ArticlePDF AvailableLiterature Review

Abstract

Vitamin D exerts its canonical roles on the musculoskeletal system and in the calcium/phosphorus homeostasis. In the last years, increasing evidences suggested several extra-skeletal actions of this hormone, indicating that vitamin D may produce effects in almost all the body tissues. These are mediated by the presence of vitamin D receptor (VDR) and thanks to the presence of the 1-α-hydroxylase, the protein that converts the 25-hydroxyvitamin (calcidiol) to the active form 1,25-dihydroxyvitamin (calcitriol). Several studies evaluated the possible role of vitamin D in the pathogenesis of thyroid diseases, and this review will focus on the available data of the literature evaluating the association between vitamin D and thyroid function, vitamin D and autoimmune thyroid diseases, including Hashimoto’s thyroiditis, Graves’ disease and post-partum thyroiditis, and vitamin D and thyroid cancer.
Sunshine vitamin and thyroid
Immacolata Cristina Nettore
1
&Luigi Albano
2
&Paola Ungaro
3
&Annamaria Colao
1
&
Paolo Emidio Macchia
1
Published online: 14 January 2017
#The Author(s) 2017. This article is published with open access at Springerlink.com
Abstract Vitamin D exerts its canonical roles on the muscu-
loskeletal system and in the calcium/phosphorus homeostasis.
In the last years, increasing evidences suggested several extra-
skeletal actions of this hormone, indicating that vitamin D
may produce effects in almost all the body tissues. These are
mediated by the presence of vitamin D receptor (VDR) and
thanks to the presence of the 1-α-hydroxylase, the protein that
converts the 25-hydroxyvitamin (calcidiol) to the active form
1,25-dihydroxyvitamin (calcitriol). Several studies evaluated
the possible role of vitamin D in the pathogenesis of thyroid
diseases, and this review will focus on the available data of the
literature evaluating the association between vitamin D and
thyroid function, vitamin D and autoimmune thyroid diseases,
including Hashimotos thyroiditis, Gravesdisease and post-
partum thyroiditis, and vitamin D and thyroid cancer.
Keywords Vitamin D .Hashimotos thyroiditis .Graves
disease .Post-partum thyroiditis .Thyroid cancer
1 Introduction
The term vitamin Dgenerally indicates two different com-
pounds, the cholecalciferol (or vitamin D3) and the
ergocalciferol (vitamin D2). Vitamin D3 is normally
synthetized in the skin upon exposure to ultraviolet B
(UVB) radiation by the action of the 7-dehydrocholesterol
reductase. In addition, it can be introduced with the diet from
few dietary sources (i.e. fatty fish). Ergocalciferol represents
the dietary source of vitamin D and it is synthesized by plants
and fungi. Both forms are transferred to the liver, were they
are hydroxylated to 25-hydroxyvitamin D (25-OH-D3, or
calcidiol). This is the major circulating and storage form of
vitamin D [1]. Evaluation of serum 25-(OH)-D3 is considered
to provide a reliable evaluation of the vitamin D status [2].
The vitamin D active form is produced by the 1-α-
hydroxylase protein. This protein, encoded by the CYP27B1
gene and expressed mainly in the kidney, determines the hy-
droxylation of calcidiol to 1,25-(OH)
2
D3 (calcitriol).
Calcitriol formation is down-regulated via a negative feedback
by calcitriol concentrations and by the fibroblast growth factor
23 (FGF23). Calctriol is inactivated by the action of the 24-
hydroxylase.
The active form of vitamin D binds nuclear vitamin D
receptor (VDR) and heterodimerizes with retinoic acid. This
complex interacts with vitamin D responsive elements of tar-
get genes to exert its effects. Also, a form of a membrane-
bound vitamin D receptor has been hypothesized, which
would mediate non-genomic, rapid effects of calcitriol [3].
Several polymorphic variants of the genes involved in me-
tabolism, transport, and activity of vitamin D have been de-
scribed in the last years. The best characterized are the four
single-nucleotide polymorphic (SNP) variants of the VDR
gene (ApaI, BsmI, FokI, and TaqI) that have been associated
with several pathological situations, including autoimmune
disorders or cancers [4,5].
Other genes, whose variants may lead to altered availability
and metabolism of vitamin D are: DHCR7, GC, CYP2R1,
CYP27B1, CYP24A1. These genes encode for proteins
*Paolo Emidio Macchia
pmacchia@unina.it
1
Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi
di Napoli BFederico II^, Via S. Pansini, 5, 80131 Napoli, Italy
2
Dipartimento di Scienze Mediche Traslazionali, Università degli
StudidiNapoliBFederico II^,Napoli,Italy
3
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR
(IEOS-CNR) BG. Salvatore^, Napoli, Italy
Rev Endocr Metab Disord (2017) 18:347354
DOI 10.1007/s11154-017-9406-3
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
mentioned above: 7-dehydrocholesterol reductase, vitamin D
binding protein (DBP), 25-hydroxylase, 1-alpha-hydroxylase,
and 24-hydroxylase, respectively.
In the last years, the idea that Vitamin D is an hormone that
acts not only on the skeletal system but on a great number of
target tissues has been supported by the identification of the
VDR in nearly all tissue types [6], including the thyroid gland
[1,7].
Herein the relationships between vitamin D and thyroid
diseases have been reviewed. The manuscript is based on an
electronic literature search of PubMed database performed in
September and October 2016. The selection of the articles was
done using the subsequent search terms in association with
vitamin D: Hashimotos thyroiditis; Gravesdisease; Post-
partum thyroiditis; thyroid cancer.
2 Vitamin D and thyroid status
Thyroid hormones (thyroxine or T4 and triiodothyronine or
T3, TH) are vital for the control of metabolism and for main-
taining specific function of several tissue and cell types.
Biosynthesis of TH occurs within the thyroid gland and it is
stimulatedby the thyroid-stimulating hormone (TSH) secreted
by the pituitary. Data on the direct interactions between
Vitamin D and circulating TH or TSH are very poor.
Experiments with rodents demonstrated that in rats the ad-
ministration of calcitriol (0.05 microgram/kg per day for
3 days) did not change TSH or T4 [8]. By contrast, rats fed
with a severely vitamin D deficient diet had lower serum TSH
but T4 levels similar to vitamin D sufficient animals [9]. In
addition, VDR knock out mice had no alterations in morphol-
ogy and function of the thyroid gland and showed only a slight
reduction in circulating TSH levels [10].
In healthy humans, no clear data are available on the effects
of vitamin D status (excess or deficiency) on thyroid function.
In a cohort of hospitalized patients without history of thy-
roid disease, no differences were observed in basal serum
TSH between patients with a very low (10 ng/mL) or high
(40 ng/mL) vitamin D status [11]. Other reports indicate
contrasting results. Chailurkit and coworkers studied a Thai
cohort and demonstrated that high vitamin D status is associ-
ated with low circulating thyrotropin [12] only in young,
while Zang and others reported a similar association also in
elderly [13].
Mackawy et al. suggested that hypothyroidism is associat-
ed to low vitamin D levels with a negative correlation between
TSH and calcidiol [14]. In contrast, Bouillon and coworkers
found that vitamin D levels had no differences between hypo-
thyroid or hyperthyroid patients and healthy subjects [15].
Finally, no effects of hyperthyroidism on circulating Vitamin
DlevelshavealsobeenreportedbybothJastrupand
Macfarlane [16,17].
3 Vitamin D and autoimmune thyroid disorders
Several studies indicated that vitamin D plays a significant
role in the modulation of the immune system [18,19].
Immune cells express both VDR and the 1-a-hydroxylase
which is responsible for 25-hydroxyvitamin D activation.
Indeed, vitamin D has important effects on both monocytes
and dendritic cells (DC) including inhibition of inflammatory
cytokines (interleukin (IL)-1, IL-6, IL-8, IL-12 and tumor
necrosis factor (TNF)-α) in monocyte and reduction of
Major Histocompatibility Complex (MHC) class II molecules
expression. Moreover, vitamin D also determines suppres-
sion of T cell proliferation [20], whose final effect is a reduc-
tion in the number of antigen-presenting cells. Globally, vita-
min D may enhance the innate immune system and regulate
the adaptive immune system, promoting immune tolerance
and acting to decrease the likelihood of developing auto-
immune disease [18].
Autoimmune thyroid diseases (AITD) are the most fre-
quent autoimmune disorders, and the most common patholog-
ical conditions of the thyroid gland occurring in approximate-
ly 5% of the population [21,22]. The AITD comprise two
main clinical presentations: Gravesdisease (GD) and
Hashimotos thyroiditis (HT). Both forms are characterized
by lymphocytic infiltration of the thyroid parenchyma, but
while GD is clinically characterized by hyperthyroidism,
ophthalmopathy and pretibial myxedema [23], the clinical
hallmarks of HT is the hypothyroidism, determined by lym-
phocytic destruction of the thyroid gland [24].
As the majority of autoimmune disorders, AITDs is the
consequence of a complex interaction between genetic sus-
ceptibility factors (i.e. thyroid-specific and immunoregulatory
genes), existential factors (sex, parity, etc.), and various envi-
ronmental triggers (i.e. cigarette smoking, stress, iodine, sele-
nium, etc.) [25].
The role of both vitamin D and VDR in the pathogenesis of
AITD have largely been investigated in the last years. Vitamin
D receptor is expressed in lymphocytes, macrophages as well
as in antigen presenting cells [26]. The innate immune system
is activated in presence of Vitamin D, while the acquired im-
mune response is inhibited. Moreover, associations between
autoimmune disease and reduction of Vitamin D circulating
levels have recently been reviewed [20]. With a specific focus
on autoimmune thyroid disorders, several observations have
been published in both animal models and in human studies.
