The Immune System which Adversely Alter Thyroid Functions: A Review on the Concept of Autoimmunity
Azad Reza Mansourian
The immune system protect individual from many pathogens exists within our environment and in human body, by destroying them through molecular and cellular mechanism of B and T cells of immune system. Autoimmunity is an adverse relation of immune system against non- foreign substances leaving behind either alters the normal function or destroying the tissue involved. Autoimmunity occur in genetically predispose persons with familial connections. The autoimmunity to the thyroid gland mainly consists of Hashimato thyroiditis and Grave's disease, the two end of spectrum in thyroid function of hypo and hyperactivity, respectively. The thyroid stimulating hormone receptor, thyroglobuline, enzymes of thyroid hormones synthesis are targeted by autoantibodies and cell- mediated reactions. The aim of this review is to explore the studies reported on the autoimmunity to the thyroid gland.
Received: April 15, 2010;
Accepted: May 23, 2010;
Published: August 18, 2010
The immune system play an important role in destroying many human pathogens
existed in our environment and within the human body, otherwise these pathogen
causes pathological damages, which hurt the various organism within the body.
The immune system does its responsibility through the two mechanisms which are
called innate and adaptive immunity. In practice the innate immune system face
antigen first and the various pathogens are meeting the innate immune system.
Prior to face adaptive immunity. Within the body when the adaptive immune system
is activated through a pathogen the tatter, antigen mostly is destroyed through
a complex reactions which happen within the immune system on meeting an antigen
(Jiang and Chess, 2006; Nelson,
2004; Kroneberg et al., 1986).
The above mentioned two systems do their function through many biochemical
molecules and different cells existed in the immune systems the soluble molecules
are lysozyme, complement, acute phase proteins, interferon and different antibody
and the participated cells immune systems are phagocytes, natural killer cells
and T- lymphocytes respectively. On condition an antigen enter the first line
of barrier the body which is the epithelial surface of various organs, the phagocyte
cells encounter the antigens and subsequently the pathogen can be destroyed,
through a complex reaction within the immune system (Schwarz
and Bhandoola, 2006).
The cells within the immune system contains of lymphoid and myeloid sub-division
producing lymphocytes and phagocytes. The lymphocytes also contain B and T-cells.
The T and B come from Thymus and Bone marrow respectively and either of B and
T cells have their own specific antigen receptor and on binding antigen to these
receptors, cellular activation occur within the immune system, to destroy the
encountering antigens, with the coordination exist between T and B cells of
immune system (Weigle, 1975; Li
et al., 2006).
Autoimmunity: Also it is absolutely clear the immune deficiency in human
leave the individual defenseless against many antigen present in our environment
which can be a topic for other study, but the other undesired upper end of spectrum
which is the main subject behind this present review and it is the activity
of immune system against body own tissues which causes tremendous problems,
through the unwanted reaction of both B and T-cells by producing various antibodies
by B-cells and many reactive T-cells against its own tissues (Sakaguchi,
2005; Weetman et al., 1990; Misaki
et al., 1984) which many diseases and abnormalities can be produced
by the unwanted immune reactions, with are called autoimmune diseases. In such
disease the immune system are activated, producing many antibodies and activated
T-cells which can be targeted at various part of the cells organelles, such
as different enzymes, key macromolecules, hormone receptors and cell nucleus
(Holborow, 1960; Mansourian et
al., 2007; Chiovato et al., 1993; Mariorri
et al., 1987). These damages can be either specific or non-specific.
The thyroid autoimmunity are specific autoimmune diseases and the thyroid gland
various cells and organelles are targeted by the individual immune systems and
the thyroid function seriously affected leaving the patients with hypothyroidism
in Hashimato and hyperthyroidism in Grave's disease (Okita
et al., 1980; Aoki and Degroot, 1979).
Genetic in autoimmunity: The base for autoimmunity is genetic and there
are many studies indicating the development of autoimmune disease originating
from evidence of association with human lymphocyte antigens. Other studies indicated
that there are few genetic factors associated with developing autoimmunity whether
it is either organ or non- organ specific. The autoimmunity to the thyroid diseases
proved to be familial (Kite and Witebsky, 1968;
Bartel, 1941; Brix et al., 1998a; Brix
et al., 2000; Nagayama et al., 1989).
There are studies indicating the Graves disease and Hashimato's thyroiditis
are thyroid disorder with genetic predisposition (Epstein,
1999; Klavinskis et al., 1988; Nagasaka
et al., 2000; Brix et al., 2001;
Ringold et al., 2002), the high level of serum
antibodies was found in serums belongs to the patients relatives, with a documented
thyroid diseases (Hall et al., 1960;
Zeitlin et al., 2007; Stenszky et al.,
There are also reports of simultaneous incidence of autoimmune thyroid disorder
and other autoimmune diseases. Examples of such a diseases are the existence
thyroid and stomach antibodies in first degree relatives with Hashimato thyroiditis
(Bartel, 1941; Brix et al.,
2001; Philips et al., 1991, 1993;
Ringold et al., 2002; Hall
et al., 1960; Zeitlin et al., 2008;
Pop et al., 1998; Weetman
and McGregor, 1994; Parkes et al., 1996;
Yanagawa et al., 1993; Stenszky et al.,
Also nearly all types autoimmune diseases demonstrate some correlation with
human lymphocyte antigen specificity,but it should be mentioned ethnicity also
play a role on the level of autoimmunity (Chen et al.,
1999; Weetman and McGrgor, 1994; Tomer
et al., 1997; Shields et al., 1994).
Diagnostic role of autoimmunity: There are three indications for the
presence of autoantibodies and other autoimmunity determinants with individual
serum which can be summarized as follow: (1) The raising autoantibodies which
are the main determinant factors for disease onset. (2) There may be an abnormality
in which through its process and the damages predispose the individual to produce
autoantibodies and finally. (3) There may be an pathogen which cause the disease
and the production of antibodies as well. In clinical practice all of above
three possibilities are routinely should be investigated for the management
and treatment of patients. The elevation of antibodies in various autoimmune
disorder and antibodies raised secondary to some diseases such as myocardial
infraction is now an instrumental to diagnose, treat and manage the cardiovascular
patients (Crile, 1954; Hubble, 1959;
Buchanan et al., 1961; Mulhern
et al., 1996; Jenkins and Weetman, 2002;
Irvine et al., 1965; Doniach
et al., 1963; Hjort et al., 1963).
