IVAN PANKIV

HYPOVITAMINOSIS D IN AUTOIMMUNE
THYROIDITIS PATIENTS WITH SUBCLINICAL
OROVERT HYPOTHYROIDISM
NIEDOBR WITAMINY D U OSB Z AUTOIMMUNOLOGICZNYM
ZAPALENIEM TARCZYCY ORAZ UTAJON LUB JAWN JEJ
NIEDOCZYNNOCI
D.F. Chebotarev Institute of Gerontology of Ukrainian National Academy of Medical Sciences, Kyiv, Ukraine

SUMMARY. There is increasing in the role vitamin D deficiency in anumber of chronic health problems including autoimmune diseases. Itwas
reported that patients with autoimmune thyroid disease have lower vitamin D levels. Therefore the study aimed at the investigation of the total
vitamin 25(OH)D in 70 autoimmune thyroiditis patients with subclinical (n=21) and overt (n=49) hypothyroidism was undertaken.
70 patients (54 females and 16 males) and 20 apparently healthy individuals with matched age and sex underwent adetailed clinical examination, thyroid function tests (TSH, fT4, fT3, thyroid peroxidase antibodies) and serum total vitamin 25(OH)D. The patient group with autoimmune
thyroiditis was classified according to the level of TSH into subclinical and overt hypothyroid groups. Levels of serum TSH were significantly
increased in subclinical (6.801.84 IU/ml) and hypothyroid (10.242.09 IU/ml) groups as compared to control group (2.160.39 IU/ml)
(p<0.05). The thyroid peroxidase antibodies level was 312.837.19 IU/ml in subclinical, hypothyroid group and 529.319,62 IU/ml in the
overt hypothyroid group. The levels of serum total 25(OH)D were significantly decreased in subclinical (21.91.1 nmol/L) and overt hypothyroid groups (18.81.2 nmol/L) as compared to control group (27.11.2 nmol/L), (p< 0.05). Ahighly significant negative correlation was
found between serum TSH, thyroid peroxidase antibodies and total 25(OH)D levels (p<0.001). Also highly significant positive correlation was
found between the levels of serum total 25(OH)D and serum fT4 (p<0.001). There was significant positive correlation between TSH and thyroid peroxidase antibodies levels (p<0.05). It could be concluded, that vitamin 25(OH)D deficiency is associated with autoimmune thyroiditis.
Key words autoimmune thyroiditis, vitamin D deficiency.
STRESZCZENIE. Obserwuje si znaczne zainteresowanie badawcze odnoszce si do roli niedoboru witaminy D wwielu przewlekych chorobach, wtym wchorobach oautoimmunologicznej patogenezie. Doniesiono, e pacjenci zautoimmunologicznymi chorobami tarczycy wykazuj
obnione poziomy witaminy D we krwi. Ztych powodw podjto badania poziomu witaminy 25 (OH)D wgrupie 70 przypadkw autoimmunologicznego zapalenia tarczycy zsubkliniczn niewydolnoci (n-21) iobjawow niedoczynnoci tarczycy (n-49). 70 pacjentw (54 kobiety i16
mczyzn) oraz odpowiednio dobranych wzgldem wieku ipci 20 zdrowych osb poddano szczegowym badaniom klinicznym, ocenie testw
czynnociowych tarczycy (TSH, fT4, fT3), obecnoci przeciwcia peroksydazowych. Uwszystkich okrelono poziom witaminy 25 (OH)D wsurowicy. Grup pacjentw zautoimmunologicznym zapaleniem tarczycy podzielono na podgrup zutajon klinicznie postaci choroby (TSH: 6.901.84
