Archambeaud, and P. Caron, “Selenium and
the thyroid gland: more good news for clinicians,” Clinical
Endocrinology, vol. 78, no. 2, pp. 155–164, 2013.
[2] B. Tiran, E. Karpf, and A. Tiran, “Age dependency of selenium
and cadmium content in human liver, kidney, and thyroid,”
Archives of Environmental Health, vol. 50, no. 3, pp. 242–246,
1995.
[3] J. K¨ohrle, F. Jakob, B. Contempr´e, and J. E. Dumont, “Selenium,
the thyroid, and the endocrine system,” Endocrine Reviews, vol.
26, no. 7, pp. 944–984, 2005.
[4] E. E. Mazokopakis and V. Chatzipavlidou, “Hashimoto’s thyroiditis and the role of selenium. Current concepts,” Hellenic
Journal of Nuclear Medicine, vol. 10, no. 1, pp. 6–8, 2007.
[5] J. K¨ohrle, “Selenium and the thyroid,” Current Opinion in
Endocrinology, Diabetes and Obesity, vol. 20, no. 5, pp. 441–448,
2013.
[6] M. P. Rayman, “The importance of selenium to human health,”
The Lancet, vol. 356, no. 9225, pp. 233–241, 2000.
[7] G. Drasch, E. Wanghofer, G. Roider, and S. Strobach, “Correlation of mercury and selenium in the human kidney,” Journal of
Trace Elements in Medicine and Biology, vol. 10, no. 4, pp. 251–
254, 1996.
7
[8] T. Leyhe and K. M¨ussig, “Cognitive and affective dysfunctions
in autoimmune thyroiditis,” Brain, Behavior, and Immunity, vol.
1591, no. 14, pp. 74–79, 2014.
[9] E. N. Pearce, A. P. Farwell, and L. E. Braverman, “Thyroiditis,”
The New England Journal of Medicine, vol. 348, no. 26, pp. 2646–
2655, 2003.
[10] U.-B. Ericsson, S. B. Christensen, and J. I. Thorell, “A high
prevalence of thyroglobulin autoantibodies in adults with and
without thyroid disease as measured with a sensitive solidphase immunosorbent radioassay,” Clinical Immunology and
Immunopathology, vol. 37, no. 2, pp. 154–162, 1985.
[11] S. Mariotti, P. Caturegli, P. Piccolo, G. Barbesino, and A.
Pinchera, “Antithyroid peroxidase autoantibodies in thyroid
disease,” The Journal of Clinical Endocrinology and Metabolism,
vol. 71, no. 3, pp. 661–669, 1990.
[12] G. Karanikas, M. Schuetz, S. Kontur et al., “No immunological
benefit of selenium in consecutive patients with autoimmune
thyroiditis,” Thyroid, vol. 18, no. 1, pp. 7–12, 2008.
[13] R. G¨artner and B. C. H. Gasnier, “Selenium in the treatment of
autoimmune thyroiditis,” BioFactors, vol. 19, no. 3-4, pp. 165–
170, 2003.
[14] O. Turker, K. Kumanlioglu, I. Karapolat, and I. Dogan, “Selenium treatment in autoimmune thyroiditis: 9-month follow-up
with variable doses,” Journal of Endocrinology, vol. 190, no. 1, pp.
151–156, 2006.
[15] C. Bal´azs, “The role of hereditary and environmental factors in
autoimmune thyroid diseases,” Orvosi Hetilap, vol. 153, no. 26,
pp. 1013–1022, 2012.
[16] L. H. Duntas, E. Mantzou, and D. A. Koutras, “Effects of a
six month treatment with selenomethionine in patients with
autoimmune thyroiditis,” European Journal of Endocrinology,
vol. 148, no. 4, pp. 389–393, 2003.
[17] S. Y. Deng, X. Y. Chen, L. Y. Wu et al., “Influence of selenium
on Hashimoto thyroiditis with normal thyroid function,” Chinese
General Practice, vol. 16, no. 70, pp. 2483–2485, 2013.
[18] C. Y. Zhu, X. J. Wang, and C. Z. Deng, “Effects of selenium
on diffuse toxic goiter autoimmune antibodies,” Jilin Medical
Journal, vol. 34, no. 16, pp. 3147–3148, 2013.
[19] W. Zhang, J. F. Wang, J. L. Li et al., “The effect of selenium
on thyroid peroxidase antibody and thyroglobulin antibody in
Hashimoto thyroiditis,” Medical Innovation of China, vol. 10, no.
14, pp. 13–14, 2013.