Thyroid autoimmune diseases: Various type of auto immune diseases in
the thyroid gland can be sub-divided as follow: (1) Grave's disease, with thyroid
enlargement, resulting with hyperthyroidism and its subsequent clinical consequence
(Sanders et al., 2003; Chazenbalk
et al., 2002, 2004; Chen
et al., 2003). (2) Hashimato's thyroiditis accompanied with goiter,
resulting in hypothyroidism or thyroid function remain with normal range and
euthyroid state (Suzuki et al., 1980; Blanchin
et al., 2007; Weetman et al., 1989;
Beierwaltes et al., 1968)
Also the autoimmunities to the thyroid gland are well documented and categorized,
but there are still some thyroid dysfunctions which can be labeled as transient
thyroid dysfunction which can happen, on its own, or may be occurred during
a particular physiological state, such as pregnancy and depression (Hidaka
et al., 1992; Bogner et al., 1995;
Weetman, 2001; Poppe et al.,
2003; Pratt et al., 1993;
Kong et al., 2009; Holmes et al., 1977;
Rapopott et al., 1998; Woolner
et al., 1959). In our study of thyroid function in pregnancy, we
found there is a high prevalence of thyroid dysfunction during pregnancy although
we did not measure the thyroid antibodies in pregnant womens, but the
growing fetus can be an antigenic determinant in production of antibody within
the thyroid gland during the pregnancy, which has been reported by other studies,
(Mansourian, 2010b; Mansourian et
al., 2010; Shahmohammadi et al., 2008;
Brix et al., 1998b). It is indicated in some pregnancies, postpartum
women and in either neonatal by hyperthyroidism or hypothyroidism the elevation
of auto antibodies were observed (Mansourian et al.,
2010; Pratt et al., 1993; Poppe
et al., 2003; Gribetz et al., 1954;
Jansson et al., 1984; Kajantie
et al., 2006; Radetti et al., 2007).
It has also been recommended by many studies, that the maternal serum concentration
of autoantibodies should be measured during the clinical investigation of thyroid
function test in routine thyroid function assessment of suspected subjects,
pregnancies and in newborns in addition to other thyroid function test, such
as thyroid stimulating hormone and thyroxin and triiodothyronine, (Mansourian,
2010b; Radetti et al., 2007;
Kajantie et al., 2006).
In addition either of hyperthyrodism and hypothyroidism have many other metabolic
disorder. dyslipidemia is among such abnormalities. It has been shown that in
hypothyroidism, the cholesterol and low density lipoprotein level are increased
(Mansourian, 2010a; Mansourian et
It should be noted, in thyroid disorder caused by autoimmunity and subsequent
dyslipidemia which can be its adverse effect, should be taken into account,
due to the cardiovascular abnormalities and particularly the atherosclerosis,
which many he accompanied by cholesterol elevation (Galesanu
et al., 2004; Vala, 2001; Mansourian,
2010b) In a study and review by author it was stated that lipid disorder
among thyroid patients and thyroid hormone alteration frequently seen during
pregnancy (Mansourian, 2010b; Pratt
et al., 1993; Poppe et al., 2003)
but on the same time as thyroid hormones assessments is carried out, thyroid
auto antibodies, iodine, lipid profile, assessment of pregnant women in particular
and other suspected individuals should be evaluated for any thyroid disorder
and possible side effect of dyslipidemia resulted from thyroid malfunctions.
(Mansourian, 2010a, b; Marjani
et al., 2008; Mansourian et al., 2008).
There are also some experimental studies on the induction of autoimmunity by
thyroid injury, which can be a topic for studies in humans (Bagchi
et al., 1995; Flynn et al., 2007).
Autoimmunity to the thyroid gland
Thyroid gland: Thyroid gland is the largest of endocrine glands in
human weighted approximately about 20 g located in front of the neck. This gland
produces the two most important hormones required for bodys metabolism
namely thyroxin (T4) and tridiothyronin (T3) in addition to latter hormones,
the thyroid produce Calcitonin, responsible for calcium and bone metabolism.
The reactions, which finally produce T4 and T3, begin with the absorption and
maintains of iodine and preparation of this element to participate in the structure
of organic molecules on the thyroglobulin macromolecule, there for the first
step in synthesis of T4 and T4 is the absorption and transferring the iodine
on the thyroids residue on the thyroglobulin.
The topic of iodine deficiency in human have been the corner stone of many
research about thyroid disorder, in fact one of the first primary tool to diagnose
the hypothyroidism is the assessment of iodine status. In our earlier study,
we found that iodine deficiency can be manifested the base for some thyroid
disorder, the findings which have been reported by many other studies (Mansourian
et al., 2007). It was already mentioned in experimental studies the
elevated iodine itself which can be observed in thyroid injury can be a base
for autoimmunity to the thyroid gland (Bagchi et al.,
1995; Flynn et al., 2007; Zois
et al., 2006).
Thyroglobulin (Tg) is produced when iodine added on the thyrosil residue of
this latter macroprotien within the thyroid gland. All these reaction leading
to production of T4 and T3 do take place by the action of thyroid stimulation
hormone (TSH), not only TSH facilitate the thyroid hormone synthesis, through
the activation of, many enzymes with the thyroid gland such as thyroxine peroxidase
and other enzymes of iodine oxidation, but the thyroid enlargement also carried
out by TSH. This latter hormone does all these physiological and biochemical
functions through cAMP. When TSH binds to the THS receptor on the thyroid gland
the sequence of event happen, on the receptor which located on the membrane,
leading to the production of cAMP, a second messenger responsible for all the
events in the thyroid gland and TSH functions. Therefore, it is the TSH receptor
which locate in the center of thyroid function and any unwanted stimulation
TSH or blocking of TSH receptor, result in over activation or suppression of
thyroid hormone production due to the alteration happen in the level of c AMP
concentration in the thyroid gland (Tonacchera et al.,
1996; Prabhakar et al., 1997). Autoimmunity
to the thyroid genetically, predisposes individuals; finally leave the patients
with the consequence of thyroid disorders. It should be mentioned also that
it is not only the TSH receptor, which can be targeted by the immune system,
but also as it was mentioned earlier T-cell mediated responses and cell destruction
can be associated with thyroid autoimmunity (Collins and
Gough, 2002; Metcalfer et al., 1997; Weetman
et al., 1982).