3.1 Animal models
Mice previously sensitized with porcine thyroglobulin have
been intraperitoneal injected with or without calcitriol (0.1
0.2 micrograms per kg body weight daily) by Fournier and
coworkers. Animals receiving these suboptimal doses of vita-
min D presented a reduction in the severity thyroid
348 Rev Endocr Metab Disord (2017) 18:347354
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
inflammation compared to placebo treated mice [27]. The ef-
fects were even higher when mice were treated with both
calcitriol and cyclosporine [28].
Liu and coworkers pretreated mice with intraperitoneal in-
jection of calcitriol (5 micrograms per kg every 48 h) before
performing sensitization with porcine thyroglobulin. Contrary
to what observed in the placebo group, the thyroid not showed
the typical inflammation signs, suggesting a protective role of
vitamin D in prevention of thyroiditis [29].
Effects of vitamin D in GD animal models have been stud-
ied by Misharin et al. [30]. BALB/c mice have been produced
as model of GD by immunization with adenovirus encoding
the A-subunit of thyrotropin receptor. Compared with mice
fed regularchow, hyperthyroid BALB/mice fed with a vitamin
D deprived diet showed fewer splenic B cells, decreased
interferon-gamma responses to mitogen and lack of memory
T-cell responses to A-subunit protein, but no differences in
TSHR antibody levels have been observed. Moreover, vita-
min D-deficient BALB/c mice had lower preimmunization T
4
levels and developed persistent hyperthyroidism suggesting
that vitamin D directly modulates thyroid function in this an-
imal model [30].
3.2 Human studies
In the last years, several studies have investigated the circulat-
ing vitamin D levels in patients with AITD. A weak connec-
tion between low vitamin D levels and AITDs was identified
in a study conducted in a population from India [31], while no
correlation between vitamin D and Ab-Tg antibodies was
demonstrated in Thai subjects [12].
By contrast, Kivity et al. observed that anti-thyroid anti-
bodies were more frequently elevated in patients with vitamin
D deficiency [32]. The same study, however, indicates that the
prevalence of vitamin D deficiency was similar between hy-
pothyroid patients with AITDs or without AITD (72% vs
52%, p= 0.08), not allowing to exclude that vitamin D defi-
ciency is determined by hypothyroidism and not a primary
phenomenon involved in AITD pathogenesis.
Tamer et al. demonstrated that patients with HT had lower
vitamin D levels when compared to age- and sex-matched
controls. Moreover, vitamin D insufficiency (<30 ng/mL) oc-
curred more frequently in patients with HT rather than in a
healthy population [33]. Nevertheless, the authors were not
able to demonstrate a significant difference among the degree
of vitamin D insufficiency between hypothyroid, euthyroid or
hyperthyroid patients with HT, suggesting that vitamin D
levels do not correlate with the progress of damage to
thyrocyte. In contrast, a potential role of vitamin D in the
development or progression of HT has been suggested by
Bozkurt et al., demonstrating a correlation between severity
of vitamin D deficiency and duration of HT, antibody levels
and thyroid volume [34].
The association between AITD and calcidiol was also in-
vestigated by Choi and coworkers in a large cross-sectional
study, involving about 6700 participants. The authors demon-
strated that the levels of serum vitamin D were significantly
lower in pre-menopausal, but not in post-menopausal women
with AITD [35].
Shin et al. reported that patients with elevated anti-thyroid
antibodies had significantly lower levels of serum 25(OH)D3
when compared to normal subjects. Moreover, after adjusting
for age, sex, and body mass index, a negative correlation
(r=0.252, p< 0.001) was recognized between 25(OH)D3
and TPOAb levels in the AITDs patients [36].
By comparing newly diagnosed AITD patients with
healthy age-matched controls, Unal et al. demonstrated that
both HT and GD patients had lower circulating 25-OH-D3
compared to controls [37].
The relationships between vitamin D levels and HT in chil-
dren have been investigated by Camurdan et al. The authors
observed lower vitamin D levels and higher prevalence of
vitamin D deficiency in children with new diagnosis of HT
compared to sex- and age-matched controls [38]. Relation
between vitamin D and AITD in young was recently studied
also in a cohort of 56 Egyptian children with AITD and 56
healthy controls [39]. Also this report indicates that vitamin D
deficiency is more frequent in the AITD group compared to
the control subjects, and a significant negative correlations can
be demonstrated between serum 25-OH vitamin D and age,
duration of the disease, BMI, anti-TPO and anti-Tg antibodies
and TSH. On the basis of these observations, the authors sup-
posed that the vitamin D level is not an independent risk for
the progression of AITD to overt hypothyroidism [39].
Sönmezgöz et al. confirmed these results in a group of 136
Turkish children. The prevalence of vitamin D deficiency was
higher (76%) in HT patients than in the control group (35%).
All hypothyroid HT patients also had a vitamin D deficiency
[40]. Similar results have also been reported by Evliyaoğlu,
who measured serum 25-OH vitamin D3 levels in 169 sub-
jects, demonstrating that levels lower than 20 ng/mL were
associated to HT in children and adolescents [41].
The relationships between vitamin D and GD have been
less investigated. Kivity et al. reported significantly higher
prevalence of vitamin D deficiency in GD patients than in
healthy individuals matched by age (64% vs 30% respective-
ly, p<0.01)[32]. Newly identified GD female patients were
studied for vitamin D levels by Yasuda et al. in 2012. The
authors reported a decrease in the circulating vitamin D levels
in GD patients and demonstrated a significant association of
vitamin D deficiency with thyroid volume, but not with TRAb
levels or thyroid function [42]. The same authors also found
lower vitamin D levels in female GD patients without remis-
sion than in those with remission [42].
All the data on the associations between vitamin D and GD
have been reviewed in a recent meta-analysis by Xu and
Rev Endocr Metab Disord (2017) 18:347354 349
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
coworkers. In this report, the authors conclude that low vita-
min D status may increase the risk of Gravesdisease, how-
ever pathogenetic mechanisms related to this association still
remains unclear, and it has not yet been clarified if supplement
of vitamin D may have beneficial effect in GD [43].
To date, several authors have studied the association be-
tween functional polymorphism in the VDR gene and AITD
risk. The VDR is the specific vitamin D receptor and its ac-
tivity can be compromised by certain polymorphisms. The
first meta-analysis performed to assess the association be-
tween the alleles of vitamin D receptor gene polymorphisms
and Gravesdisease was performed by Zhou and coworkers in
2008. The authors concluded that ApaI, BsmI and FokI
polymorphisms of the VDR gene were associated with sus-
ceptibility to GD in Asian populations, while ApaI, BsmI,
TaqI and FokI polymorphisms were not associated with GD
in Caucasian populations [44]. In 2013, Feng and coworkers
performed a meta-analysis demonstrating a relevant link be-
tween VDR polymorphism and autoimmune thyroiditis [45].
The results indicated that the BsmI (rs1544410) or TaqI
(rs731236) polymorphisms were significantly associated with
AITD risk, while ApaI (rs7975232) or FokI (rs2228570) poly-
morphisms were not. Later, it has been demonstrated that the
frequency of allele TT for the TaqI was higher in GD patients
rather than in HT patients, while the frequency of the C allele
for the ApaI was higher in GD patients than in normal controls
[46]. Meng et al. [47] also demonstrated a higher frequency of
allele A in ApaI in GD patients compared to controls, but no
significant difference were found in BsmI, FokI and TaqI
polymorphisms.
In conclusion, despite the number of papers studying the
associations between vitamin D and AITD is constantly in-
creasing, data are still not conclusive. There are suggestions
indicating that vitamin D deficiency may be a condition asso-
ciated with a higher risk of developing AITD, but it is still
unclear whether this has a specific role in the pathogenesis of
the diseases or is a consequence of the disease. Moreover, it
has not been defined if vitamin D supplementation may mod-
ulate the evolution or the treatments of AITD.
4 Vitamin D and post-partum thyroiditis
Postpartum thyroiditis is a form of subacute thyroiditis that
normally occurs within 612 months after delivery. The prev-
alence of postpartum thyroiditis ranges from 1.1 to 16.7% of
all pregnancies, with an overall incidence of 7.5% [48]. As
most of the subacute thyroiditis the clinical course is charac-
terized by a thyrotoxic phase occurring 13monthsafterpar-
turition, followed by hypothyroidism at 36 months after de-
livery [49]. Finally, normal thyroid function is usually
achieved within a year, however about 25% of women with
a history of PPT will develop permanent hypothyroidism in
the ensuing 10 years [50].
Several papers have recently analyzed the association be-
tween circulating levels of vitamin D and postpartum thyroid-
itis (PPT).
Krysiak and coworkers investigated the levels of 25-
hydroxyvitamin D and parathyroid hormone in four groups
of non-lactating women who gave birth within 12 months
before the beginning of the study: group A was composed
by hypothyroid women with post-partum thyroiditis
(n= 14), group B by euthyroid females with post-partum thy-
roiditis (n= 14); group C by women with non-autoimmune
hypothyroidism (n= 16) and group D by healthy euthyroid
females (n= 15). Serum levels of 25-hydroxyvitamin D were
lower and PTH levels were higher in patients with post-
partum thyroiditis than in patients without thyroid autoimmu-
nity. L-thyroxine treatment increased 25-hydroxyvitamin D
and reduced PTH levels only in hypothyroid women with
post-partum thyroiditis. The results suggested an association
between vitamin D status and post-partum thyroiditis, despite
the authors had to admit several limitations of the study [51].
