Hashimoto's thyroiditis (HT) is one of the most common human autoimmune diseases responsible for numerous morbidity in women. Hashimoto’s disease is also called Hashimoto’s thyroiditis, chronic lymphocytic thyroiditis, or autoimmune thyroiditis. Hashimoto’s disease is at least 8 times more common in women than men. Although the disease may occur in teens or young women, it more often appears between ages 40 and 60. Your possibility of developing Hashimoto’s thyroiditis increases if other family members have the disease. It is an organ-specific T-cell mediated disease that affects the thyroid gland, and genetics play a contributory role in its complexity. To date, significant progress has been made in identifying and characterizing those genes involved in the disease.

1. HASHIMOTO'S THYROIDITIS
CLS – MICROBIOLOGY MODULE
YOUSIF RAHMAN ALWAN
2ND
GRADE
UNIVERSITY OF
BAGHDAD
COLLEGE OF MEDICINE
2017 / 2018

2. 1
Contents
1- Introduction ………….…………………………………………………. 2
2- Search board and discussion:
 History and epidemiology ………………….…………………….. 3
 Etiology …………………………………………………………... 4
 Signs and symptoms ……………………………………………… 6
 Risk factors ……………………………………………………….. 8
 Pathology ……………………………………………………..…. 10
 Complications …………………………………………………… 13
 Diagnosis ………………………………………………………… 14
 Treatment and management ……………………………………... 18
 Prevention ………...……………………………………………... 21
 Prognosis ………………………………………………………… 22
3- Summary ………………………………………………………………. 23
4- References ……………………………………………………………... 24
5- Figures' references ………………………………………………..…….27

3. 2
Introduction
Hashimoto's thyroiditis (HT) is one of the most common human autoimmune
diseases responsible for numerous morbidity in women.[1] Hashimoto’s disease
is also called Hashimoto’s thyroiditis, chronic lymphocytic thyroiditis, or
autoimmune thyroiditis. Hashimoto’s disease is at least 8 times more common
in women than men. Although the disease may occur in teens or young women,
it more often appears between ages 40 and 60. Your possibility of developing
Hashimoto’s thyroiditis increases if other family members have the disease.[2]
It is an organ-specific T-cell mediated disease that affects the thyroid gland,
and genetics play a contributory role in its complexity. To date, significant
progress has been made in identifying and characterizing those genes involved
in the disease.
In this review, we summarize recent advances in our understanding of the
genetic contribution to the pathogenesis of HT. Various studies have
successfully outlined the genetic and environmental factors responsible for the
causation of the disease. The etiological factors and the pathophysiological
changes which lead to the development of disease will be discussed. Common
diagnostic modalities will be described, and the need for correlation between the
various available diagnostic tests is explained. Various treatment strategies and
the appropriate choice for different forms of presentation are discussed.

4. 3
History and epidemiology
In 1912 Dr. Hakaru Hashimoto (Figure1) described four patients with a
chronic disorder of the thyroid, which he termed struma lymphomatosa. The
thyroid glands of these patients were characterized by the diffusion of
lymphocytic infiltration, fibrosis, parenchymal atrophy, and an eosinophilic
change in some of the acinar cells. [3] Clinical and pathologic studies of this
disease have become clear frequently since Hashimoto's original description. [4]
The disorder affects up to 2% of the general population [5] and is more
common in older women and ten times more frequent in women than in men
[6]. In the NHALES III study, performed in the USA, the prevalence of
subclinical and clinical hypothyroidism was 4.6% and 0.3% respectively [7].
Another US epidemiological study, the Wickham survey, showed the
prevalence of spontaneous hypothyroidism to be 1.5% in females and less than
0.1% in males [8]. These prevalence rates are similar to those reported in Japan
[9] and Finland [10]. It occurs especially during the decades from ages 30 to 50,
but may be seen in any age group, including children. [11,12] In children, the
most common age at presentation is adolescence but the disease may occur at
any time, rarely even in children under 1 year of age. [13]
Figure.1. Dr. Hakaru Hashimoto