The molecular bases for autoimmunity to the thyroid gland: T-cell and
B-cell, which mainly originated from Thymus and Bone marrow cell are behaved
to destroy only individual foreign antigens in a complex molecular mechanism
and through other pathways, the immune system, behaved in such way to recognize
the non- foreign antigen, within the thyroid, in other word the bodys
thyroid own cells and tissues are protected by the immune system and it behaved
to recognized the self thyroid antigens. Only on condition that the immune system
does not recognize and discriminate the thyroid non- foreign antigen, only on
that condition the predispose persons thyroid will be attacked by self immune
system, with all its adverse effects, on the thyroid metabolism. Such immunity
against persons own thyroid is called thyroid autoimmunity, it means a molecule
within the person thyroid is considered a foreign molecule and the immune system
begin to react against that molecule (Weetman et al.,
1982; Drehage, 1996; Owen and
Smart, 1985; Benvenga et al., 1987; Sakaguchi,
2005; Shields et al., 1994; Tomer
et al., 1997; Lamki et al., 1973;
McIntosh et al., 1993). In fact that molecule
stimulates all the reactions required by the immune system to destroy the normal
procedures of the thyroid gland molecules and reactions. There are many reports,
indicating the gender play an important role in triggering the autoimmunity.
Thyroid autoimmunity proved to be sex- related and high incidence of autoantibodies
were found among females (Mansourian et al., 2010).
In fact also in our study we did not measure the level of autoantibodies in
our women sample population but incidence of thyroid disorder and in particular
hypothyroidism was more common among females (Mansourian
et al., 2008).
The autoimmunity in thyroid mainly consists of Hashimato thyroiditis and Graves
disease. The two end of thyroid diseases spectrum leaving the patients in hypothyroid
and hyper thyroid conditions, respectively (Endo et
al., 1983; Amino et al., 1982; Bogner
et al., 1984).
Hashimato thyroiditis: Hashimato thyroiditis is an autoimmune thyroid
disease. In this thyroid disorder, the immune system activated against self-
organ and attack, the thyroid gland. The consequence of thyroid attack by the
immune system is the reduction of thyroid hormone synthesis and thyroid gland
in compensation to this latter reaction continue to produce hormone to reach
to the normal level, which the body required for that level of thyroid hormone,
by doing so the thyroid gland enlarged and it is developed into goiter, this
type of goiter which the body gain normal level of thyroid hormones is called
simple goiter, it means, it is only the enlargement of thyroid gland without
any toxicity due to the enhanced production and the hyperplasia of the gland,
but the thyroid finally enter into hyperthyroid state (Buchanan
et al., 1961; Fatourechi et al., 1971;
Eason, 1928; Suzuki et al.,
1980; Benvenga and Trinarchi, 2008; Pearce
et al., 2003).
The side- effects of Hashimatos d sease includes: fatigue weight gain,
depression, gastrointestinal, abnormality, intolerance to cold constipation,
dry skin and hair, speech and vision abnormalities. Those Hashimatos patients
without any successful treatment, eventually face, reduction in their heart
rate, drop in their body temperature and their eye become puffy around their
eyes. If the Hashimatos disease remain untreated and in advance cases,
it will end up with heart failure.. the molecular and cellular mechanism behind
cell destruction with the thyroid gland, is a combination of T-cell autoimmunity
activity in the thyroid accompanied with autoantibodies raised against thyroglobulin,
thyroid peroxidase enzymes (Kohno et al., 1988;
Protmann et al., 1985; Mclachian
and Rapoport, 1992; Tomer, 1997;
Lindberg et al., 2001; Noma et al., 1982;
Pop et al., 1998; Okamoto
et al., 1989). It seems that T-cell destruction is step forward for
the production of autoantibodies against the thyroglobulin and the thyroid peroxidase
enzymes (Komiya et al., 2001). T-cell autoimmunity
seems to be adversely effect the thyroid cells and it seems this procedure is
the first step toward the creation of goiter in the thyroid gland, with the
infiltration of lymphocyte and production of compensatory thyroid cells, leading
to the hypothyroid and enlargement of thyroid gland the raised autoantibodies
within patients thyroid gland, also accompanied with T-cell mediate cell
destruction in the thyroid gland with reduction of thyroid hormone synthesis,
but as it was mentioned earlier, it is the T-cell mediated autoimmunity against
the thyroid gland which fundamentally destroy the thyroid cells and these reaction
predispose the gland to face eventually the inflammation seen in Hashimatos
disease, with associated syndrome (Komiya et al.,
2001). It is reported also the Hashimato, disease can be accompanied with
some cancer of thyroid gland. Gravers disease a topic which should have
been taken seriously for the management of Hashimato patients (Woolner
et al., 1959; Holmes et al., 1977;
Giani et al., 1996; Smyth
et al., 1998; Kohn et al., 1997; DeGroot
et al., 1997; Dailey et al., 1955;
Giani et al., 1996).
Graves disease: Graves disease is an autoimmune thyroid disorder, resulting in the over activity and the elevated level of thyroid hormones much more than the healthy body metabolism required, eventually lead to weight loss, nervousness and increasing heart rate intolerance to heat, sleeping problem.
Weakness, tremors, alteration in vision, with eventual, ophthalmopathy. The bases for thyroid disorder in this disease related to the over activity and unwanted immunological reactions by the individual immune system.
The antibodies against peroxidease (TPO) enzyme are found, within the serum
of effected persons (Di Cerbo et al., 1995;
Sawai and Degroot, 2000; Davies
et al., 1993; Caso- Pleaez et al., 1995;
Kite and Witebsky, 1968; Tomer and
Davies, 1993; McLachlan and Rapoport, 1992,
2004; Protmann et al., 1985; Kohno
et al., 1988; Dechairo et al., 2005;
Wong and Cheng, 2001; Kondrashova
et al., 2008; Brix et al., 1998b;
Vali et al., 2000). As it was mentioned earlier Graves disease is
a familial disease and the genetic susceptibility lead the synthesis of autoantibodies
against Tg and TPO. The other most autoantibody which is produced and targeted
against thyroid gland is antibody against receptor of Thyroid Stimulating Hormone
(TSH), the antibody against the TSH receptor which is also known as Thyroid
Stimulating Immunoglobulin (TSI).
TSI binds to the receptor of TSH on the thyroid gland stimulate and mimic the
physiological effect of TSH, producing cAMP the second messenger responsible
for the enlargement of thyroid gland and also the elevated production of T4
and T3 through the stimulation of many enzymes responsible for hormone production.
TSI is not under the negative conyr T4 and T3, therefore the syntheses of T4
and T3 are continued. In healthy persons when T4 and T3 are elevated the negative
feed -back control the hormones production by sending the message to the hypothalamus
and pituitary to slower down the release of TSH and consequently the production
of T4 and T3 are reduced. Also it should be mentioned the at same times the
raised autoantibody against the TSH receptor blocks the TSH receptor in such
way that even TSH can not binds to the TSH receptor and consequently the production
of T4 and T3 are halted and hypothyroidism occur (Tonacchera
et al., 1996; Prabhakar et al., 1997;
Libert et al., 1989; Nagayama
et al., 1989).