IU/ml) oraz klinicznie jawn postaci (TSH: 10.242.09 IU/ml). Wgrupie porwnawczej osb zdrowych poziom TSH wynosi 2.160.39 IU/
ml (p<0,05). Poziom przeciwcia peroksydazowych wpodgrupie utajonej niedoczynnoci tarczycy wynosi 312.837.19 IU/ml oraz wpodgrupie jawnej niedoczynnoci 529.319.62 IU/ml. Wpodgrupie utajonej niedoczynnosci tarczycy poziom witaminy 25 (OH)D by istotnie obniony
21.91.1 nmol/l, jeszcze bardziej by niski wpodgrupie zjawn niedoczynnoci tarczycy 18.81.2 nmol/l. Wpodgrupie kontrolnej osb
zdrowych poziom witaminy 25 (OH)D wynosi 27.11.2 nmol/l (p<0,05). Stwierdzono take bardzo istotn, negatywn korelacj pomidzy poziomem TSH wsurowicy iprzeciwcia peroksydazowych apoziomami witaminy 25 (OH)D (p<0,001). Pozytywn korelacj stwierdzono midzy
poziomem witaminy 25 (OH)D asteniem fT4 wsurowicy (p<0,001), oraz take TSH apoziomem przeciwcia peroksydazowych (p<0,05).
Naley stwierdzi, e wautoimmunologicznym zapaleniu tarczycy wystpuje niedobr witaminy 25 (OH)D.
Sowa kluczowe Autoimmunologioczne zapalenie tarczycy, niedobr witaminy.
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INTRODUCTION
There is increasing interest in the role of vitamin D
deficiency in anumber of chroni health problems including autoimmune diseases (1, 2). Over abillion people
worldwide are vitamin D deficient or insufficient (3). The
etiology and pathogenesis of most autoimmune disorders
remain obscure and anumber of factors have been implicated in their pathogenesis, one of the most recent agents
found to be associated with autoimmunity is vitamin
25(OH)D (4). The demonstration of vitamin D receptor
in monocytes, dendritic cells and activated T cells indicate significant interaction between vitamin D and immune
system (5).
Autoimmunity of the thyroid gland results in aspectrum of thyroid diseases. Etiologically patients with autoimmune thyroiditis are usually hypothyroid (1).
Vitamin D deficiency has been shown to be associated with autoimmune diseases, including rheumatoid
arthritis, systemic lupus erythematosus, inflammatory
bowel disease, multiple sclerosis and type 1 diabetes
mellitus, and that vitamin D supplementation prevents
the onset and/or development of these autoimmune diseases (6). Furthermore, it was reported that patients with
Hashimotos thyroiditis, an autoimmune thyroid disease
had lower vitamin D levels (7).
Serum 25(OH) D, the most abundant circulating precursor of active vitamin D, is the most widely accepted
indicator of vitamin D status and refects combined contributions from cutaneous synthesis (3). Importantly, both
vitamin D and thyroid hormone bind to similar receptors
called steroid hormone receptors. Adifferent gene in the
vitamin D receptor was shown to predispose people to autoimmune thyroid disease including Graves disease and
Hashimotos thyroiditis (8).
Thus, the aims of the study was to assess total vitamin
25 (OH) D status in patients with autoimmune thyroiditis
with subclinicl and overt hypothyroidism.