5. 4
Etiology
The etiology of Hashimoto’s thyroiditis is considered to be multifactorial,
involving the interplay of different environmental and genetic factors. The
thyroid gland is typically goitrous but may be atrophic or normal in size.
Antibodies binding to and blocking the thyroid-stimulating hormone (TSH)
receptor, thyrotropin receptor blocking antibodies (TBII) have also been
described and may contribute to impairment in thyroid function. The result is
inadequate thyroid hormone production and secretion, although initially,
preformed thyroxine (T4) and triiodothyronine (T3) may "leak" into the
circulation from damaged cells. [14]
Studies conducted on the genetic associations of Hashimoto’s thyroiditis have
shown that the human leukocyte antigen (HLA) region, that plays a major role
in other autoimmune disorders, is associated with development of Hashimoto’s
thyroiditis. [15] The association of Hashimoto’s thyroiditis with various other
autoimmune diseases has further reinforced the probable involvement of genetic
factors in the etiology. The major histocompatibility complex (MHC), cytotoxic
T-lymphocyte association (CTLA-4) and the human leukocyte antigen (HLA)
are the genetic factors which are intended to play a major role in the
pathogenesis. [16]
A study by Mazokopakis et al indicated that an association may exist between
vitamin D deficiency and the development of Hashimoto's thyroiditis. The study,
which included 218 patients with Hashimoto thyroiditis, found serum 25-
hydroxy vitamin D levels to be negatively correlated with anti-TPO levels in all
patients, with the anti-TPO levels being significantly greater in the 186 patients
who were vitamin D deficient. After receiving oral vitamin D3 supplementation
of 1200-4000 IU daily for 4 months, serum anti-TPO levels in the vitamin D
deficient patients were determined to be significantly decreased. [17]
In addition to the genetic factors, many external factors also play a vital role
in the etiology of the disease, preferentially affecting genetically predisposed
individuals. The common environmental factors which act as triggers to initiate
the insult on thyroid tissue include infections, cytokine therapy, selenium and
iodine intake. Epidemiological studies and animal models have shown that
among the factors that initiate the process, iodine appears to be the most
significant. [18] Some studies have established smoking as an important risk

6. 5
factor for the causation of hypothyroidism in patients with Hashimoto’s
thyroiditis.
Environmental Factors:
Iodine: It has been well documented that the incidence of AITD is proportional
to dietary iodine content. In Europe the prevalence of GD increases with national
iodine intake programs. Iodine increases the antigenicity of TG with
exacerbation of experimental thyroiditis in animals. Recent in vitro studies in
NOD.H2h4 mouse have shown that high iodine doses alone may damage
thyrocytes and enhances the disease progression in a dose-dependent manner.
Infection: No convincing evidence has indicated a role infection in AH except
congenital rubella syndrome. An association has been proved between Yersinia
infection and GD. Yersinia contains proteins that mimic TSH-R
immunologically. Recently, retrovirus has received attention but the results are
conflicting.
Stress: Some studies suggest an association between antecedent major life
events and Graves’ disease, but a causal role of stress in autoimmune process
remains to be clearly established. Smoking is a minor risk factor for the
development of thyroid ophthalmopathy. The female preponderance of thyroid
autoimmunity is most likely because of the influence of sex steroids. Estrogen
use is associated with a lower risk, and pregnancy with a higher risk for
developing hyperthyroidism. [19]

7. 6
Signs and symptoms
The clinical features depending on type and stages of the disease. Hashimoto’s
thyroiditis presents with small to large firm and painless goiter (Fig. 2). Patients
slowly develop progressive hypothyroidism, but a fewer number with moderate
or even severe hypothyroidism eventually become euthyroid. Hypothyroid
patient may recover after the loss of TSH-receptor blocking antibody, removal
of causative agent (such as iodine) or recovery from destructive thyroiditis.]20[
In some instances the thyroid gland may enlarge quickly; rarely, it is associated
with dyspnea or dysphagia from pressure on structures in the neck, or with mild
pain and tenderness. Rarely, pain is persistent and unresponsive to medical
treatment and requires medical therapy or surgery. The goiter of Hashimoto's
thyroiditis may remain unchanged for decades]21[ but usually it gradually
increases in size. Occasionally the course is marked by symptoms of mild
thyrotoxicosis, especially during the early phase of the disease. Symptoms and
signs of mild hypothyroidism may be existing in 20% of patients when first seen
[22], or commonly develop over a period of several years.
Presentations of Hashimoto's Thyroiditis:
1. Euthyroidism
2. goiter (Fig.2)
3. Subclinical hypothyroidism and goiter
4. Primary thyroid failure
5. Hypothyroidism
6. Adolescent goiter
7. Painless thyroiditis or silent thyroiditis
8. Postpartum painless thyrotoxicosis
9. Alternating hypo- and hyperthyroidism
Fig.2. goiter
It has been suggested that thyroiditis predisposes to vascular disease and
coronary occlusion. Abnormally elevated titers of thyroid autoantibodies and the
morphologic changes of thyroiditis are said to happen with an increased
frequency among patients with coronary artery disease. Mild hypothyroidism
[23] associated with asymptomatic atrophic thyroiditis could predispose patients
to heart disease. Others have failed to discover increased TG Ab in-patients with