In our earlier studies we found high incidence of hyperthyroidism, among pregnant
women and also many of them remained at euthyroid state. In the latter study
we argued the elevated thyroid hormone level was the physiological requirement
pregnancy, but it seems further, studies should have been done to clarify whether
the hyperthyroidism or euthyroid condition observed during pregnancy are either
the direct consequence of pregnancy or the raised autoantibodies against the
thyroid gland enzymes and TSH receptor (Shahmohammadi et
al., 2008; Kung and Jones, 1998; Pratt
et al., 1993; Poppe et al., 2003).
The feature related to the Graves disease is the production of autoantibodies
and T-cell mediated on to autoimmune response.
It should be mentioned that many reports indicated the simultaneous incidence
of autoimmunity to the thyroid gland with the gland hyper activities and the
thyroid gland carcinoma, or even some infection within the thyroid gland (Tomer
and Davies, 1993; Bartalena et al., 1996;
Wenzel et al., 1988; DeGroot
and Paloya, 1973; Woolner et al., 1959; Giani
et al., 1996; Bach, 2002; Smyth
et al., 1998).
The reviews main points are as follow:
||The importance of immune system in protecting the individual
from invading foreign pathogen described
||The adverse effect of autoimmunity against self-antigen explored
||Autoimmunity has a genetic background with familial connection
||The determination of autoantibodies measurements are valuable
diagnostic tools in medical practice
||Autoimmunity to the thyroid gland can be assessed by measuring
autoantibodies raised against thyroglobulin, TSH recpector and thyroid peroxidase
enzyme, involved in T4 and T3 production
||Hashimato thyroiditis and Graves disease are the two
end of spectrum of hypo and hyperthyroidism in thyroid autoimmunity, respectively
||Although, the main focus was on the production of antibodies
in thyroid autoimmunity but it should be remembered that autoantibodies
within the thyroid gland are also produced not only by the autoimmunity
to the gland but also some other diseases such as thyroid cancer and
in during some pregnancies, the elevated autoantibodies to the thyroid gland
has been detected therefore the assessment of thyroid autoimmunity status
should have been taken into account when thyroid cancer and pregnancies
are medically examined
1: Amino, N., H. Mori,Y. Iwatani, S. Asari, Y. Izumiguchi and K. Miyai, 1982. Peripheral K lymphocytes in autoimmune thyroid disease: Decrease in Graves disease and increase in Hashimotos disease. J. Clin. Endocrinol. Metab., 54: 587-591.
2: Bach, J.F., 2002. The effect of infections on susceptibility to autoimmune and allergic diseases. N. Engl. J. Med., 347: 911-920.
Direct Link |
3: Bagchi, N., T.R. Brown and R.S. Sundick, 1995. Thyroid cell inuury is an initial event in the induction of autoimmune thyroiditis by iodine in obese strain chikens. Endocrinol., 136: 5054-5060.
Direct Link |
4: Bartalena, L., F. Bogazzi, F. Pecori and E. Martino, 1996. Graves disease occurring after subacute thyroiditis: Report of a case and review of the literature. Thyroid, 6: 345-348.
5: Beierwaltes, W.H., R.H. Nishyama and D. Thyroiditis, 1968. Occurrence and similarity to Hashimotos struma. Endocrinol., 83: 501-508.
6: Benvenga, S., F. Trimarchi and J. Robbins, 1987. Circulating thyroid hormone autoantibodies. J. Endcrinol. Invest., 10: 605-619.
7: Benvenga, S. and F. Trinarchi, 2008. Changed presentation of Hashimotos thyroiditis in North- Easternb Sicilt and Calabria Southern Ital based on a 31- year experience. Thyroid., 18: 429-441.
Direct Link |
8: Bogner, U., L. Hegedus, J.M. Hansen, R. Finke, and H. Schleusener, 1995. Thyroid cytotoxic antibodies in atrophic and goitrous autoimmune thyroiditis. Europ. J. Endocrinol., 132: 69-74.
9: Bogner, U., H. Schleusener and J.R. Wall, 1984. Antibody dependent cell mediated cytotoxicity against human thyroif cells in Hashimotos thyroiditis but not Graves disease. J. Clin. Endocrinol. Metab., 59: 734-738.
10: Brix, T., K.O. Kyvik and L. Hegedus, 2000. A population- based study of chronic autoimmune hypothyroidism in Danish twins. J. Clin. Endocrinol. Metab., 85: 536-539.
Direct Link |
11: Brix, T.H., K.O. Kyvik, K. Christensen and L. Hegedus, 2001. Evidence for a major role of heterdity in Graves disease: A population- based study of two Danish twin cohorths. J. Clin. Endocrinol. Metab., 86: 930-936.
12: Brix, T.H., K.O. Kyvik and L. Hegedus, 1998. What is the evidence of genetic factors in the etiology of Graves disease? A brief review. Thyroid., 8: 727-734.
13: Brix, T.H., K. Christensen, N.V. Holm, B. Harvald and L.A. Hegedus, 1998. Population- based study of Graves disease in Danish twins. Clin. Endocrinol., 48: 397-400.
14: Buchanan, W.W., J. Crooks, W.D. Alexande, D.A. Kouteras, E.J.M. Wayne and K.G. Gray, 1961. Association of Hashimotos and rheumatoid arthritis. Lancet, 1: 245-245.
15: Caso-Pleaez, E., A.M. McGregor and J.P. Banga, 1995. A polyclonal T cell repertoire of V-alpha and V-beta T cell receptor gene families in intrathyroidal T lymphocytes of Graves disease patients. Scand. J. Immunol., 14: 141-147.
16: Collins, J. and S. Gough, 2002. Autoimmunity in thyroid disease. Eur. J. Nucl. Med. Mol. Imaging., 29: 417-424.
17: Chazenbalk, G.D., F. Latrofa, S.M. Mclachlan and B. Rappoport, 2004. Thyroid stimulation does not require antibodies with identical epitopes but does involve recognition of a critical conformation at the N terminus the thyrotropin A- subinit. J. Clin. Endcrinol. Metab., 89: 1788-1793.
18: Chazenbalk, G.D., P. Pichurin, C.R. Chen, F. Latrofa, A.P. Johnstone, S.M. Mclachian and B. Rapoport, 2002. Thyroid-stimoulating autoantibodies in Graves disease preferentially recognize the free A subunit, not the thyrotropin holoreceptor. J. Clin. Invest., 110: 209-217.