MATERIAL AND METHODS

Ninety subjects were involved in the present study.
They were living in Kolomyja region and recruiting to
outpatient clinic of Central Regional Hospital during the
period from September 2013 to July 2014. Written consent was taken from all participants in this study. They
were classified into three main groups: Group I. Patients
with autoimmune thyroiditis and subclinical hypothyroidism. It included 21 patients (3 male (14.3%) and 18 female (85.7%)), their mean ages 46.36 2.84 years. They
were diagnosed as patients with subclinical hypothyroidism if thyroid-stimulating hormone (TSH) level was

30

higher than 4.0 ulU/ml with normal levels of free triiodothyronine (fT3) and free thyroxine (fT4).
Group II. Patients with autoimmune thyroiditis and
overt hypothyroidism. It included 49 patients (13 mae
(26.5%) and 36 female (73.5%)), their mean ages 48.16
3.19 years. They were diagnosed as patients with overt
hypothyroidism if TSH level was higher than 4.0 ulU/ml
with lower levels of fT3 and fT4 than normal value.
Group III. Control group included 20 apparently healthy individuals (3 male (15%) and 17 female (85%)),
their mean ages are 47.2 2.78 years. They were not complaining from any chronic medical diseases with normal
clinical examinations.
It was no history of thyroid diseases or any chronic
illness, which could interfere with our results. They were
not on vitamin D supplements
All cases included in this study were subjected to the
followings: complete\history taking, complete clinical
examination. Laboratory investigations included: serum
fT3, fT4 and TSH for thyroid dysfunction patients with
reference range (2.5 - 4.3 pg/ml for fT3), (0.93 - 1.7 ng/dl
for fT4) and (0.27 - 4.0 ulU/ml for TSH); estimation of serum 25 (OH) D levels using spectrophotometric method.
Vitamin D deficiency was defined as a serum level of
25(OH)D of < 50 nmol/L and insufficiency as a serum
level between >50 nmol/L and <75 nmol/L and normal
>or=75 nmol/L (3).
Results were statistically analyzed by SPSS 11.5 for
Windows. Differences in mean values of variables described by the interval or ratio scale were tested in all groups
with the t-Student test. When the distribution did not meet
the assumptions of normality and homogeneity of variance of the t-Student test, the non-parametric Mann-Whitney Utest was applied. The correlations between serum
vitamin D and TSH were presented by correlation coefficient. Results considered significant or non-significant
when p> or < 0.05, respectively. .

RESULTS
The mean values of all studied parameters, age and
sex distribution in all studied groups are shown in table 1.
There were no statistical difference (p>0.05) between
groups regarding age and sex. The mean values of complete lipid profile tests, fasting blood glucose and creatinine show no significant statistical difference between
groups (p> 0.05) (tab. 2).
Levels of serum TSH were significantly increased in subclinical (6.80 1.84 lU/ml) and hypothyroid (14.72 3.19 lU/ml) groups as compared to control
group (2.16 0.39 ulU/ml) (p< 0.05).
The thyroid peroxidase antibodies level was
312.81 7.19 IU/ml in subclinical hypothyroid group
and was 527.31 9.62 IU/ml in the hypothyroid group as

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Tab. 1. Demographic characteristics and basic laboratory results of the studied groups (Mm).
Characteristics
Age, years
Sex
Hemoglobin, g/l
Glycemia, mmol/1
Creatinine, mol/1
Cholesterol, mmol/1
Triglycerides,
mmol/1
High-density
lipoprotein
cholesterol, mmol/1
Low-density
lipoprotein
cholesterol, mmol/1
Very low-density
lipoprotein
cholesterol, mmol/1

Subclinical hypothyroidism,
n=21
46.362.84
Female 18
Male 3
125.892.43
5.280.11
68.594.09
4.910.85
0.920.11

Overt hypothyroidism,
n=49
48.163.19
36 13

Control group, n=20

P value

121.862.84
5.020.36
73.905.99
5.340.91
0.960.14

126.712.29

>0.05

4.990.21
65.573.12
4.820.72
0.710.11

>0.05
>0.05
>0.05
>0.05

1.360.06

1.380.04

1.440.06

>0.05

3.070.06

3.190.08

3.140.06

>0.05

0.340.04

0.360.05

0.320.04

>0.05

47.22.78
17 3

>0.05
>0.05

Tab. 2. The levels of serum TSH, fT3, fT4, thyroid peroxidase antibodies and vitamin D in the studied groups (Mm).
Characteristics
TSH, lU/ml
fT4, ng/dl
fT3, pg/dl
Thyroid
peroxidase
antibodies,
IU/ml
25(OH) D,
nmol/1

Subclinical hypothyroidism,
n=21
6.801.84*
1.190.11
3.170.42
312.8331.96*

21.91.1*

Overt hypothyroidism,
n=49
10.242.09*
0.690.07*
2.270.21*
529.3146.82*

Control group, n=20

18.81.2*

illustrated in table 2. The levels of serum total 25(OH)D were

significantly decreased in subclinical (18.8 1.2 nmol/L)
and hypothyroid groups (21.91.1 nmol/L) as compared
to control group (27.11.2 nmol/L), (p<0.05). A highly
significant negative correlation was found between serum
TSH, thyroid peroxidase antibodies and total 25(OH)D
levels (p<0.001). Also highly significant positive correlation was found between the levels of serum total 25(OH)D
and serum fT4 (p<0.001). There was significant positive
correlation between TSH and thyroid peroxidase antibodies levels (p< 0.05).