More recently, the same group has studied 38 non-lactating
L-thyroxine-treated women with postpartum thyroiditis (PPT)
and 21 matched healthy postpartum women. 25-hydroxy vi-
tamin D levels were lower in women with PPT than in healthy
women, and anti-TPO and anti-Tg antibody titers inversely
correlated with vitamin D status. The authors noted that vita-
min D supplementation was able to reduce titers of thyroid
peroxidase and suggested that vitamin D supplementation
may bring benefits to L-thyroxine-treated women with PPT
[52]. This work, however, received strong critics in a letter in
the same issue of the journal [53] and data on the role of
vitamin D in PPT, in our view, are still incomplete and very
controversial.
5 Vitamin D and thyroid cancer
In addition to its main role in calcium homeostasis, vitamin D
has been associated with risk for several types of cancer, prob-
ably in consequence of its effects on cell proliferation, differ-
entiation, apoptosis, and anti-angiogenesis [54,55]. Several
studies suggest that vitamin D may play a role in the patho-
genesis, progression, and therapy for cancer. It has been sug-
gested that lower serum vitamin D levels can be associated
with higher riskof cancers. In this view, suboptimal vitamin D
concentrations in serum have been proposed as an important
cancer risk factor for several types of tumors, including thy-
roid cancers [3,56].
To date, very limited data are available on the clinical sig-
nificance of vitamin D supplementation as measure to reduce
the risk of cancer. Many in vitro and animal studies indicate
that high concentrations vitamin can reduce the progression of
350 Rev Endocr Metab Disord (2017) 18:347354
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
cell cycle, may induces apoptosis and slow neoplastic cell
growth. Moreover, vitamin D has been also demonstrated to
potentiates the antitumor activity of various anticancer drugs,
however the mechanisms that underlie the antitumor activities
of vitamin D are still unclear. In view additional studies are
required in order to better define the role of vitamin D in
cancer, and this is true also for thyroid cancers [57]. Here,
the effects of vitamin D potential role in thyroid cancers will
be reviewed, considering the in vitro,in vivo and human avail-
able data.
5.1 In vitro evidences
The vitamin D activity is mediated by binding to VDR, which
is expressed in both normal and malignant epithelial thyroid
cells. Both VDR and 1-α-hydroxylase were found to be in-
creased in papillary thyroid carcinoma (PTC) compared with
normal thyroid tissue [58]. Moreover, VDR expression was
reduced in metastatic lymph nodes of PTC compared with
both normal thyroid tissue and primary PTC, suggesting that
vitamin D pathway may be associated with differentiation and
reduced proliferation in PTC [58]. Additional in vitro studies
demonstrated that 25(OH)D3 was able to decrease prolifera-
tive activity of follicular thyroid cells [59] and modulate ex-
pression of ECM protein-1 (ECM1) and the type II transmem-
brane serine protease-4 (TMPRSS4), two independent predic-
tor of thyroid carcinoma [60]. Indeed, RT-PCR experiments
revealed a higher mRNA expression of ECM1, TMPRSS4
and VDR in the malignant thyroid tissues compared to the
normal thyroid tissues from the same patients. ECM1 has been
detected in numerous malignant epithelial tumors, while
TMPRSS4 is a protein involved in invasion, metastasis, mi-
gration, adhesion, and epithelial-mesenchymal transition in
cancer cells. Therefore, the association between VDR to
ECM1 and TMPRSS4, suggested a potential role of VDR in
thyroid carcinoma [60].
The study by Clickspoor and coworkers demonstrated an
increased expression of VDR, CYP24A1 and CYP27B1
genes, all key players involved in local vitamin D signaling,
in benign and differentiated malignant thyroid tumors. A de-
crease in these genes expression was observed in local nodal
and distant metastasis, suggesting a local antitumor response
to vitamin D in early cancer stages [61].
The function of vitamin D in cancer has been also validated
with synthesis of vitamin D analogs, such as MART-10. It has
been demonstrated that MART-10 is more potent than
1α,25(OH)2D3 to repress cancer growth and metastasis in
undifferentiated thyroid cancer cells. These results require fur-
ther investigations and in vivo study to use MART-10 as po-
tent drug to inhibit anaplastic thyroid cancer cell metastatic
potential [62].
Finally, very recently, the effects of calcitriol have been
investigated also in a model of thyro-spheres of cell derived
from anaplastic carcinomas. The results indicated that
calcitriol inhibited proliferation of the anaplastic thyroid car-
cinoma cells with a more pronounced effect on doxorubicin-
resistant cells. Moreover, it reduced the capacity to form stem
cell-derived spheres and decreased the size of these spheres,
indicating that, also in this model, vitamin D exert a pro-
differentiation effect [63].
5.2 Animal models
Dackiw and coworkers implanted in the neck of 4- to 5-
weeks-old female SCID mice human thyroid follicular carci-
noma derived (WRO). Animals were treated with i.p. injection
of 0.75 microg/kg calcitriol or vehicle for 21 day. Average
tumor volume presented a 38% reduction (P<0.003) in ani-
mals treated with vitamin D. Moreover, tumors excised from
calcitriol-treated animals demonstrated signs of differentiation
with restoration of thyroglobulin staining not observed in
vehicle-treated mice. The results suggested that calcitriol ad-
ministration can restore p27 accumulation in thyroid carcino-
ma cells, reducing tumor size and preventing metastatic
growth [59]. The results reported by Liu et al. were in the same
direction were, demonstrating that calcitriol treatment was
able to determine a 50% reduction of tumor weight and a
22% reduction of tumor volume in mice xenografted with
tumor cancer cells [64].
5.3 Human studies
The antiproliferative effects of vitamin D have been well char-
acterized in vitro and in vivo using animal models, and a pro-
tective role of vitamin D for non-cutaneous cancer has also
been proposed [65]. However, clinical data are still not suffi-
cient to determine whether low circulating vitamin D can be
considered a risk factor for cancers, and it is not yet possible to
draw definitive conclusions on the effect of vitamin D supple-
mentation on cancer risk [66]. This is true especially for thy-
roid cancer.
Several reports indicate no significant differences compar-
ing vitamin D levels between cancer patients and healthy con-
trols. In 2010, Laney and coworkers evaluated serum calcium,
creatinine, albumin, and 25-hydroxy vitamin D (25-OH-D) in
patients with thyroid nodule (42), thyroid cancer in remission
(45), and active thyroid cancer (24) and found that serum 25-
OH-D was not different between groups. Multivariate regres-
sion analysis showed that only a BMI of 30 kg/m
2
can be a
good predictor of vitamin D deficiency [67]. No difference in
concentrations of 25(OH)D3 between patients with papillary
thyroid cancer and patients with HT have been observed by
Lizis-Kolus et al. Moreover, in this study, no relationship has
been demonstrated between serum 25(OH)D3 and clinical
stage of the disease or TSH level in patients with papillary
thyroid carcinoma [68]. Also Jonklaas and coworkers
Rev Endocr Metab Disord (2017) 18:347354 351
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
demonstrated no associations between vitamin D concentra-
tion and thyroid cancer. In addition, serum vitamin D concen-
trations were not associated with disease stage or other prog-
nostic features [69]. Very recently, Ahn and coworkers evalu-
ated a large group of patients (820) with papillary thyroid
cancer. Among those, 795 had insufficient vitamin D levels
(<30 ng/mL), however serum vitamin D levels were not asso-
ciated with disease aggressiveness and poor outcomes [70].
Finally, indirect evidences suggesting no association between
vitamin D and thyroid cancers were provided by OGrady
et al. In their report the authors investigated the dietary intake
of several micronutrients and were able to establish a relation-
ship only between thyroid cancer and low vitamin C intake,
but not with other micronutrients, including vitamin D [71].
Contrasting data suggesting an association between serum
vitamin D levels and thyroid cancer have been reported by
other groups.
Roskies et al. performed a retrospective cohort study on
212 patients undergoing thyroidectomy. Preoperative 25-
hydroxyvitamin D(3) levels were recorded and patients were
stratified based on vitamin D status as vitamin D deficiency
(VDD) or vitamin D sufficiency (VDS). The comparison of
malignancy prevalence between VDD (75%) and VDS
(37.5%) indicate a relative risk of 2.0 (p= .03, 95% CI 1.07-
2.66) associated to vitamin D deficiency, suggesting that vita-
min D may be a modifiable risk factor for thyroid cancer [72].
Similarly, Sahin et al. demonstrated the presence of low serum
vitamin D (calcidiol < 20 ng/mL) in 71% of patients with pap-
illary thyroid carcinomas, but only in 59% of controls [73].
Kim et al. studied a total of 548 female patients who
underwent total thyroidectomy for PTC. Patients were catego-
rized into four quartiles according to the preoperative serum
25(OH) vitamin D levels, and clinicopathologic features of
PTC were analyzed. The results indicated that lower preoper-
ative serum 25(OH) vitamin D levels appear to be associated
with poor clinicopathologic features in female patients with
PTC [74].
6 Conclusion
The majority of the data here reported suggest that vitamin D
insufficiency or deficiency may be associated with increased
risk of thyroid autoimmunity and that reduced serum concen-
trations of vitamin D are linked with a major aggressiveness of
thyroid cancers. It has to be noted, however, that data are still
inconclusive and many papers present contradictory results.
