Introduction
hyroid diseases include wide range
of disease like thyroid nodule,
multinodular colloid goiter (MNG),
thyroiditis and thyroid tumor, benign and
malignant [1]. Clinically patients with
Thyroid diseases presented with
euthyroid, hyperthyroidism or hypothyroidism
[2].
Thyroid hormones play a significant
role in the pace of many processes in the
body. Overproduction of thyroid hormone
(hyperthyroidism) cause nervousness,
irritability, anxiety, tremors, fine brittle
hair and weakness in muscle, frequent
bowel movements and loss of weight
.While low secretion of thyroid hormones
(hypothyroidism) cause hyporeflexia,
weight gain, constipation, bradycardia and
joint pain, the normal thyroid hormone
secretion (euthyroid) associated with local
thyroid pressure symptoms [3].
Thyroid nodule is very common about
4% of women and 2% of men in
worldwide. A nodule is a swelling or lump
which can be solitary or multiple, solid or
cystic, about 95% benign and 5%
cancerous [4]. MNG arise for a variety of
reasons, including genetic predisposition,
lack of iodine in the diet. It typically
presents as a painless mass in the neck.
Some goiters can grow behind the sternum
bone and remain hidden from view. When
a goiter is very large, it can interfere with
swallowing and breathing in addition to
causing unsightly fullness of the neck.
Large goiters are typically removed
surgically [5]. Hashiomato thyroiditis
(H.T), also known as chronic lymphocytic
thyroiditis, It is the immune thyroiditis
with an underactive thyroid gland
(hypothyroidism), it is the most common
cause of hypothyroidism in the United
States, it primarily affects middle-aged
women, but also can occur in both sex of
any age and in children [6]. Thyroid
carcinoma is a relatively frequent thyroid
disease includes the following: papillary
carcinoma (>85% of cases), follicular
carcinoma (5% to 15% of cases),
medullary carcinoma (5% of cases), and
anaplastic (undifferentiated) carcinoma
(<5% of cases) [7].
Immunological changes especially in
IgM, IgG, IgA, C3 and C4 seen in
inflammatory thyroid disease like H.T and
other thyroid disease [8]. Patients with
preexisting autoantibodies are more
susceptible to the exacerbation of thyroid
autoimmunity probably since interferon
enhances the level of autoimmunity [9].
Subjects and Methods:
The present study was conducted in the
city of Hilla from November 2013 to
August 2014. All cases were collected
from different sites depending on
presented data of age, sex, including
consultant clinic and emergency in Al-
Hilla Teaching Hospital and Al-Hayat
Hospital. The practical side of the study
was done at the laboratories of College of
Medicine / University of Babylon and in
Al- Hilla Teaching Hospital.
This study included 101 cases (13 male
and 88 female) dividing into three groups
according to the histopathological
diagnosis. Criteria to be included (for the
three groups) are: Patients are having
hyperthyroidism. The diagnosis of
hyperthyroid disease was made on the
basis of clinical features such as diffuse
goiter, exophthalmos, tachycardia, tremor
and sweating, and laboratory data such as
decreased level of serum TSH and
elevated levels of serum T3 and T4 the
levels(TSH<0.4 mIU /L, T3>2.33 nmol/L,
T4>120 nmol/L), the existence of
symptoms and signs of hypothyroidism
patients, and laboratory data such as low
levels of T3 and T4 and elevation levels of
TSH were accepted as sufficient criteria in
diagnosing of hypothyroidism (TSH >4.5
mIU /L, T3<1.2 nmol/L, T4<60 nmol/L).
The patients who had normal thyroid
functional tests and were thus registered as
a euthyroid state (T3:0.99-2.33 nmol/L;
T4:60-120 nmol/L; TSH: 0.35-4.5 mIU/L.
About three milliliters of venous blood
was aspirated put in gel tube for separation
of serum, and then take the serum into
plane tube and stored in -20C? until time of
use.
For all cases, Thyroid hormonal study
triiodothyronine (T3), thyroxin (T4), and
thyroid stimulating hormone (TSH) were
estimated using Mini-VIDAS technique
(BioMerieux/Italy) with principle of
combined an enzyme immunoassay
sandwich method with a final fluorescent
detection (ELFA). Immunological analysis
studies included immunoglobulins (Igs)
(IgM, IgA, and IgG) and complement
components (C3, and C4). The (IgM, IgA,
IgG, C3, and C4) levels were estimated by
nephlometric method by using mindary
technique (ACCENT- 200/ Poland). And
all cases of thyroid disease patients
underwent for total thyroidoctomy put in
10%formalin for fixation the processing
was done then paraffin block was done
and slides stained by hemotoxilin (H) and
eosin (E) stain and examined by
specialized pathologist for histopathological
diagnosis.
Statistical analyses
Statistical analysis was carried
out using SPSS version 20. Categorical
variables were presented as frequencies
and percentages. Continuous variables
were presented as (Means ± SD).
Pearson’s chi square (X2) test and fisher
exact test were used to find the association
between the categorical variables. A pvalue
of ? 0.05 was considered as
significant.
Results
(1) The mean age of patients with nodular
changes was (43.38±12.87) years old,
meanwhile it were (38.18±11.72) and
(37.62±16.51) years old for tumor changes
and thyroiditis, respectively was show in
figure (1).
(2) The distribution of thyroid patients by
sex, majority (46.20%) and (70.40%) of
the male and female had nodular changes,
respectively, was show in figure (2)
(3) The result showed that the mean IgM
was highest among patients with nodular
changes (2.75±4.98) g/L, meanwhile, the
mean IgA was highest among patients with
tumor changes (2.62±2.35) g/L. The mean
IgG was highest among patients with
nodular changes (17.43±6.53) g/L in
figure (3).