8. 7
coronary artery disease [24] or increased coronary disease in association with
thyroiditis. Musculoskeletal symptoms, including chest pain, fibrositis, and
rheumatoid arthritis, happen in one-quarter of patients [25] and of course, any of
the musculoskeletal symptoms of hypothyroidism may similarly occur.
When goiter is induced by iodine administration, lymphocytic thyroiditis is
frequently found and thyroid autoantibodies are frequently present [26].
Painless (silent) and Postpartum Thyroiditis
In the last decade numerous syndromes involving clinically significant, but self-
limited, exacerbations of AITD have been delineated. Silent (painless)
thyroiditis is a syndrome that has a clinical course of thyroid dysfunction similar
to subacute thyroiditis but with no anterior neck pain and no tenderness of the
thyroid. Initially, patients have a thyrotoxic phase, later passing through
euthyroidism to hypothyroidism and, finally, return to euthyroidism. Postpartum
thyroiditis occurs within 6 months after delivery and runs an identical clinical
course. Postpartum thyroiditis is today considered to be identical to silent
thyroiditis, and this term is used for patients who developed silent thyroiditis in
the postpartum period. [27]
Iodine Metabolism and Effects
Many patients with Hashimoto's thyroiditis do not respond to injected TSH
with the estimated increase in RAIU or release of hormone from the gland. [28]
These results probably mean that the gland is partially destroyed by the
autoimmune attack and is unable to augment iodine metabolism further. Further,
the thyroid gland of the patient with Hashimoto's disease does not organify
normally. [29] Iodide is actively conveyed from blood to thyrocytes and recently
the sodium / iodide symporter (NIS) has been cloned. Antibodies against NIS
were found in autoimmune thyroid disease [30]. This antibody has an inhibitory
activity on iodide transport and may modulate the thyroid function in
Hashimoto's thyroiditis. More recent studies reported rather low prevalence (less
than 10%) of anti-NIS antibodies in Hashimoto's disease and clinical relevance
is still indefinite [31], [32].

9. 8
Risk factors
Each patient has a background inherited predisposition to autoimmunity, with
additional environmental and hormonal factors that prompt or contribute to the
development of disease.
Environmental factors:
Environmental factors either trigger or enhance development of thyroid
autoimmunity. High dietary iodine intake improves thyroglobulin immune
reactivity. [33] Pathogenic role of infective agents in initiating AITD is
indistinct; organisms like rubella, Epstein Barr virus, yersinia and recently,
retrovirus have been implicated. Stress disorders are shown to be associated with
Graves’ disease probably by altering neuroendocrine interaction with immune
system. [34]
Genetic factors:
The concordance rate in monozygotic twins is 35-55% as compared to less
than 5% in dizygotic twins. The predisposition to Graves’ disease is genetic in
79% case while only 21% cases are owning to non-genetic (environmental and
hormonal) factors. Thyroid antibodies have been found in nearly half of the
relatives of AITD patients against only 8-27% in general population. The risk of
AITD in female sibling and children of patient with Graves’ disease is 5-8%
against the background frequency of 0.6% [35] In other autoimmune disorders,
higher prevalence of AITD has been found in patients and their relatives. AITD
is a constituent of some rare monogenic syndromes. Autoimmune
hypothyroidism affects patient with type 1 polyendocrinopathy; immune
dysregulation, ‘polyendocrinopathy’ and enteropathy [IPEX]. Different alleles
of MHC class I molecule are shown to be associated with Graves’ disease in
different ethnic group e.g. HLA-A10, B8 and DQw2 is seen in India. [36]
Cytotoxic T lymphocyte antigen-4 (CTLA-4), an immunomodulatory molecule
expressed on the surface of activated T cell, is its key negative regulator. CTLA-
4 gene is a major candidate gene for common autoimmune disorders like Graves’
disease, Type-1 diabetes and Hashimoto’s thyroiditis.
Sex: Women are much more likely to get Hashimoto's disease.
Age: Hashimoto's disease can occur at any age but more commonly occurs
during middle age.