Several racial differences have been reported in the scientific
literature that may suggest that vitamin D metabolism has also
differences linked to ethnicity, which can, at least in part,
explain the observed differences.
It is likely that, in order to better understand the role of
vitamin D in thyroid disease, several and more extensive
prospective studies need to be performed. In addition, in thy-
roid cancer, it will be necessary to perform long-term supple-
mentation studied to evaluate if higher concentrations of vita-
min D may influence the patient outcome.
7 Founding
This work has been partially supported with the 2012
founding of the PRIN, from the Italian Ministry for
University and Research to PEM.
Compliance with ethical standards
Conflict of interests All the authors declare that there is no conflict of
interest that could be perceived as prejudicing the impartiality of the
research reported. The authors declare no support from any commercial
organization for the submitted work.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appro-
priate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
References
1. Kmiec P, Sworczak K. Vitamin D in thyroid disorders.
Experimental and clinical endocrinology & diabetes: official jour-
nal, German Society of Endocrinology [and] German Diabetes
Association. 2015;123(7):38693. doi:10.1055/s-0035-1554714.
2. Muscogiuri G, Mitri J, Mathieu C, Badenhoop K, Tamer G, Orio F,
et al. Mechanisms in endocrinology: vitamin D as a potential con-
tributor in endocrine health and disease. European journal of endo-
crinology. 2014;171(3):R10110. doi:10.1530/EJE-14-0158.
3. Wacker M, Holick MF. Sunlight and vitamin D: a global perspec-
tive for health. Dermato-endocrinology. 2013;5(1):51108.
doi:10.4161/derm.24494.
4. DAurizio F, Villalta D, Metus P, Doretto P, Tozzoli R. Is vitamin D
a player or not in the pathophysiology of autoimmune thyroid dis-
eases? Autoimmunity reviews. 2015;14(5):3639. doi:10.1016/j.
autrev.2014.10.008.
5. Xu Y, He B, Pan Y, Deng Q, Sun H, Li R, et al. Systematic review
and meta-analysis on vitamin D receptor polymorphisms and can-
cer risk. Tumour Biol. 2014;35(5):415369. doi:10.1007/s13277-
013-1544-y.
6. Stocklin E, Eggersdorfer M. Vitamin D, an essential nutrient with
versatile functions in nearly all organs. Int J Vitam Nutr Res.
2013;83(2):92100. doi:10.1024/0300-9831/a000151.
7. Vondra K, Starka L, Hampl R. Vitamin D and thyroid diseases.
Physiological research. 2015;64 Suppl 2:S95S100.
8. Tornquist K, Lamberg-Allardt C. Systemic effects of 1,25-
dihydroxyvitamin D3 on the pituitary-hypothalamic axis in rats.
Acta endocrinologica. 1987;115(2):2258.
9. Egrise D, Burniat A, Lefort A, Libert F, Miot F, Goldman S et al.
Vitamin D deficiency modulates the regulation of the pituitary-
352 Rev Endocr Metab Disord (2017) 18:347354
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
thyroid axis and thyroid gene expression. 14th International
Thyroid Congress (ITC); Paris, France 2010.
10. Clinckspoor I, Verlinden L, Mathieu C, Bouillon R, Verstuyf A,
Decallonne B. Vitamin D in thyroid tumorigenesis and develop-
ment. Progress in histochemistry and cytochemistry. 2013;48(2):
6598. doi:10.1016/j.proghi.2013.07.001.
11. Clinckspoor I, Gerard AC, Van Sande J, Many MC, Verlinden L,
Bouillon R, et al. The vitamin d receptor in thyroid development
and function. European thyroid journal. 2012;1(3):16875.
doi:10.1159/000342363.
12. Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. High vita-
min D status in younger individuals is associated with low circulat-
ing thyrotropin. Thyroid : official journal of the American Thyroid
Association. 2013;23(1):2530. doi:10.1089/thy.2012.0001.
13. Zhang Q, Wang Z, Sun M, Cao M, Zhu Z, Fu Q, et al. Association
of high vitamin d status with low circulating thyroid-stimulating
hormone independent of thyroid hormone levels in middle-aged
and elderly males. International journal of endocrinology.
2014;2014:631819. doi:10.1155/2014/631819.
14. Mackawy AM, Al-Ayed BM, Al-Rashidi BM. Vitamin d deficiency
and its association with thyroid disease. International journal of
health sciences. 2013;7(3):26775.
15. Bouillon R, Muls E, De Moor P. Influence of thyroid function on
the serum concentration of 1,25-dihydroxyvitamin D3. The Journal
of clinical endocrinology and metabolism. 1980;51(4):7937.
doi:10.1210/jcem-51-4-793.
16. Jastrup B, Mosekilde L, Melsen F, Lund B, Lund B, Sorensen OH.
Serum levels of vitamin D metabolites and bone remodelling in
hyperthyroidism. Metabolism: clinical and experimental.
1982;31(2):12632.
17. MacFarlane IA, Mawer EB, Berry J, Hann J.Vitamin D metabolism
in hyperthyroidism. Clinical endocrinology. 1982;17(1):519.
18. Tamer G, MesçiB. Role ofvitamin D in the immune system. Turk J
Endocrinol Metab. 2013;17:57.
19. Rosen Y, Daich J, Soliman I, Brathwaite E, Shoenfeld Y. Vitamin D
and autoimmunity. Scand J Rheumatol. 2016;45(6):43947.
doi:10.3109/03009742.2016.1151072.
20. Bizzaro G, Shoenfeld Y. Vitamin D and thyroid autoimmune dis-
eases: the known and the obscure. Immunologic research.
2015;61(12):1079. doi:10.1007/s12026-014-8591-3.
21. Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clin-
ical and diagnostic criteria. Autoimmunity reviews. 2014;13(45):
3917. doi:10.1016/j.autrev.2014.01.007.
22. Menconi F, Marcocci C, Marino M. Diagnosis and classification of
Gravesdisease. Autoimmunity reviews. 2014;13(45):398402.
doi:10.1016/j.autrev.2014.01.013.
23. DeGroot LJ. GravesDisease and the Manifestations of
Thyrotoxicosis. In: De Groot LJ, Beck-Peccoz P, Chrousos G,
Dungan K, Grossman A, Hershman JM et al., editors. Endotext.
South Dartmouth (MA) 2000.
24. Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi
P. Autoimmune thyroid disorders. Autoimmunity reviews.
2015;14(2):17480. doi:10.1016/j.autrev.2014.10.016.
25. Effraimidis G, Wiersinga WM. Mechanisms in endocrinology: au-
toimmune thyroid disease: old and new players. European journal
of endocrinology. 2014;170(6):R24152. doi:10.1530/EJE-14-
0047.
26. Yin K, Agrawal DK. Vitamin D and inflammatorydiseases. Journal
of inflammation research. 2014;7:6987. doi:10.2147/JIR.S63898.
27. Fournier C, Gepner P, Sadouk M, Charreire J. In vivo beneficial
effects of cyclosporin A and 1,25-dihydroxyvitamin D3 on the in-
duction of experimental autoimmune thyroiditis. Clinical immunol-
ogy and immunopathology. 1990;54(1):5363.
28. Chen W, Lin H, Wang M. Immune intervention effects on the in-
duction of experimental autoimmune thyroiditis. Journal of
Huazhong University of Science and Technology Medical
sciences= Hua zhong ke ji da xue xue bao Yi xue Ying De wen
ban = Huazhong keji daxue xuebao Yixue Yingdewen ban.
2002;22(4):3435. 54.
29. Liu S, Xiong F, Liu EM, Zhu M, Lei PY. Effects of 1,25-
dihydroxyvitamin D3 in rats with experimental autoimmune thy-
roiditis. Nan fang yi ke da xue xue bao = Journal of Southern
Medical University. 2010;30(7):15736.
30. Misharin A, Hewison M, Chen CR, Lagishetty V, Aliesky HA,
Mizutori Y, et al. Vitamin D deficiency modulates Graveshyper-
thyroidism induced in BALB/c mice by thyrotropinreceptor immu-
nization. Endocrinology. 2009;150(2):105160. doi:10.1210
/en.2008-1191.
31. Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V,
Tomar N, et al. Prevalence of vitamin D deficiency and its relation-
ship with thyroid autoimmunity in Asian Indians: a community-
based survey. The British journal of nutrition. 2009;102(3):3826.
doi:10.1017/S0007114509220824.
32. Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Danko
K, et al. Vitamin D and autoimmune thyroid diseases. Cellular &
molecular immunology. 2011;8(3):2437. doi:10.1038
/cmi.2010.73.
33. Tamer G, Arik S, Tamer I, Coksert D. Relative vitamin D insuffi-
ciency in Hashimotos thyroiditis. Thyroid : official journal of the
American Thyroid Association. 2011;21(8):8916. doi:10.1089
/thy.2009.0200.
34. Bozkurt NC, Karbek B, Ucan B, Sahin M, Cakal E, Ozbek M, et al.
The association between severity of vitamin D deficiency and
Hashimotos thyroiditis. Endocr Pract. 2013;19(3):47984.
doi:10.4158/EP12376.OR.
35. Choi YM, Kim WG, Kim TY, Bae SJ, Kim HK, Jang EK, et al. Low
levels of serum vitamin D3 are associated with autoimmune thyroid
disease in pre-menopausal women. Thyroid : official journal of the
American Thyroid Association. 2014;24(4):65561. doi:10.1089
/thy.2013.0460.