(4) Table (1): Shows the association of
thyroid changes with TSH. There was
significant association between thyroid
changes with TSH, patients with
thyroiditis were most likely to be
hypothyroidism, p<0.05.
1. Figure (4) Multinodular goiter high
power × 40
2. Figure (5) Toxic follicular adenoma
high power × 40 shows at the right side
intact capsule surrounding thyroid follicles
with hyperplastic changes (no invasion of
capsule).
3. Figure (6) In this papillary carcinoma
of thyroid note the small psammoma body
in the center. The cells of this neoplasm
often have nuclei with a central clear
appearance from fixation.
Discussion
In this cross sectional study
Hashiomato s thyroiditis (H.T) is
autoimmune disease associated with
rearrangement or defect in immune
system, and the patients with H.T suffering
from hypothyroidism and disorders in
immune system such as decreased weight
and cellularity of lymphoid organs and
decreased count of lymphocytes [10].
In the present study there is 14(13.8%)
of cases H.T and this similar to Stai et al.
in which 13.4% of goiter diagnosed as H.T
but our study different from a series of
(shinmed etal) where the H.T cases are
6.6% only. There is high incidence of H.T
in present study may be due to most
patients with H.T coming in hypothyroidism
clinical state, so the surgery
done for this patients and the small
number groups included in this study [11].
In our work 64.5% of H.T patients
clinically suffering from hypothyroidism,
this result is slightly different from the
result of (Pirainop et al.) in which the
incidence of hypothyroidism in H.T is
81%., most of patients with HT coming to
clinical attention after suffering of
hypothyroidism clinical presentation, so
most of thyroid follicles were damaged by
lymphocytes and plasma cells.
The immunological changes in H.T
patients are include increase in IgG level
78.6% of patients only while the IgM and
IgA remain normal and this result is
different from (Jafarzadeh et al.) where
67% IgG level increased. The IgG regard
protein secreted from plasma cells play
role in the immunity of body in chronic
condition, the H.T is chronic auto immune
disorder so associated with increase in IgG
in most of cases [12]. The serum C3 level
are low in 64.3% of patients this is
different from (Jafarzadeh et al.) in which
only 15% low levels. That has been
reported as some inflammatory parameters
such as C - reactive protein increase in
H.T the same inflammatory mediators in
H.T patients may inducing C3 and C4
production by hepatocytes epithelial cells
and fibroblasts [13].
And in present study the MNG
represent 67% of all cases and this result
mildly more than (Cifter et al.) where
60.6%. This difference between two
studies because of us added the
hyperplastic nodule in background of
goiter to Multinodular goiter. In our study
the MNG patients presented with
euothyroid is 75%, this result is slightly
more than (Tadesse B et al.) where the
62.1% of MNG patients present in
euothyroid state. The patient with MNG
remain in euothyroid state even the
iodine deficiency is present, so the thyroid
gland enlarged and the TSH become above
the normal to maintain the T3 and T4
within normal, then some of patient enter
in hypothyroid condition when the MNG
patients exposure to more metabolic
demand and more iodine deficiency state
and this may be explain the slight different
between these studies [14].
The result of the present study of
immunological profile in MNG patients
show 72.1% are different from Jafarzadeh
et al where the 38% of patients present
with high IgG level, no significant change
in other types of Igs (IgM, IgA). The result
can be explained in the MNG, the patients
clinically may be presented with
hyperplastic nodule in MNG background
and associated with hyperthyroidism and
may be presented with hypothyroidism
clinical manifestation, and in animal
models it was found that the humoral
immune response is positively modulated
by thyroid hormones, the difference
between two studies may be due to
variation in sample number, the level of
IgG is high it s may be related to other
previous disease [15].
In present study, the MNG patients
38.2% low level of C3 and this result
differ from Jafarzadeh et al. where 15%
of patients. While the serum C4 level
except 44.2% low while the other cases
remain within normal, it has been reported
that the C3 synthesis is dependent upon
interleukins (IL-1, IL-2) and tumor
necrosis factor (TNF-?), whereas C4
production is dependent upon IL-6 and
TNF-? cytokines accordingly, the presence
of a differently cytokine profiles in MNG
patients may differentially induce C3
production [16].
Also In present study the
immunoglobulins level are high in IgG and
IgM as 63.2% and 21.1% respectively and
this result is slightly lower than the study
of (Jafarzadeh et al.) where the level of
IgG is 73.7% while the IgM there is slight
different between them. The level of IgG
is high in different type of thyroid tumors
this may be due to response of body
immunity against the tumor, while the IgM
level is slightly lower than (Jafarzadeh et
al.) 22.5%, this increasing in the level of
IgM may be related to immunological
condition of the patients and the type of
tumor, size and behavior of tumor
metastasis or not, immunological status of
patient if any other chronic disease or
syndrome effects the immune system.
In our study the C4 level is high in
about 36.8% of patients, this result is
slightly higher than (Jafarzadeh et al.) the
C4 34.3%, the C4 is a part of complement
system may activated in thyroid tumor by
different pathway the tumor cells secrete
interleukin (IL-2) and interferon (IFN-&)
while the IL4, IL5, IL10 stimulate the
activation of C4 in minor way especially if
there is hormonal changes [17]. C3 level
is high in 5.3% only of patients but low in
10.5% , this variation may be explain in
different in thyroid tumor and evoked
immune response and activated T-cell.