19: Chen, C.R., P. Pichurin, C.R. Chen, F. Latrofa, A.P. Johnstone, S.M. Mclachian and B. Raporter,q 2003. Thyroid reporter autoantigen in Gravers disease in the culprit as well as the victim. J. Clin. Invest., 111: 897-1904.
20: Chen, Q.Y., W. Huang, J.X. She, F. Baxter, R. Volpe and N.K. Maclaren, 1999. HLA-DRB1*03/DRB3*0101 and DRB3*0202 are susceptibility genes for Graves disease in North American Caucasians, whereas DRB1*07 is protective. J. Clin. Endocrinol. Metab., 84: 3182-3186.
21: Chiovato, L., P. Bassi, F. Santini, C. Mammoli, P. Lapi, P. Carayon and A. Pinchera, 1993. Antibodies producing complement- mediated thyroid cytotoxicity in patients with atrophic or goitrous auto immune thyroiditis. J. Clin. Endocrinol. Metab., 77: 1700-1705.
Direct Link |
22: Crile, G. Jr., 1954. The treatment of diseases of the thyroid gland. Ann. R. Coll. Surg. Engl., 14: 158-158.
23: Dailey, M.E., S. Lindsay and R. Skahen, 1955. Relation of thyroid neoplasms to Hasgimatos disease of the thyroid gland. Arch. Surg., 70: 291-297.
24: Davies, T.F., E.S. Concepcion, A. Ben-Nun, P. Graves and G. Tatjan, 1993. T-cell receptor V gene use in autoimmune thyroid disease: Direct assessment by thyroid aspiration. J. Clin. Endocrinol. Metab., 76: 660-666.
Direct Link |
25: DeGroot, L.I., K. Hoye, S. Refetoff, A.J. Van Herle, G.T. Asteris and H. Rochman, 1997. Serum antigens and antibodies in the diagnosis of thuroid cancer. J. Clin. Endocrimol. Metab., 45: 1220-1223.
26: DeGroot, L.J. and E. Paloya, 1973. Thyroid carcinoma and adiation. A Chicago endemic. J. Amer. Med. Assn., 225: 487-491.
27: Di Cerbo, A., R. Di Paola, M. Bonati, M. Zingrillo, V. De Filippis and D. Corda, 1995. Subgroups of Graves patients identified on the basis of the biochemical activities of their immunoglobulins. J. Clin. Endpcrinol. Metab., 80: 2785-2790.
Direct Link |
28: Drehage, H.A., 1996. Auto immunity and thyroid growh. Where do we stand? Europ. J. Immunol., 135: 39-45.
29: Eason, J., 1928. Correalation of Graver diseases and thyroiditis. Edinburgh. Med. J., 35: 169-169.
30: Endo, Y., Y. Aratake, I. Yamammoto, H. Nakagawa, T. Kuribayashi and S. Ohtaki, 1983. Peripheral K cells in Graves disease and Hashimotos thyroiditis in relation to circulating, immune complexes. Clin. Endocrinol., 18: 187-194.
31: Epstein, F.H., 1999. Molecular mimicry and autoimmunity. New Engl. J. Med., 341: 2068-2074.
32: Fatourechi, V., W.M. McConahey and L.B. Oolner, 1971. Hyperthyroidism associated with histilogic Hashimatos thyroiditi. Mato. Clin. Proc., 46: 682-682.
33: Flynn, J.C., C. Meroueh, D.P. Snower, C.S. David and Y.M. Kong, 2007. Depletion of CD4+CD25+regulatory T cells exacerbates sodium iodide- induced experimental autoimmune thyroiditis in human leucocyte antigen DR3 (DRB1*0301) transgenic class II- knock- out non- obese diabetic mice. Clin. Exp. Immunol., 147: 547-554.
34: Galesanu, C., N. Lisnic, R. Teslaru, L. Apostu and E. Zbranca et al., 2004. Lipidprofile in group of hypothyroidpatients Vs treated hypothyroidpatients. Rev. Med. Chir. Soc. Med. Nat. Lasi., 108: 554-560.
35: Giani, C., P. Fierabrancci, R. Bonacci, A. Gigoliotti and F. De Megri et al., 1996. Relationship between breast cancer and thyroid disease: Relevance of auto immune thyroid in breast maligany. J. Clin. Endocrinol. Metab., 81: 990-994.
36: Gribetz, D., N.B. Talbot and J.D. Crawford, 1954. Goiter due to lynphochtic thyroiditis (Hashimatos struma): Its occurrence in predolescent and adolescent girls N. Engl. J. Med., 250: 555-555.
37: Hall, R., S.G. Owen and G.A. Smart, 1960. Evidence for genetic predisposition to formation of formation of thyroid auto antibodies. Lancet, 2: 187-188.
38: Hidaka, Y., N. Amino, Y. Iwatani, T. Kaneda and M. Nasu et al., 1992. Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease. Autoimmunity, 11: 239-246.
39: Hjort, T., F. Jeppesen, K. Okholm and J. Temler, 1963. The Prognostic significance of thyroid autoantibodifes in the development of postoperative myxedema. Dan. Med. Bull., 10: 159-167.
40: Holborow, E.J., 1960. Serum anticlear factor and autoimmunity. Proc. R. Soc. Med., 53: 625-627.
Direct Link |
41: Holmes, H.B., A.O. Kreutner and A.P.H. Brien, 1977. Hashimatos thyroiditis. Its relationship to other thyroid diseases. Surg. Gynecol. Obstet., 144: 887-887.
42: Hubble, D., 1959. The diagnosis and yreatment of auto immunizing thyroiditis. Scott. Med. J., 4: 55-55.
43: Jenkins, R.C. and A.P. Weetman, 2002. Disease associations with auto immune thyroid disease. Thyroid., 12: 977-988.
44: Jiang, H., and L. Chess, 2006. Regulation of immune responses by T cells. New Engl. J. Med., 354: 1166-1176.
Direct Link |
45: Komiya, I., T. Yamada, A. Sato, T. Koukinishimori and N. Takasu, 2001. Remissionand recurrence of hyperthyroid Graves disease during and after methimazole tratmeent when assessed by IgE and interlukin 13. J. Clin. Endocrinol. Metab., 86: 3540-3544.
46: Kajantie, E., D.I. Philips, C. Osmond, D.J. Barker, T. Forsen and J.G. Erikson, 2006. Spontaneous htpothyroidism in adult women is predicted by small boy size a birth and during children. J. Clin. Endocrimol. Metab., 91: 4953-4956.