36. Shin DY, Kim KJ, Kim D, Hwang S, Lee EJ. Low serum vitamin D
is associated with anti-thyroid peroxidase antibody in autoimmune
thyroiditis. Yonsei medical journal. 2014;55(2):47681.
doi:10.3349/ymj.2014.55.2.476.
37. Unal AD, Tarcin O, Parildar H, Cigerli O, Eroglu H, Demirag NG.
Vitamin D deficiency is related to thyroid antibodies in autoimmune
thyroiditis. Central-European journal of immunology. 2014;39(4):
4937. doi:10.5114/ceji.2014.47735.
38. Camurdan OM, Doger E, Bideci A, Celik N, Cinaz P. Vitamin D
status in children with Hashimoto thyroiditis. Journal of pediatric
endocrinology & metabolism : JPEM. 2012;25(56):46770.
39. Metwalley KA, Farghaly HS, Sherief T, Hussein A. Vitamin D
status in children and adolescents with autoimmune thyroiditis.
Journal of endocrinological investigation. 2016;39(7):7937.
doi:10.1007/s40618-016-0432-x.
40. Sonmezgoz E, Ozer S, Yilmaz R, Onder Y, Butun I, Bilge S.
Hypovitaminosis D in children with hashimotos thyroiditis.
Revista medica de Chile. 2016;144(5):6116. doi:10.4067/S0034-
98872016000500009.
41. Evliyaoglu O, Acar M, Ozcabi B, Erginoz E, Bucak F, Ercan O,
et al. Vitamin D deficiency and Hashimotos thyroiditis in children
and adolescents: a critical vitamin D level for this association?
Journal of clinical research in pediatric endocrinology. 2015;7(2):
12833. doi:10.4274/jcrpe.2011.
42. Yasuda T, Okamoto Y, Hamada N, Miyashita K, Takahara M,
Sakamoto F, et al. Serum vitamin D levels are decreased and asso-
ciated with thyroid volume in female patients with newly onset
Gravesdisease. Endocrine. 2012;42(3):73941. doi:10.1007
/s12020-012-9679-y.
43. Xu MY, Cao B, Yin J, Wang DF, Chen KL, Lu QB. Vitamin D and
Gravesdisease: a meta-analysis update. Nutrients. 2015;7(5):
381327. doi:10.3390/nu7053813.
Rev Endocr Metab Disord (2017) 18:347354 353
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
44. Zhou H, Xu C, Gu M. Vitamin D receptor (VDR) gene polymor-
phisms and Gravesdisease: a meta-analysis. Clinical endocrinolo-
gy. 2009;70(6):93845. doi:10.1111/j.1365-2265.2008.03413.x.
45. Feng M, Li H, Chen SF, Li WF, Zhang FB. Polymorphisms in the
vitamin D receptor gene and risk of autoimmune thyroid diseases: a
meta-analysis. Endocrine. 2013;43(2):31826. doi:10.1007
/s12020-012-9812-y.
46. Inoue N, Watanabe M, Ishido N, Katsumata Y, Kagawa T, Hidaka
Y, et al. The functional polymorphisms of VDR, GC and CYP2R1
are involved in the pathogenesis of autoimmune thyroid diseases.
Clinical and experimental immunology. 2014;178(2):2629.
doi:10.1111/cei.12420.
47. Meng S, He ST, Jiang WJ, Xiao L, Li DF, Xu J, et al. Genetic
susceptibility to autoimmune thyroid diseases in a Chinese Han
population: role of vitamin D receptor gene polymorphisms.
Annales dendocrinologie. 2015;76(6):6849. doi:10.1016/j.
ando.2015.01.003.
48. Stagnaro-Green A. Postpartum thyroiditis. Best Pract Res Clin
Endocrinol Metab. 2004;18(2):30316. doi:10.1016/j.
beem.2004.03.008.
49. Akamizu T. Postpartum Thyroiditis. In: De Groot LJ, Beck-Peccoz
P, Chrousos G, Dungan K, Grossman A, Hershman JM et al., edi-
tors. Endotext. South Dartmouth (MA) 2000.
50. Premawardhana LD, Parkes AB, Ammari F, John R, Darke C,
Adams H, et al. Postpartum thyroiditis and long-term thyroid status:
prognostic influence of thyroid peroxidase antibodies and ultra-
sound echogenicity. The Journal of clinical endocrinology and me-
tabolism. 2000;85(1):715. doi:10.1210/jcem.85.1.6227.
51. Krysiak R, Kowalska B, Okopien B. Serum 25-hydroxyvitamin D
and parathyroid hormone levels in Non-lactating women with post-
partum thyroiditis: the effect of L-thyroxine treatment. Basic Clin
Pharmacol Toxicol. 2015;116(6):5037. doi:10.1111/bcpt.12349.
52. Krysiak R, Kowalcze K, Okopien B. The effect of vitamin D on
thyroid autoimmunity in non-lactatingwomen with postpartum thy-
roiditis. Eur J Clin Nutr. 2016;70(5):6379. doi:10.1038
/ejcn.2015.214.
53. Sahin M, Corapcioglu D. The effect of vitamin D on thyroid auto-
immunity in non-lactating women with postpartum thyroiditis. Eur
J Clin Nutr. 2016;70(7):864. doi:10.1038/ejcn.2016.56.
54. Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson
JE, et al. The nonskeletal effects of vitamin D: an endocrine society
scientific statement. Endocr Rev. 2012;33(3):45692. doi:10.1210
/er.2012-1000.
55. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H,
Mohr SB, et al. The role of vitamin D in cancer prevention. Am J
Public Health. 2006;96(2):25261. doi:10.2105
/AJPH.2004.045260.
56. Giovannucci E. Vitamin D, and cancer incidence in the Harvard
cohorts. Annals of epidemiology. 2009;19(2):848. doi:10.1016/j.
annepidem.2007.12.002.
57. Trump DL, Deeb KK, Johnson CS. Vitamin D: considerations in
the continued development as an agent for cancer prevention and
therapy. Cancer J. 2010;16(1):19. doi:10.1097/PPO.0b013e3181
c51ee6.
58. Khadzkou K, Buchwald P, Westin G, Dralle H, Akerstrom G,
Hellman P. 25-hydroxyvitamin D3 1alpha-hydroxylase and vitamin
D receptor expression in papillary thyroid carcinoma. The journal
of histochemistry and cytochemistry : official journal of the
Histochemistry Society. 2006;54(3):35561. doi:10.1369/jhc.5
A6734.2005.
59. Dackiw AP, Ezzat S, Huang P, Liu W, Asa SL. Vitamin D3 admin-
istration induces nuclear p27 accumulation, restores differentiation,
and reduces tumor burden in a mouse model of metastatic follicular
thyroid cancer. Endocrinology. 2004;145(12):58406. doi:10.1210
/en.2004-0785.
60. Izkhakov E, Somjen D, Sharon O, Knoll E, Aizic A, Fliss DM, et al.
Vitamin D receptor expression is linked to potential markers of
human thyroid papillary carcinoma. The Journal of steroid bio-
chemistry and molecular biology. 2016;159:2630. doi:10.1016/j.
jsbmb.2016.02.016.
61. Clinckspoor I, Hauben E, Verlinden L, Van den Bruel A,
Vanwalleghem L, Vander Poorten V, et al. Altered expression of
key players in vitamin D metabolism and signaling in malignant
and benign thyroid tumors. The journal of histochemistry and cy-
tochemistry : official journal of the Histochemistry Society.
2012;60(7):50211. doi:10.1369/0022155412447296.
62. Chiang KC, Kuo SF, Chen CH, Ng S, Lin SF, Yeh CN, et al.
MART-10, the vitamin D analog, is a potent drug to inhibit ana-
plastic thyroid cancer cell metastatic potential. Cancer letters.
2015;369(1):7685. doi:10.1016/j.canlet.2015.07.024.
63. Peng W, Wang K, Zheng R, Derwahl M. 1,25 dihydroxyvitamin D3
inhibits the proliferation of thyroid cancer stem-like cells via cell
cycle arrest. Endocr Res. 2016;41(2):7180. doi:10.3109
/07435800.2015.1037048.
64. Liu W, Asa SL, Ezzat S. 1alpha,25-Dihydroxyvitamin D3 targets
PTEN-dependent fibronectin expression to restore thyroid cancer
cell adhesiveness. Mol Endocrinol. 2005;19(9):234957.
doi:10.1210/me.2005-0117.
65. Bikle DD. Vitamin D, and cancer: the promise not yet fulfilled.
Endocrine. 2014;46(1):2938. doi:10.1007/s12020-013-0146-1.
66. Tagliabue E, Raimondi S, Gandini S. Vitamin D, cancer risk, and
mortality. Adv Food Nutr Res. 2015;75:152. doi:10.1016/bs.
afnr.2015.06.003.
67. Laney N, Meza J, Lyden E, Erickson J, Treude K, Goldner W. The
prevalence of vitamin D deficiency is similar between thyroid nod-
ule and thyroid cancer patients. International journal of endocrinol-
ogy. 2010;2010:805716. doi:10.1155/2010/805716.
68. Lizis-Kolus K, Hubalewska-Dydejczyk A, Trofimiuk-Muldnerz M,
Sowa-Staszczak A, Kowalska A. Assessment of 25(OH)D3, con-
centration levels in patients with papillary thyroid cancer compared
to patients with Hashimotos thyroiditis. Przegl Lek. 2013;70(11):
9205.