[20] M. Z. Yan, S. Wang, J. Miao et al., “Effect of selenium on the
Hashimoto thyroiditis,” Chinese Journal of Endocrinology and
Metabolism, vol. 24, no. 2, pp. 194–195, 2008.
[21] L. Shou, Y. H. Liu, and Y. Z. Ren, “Changes of T lymphocyte
subsets with selenium treatment on Hashimoto’s thyroiditis,”
Chinese Journal of Primary Medicine and Pharmacy, vol. 20, no.
8, pp. 1241–1242, 2013.
[22] A. R. Jadad, R. A. Moore, D. Carroll et al., “Assessing the quality
of reports of randomized clinical trials: is blinding necessary?”
Controlled Clinical Trials, vol. 17, no. 1, pp. 1–12, 1996.
[23] J. P. T. Higgins and S. G. Thompson, “Quantifying heterogeneity
in a meta-analysis,” Statistics in Medicine, vol. 21, no. 11, pp. 1539–
1558, 2002.
[24] J. P. T. Higgins, S. G. Thompson, J. J. Deeks, and D. G. Altman,
“Measuring inconsistency in meta-analyses,” British Medical
Journal, vol. 327, no. 7414, pp. 557–560, 2003.
[25] D. Petricca, D. Nacamulli, C. Mian et al., “Effects of selenium
supplementation on the natural course of autoimmune thyroiditis: a short review,” Journal of Endocrinological Investigation, vol. 35, no. 4, pp. 419–424, 2012.
8
[26] Z. Huang, A. H. Rose, and P. R. Hoffmann, “The role of selenium
in inflammation and immunity: from molecular mechanisms
to therapeutic opportunities,” Antioxidants and Redox Signaling,
vol. 16, no. 7, pp. 705–743, 2012.
[27] K. A. Toulis, A. D. Anastasilakis, T. G. Tzellos, D. G. Goulis,
and D. Kouvelas, “Selenium supplementation in the treatment
of Hashimoto’s thyroiditis: a systematic review and a metaanalysis,” Thyroid, vol. 20, no. 10, pp. 1163–1173, 2010.
[28] R. Negro, G. Greco, T. Mangieri, A. Pezzarossa, D. Dazzi, and
H. Hassan, “The influence of selenium supplementation on
postpartum thyroid status in pregnant women with thyroid
peroxidase autoantibodies,” Journal of Clinical Endocrinology
and Metabolism, vol. 92, no. 4, pp. 1263–1268, 2007.
[29] R. Negro, G. Formoso, T. Mangieri, A. Pezzarossa, D. Dazzi, and
H. Hassan, “Levothyroxine treatment in euthyroid pregnant
women with autoimmune thyroid disease: effects on obstetrical complications,” The Journal of Clinical Endocrinology &
Metabolism, vol. 91, no. 7, pp. 2587–2591, 2006.
[30] J. Jin, Y. M. Hu, and W. Liu, “Systematic evaluation of selenium
in treatment of autoimmune thyroiditis,” Journal of Shanghai
Jiaotong University (Medical Science), vol. 30, no. 11, pp. 1356–
1360, 2010.
[31] R. G¨artner, B. C. H. Gasnier, J. W. Dietrich, B. Krebs, and
M. W. A. Angstwurm, “Selenium supplementation in patients
with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations,” Journal of Clinical Endocrinology and
Metabolism, vol. 87, no. 4, pp. 1687–1691, 2002.
[32] D. Nacamulli, C. Mian, D. Petricca et al., “Influence of physiological dietary selenium supplementation on the natural course
of autoimmune thyroiditis,” Clinical Endocrinology, vol. 73, no.
4, pp. 535–539, 2010.
International Journal of Endocrinology
MEDIATORS
of
INFLAMMATION
The Scientific
World Journal
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Gastroenterology
Research and Practice
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com
Diabetes Research
Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
International Journal of
Journal of
Endocrinology
Immunology Research
Hindawi Publishing Corporation
http://www.hindawi.com
Disease Markers
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Volume 2014
Submit your manuscripts at
http://www.hindawi.com
BioMed
Research International
PPAR Research
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Volume 2014
Journal of
Obesity
Journal of
Ophthalmology
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Evidence-Based
Complementary and
Alternative Medicine
Stem Cells
International
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Journal of
Oncology
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Parkinson’s
Disease
Computational and
Mathematical Methods
in Medicine
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
AIDS
Behavioural
Neurology
Hindawi Publishing Corporation
http://www.hindawi.com
Research and Treatment
Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Oxidative Medicine and
Cellular Longevity
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
1/--pages
Report inappropriate content