10. 9
Heredity: You're at higher risk for Hashimoto's disease if others in your
family have thyroid or other autoimmune diseases.
Other autoimmune disease: Having another autoimmune disease — such
as rheumatoid arthritis, type 1 diabetes or lupus — increases your risk of
developing Hashimoto's disease.
Radiation exposure: People exposed to excessive levels of environmental
radiation are more disposed to Hashimoto's disease. [37]

11. 10
Pathology
Autoimmune thyroid disease is
characterized by lymphoid infiltration of
the thyroid gland including T and B cells.
In classic different, the gland is usually
diffusely enlarged. Firm in consistency
and soft grayish in cut section (Fig.3).
Therefore, both cellular and humoral
immunity have a role in the pathogenesis
of thyroid autoimmunity.
Fig.3. Figure showing cut sec on of thyroid in Hashimoto
Cellular immunity
In autoimmune thyroid disease, T cells migrate from the periphery into the
thyroid gland and actively participate in the autoimmune process. The main
cellular pathways that contribute to thyroid destruction are discussed with
special focus on latest developments in the field.
1. Suppressor and regulatory T cell defects:
Suppressor T cells were initially considered to be specific CD8+ cells
tasked with inhibiting undesirable immune responses. Early work
demonstrated defects in T suppressor cell response to thyroid-specific
antigens in autoimmune hypothyroidism, implicating antigen-specific T
suppressor failure in disease pathogenesis. [38] However, findings were
criticised for the nonphysiological experimental conditions and poor
reproducibility of data, casting doubts on the importance of this putative
pathway in disease pathogenesis. Some of the functions of suppressor T
cells now seem to be those of regulatory T cells (Tregs) which represent 5-
10% of CD4+ cells. [39]
2. Follicular helper T cells

12. 11
Follicular helper T cells (Tfh) are somewhat newly identified subset of T
helper cells, involved in promoting antigen-specific B cells through the
production of IL-21. [40] These cells express chemokine receptor CXCR5
together with inducible costimulator (ICOS) protein, which represents one
of the molecules required for normal cellular function. Using flow
cytometry, Zhu and colleagues have shown increased Tfh cells in the
peripheral blood of HT patients, which correlated with thyroid-specific
antibody levels. Moreover, CD4+CXCR5+ ICOShigh cells were found in
HT thyroid tissue, additional implicating these cells in disease
pathogenesis. [41]
3. Cytotoxicity and apoptosis
CD8+ T cells against both TPO and TG are noticed in patients with ATD
and mediate gland destruction [42] However, only 2-3% of infiltrating
CD8+ cells recognize TPO/TG, suggesting the majority of these cells are
not thyroid autoantigen-specific. This is not unprecedented as similar data
have been reported in type 1 diabetes, extra organ-specific autoimmune
condition. [43]
Humoral immunity
Thyroid-specific antibody production is a key feature of ATD. We briefly
summarize the main thyroid antibodies with the most recent developments in
this area.
1. TPO/TG antibodies and immunoglobulin subclass
Antibodies against TG and TPO are present nearly in all patients with HT.
[44] In addition to aiding the diagnosis, TPO antibodies can be used to help
predict development of hypothyroidism, particularly when combined with
measurement of TSH levels. [45]
2. Sodium iodide symporter (NIS) and pendrin antibodies
The NIS mediates iodine uptake by the thyroid gland, while pendrin is
responsible for the efflux of iodine through TFCs. NIS antibodies are
found in 17-31% of patients with ATD and in some cases these
antibodies have a functional character in vitro by inhibiting the activity
of the symporter. [46] Antibodies against pendrin are perceived in only
9-11% of patients with ATD. [47] Although the frequency of NIS and
pendrin antibodies is slightly lower in HT compared with GD, the
marginal difference indicates that these antibodies are unlikely to
determine disease presentation.
3. Thyroid stimulating hormone receptor (TSHR) antibodies

13. 12
Antibodies against the TSHR receptor have a clear functional role in
GD by stimulating receptor function (thyroid stimulating antibodies or
TSAb). Less commonly, however, these antibodies possess blocking
activity. The balance between TSAb and TBAb (thyroid blocking
antibodies) can determine disease presentation (hyper- or
hypothyroidism), which explains the changeable thyroid hormone levels
in some patients with ATD. A number of factors can modulate the
balance between TSAb and TBAb, including antithyroid drugs or
thyroxine treatment and pregnancy. [37]
Fig. 4. A schematic presentation of etiopathogenesis of Hashimoto’s thyroiditis.