69. Jonklaas J, Danielsen M, Wang H. A pilot study of serum selenium,
vitamin D, and thyrotropin concentrations in patients with thyroid
cancer. Thyroid : official journal of the American Thyroid
Association. 2013;23(9):107986. doi:10.1089/thy.2012.0548.
70. Ahn HY, Chung YJ, Park KY, Cho BY. Serum 25-hydroxyvitamin
D level does Not affect the aggressiveness and prognosis of papil-
lary thyroid cancer. Thyroid : official journal of the American
Thyroid Association. 2016;26(3):42933. doi:10.1089
/thy.2015.0516.
71. OGrady TJ, Kitahara CM, DiRienzo AG, Gates MA. The associ-
ation between selenium and other micronutrients and thyroid cancer
incidence in the NIH-AARP Diet and Health Study. PLoS One.
2014;9(10), e110886. doi:10.1371/journal.pone.0110886.
72. Roskies M, Dolev Y, Caglar D, Hier MP, Mlynarek A, Majdan A,
et al. Vitamin D deficiency as a potentially modifiable risk factor for
thyroid cancer. J Otolaryngol Head Neck Surg. 2012;41(3):1603.
73. Sahin M, Ucan B, Ginis Z, Topaloglu O, Gungunes A, Bozkurt NC,
et al. Vitamin D3 levels and insulin resistance in papillary thyroid
cancer patients. Med Oncol. 2013;30(2):589. doi:10.1007/s12032-
013-0589-5.
74. Kim JR, Kim BH, Kim SM, Oh MY, Kim WJ, Jeon YK, et al. Low
serum 25 hydroxyvitamin D is associated with poor clinicopatho-
logic characteristics in female patients with papillary thyroid cancer.
Thyroid : official journal of the American Thyroid Association.
2014;24(11):161824. doi:10.1089/thy.2014.0090.
354 Rev Endocr Metab Disord (2017) 18:347354
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
1.
2.
3.
4.
5.
6.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
apply.
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
not:
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
control;
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
writing;
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
content.
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
onlineservice@springernature.com
... Because almost all women included in the present study were vitamin D insuffi cient during wintertime, we did not use winter data for statistical analysis. Other factors such as sun exposure, diet, smoking, physical activity, etc., may participate in achieving different results (28). However, we did not take into account these factors, which can be one of several limitations of this study. ...
Article
Unlabelled: The role of vitamin D (VD) in the etiopathogenesis of autoimmune diseases (AI) is extensively studied. However, its association with autoimmune thyroid disease (AITD) is still controversial. AIM of this study was to assess the relationship between the vitamin D status and thyroid autoimmunity in Slovak premenopausal women with newly diagnosed AITD. Subjects and methods: This prospective case-control study included 57 women with AITD and 41 age- and BMI-matched controls. All subjects were examined for summer and winter serum 25(OH)D, thyroid autoantibodies (a-TPO, a-TG), freeT4 and TSH concentrations. Thyroid volume was measured by ultrasound. Results: There were no significant differences in serum 25(OH)D between AITD and control groups. No significant correlation between 25(OH)D and thyroid autoantibodies was found either in the whole cohort or in AITD women. The prevalence of vitamin D insufficiency was 60.31 % in AITD women and 52.5 % in the control group. No significant association between VD and thyroid autoantibodies, thyroid hormones and thyroid volume was detected in this study. Conclusion: Authors conclude that VD insufficiency is common in Slovak premenopausal women independently of the presence of AITD. Vitamin D insufficiency is not associated with thyroid autoimmunity in patients with early diagnosis of AITD (Tab. 3, Ref. 31). Text in PDF www.elis.sk Keywords: vitamin D, autoimmune thyroid disease, thyroid autoantibodies.
... Одним з таких варіантів є поліморфізм BSML гену VDR. Дослідження показали, що мутація поліморфізму спостерігається при онкопатології, захворюваннях серцево-судинної та нервової систем, системних та автоімунних захворюваннях (остеопороз, остеоартроз, цукровий діабет та ін.), але популяційних досліджень щодо розповсюдження цього гену в населення України, яке не має хронічних захворювань, не проводилося або вибірка була недостатньою [9][10][11]. Відомо, що наявність гетерозиготної чи гомозиготної мутації гену VDR знижує функціональну ефективність рецептора вітаміну D, що, у свою чергу, призводить до того, що навіть при адекватному рівні цього вітаміну, біохімічні процеси, за які він відповідає, не запускаються в повному обсязі. ...
Article
Full-text available
Мета дослідження – встановити особливості статусу вітаміну D та мінерального обміну в дітей в період другого ростового спурту залежно від поліморфізму BSML гену VDR. Матеріали та методи. Обстежено 205 дітей віком 9–17 років, які були розподілені на групи залежно від наявності ростового спурту та його інтенсивності. I групу склали 50 дітей, які за поточний рік прибавили в зрості 8–12 см; у II групу ввійшли 46 дітей, які за поточний рік прибавили у зрості більш ніж 12 см; III група – 109 дітей, які не мали ростового спурту. Обстеження включало аналіз даних анамнезу, оцінку рівня фізичного та статевого розвитку, визначення рівнів кальцію, фосфору, магнію, вітаміну D та поліморфізму гену VDR. Результати дослідження та їх обговорення. В усіх групах дітей спостерігалося зниження рівня кальцію. Так, середній рівень загального кальцію у дітей І групи склав (2,22±0,15) ммоль/л, іонізованого кальцію – (1,12±0,28) ммоль/л. У дітей ІІ групи рівень загального кальцію склав (2,13±0,11) ммоль/л, іонізованого – (0,99±0,10) ммоль/л, у дітей ІІІ групи – (2,26± 0,18) ммоль/л та (1,12±0,10) ммоль/л відповідно. У всіх дітей було діагностовано недостатність або дефіцит вітаміну D. Середній рівень вітаміну D у дітей I групи склав (40,80±9,44) нмоль/л, недостатність виявлено у 9 (18,0 %) дітей та дефіцит – у 41 (82,0 %) дитини. У дітей II групи середній рівень вітаміну D склав (45,6±5,14) нмоль/л, недостатність діагностовано у 6 (13,04 %) дітей, а дефіцит – у 40 (86,96 %) дітей. У дітей III групи середній рівень вітаміну D по групі склав (40,47± 9,49) нмоль/л, недостатність вітаміну виявлено у 18 (16,5 %) дітей, дефіцит – у 91 дитини (83,5 %). При проведені молекулярного дослідження встановлено, що у 48,76 % дітей не виявлено мутацій поліморфізму BSML гену VDR, у 41,32 % дітей виявлено гетерозиготну мутацію, у 9,92 % дітей – гомозиготну мутацію. Висновки. Зниження забезпечення кальцієм на тлі низького рівня вітаміну D впливає на мінералізацію кісткової тканини, проте в період інтенсивного росту дитини більший вплив має неспроможність дитячого організму щодо адекватного формування кісткової тканини. У 100 % дітей рівень вітаміну D не сягав референтних значень.
... 18 Neste trabalho não houve associação entre a hipovitaminose e a insuficiência comparado às doenças psiquiátricas e ao hipotireoidismo, diferindo de outros estudos. [19][20][21] Além disso, o cálcio foi analisado devido a sua participação e sua fundamental importância no metabolismo da vitamina D, porém não foi encontrada relevância entre sua dosagem e as doenças estudadas. ...
... Many studies have estimated the impact of vitamin D in the pathogenesis of thyroid dysfunctions [39], although the relationship between vitamin D deficiency and thyroid cancer remains questionable. Some studies have approved the fact that high vitamin D levels could protect against thyroid cancer, while others revealed that reduced vitamin D levels are related to an increased risk of thyroid cancer and aggressiveness [40]. ...
Article
Full-text available
Thyroid cancer is the most common endocrine tumor, accounting for about 1% of all human malignancies. There are environmental factors that can potentiate the onset of thyroid cancer, in particular pollutants, lifestyle or radiation exposure. Another major cause responsible for the appearance of thyroid cancer is the habitat in endemic areas where there is a deficit of iodine in the soil, drinking water and food. We operated using the PubMed database in order to find the articles of interest. After a wary review of the literature, we designated the relevant articles necessary for our study including various factors such as alimentation, effects of the Chernobyl fallout radiation and the iodine and vitamin D deficiency in Romania. The aim of this article is to make a correlation between the different environmental and dietary factors in Romania, and the increased incidence of thyroid cancer.
... Besides, Kazakhstan is an iodine-deficient area [30] and this plays a role in the spread of thyroid disorders. Finally, Vitamin D deficiency is prevalent in Kazakhstan [31] and reduction of Vitamin D circulating levels has been recently reported to play a role in TAIDs [32]. This study has a number of drawbacks that deserve to be considered in detail. ...
Article
Full-text available
Background Antibodies against thyroid peroxidase (anti-TPO) serve as clinical markers of thyroid autoimmune diseases (TAIDs). By trying to elucidate the causes of heterogeneity in autoantibody levels among patients with different TAIDs it becomes possible to clarify the pathophysiology of GD and HT. Objective To investigate the heterogeneity of epitopes recognized by anti-TPO in patients with Hashimoto’s thyroiditis (HT), Graves’ disease (GD) and overlap-syndrome. Methods We carried out a cross-sectional study on 398 patients with GD, HT and overlap syndrome and analyzed the specificity of epitopes and binding constants of TPO with monoclonal antibodies (MAbs). Ten MAbs to TPO were used, of which five were reactive with native TPO and the rest were reactive with denaturated TPO. Results The autoantibodies in blood serum of HT patients inhibited the binding of MAb63 more significantly than those in serum of GD patients: 59.62 % versus 54.02 %, respectively (p = 0.001). The anti-TPOs in serum of GD patients inhibited the binding of MAb77 more significantly than those in serum of HT patients: 54.36 % versus 51.13 %, respectively (p = 0.047). The binding of MAb45 was more inhibited in serum of patients with anti-TPO concentration over 1000 IU/ml (58.36 %). The blood serum of patients with overlap-syndrome showed less significant inhibition of MAb63 binding than that of patients with no overlap-syndrome: 52.47 % versus 58.81 %, respectively (p = 0.043). Conclusion Mapping the epitopes to TPO with the help of MAbs may improve the differential diagnosis between different thyroid autoimmunities.