47: Kite, J.H. and E. Witebsky, 1968. Hereditary autoimmune thyroiditis in the fowl. Sci., 160: 1357-1358.
48: Klavinskis, L.S., A.L. Notkins and M.B.A. Otdstone, 1988. Persistent viral infection of the thyroid gland: Alteration of thyroid function in the absence of tissue injury. Endocrinology, 122: 567-575.
49: Kong, Y.C., G.P. Morris, N.K. Brown, Y. Yan, J.C. Flynn and C.S. David, 2009. Autoimmune thyroiditis: A model uniquely suited to probe regulatory T cell function. J. Autoimmun., 33: 239-246.
50: Kung, A.W.C. and B.M. Jones, 1998. A Change from stimulatory to blocking antibody activity in Graves disease during pregnancy. J. Clin. Endocrinol. Metab., 83: 514-518.
Direct Link |
51: Lamki, L., V.V. Row and R. Volpe, 1973. Cell mediated immunity in Graves disease and in Hashimotos thyroiditis as shown by the demonstration of migration inhibition factor (MIF). J. Clin. Endocrinol. Metab., 36: 358-364.
52: Libert, F., A. Lefort, C. Gerard, M. Parmentier and J. Perret et al., 1989. Cloning, sequencing, and expression of the human thyrotropin (TSH) receptore: Evidence for binding of auto antibodies. Biochem. Biophys. Ren. Commun., 165: 1250-1255.
53: Li, J., D.R. Barreda, Y. Zhang, H. Boshra and A.E. Gelman et al., 2006. B-Lymphocytes from early vertebrates have potent phagocytes abilities. Nat. Immunol., 7: 1116-1124.
54: Lindberg, B., J. Svensson, U.B. Erisson, P. Nilsson, E. Svenonius and S.A. Ivarson, 2001. Comparision of some different methods for analysis of thyroid autoantibodies: Importance of thyroglobulin autoantibodies. Thyroid., 11: 265-269.
55: Mariorri, S., S. Anelli, R. Ruf Bechi, B. Czarnocka, A. Lombardi, P. Carayon and A. Pinchera, 1987. Comparison of serum thyroid microsomal and thyroid peroxidase autoantibodies in thyroid diseases. J. Clin. Endocrinok. Metab., 65: 987-993.
56: McIntosh, R.S., N. Tandon, A.P. Pickerill, R. Davies, D. Barnett and A.P. Weetman, 1993. IL-2 receptor positive intrathyroidal lymphocytes in Graves disease: Analysis of V transcript microheterogeneity. J. Immunol., 91: 3884-3893.
Direct Link |
57: Mclachlan, S.M. and B. Rapoport, 2004. Why measure thyroglobulin autoantibodies rather than thyroid peroxidas autoantibodies? Thyroid., 14: 510-520.
58: Metcalfer, R.A., Y.S. Oh, C. Stroud, K. Arnold and A.P. Weetman, 1997. Analysis of antibody- dependent cell- mediated cytotoxicity in auto immune thyroid disease. Auto Immunity, 5: 65-72.
Direct Link |
59: Nagasaka, A., A. Nakai, N. Oda, M. Kotake, K. Iwase and S. Yoshida, 2000. Reverse transcriptase is elevated in the thyroid tissue from Graves disease patients. Clin. Endocrinol., 53: 155-159.
60: Nagayama, Y., K.D. Kaufman, P. Seto and B. Rapoport, 1989. Molecular cloning, sequence and functional expression of the cDNA for the human thyrortopin receptor. Biochem. Biophys. Res. Commun., 165: 1184-1190.
61: Nelson, B.H., 2004. IL-2, regulatory T cells, an tolerance. J. Immune., 172: 3983-3988.
Direct Link |
62: Okamoto, Y., N. Hamada, H. Saito, M. Ohno, J. Noh, L. Ito and H. Morii, 1989. Thyroid peroxidase activity inhibiting immunoglobulins in patients with auto immune thyroid disease. H. Clin. Endocrinol. Metab., 68: 730-734.
63: Owen, S.G. and G.A. Smart, 1985. Thyroid antibodies in myxedema. Lancet, 2: 1034-1034.
64: Parkes, A.B., C. Darke, S. Othman, M. Thomas and N. Young et al., 1996. Major histocompatibility complex class II and complement polymorphisms in postpartum thyroiditis. Europ. J. Endocrinol., 134: 449-453.
65: Pearce, E.N., A.P. Farwell and L.E. Braverman, 2003. Thyroiditis. N. Engl. J. Med., 348: 2646-2655.
66: Philips, D.I.W., D.C. Shields, J.M. Dougoujon, L. Prentice, P. McGuffin and B. Rees Smith, 1993. Complex segregation analysis of thyroid autoantibodies: Are they inherited as an autosomal dominant trait? Hum. Hered., 43: 141-146.
67: Poppe, K., D. Glinoer, H. Tournate, P. Deveroey, A. Van Stierteghem, L. Kaufman and B. Velkeniers, 2003. Assisted reproduction and thyroid auto immunity: An unfortunate combination? J. Clin. Endocrinol. Metab., 88: 4149-4152.
68: Prabhakar, B.S., J.L. Fan and G.S. Seetharamaiah, 1997. Thyrotropin- receptor- mediated diseases: A paradigm for receptor autoimmunity. Immune. Today, 18: 437-442.
69: Protmann, L., N. Hamada, G. Heinrich and L.J. DeGroat, 1985. Antithyroid peroxidase antibody in patient with autoimmunue thyroid disease: possible identity wit microsomal antibody. J. Clin. Endocrinol. Metab., 61: 1001-1003.
70: Rapopott, B., G.D. Chacenblack, J.C. Jaume and S.M. Mclachian, 1998. The thyrotrophine (TSH)- releasing hormone receptor: Interaction with TSH and autoantibodies. Endocrine. Rev., 19: 673-716.
71: Ringold, D.A., J.T. Nicoloff, M. Kesler, H. Davis, A. Hamilton and T. Mack, 2002. Further evidence for a strong influence on the development od autoimmune thyroid diseas: The California twin study. Thyrouid., 12: 647-653.
72: Sakaguchi, S., 2005. Naturally arising Foxp3- expressing CD25+ CD25+ regulatory T cells in immunological tolerance to self and non- self. Nat. Immune., 6: 345-352.
73: Sanders, J., M. Evans, L.D.K.E. Premawardhand, J. Defferyes, T. Richards, J. Furmaniak and B Rees Smith, 2003. Human, monoclonal thyroid stimulating antibody. Lancet, 362: 126-128.