14. 13
Complications
Left untreated, an underactive thyroid gland (hypothyroidism) caused by
Hashimoto's thyroiditis can lead to a number of health problems:
1. Goiter: Constant stimulation of your thyroid to release more hormones
may cause the gland to become enlarged, a condition known as goiter.
Hypothyroidism is one of the most common causes of goiters. Although
generally not uncomfortable, a large goiter can affect your appearance and
may interfere with swallowing or breathing.
2. Heart problems: Hashimoto's disease also may be associated with an
increased risk of heart disease, primarily because high levels of low-
density lipoprotein (LDL) cholesterol — the "bad" cholesterol — can occur
in people with an underactive thyroid gland (hypothyroidism). If left
untreated, hypothyroidism can lead to an enlarged heart and, possibly,
heart failure.
3. Mental health issues: Depression may occur early in Hashimoto's disease
and may become more severe over time. Hashimoto's disease can also
cause sexual desire (libido) to decrease in both men and women and can
lead to slowed mental functioning.
4. Myxedema (miks-uh-DEE-muh): This rare, life-threatening condition
can develop due to long-term hypothyroidism as a result of untreated
Hashimoto's disease. Its signs and symptoms include drowsiness followed
by profound lethargy and unconsciousness.
5. A myxedema coma: may be triggered by exposure to cold, sedatives,
infection or other stress on your body. Myxedema requires immediate
emergency medical treatment.
6. Birth defects: Babies born to women with untreated hypothyroidism due
to Hashimoto's disease may have a higher risk of birth defects than do
babies born to healthy mothers. Doctors have long known that these
children are more prone to intellectual and developmental problems. There
may be a link between hypothyroid pregnancies and birth defects, such as
a cleft palate.
A connection also exists between hypothyroid pregnancies and heart, brain and
kidney problems in infants. If you're design to get pregnant or if you're in early
pregnancy, be sure to have your thyroid level checked. [37]

15. 14
Diagnosis
Assessing the metabolic status of the patient and identifying the type of lesion
present are of vital importance in making an accurate diagnosis of Hashimoto’s
thyroiditis. The first step is to assess the thyroid hormone status, which reflects
glandular function. Although the presence of goiter alone, without associated
hyperthyroid symptoms, is suggestive of Hashimoto’s thyroiditis, the presence
of a goiter in a hypothyroid patient is considered to be strongly indicative of
Hashimoto’s thyroiditis. Triiodothyronine (T3), tetraiodothyronine (T4) and
thyroid stimulating hormone (TSH) levels are the commonly employed lab
studies used to evaluate the level of function of the thyroid gland. Among these
parameters, TSH has been reported to be the most sensitive marker of
hypothyroidism. Even after the diagnosis is established, frequent monitoring of
TSH is done to assess the response to treatment and progression of the disease.
After the assessment of patient’s thyroid function status, the focus shifts to
indentifying the presence of antithyroid antibodies. It should be noted that while
the presence of antithyroid peroxidase (ATPO) and antithyroglobulin (TGAB)
antibodies are both positively correlated with Hashiomoto’s thyroiditis, the
correlation is slightly higher for TGAB than ATPO. [49] Even in the absence of
hypothyroid symptoms, the presence of antithyroid antibodies would show
underlying lymphocytic infiltration of the gland, and be indicative of
autoimmune disease. [50]
Radioactive iodine uptake (RAIU) is another modality which is commonly
active in diagnosing thyroid disorders. The role of RAIU in the diagnosis of
Hashimoto’s thyroiditis has been debated for many years [51] A potentially less
obtrusive study which may be performed to discern thyroid pathology is an
ultrasound. Ultrasonography provides information regarding anatomic
characteristics of the gland and identifies any major changes in the gland.
Ultrasonography can be helpful in discerning Hashimoto’s thyroiditis in goiters
of unknown etiology and can identify the cause of functional impairment as well
as the essential for treatment. [52]
The physical features of the thyroid gland, serum TSH levels, serum
antithyroid antiglobulin titer, radioactive iodine uptake of the gland, and the
response to the perchlorate discharge test are widely used in making an accurate
diagnosis of the disease. Indeed, the clinician can feel reasonably confident in
their diagnosis of Hashimoto’s thyroiditis if at least two of the above mentioned
tests support the diagnosis. [53] Some recent studies have subclassified
Hashimoto’s thyroiditis as IgG-4 thyroiditis and nonIgG-4 thyroiditis. This