Conference Paper
Cross sectional study was carried out to evaluate the prevalence of vitamin D deficiency in patients with Gout and identify the correlation between high concentrations of serum uric acid within the oxidative stress.The study was conducted to 125 specimens of serum sample collected from patients with gout and healthy individuals, 82 of them from patients aged between 35 to 70 year, and 43 specimens for healthy individuals as control group. All samples were collected from external medical laboratory in Al-Duloua from the period 1/9/2020 until 1/11/2020. The study includes determination of serum uric acid-UA, Vitamin D, Total antioxidant capacity-TAC, Glutathione and Malondialdehyde-MDA. The results indicate that the prevalence of Vitamin D deficiency between patients with gout was 92.7% and 7.3% with normal concertation of serum vit D. The results obtained from the present study showed that the level of serum UA and TAC significantly(P≤0.05 ) increased in sera of patients with gout, while the level of Vit D and MDA significantly decreased (P≤0.05) in sera of patients as compared with control group, with no significant change in the level of GSH. So, we can conclude from the present study, that the high serum UA level was found to be closely associated with vit. D deficiency, and also the level of Serum uric acid is related to oxidative status. Therefore, uric acid may be act as antioxidant agent in humans.
Article
Full-text available
Background: Autoimmune thyroiditis (AIT) is the most common autoimmune disease, affecting 3-5% patients worldwide. In recent years, approximately 200 articles on AIT have been published annually in various journals. However, to date, no article has systematically assessed the related literature. Therefore, we conducted a bibliometric analysis on AIT to reveal the dynamic scientific developments and help researchers gain a global perspective while exploring the hotspots and development trends. Methods: AIT-related articles and reviews from 2000 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The following search terms were used to extract document data: TS= (" autoimmune thyroiditi*") OR TI= ("chronic lymphocytic thyroiditi*") OR TI=(hashimoto*) OR TI= ("postpartum thyroiditis"). We selected articles and reviews published in English from 2000 to 2022. Three software programs (VOSviewer, CiteSpace, Pajek) were employed to analyze the contribution and co-occurrence relationships of different references, countries/regions, institutes, journals and also keywords in this field. Results: This scientometric study included 2290 English papers published in 723 journals with 39661 co-cited references from 561 institutions in 120 countries/regions. Based on the reference and keyword analysis, researchers used to focus on "apoptosis", "insulin resistance", "encephalopathy", "IFN-γ" related to AIT during the past 20 years. However, with the development of other novel directions such as "papillary thyroid cancer" (2018-2022), "Vitamin D" (2016-2022), "oxidative stress" (2018-2022), "polymorphism" (2019-2022) and "association" (2020-2022), researchers are more interested in the relationship between papillary thyroid carcinoma and AIT, the effect of vitamin D supplementation on AIT, the oxidative stress in thyroid disease as well as the influence of polymorphism. Conclusion: Bibliometric analysis of the outputs of AIT shows an overview of the current status of the research on AIT. The associations between papillary thyroid carcinoma, vitamin D, oxidative stress, polymorphism and AIT are major research frontiers. However, further research and collaboration are still required worldwide. Our findings can help researchers grasp the research status of AIT and quickly determine new directions for future research.
Thesis
Full-text available
Abstract This study was conducted at Azadi Teaching Hospital in the city of Kirkuk from (November 2019 to February 2020) for people suffering from infertility and low fertility diagnosed by doctors, as 75 samples were collected at ages ranging between (50-25) years, including (60) Sample suffers from infertility and lack of fertility. The samples were distributed into five groups, each the group contained (15) samples and agencies: Azoospermia group, Teratozospermia group, Oligozoospermia group, Asthenozoospermia group and the fifth group which includes fifteen 15 healthy individuals able to give birth are considered as a control group. The study included measuring some biochemical parameters in the serum and plasma samples, represented by measuring the levels of vitamin D, Zinc, Magnesium and some sex hormones such as Testosterone, Follicle stimulating hormone (FSH), and the Luteinizing hormone (LH), in addition to measuring some of the oxidant-antioxidant parameters, which included Mallon dialdehyde (MDA), Glutathione (GSH), Glutathione Peroxidase (GPx) and Super Oxide Dismutase (SOD) The results of the current study, which are analyzed statistically according to an Anova One Way program by SPSS application at a significant level P< 0.05 indicated a significant decrease in Vitamin D levels in the experimental groups: The Azoospermia group, Teratozospermia group, Oligozoospermia group and Asthenozoospermia group compared to the control group, The results also showed a significant decrease in testosterone levels In Oligozoospermia group, and Asthenozoospermia Compared to a control group. while there were no significant differences in Testosterone hormone levels for the Azoospermia and Teratozospermia group as compared to control group. The results also showed a significant increase in the levels of B follicle stimulating hormone (FSH) in the experimental groups: Azoospermia group, Oligozoospermia group and Asthenozoospermia group as compared to control group. Compared to the control group, there was a significant decrease in FSH levels in the experimental group Teratozospermia group as compared to the control group. The results showed a significant decrease in the LH levels in experimental groups: Teratozospermia group, Oligozoospermia group and Asthenozoospermia group, while there is no significant difference in Azoospermia group as compared with the control group. The study determined a positive correlation (direct) between Vitamin D level and Testosterone hormone where was the correlation coefficient (r=0.4434), also there was a negative correlation (indirect) between Vitamin D levels and FSH levels where was the correlation coefficient (r=0.6894). In addition positive correlation (direct) determined between Vitamin levels and LH levels where was the correlation coefficient between them (r=0.3331). The study reported a significant increase in MDA levels as an antioxidant indicator in the Asthenozoospermia group, Teratozospermia group, Oligozoospermia group and Azoospermia group with a significant decrease in the SOD levels, GPx and GSH in the experimental groups as compared to the control group. The study results showed a negative correlation between Vitamin D levels and MDA levels where was the correlation coefficient between them (r=- 0.5863), also a positive direct correlation between Vitamin levels and antioxidant enzymes GSH The correlation coefficients were (r=0.5154), GPx (r=0.8507) and SOD (r=0.7254) respectively. The study results revealed a significant decrease in trace elements levels Zn and Mg in the experimental groups: Azoospermia group, Teratozospermia C group, Oligozoospermia group and Asthenozoospermia group compared to the control group. The results also showed a positive direct correlation between Vitamin D levels with Zn levels The correlation coefficients were (r=0.7049) and Mg (r=0.5548). By presenting the results, we conclude that the level of vitamin D has a vital and essential role in the case of infertility and decreased fertility and is directly related to the state of oxidative stress and the lack of micronutrients necessary for the work of many effective enzymes such as Zinc and Magnesium in addition to its direct effect on sex hormones such as Testosterone and FSH and LH.
Article
Full-text available
Background: Vitamin D deficiency or insufficiency may play a role in the pathogenesis of certain autoimmune diseases. Aim: To measure vitamin D levels in children with Hashimoto’s thyroiditis (HT) (either with subclinical or marked hypothyroidism) and in healthy controls. Material and Methods: We included 68 children with HT aged 12 ± 4 years (39 females) from a pediatric outpatient clinic and 68 healthy children aged 10 ± 4 years (37 females). Calcium metabolism parameters, thyroid function tests and anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) and 25 hydroxy vitamin D (25OHD) levels were measured. Results: Patients were older than controls but well matched by gender distribution. Mean 25OHD levels were significantly lower in HT patients than controls (16.8 ± 9.3 and 24.1 ± 9.4 ng/mL respectively, P < 0.01). Frequency of vitamin D deficiency was 76 and 35% in HT patients and controls, respectively (P < 0.001). Conclusions: Vitamin D deficiency is more common in children with HT than healthy controls. Key words: Hashimoto Disease; Hypothyroidism; Vitamin D Deficiency.
Article
Full-text available
In this review we summarize recent opinions on the possible role of vitamin D in the risk of thyroid diseases development. It may be concluded from the available data that vitamin D deficiency, particularly levels below 12.5 ng/ml should be considered as an additional, but important risk factor for development of thyroid autoimmunity, both chronic autoimmune thyroiditis and Graves' disease. A higher risk of Graves' disease development is also associated with several polymorphisms in the gene encoding for vitamin D binding protein and for the specific receptor of active form of vitamin D - 1,25-(OH)(2)D-3 in the respective target cells. Important for development of thyroid cancer appeared polymorphisms of genes encoding for vitamin D receptors and of genes encoding for the participating hydroxylating enzymes in thyroid tissue, leading to a diminished local 1,25-(OH)(2)D-3 formation capacity with following alteration of antiproliferatory, antiapoptotic and prodifferentiating efficacy of the latter. Whether supplementation with high doses of vitamin D or its analogues possesses preventive or therapeutic effect is an object of intensive studies.