Direct Link |
74: Sawai, Y. and L.J. DeGroot, 2000. Binding of human thyrotropin receptor peptides to a Graves disease predisposing human leukocyte antigen class II molecule. J. Clin. Endocrinol. Metab., 85: 1176-1179.
Direct Link |
75: Schwarz, B.A. and A. Bhandoola, 2006. Trafficking from Bone marrow to thymuss prerequisite for thymopoiesis. Immunol. Rev., 209: 47-57.
76: Kohno, Y., N. Naito, Y. Hiuama, N. Shimojo and N. Suzuki et al., 1988. Thyroglobulin and thyroid peroxidase share common epitopes recognize by autoantibodies in patients with chronic autommune thyroiditis. J. Clin. Endocrinol. Metab., 67: 899-907.
77: Shields, D.C., S. Ratanachaiyavong, A.M. McGregor, A. Collins and N.E. Morton, 1994. Combined segregation and linkage analysis of Graves disease with a thyroid autoantibody diathesis. Am. J. Human Genet., 55: 540-554.
78: Smyth, P.P.A., S.G. Shering, M.T. Kilbane, M.J. Murray, E.W.M. McDermott, D.F. Smith and N.J. O'Higgins, 1998. Serum thyroid peroxiedase auto antibodies, thyroid volume and outocome breast caricinoma. J. Clin. Endocrinol. Met., 83: 2711-2716.
Direct Link |
79: Stenszky, V., L. Kozma, C. Balazs, S. Rochitz, J.C. Bear and N.R. Farid, 1985. The genetics of Graves disease: HLA and disease susceptibility. J. Clin. Endocrinol. Metab., 61: 735-740.
80: Suzuki, S., M. Misunaga, Miyshi, S. Hirakw and O. Nakawa et al., 1980. Cytophilic antithyroglubulin antibody and antibody dependent monocyte mediated cyotoxity in Hashimatos thyroiditis. J. Clin. Endocrinol. Metab., 51: 446-446.
81: Tomer, Y., G. Barbesino, M. Kedache, D.A. Greenbarg and T.F. Davies, 1997. Mapping of a major susceptibility locus for Graves disease (GD1) to chromosome 14q31. J. Clin. Endocrinol. Metab., 82: 1645-1648.
Direct Link |
82: Tomer, Y. and T.F. Davies, 1993. Infection, thyroid disease and autoimmunity. Endocrine. Rev., 14: 107-120.
83: Tonacchera, M., J. Van Sande, J. Parma, L. Duprez and F. Cetani et al., 1996. TSH receptor and disease. Clin. Endocrinnol., 44: 621-633.
84: Vali, M., N.R. Rose and P. Caturegil, 2000. Thyroglobulin as auntoantigen: Strucure- function relationships. Rew. Endocr. Met. Dis., 1: 69-77.
85: Vala, B.S., 2001. Endocrinology Andtheheart. In: Cardiology, Mickel, H., C. John and P. Di Marco (Eds.), Mosby, London.
86: Weetman, A.P., C.M. Black, S.B. Cohen, R. Tomlinson, J.P. Banaga and C.B. Reimer, 1989. Affinity purification of subckasses and the distrivution of thyroid auto- antibody reactivity in Hashimatos thyroiditis. Scand. J. Immonol., 30: 73-82.
87: Weigle, W., 1975. Cyclicproduction of antibody as a regulatory mechanism in the immune response. Adv. Immol., 21: 87-87.
88: Weetman, A.P. and A.M. McGregor, 1994. Autoimmune thyroid disease: Further development in our understanding. Endocring Rev., 15: 788-830.
89: Weetman, A.P., M.E. Yateman, P.A. Ealey, C.M. Black and C.B. Reimer et al., 1990. Thyroid stimulating antibody activity between different immunogolubin G Subclasses. J. Clin. Invest., 86: 723-727.
90: Weetman, A.P., 2001. Determinants of autoimmune thyroid disease. Nat. Immunol., 2: 769-770.
91: Wenzel, B.E., J. Heesemann, K.W. Wenzel and P.C. Scriba, 1988. Patients with autoimmune thyroid diseases have antibodies to plasmid encoded proteins of enteropathogenic Yersinia. J. Endocrinol. Invast., 11: 139-140.
92: Yanagawa, T., A. Mangklabruks, Y.B. Chang, Y. Okamoto, M.E. Fisfalen, P.G. Curran and L.J. DeGoot, 1993. Human histocompatibility leukocyte antigen- DQA1*0501 allele associated with genetic susceptibility to Graves disease in a Caucasian population. J. Clin. Endocrinol. Metab., 76: 1569-1574.
Direct Link |
93: Zeitlin, A.A., M.J. Simmonds, S.C. Gough, S. Blanchin and C. Coffin et al., 2007. Anti thyroperoxidase antibodies from patients with Hashimatos encephalopathy bind to cerebellar astrocytes. J. Neuroimmunol., 192: 13-20.
94: Aoki, N. and L. Degroot, 1979. Lymphocyte blastogenic response to human thyroglobulin in Graves disease, Hashimatos thyroiditis and metastatic thyroid cancer. Clin. Exp. Immune., 38: 523-523.
95: Dechairo, B.M., D. Zabaneh, J. Collins, O. Brand and G.L. Dawson et al., 2005. Association of the TSHR gene with Graves disease: The first disease specific locus. Eur. J. Hum. Gemet., 31: 1223-1230.
96: Doniach, D., I.M. Roitt and K.B. Taylor, 1963. Auto immune phenomena in pernicious anemia. Serological overlap thyroiditis, thyrotoxicosis and systemic lupus erythematosus. Br Med J., 1: 1374-1379.
PubMed | Direct Link |
97: Irvine, W.J., S.H. Davies, S. Teitkbaum, I.W. Delamore and A.W. Wiliams, 1965. The clinical and pathological significance of gatric parietal cell antibodu. Ann. Acad. Sci., 124: 657-691.
98: Jansson, R., S. Bernader, A. Karlsson, K. Levin and G. Nilsson, 1984. Aytoimmune thyroid dysfunction in the postparyum period. J. Clin. Endocrinol. Metab., 58: 681-687.
99: Kohn, L.D., K. Suzuki, W.H. Hoffman, D. Tonbaccini and N. Shimojo et al., 1997. Characterization of monoclonal thyroid- simulating and thyrotropin ginding- inhibiting auto antibodies from a Hashimatos patient whose children had intrauterine and neonatal thyroid disease. J. Clin. Endocrinol. Metab., 82: 3998-4002.