DISCUSSION
Vitamin D deficiency has been associated with awide
range of non-skeletal effects including predisposition towards autoimmune disorders (9). Vitamin D is known for
its primary role in bone and mineral homeostasis, and it
has been shown recently that its deficiency is associated

P value

2.160.39
1.310.08
3.220.46

<0.05
<0.05
<0.05

19.521.34

<0.001

27.11.2

<0.05

with various diseases such as cardiovascular disease, cancer, infection, and adiposity as well as osteoporosis (10).
Interestingly, it has been shown recently that vitamin D
has potent immunomodulatory effects and plays important roles in the pathogenesis of autoimmune diseases
(11). Serum concentration of 25(OH)D is the best indicator of vitamin D status.
Our study demonstrated that there was ahighly significant decrease in (250H) D levels in autoimmune thyroiditis patients both in the subclinicl (21.91.1 nmol/L)
and overt hypothyroid groups (18.81.2 nmol/L) as compared to control group (27.1 1.2 nmol/L) (p< 0.05).
The autoimmunity of those patients was proved by assessment of thyroid peroxidase antibodies and the result
of it was (312.8331.96 IU/ml) in group with subclinical
hypothyroidism and (529.31 46.82 IU/ml) in the overt
hypothyroidism group where it was negative in the control group.

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On the same side Kivity S. et al. (5) found that the

prevalence of vitamin D deficiency was significantly
higher in patients with autoimmune thyroid diseases
compared with healthy individuals (72% versus 30.6%;
p<0.001) as well as in patients with Hashimotos thyroiditis compared to patients with non-autoimmune thyroid
diseases (79% versus 52%; p<0.05).
We also found that there is ahighly significant negative correlation between serum TSH, thyroid peroxidase
antibodies and vitamin 25(OH)D levels (p<0.05) in both
groups of autoimmune thyroiditis patients. This means
that vitamin D deficiency also correlated to the presence
of antithyroid antibodies and abnormal thyroid function
tests suggesting the involvement of vitamin D in the
pathogenesis of autoimmune thyroiditis.
These results depend on the fact that vitamin D mediates its effect though binding to vitamin D receptor (VDR),
and activation of VDR-responsive genes, while VDR gene
polymorphism was found to be associated with autoimmune thyroid diseases. One of two mechanisms may explain
the low levels of vitamin D in patients with hypothyroidism. First, the low levels of vitamin D may be due to poor
absorption of vitamin D from the intestine. Second, the
body may not activate vitamin D properly (12).
Also Goswami R. et al. (13) found that there is significant
inverse association between 25 (OH) D level and thyroid autoimmunity as reflected by thyroid peroxidase antibodies titers.
On the other hand Effraimidis G. et.al. (14) found that
early stages of thyroid autoimmunity are not associated
with low 25(OH)D levels, and this is my be in early stage
of the disease in which the level of autoantibody is not
enough to affect level of CYP24, the enzyme primarily
responsible for breaking 1,25-D down into
Low levels of 25(OH)D have been tied to ahigher incidence of autoimmune disease, leading to the consensus
that vitamin D deficiency may be arisk factor for autoimmune disease (8).
Further studies are needed to determine whether its deficiency is the causal factor or the consequence of the disease.
Screening for vitamin D deficiency recommended for
all patients with autoimmune thyroiditis
Concluding, we showed that there was ahighly significant decrease in 25(0H)D levels in autoimmune thyroiditis patients both in the subclinical and overt hypothyroid
groups as compared to control group. Ahighly significant
negative correlation was found between serum TSH, thyroid peroxidase antibodies and total 25(OH)D levels. Also
highly significant positive correlation was stated between
the levels of serum total 25(OH)D and serum fT4

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Adres do korespondencji:
I.V.Pankiv
Centre of Endocrinology
Klovskyj Uzviz 13A/517
01021 Kyiv, Ukraine
endocr@i.ua

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