Article
Full-text available
Background: Vitamin D deficiency has been known to be associated with the aggressiveness and prognosis of several cancers. In this study, we evaluated the effect of preoperative serum vitamin D level on the aggressiveness and prognosis of papillary thyroid cancer. Methods: In total, 820 patients with papillary thyroid cancer were enrolled. Vitamin D levels were measured in blood samples before surgery. Clinical, pathologic, and recurrence data were accessed to examine the prognostic effects of vitamin D. Patients were categorized into four quartiles by preoperative serum vitamin D levels. Results: Of the enrolled patients, 795 (97%) had insufficient vitamin D levels (< 30 ng/mL). Vitamin D levels showed positive correlations with age and body mass index (BMI) and negative correlations with serum thyroid-stimulating hormone (TSH) levels and anti-thyroid peroxidase antibody titers. The association between vitamin D quartile and the risks of extrathyroidal invasion, lymph node metastasis, advanced cancer stages (III or IV) and risk of recurrence were not significant after adjusting for age, sex, BMI, preoperative ionized calcium and PTH. Additionally, serum vitamin D was not associated with recurrent or persistent papillary thyroid cancer. Conclusion: Serum vitamin D levels are not associated with either disease aggressiveness or poor outcomes among patients with papillary thyroid cancer and vitamin D insufficiency.
Article
Objectives: To review and evaluate the role of vitamin D in autoimmune diseases based on current studies. Method: We searched PubMed using keywords such as 'vitamin D', 'autoimmune disease', and 'autoimmunity'. We compiled and reviewed various studies including prospective cohorts, cross-sectional studies, longitudinal evaluations, genetic studies, and experimental models that investigated the role of vitamin D in autoimmune diseases. Results: There is evidence based on these various studies that several key autoimmune diseases are modulated by vitamin D. These diseases include, but are not limited to, multiple sclerosis (MS), scleroderma or systemic sclerosis (SSc), autoimmune thyroid diseases, rheumatoid arthritis (RA), and primary biliary cirrhosis (PBC). Conclusions: Although there is evidence for vitamin D as a factor in the pathophysiology of autoimmune diseases, the mechanism for this association has yet to be elucidated. Additional data are needed to corroborate these findings.
Article
We read with great interest the manuscript entitled 'The effect of vitamin D on thyroid autoimmunity in non-lactating women with postpartum thyroiditis'.¹ Vitamin D supplementation may have an impact on postpartum thyroiditis. But we would like to comment on several aspects.
Article
Background: An anti-proliferative effect of vitamin D has been reported in different carcinomas, including thyroid cancer. Cancer stem cells (CSCs), a very small fraction of cancer cells, are widely believed to be responsible for cancer initiation, relapse and metastasis. Objectives: We addressed the question as to whether CSCs derived from the anaplastic thyroid carcinoma cell lines SW1736, C643, HTh74 and its doxorubicin-resistant subline HTh74R are also a target of vitamin D action. Methods: The effect of calcitriol on growth of HTh74, HTh74R, SW1736 and C643 cell lines was investigated by cell viability assays. In stem-enriched cells derived from thyro-spheres, cell cycle analysis and apoptotic assays were performed. Furthermore, the role of calcitriol in the formation of cancer thyro-spheres and its putative differentiation-inducing effect were analysed. Results: CSCs isolated as thyro-spheres from all the four anaplastic thyroid carcinoma cells expressed vitamin D receptors as did their parental cells. Calcitriol inhibited proliferation of anaplastic thyroid carcinoma cells with a more pronounced effect on doxorubicin-resistant HTh74R cells, and it significantly reduced the capacity to form stem cell-derived spheres and decreased the size of these spheres that consist of CSCs and their progenitor cells. As revealed by cell cycle analysis, calcitriol-induced G2/M phase arrest in thyro-sphere cells derived cells from HTh74, HTh74R and C643 but did not affect apoptosis. Finally, calcitriol altered morphology of CSCs. Conclusion: Calcitriol inhibited the growth of CSCs derived from anaplastic thyroid cancer cells. It may also exert a pro-differentiation effect in thyroid CSCs.
Article
Genes regulated cell-cell and cell-matrix adhesion and degradation of the extracellular matrix (ECM) have been screened as potential markers of malignant thyroid nodules. The mRNA expression levels of two of them, the ECM protein-1 (ECM1) and the type II transmembrane serine protease-4 (TMPRSS4), were shown to be an independent predictor of an existing thyroid carcinoma. The vitamin D receptor (VDR) is expressed in epithelial cells of the normal thyroid gland, as well as in malignant dividing cells, which respond to the active metabolite of vitamin D by decreased proliferative activity in vitro. We evaluated the relationship between mRNA gene expressions of TMPRSS4, ECM1 and VDR in 21 papillary thyroid carcinoma samples and compared it to 21 normal thyroid tissues from the same patients. Gene expression was considered as up- or down-regulated if it varied by more or less than 2-fold in the cancer tissue relative to the normal thyroid tissue (Ca/N) from the same patient. We found an overall significant adjusted correlation between the mRNA expression ratio (ExR) of VDR and that of ECM1 in Ca/N thyroid tissue (R = 0.648, P < 0.001). There was a high ExR of VDR between Ca/N thyroid tissue from the same patient (3.06 ± 2.9), which also exhibited a high Ca/N ExR of ECM1 and/or of TMPRSS4 (>2, P = 0.05).The finding that increased VDR expression in human thyroid cancer cells is often linked to increased ECM1 and/or TPMRSS4 expression warrants further investigation into the potential role of vitamin D analogs in thyroid carcinoma.
Article
Background Vitamin D deficiency is a global health problem. Its role as an immune modulator has been recently emphasized. There is increasing evidence for the significant role of vitamin D in reducing the incidence of autoimmune diseases. However, little is known about the status of vitamin D in children and adolescents with autoimmune thyroiditis (AIT). Objective The goal of the present study was to assess vitamin D status in Egyptian children and adolescents with AIT and to explore its relation to biomarkers of autoimmunity and thyroid function. Design A prevalence case–control study that included 56 children with AIT and 56 healthy, age- and sex-matched subjects that served as the control group. The following was done for all participants: thorough history, physical examination, thyroid ultrasound, measurement of thyroid-stimulating hormone (TSH), free thyroxin (FT4), anti-thyroid peroxidase antibodies (TPOAb), anti-thyroglobulin antibody (TgAb) and assessment of serum 25-hydroxy vitamin D (25OHD) level. Results Overt hypothyroidism was detected in 42/56 while subclinical hypothyroidism was detected in 14/56 of the studied patients. Vitamin D deficiency rate was significantly higher in the AIT group compared to the control subjects (71.4 vs 21.4 %, P < 0.001). In AIT group, the mean level of 25OHD was significantly lower compared to the control group (16.2 ± 8.2 vs 33.9 ± 12.7 nmol/L, P < 0.001). The difference was more evident in patients with overt hypothyroidism than those with subclinical hypothyroidism (P < 0.01). There were significant negative correlations between serum 25OHD and age, duration of the disease, BMI, anti-TPOAb, anti-TGAb and TSH (P < 0.001 each). On the other hand, serum 25OHD correlated positively with FT4 levels. While 25OHD level was an independent risk factor for AIT, it failed to qualify as an independent risk for the progression of AIT to overt hypothyroidism after adjustment for other potential confounding factors; age, sex and BMI. Conclusions Low serum vitamin D is significantly associated with AIT in Egyptian children. However, vitamin D level is not an independent risk for the progression of AIT to overt hypothyroidism. BMI may have an influence on serum 25OHD levels.
Article
The study included 38 non-lactating l-thyroxine-treated women with postpartum thyroiditis (PPT) and 21 matched healthy postpartum women. Women with vitamin D deficiency were treated with oral vitamin D (4000 IU daily), whereas women with vitamin D insufficiency and women with normal 25-hydroxy vitamin levels were either treated with vitamin D (2000 IU daily) or left untreated. Serum hormone levels and thyroid antibody titers were measured at the beginning of the study and 3 months later. 25-hydroxy vitamin D levels were lower in women with PPT than in healthy women. Thyroid peroxidase and thyroglobulin antibody titers inversely correlated with vitamin D status. Apart from increasing serum levels of 25-hydroxy vitamin D and decreasing serum levels of parathyroid hormone, vitamin D reduced titers of thyroid peroxidase antibodies and this effect was stronger in women with vitamin D deficiency. The study's results suggest that vitamin D supplementation may bring benefits to l-thyroxine-treated women with PPT.European Journal of Clinical Nutrition advance online publication, 13 January 2016; doi:10.1038/ejcn.2015.214.
Article
Purpose: Previous studies have found that some immune-related genes were associated with autoimmune thyroid diseases (AITDs). A couple of studies have explored the association between vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR) gene polymorphisms and susceptibility to AITDs in different populations and found conflicting results. This case-control study was designed to evaluate the role of polymorphisms of VDR gene in the predisposition of AITDs in a Chinese Han population. Methods: A total of 417 patients with Graves' disease (GD), 250 patients with Hashimoto's thyroiditis (HT) and 301 healthy subjects were enrolled. The Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform was applied to detect four SNPs (rs1544410, rs2228570, rs731236 and rs7975232) in the VDR gene. Results: In the rs7975232 allele A frequency showed a significant increase in GD patients (30.34% vs. 25.42% in controls; P=0.041, OR=1.278, 95%CI=1.010-1.617). However, no relationship was found between clinical phenotypes and the four SNPs. Conclusions: This result suggests that the VDR gene may be one susceptibility gene which contributes to the risk of GD.