100: Kondrashova, A., H. Visjari. A.M. Haapala, T. Seikari, P. Kulmala. J. Ilonen and H. Hyoty, 2008. Serological evidence of thyroid auto immunity among schoolchildren in two different socioeconomic environments. J. Clin. Endocrinol. Metab., 93: 729-734.
101: Kroneberg, M., G. Siu, L.E. Hood and N. Shastri, 1986. The molecular genetics of the T- cell abtigen and T-cell antien recognition. Ann. Rev. Immunol., 4: 529-529.
102: Mansourian, A.R., E. Ghaemi, A.R. Ahmadi, A. Marjani, A. saifi and S. Bakhshandehnosrat, 2008. Serum lipid level alteration in subclinical hypothyroidpatients in Gorgan (South east Caspian Sea). Chinese Clin. Med., 3: 206-221.
Direct Link |
103: Mansourian, A.R., 2010. Thyroid function tests during first trimester of pregnancy: A review of literature. Pak. J. Biol. Sci.,
104: Mansourian, A.R., A.R. Ahmadi, H.R. Mansourian, A. Saifi, A. Marjani, G.R. Veghari and E. Ghaemi, 2010. Maternal thyroid stimulating hormone level during the first trimmester of pregnancies at thesouth east ofCaspian Sea in Iran. J. Clin. Diagnostioc. Res., 4: 2472-2477.
105: Marjani, A., A.R. Mansourian, E.O. Ghaemi, A. Ahmadi and V. Khori, 2008. Lipid peroxidation in the serumof hypothyroid patients in Gorgan, south east of Caspian sea. Asian J. Cell. Biol., 3: 47-50.
106: Misaki, T., J. Konishi, Y. Iida, K. Endo and K. Torizuka, 1984. Altered balance of immunoregulatory lymphocyte sybsets in auto immunity thyroid disease. Acta. Endocrinol., 105: 200-204.
107: Noma, T., J. Yata, Y. Shishiba and B. Inatsuki, 1982. In vitro detection of anti thyroglobulin antibody forming cells from the lymphocytes of chronic thyroiditis patients and analysis of their regulation. Clin. Exp. Immunol., 49: 565-571.
Direct Link |
108: Okita, N., A. Kidd, V.V. Roww and R. Volpe, 1980. Sentiziation of T lymphocytes in Graves and Hashimatos diseases. J. Clin. Endoccrinol. Metab., 51: 316-316.
109: Pop, V.J., L.H. Maartens, G. Leusink, A.A. Van Son Konttnerus, A.M. Ward, R. Mercalfe and A.P. Weetman, 1998. Are auto immune thyroid dysfunction and depression related? J. Clin. Endocrinol. Metab., 83: 3194-3997.
Direct Link |
110: Pratt, D.E., G. Kaberlein, A. Dudkiewicz, V. Karande and N. Gleicher, 1993. The association of anythyroides in eutyroid nonpregnant women with recurrent first trimester abortions the next pregnanc. Fittil. Steril., 60: 1001-1005.
111: Radetti, G., A. Fanolla, L. appalardo and E. Gottardi, 2007. Prenaturity my be a risk factor for thyroid dysfunction in childhood. J. Clin. Endocrinol. Metab., 92: 155-159.
112: Shahmohammadi, F., A.R. Mansourian and H.R. Mansourian, 2008. Serum thyroidhormon level in women withnausea and vomiting in early pregnancy. J. Med. Sci., 8: 507-510.
113: Weetman, A.P., AM McGregor, J.H. Lazarus and R. Hall, 1982. Thyroid antibodies are produced by thyroid derived lymphocytes. Clin. Exp. Immune., 48: 196-200.
Direct Link |
114: Wong, G.W.K. and P.S. Cheng, 2001. Increasing incidence of childbooh Graves; disease in Hong Kong: A follow- up study. Clin. Endocrinol., 54: 547-550.
115: Woolner, L.B., W.M. McConahy and O.H. Beahr, 1959. Stroma lymphomatosa and related thyroidal disorders. J. Clin. Endpcrinol. Metab., 19: 53-61.
116: Zois, C., I. Sravrou, E. Svarna, K. Seferidis and A. Tsarsoulis, 2006. Natural Course of auto immune thyroiditis after elimination of iodine deficiency in north western Greece. Thyroid., 16: 289-293.
117: Bartel, E.D., 1941. Heredity in Graves Disease. Enjnar Munksgaards Forlag, Copenhagen, Denmark.
118: Phillips, D.L., M. Prentice, M. Upadhyaya, P. lunt and S. Chamberlain et al., 1991. Autosomal dominant inheritance of autoantibodies to thyroid peroxidase and thyrogolobuline-studies in families not selected for autoimmune thyroid disease. J. Clin. Endocrinol. Metab., 72: 973-975.
119: Zeitlin, A.A., M.J. Simmonds and S.C. Gough, 2008. Genitic developments in autoimmune thyroid disease: An evolutionary process. Clin. Endocrinol., 68: 671-682.
120: Mulhern, L.M., A.T. Masi and L.E. Shulman, 1966. Hashimato disease: A search for associated disorders in 170 clinically detected cases. Lancet, 2: 508-511.
121: Blanchin, S., C. Coffin, F. Viader, J. Ruf and P. Carayon et al., 2007. Antithyroperoxidase antibodies from patients with Hashimato encephalopathy bind to cerebellar astrocytes. J. Neuroimmunol., 192: 13-20.
122: Tomer, Y., 1997. Anti-thyroglobulin autoantibodies in autoimmune thyroid diseases: Cross-reactive or pathogenic. Clin. Immunol. Immunopathol., 82: 3-11.
CrossRef | PubMed |
123: Mclachian, S.M. and B. Rapoport, 1992. The molecular biology of thyroid peroxidase: Cloning, expression and role as autoantigen in autoimmune thyroid disease. Endocrine. Rev., 13: 192-206.
124: Mansourian, A.R., 2010. The state of serum lipids profiles in sub-clinical hypothyroidism: A review of the literature. Pak. J. Biol. Sci., 13: 556-562.
CrossRef | Direct Link |
125: Mansourian, A.R., E.O. Ghaemi, A.R. Ahmadi, A. Saifi, A.V. Moradi and S. Bakhshandeh-Nosrat, 2007. A survey of urinary iodine concentration in South-East of Caspian Sea in Northern, Iran. Pak. J. Biol. Sci., 10: 2166-2171.
CrossRef | PubMed | Direct Link |