16. 15
distinction may be important in that IgG-4 thyroiditis has been associated with
severe lymphoplasmacytic infiltration, marked fibrosis, and lymphoid follicle
formation in contrast to nonIgG-4 thyroiditis, which displays more mild
histopathological changes. [54] Thus, this classification might be helpful in
assessing the severity of the disease and could be used in determining the most
appropriate treatment options for patients.
Also, the disease process must be differentiated from some commonly
occurring thyroid disorders such as nontoxic nodular goiter and Graves’ disease.
The presence of a multinodular goiter with gross nodularity is usually considered
to be evidence against the diagnosis of Hashimoto’s thyroiditis but it cannot be
ruled out based on this finding. [55] Unlike Hashimoto’s thyroiditis,
multinodular goiter is usually characterized by euthyroid status and absence of
antithyroid antibodies. Hashimoto’s thyroiditis and multinodular goiter
commonly coexist in patients thus, FNA is commonly employed to differentiate
these two entities. Tumor of thyroid gland is another object which has to be
differentiated from Hashimotos’ thyroiditis. Rapid growth of the gland and
persistent pain usually arouses suspicion of tumor. The confirmatory diagnosis
of tumor is usually performed with the aid of FNA. Thyroid lymphoma may
develop in some cases of Hashimoto’s thyroiditis. Some studies have indicated
that using reverse transcriptase polymerase chain reaction might be helpful in
differentiating thyroid lymphoma and Hashimoto’s thyroiditis. [56]
Furthermore, although Hashimoto’s thyroiditis typically presents with
hypothyroid symptoms, patients may occasionally present with hyperthyroidism
and thyrotoxicosis. This necessitates the differentiation of Hashimoto’s
thyroiditis from Graves’ disease, in cases associated with symptoms of excess
thyroid hormone.
Physical examination:
Physical findings are variable and depend on the extent of the hypothyroidism
and other factors, such as age. Examination findings may include the following:
1. Puffy face and periorbital edema typical of hypothyroid facies
2. Cold, dry skin, which may be rough and scaly.
3. Bradycardia.
4. Macroglossia.
5. Slow speech.
6. Ataxia.
7. Elevated blood pressure (typically diastolic pressure)

17. 16
Testing
Laboratory studies and potential results for patients with suspected Hashimoto
thyroiditis include the following:
1. Serum thyroid-stimulating hormone (TSH) levels: Sensitive test of thyroid
function; levels are invariably raised in hypothyroidism due to Hashimoto
thyroiditis and in primary hypothyroidism from any cause
2. Free T4 levels: Needed to correctly interpret the TSH in some clinical
settings; low total T4 or free T4 level in the presence of an elevated TSH
level further confirms diagnosis of primary hypothyroidism
3. T3 levels: Low T3 level and high reverse T3 level may aid in the diagnosis
of nonthyroidal illness
4. Thyroid autoantibodies: Presence of typically anti-TPO (anti-thyroid
peroxidase) and anti-Tg (anti-thyroglobulin) antibodies delineates the
cause of hypothyroidism as Hashimoto thyroiditis or its variant; however,
10-15% of patients with Hashimoto thyroiditis may be antibody negative.
Imaging tests:
Features of Hashimoto thyroiditis are usually identifiable on an ultrasonogram;
however, a thyroid ultrasonogram is usually not necessary for diagnosing the
condition. This imaging modality is useful for assessing thyroid size,
echotexture, and, most importantly, whether thyroid nodules are present.
Chest radiography and echocardiography are not usually performed and are
not necessary in routine diagnosis or evaluation of hypothyroid patients.
Procedures:
Hashimoto thyroiditis is a histologic diagnosis. So, perform fine-needle
aspiration of any dominant or suspicious thyroid nodules to exclude malignancy
or the presence of a thyroid lymphoma in fast-growing goiters. [57]
The following tests are not necessary for the diagnosis of primary
hypothyroidism but may be used to evaluate complications of hypothyroidism
in some patients, as indicated:
1. Complete blood count: Anemia in 30-40% of patients with hypothyroidism
2. Total and fractionated lipid profile: Possibly elevated total cholesterol,
LDL, and triglyceride levels in hypothyroidism

18. 17
3. Basic metabolic panel: Decreased glomerular filtration rate, renal plasma
flow, and renal free water clearance in hypothyroidism; may result in
hyponatremia
4. Creatine kinase levels: Frequently elevated in severe hypothyroidism
Differential diagnosis:
Hashimoto's thyroiditis is to be distinguished from nontoxic nodular goiter or
Graves' disease. The presence of gross nodularity is strong evidence against
Hashimoto's thyroiditis, but differentiation on this basis is not infallible. In
multinodular goiter, thyroid function test results are usually normal, and the
patient is only rarely clinically hypothyroid. Thyroid autoantibodies tend to be
absent or titers are low, and the scan result is typical. FNA can resolve the
question but is usually unnecessary. In fact, the two conditions quite commonly
occur together in adult women. Whether this is by chance, or due to the effect of
thyroid growth stimulating antibodies (or other causes) is unknown.
Occasionally the picture of Hashimoto's thyroiditis blends rather imperceptibly
into that of thyrotoxicosis, and some patients have symptoms of mild
thyrotoxicosis, but then develop typical Hashimoto's thyroiditis. In fact, it is best
to think of Graves' disease and Hashimoto's thyroiditis as two very closely
related syndromes produced by
thyroid autoimmunity.
Categorization depends on
associated eye findings and the
metabolic level, but the
pathogenesis, histologic picture,
and function may overlap.
Likewise, we have seen patients
who appear to have a mixture of
Hashimoto's thyroiditis and
subacute thyroiditis, with goiter,
positive thyroid autoantibodies,
normal or low FT4, and biopsies
which have suggested Hashimoto's
on one occasion and included giant
cells on another. A form of painful
chronic thyroiditis with amyloid
infiltration has also been described,
and is possibly etiologically distinct
from Hashimoto's thyroiditis (Fig.5). [58]
Fig. 5. Flow diagram representing the
diagnosis of Hashimoto’s thyroiditis

19. 18
Treatment and Management
The treatment of choice for Hashimoto thyroiditis (or hypothyroidism from
any cause) is thyroid hormone replacement. The drug of choice is orally
administered levothyroxine sodium, frequently for life.
Tailor and titrate the dose of levothyroxine sodium to meet the individual
patient's requirements. The goal of therapy is to restore a clinically and
biochemically euthyroid state. The standard dose is 1.6-1.8 mcg/kg lean body
weight per day, but the dose is patient dependent. The free T4 and TSH levels
are within reference ranges in the biochemically euthyroid state, with the TSH
level in the lower half of the reference range.
Patients younger than 50 years who have no history or evidence of cardiac
disease can usually be started on full replacement doses.
Elderly patients usually require a slighter replacement dose of levothyroxine,
sometimes less than 1 mcg/kg lean body weight per day. Elderly patients and
patients on androgens for various reasons usually require decreased
levothyroxine replacement dosing.
Patients who have undergone bowel resection and have short-bowel syndrome
(or malabsorption for any reason) often require increased doses of levothyroxine
to maintain the euthyroid state. In their previously described study of 830
patients with Hashimoto thyroiditis, Tagami et al found that, following treatment
with small doses of levothyroxine in 32 of the study's patients with subclinical
hypothyroidism, significant decreases occurred in the patients' total cholesterol,
LDL, and non-HDL levels, as well as in their LDL/HDL ratios. [59]
Synthetic hormones
If Hashimoto's disease causes thyroid hormone deficiency, you may need
replacement therapy with thyroid hormone. This usually involves daily use of
the synthetic thyroid hormone levothyroxine (Levoxyl, Synthroid, others).
Synthetic levothyroxine is identical to thyroxine, the natural version of this
hormone made by your thyroid gland. The oral medication restores adequate
hormone levels and reverses all the symptoms of hypothyroidism.
Treatment with levothyroxine is usually all-time, but because the dosage you
need may change, your doctor is likely to check your TSH level about every 12
months. [37] Some patients do not fit easily into the usual diagnostic categories;

20. 19
accordingly, choosing an appropriate course of therapy is more difficult.
Frequently, it is impossible to differentiate Hashimoto's thyroiditis from
multinodular goiter short of performing an open biopsy. In these cases, if there
is no suggestion of carcinoma, it is logical to treat the patient with hormone
replacement and to observe closely. A reduction in the goiter justifies
continuation of the therapy, even in the absence of a diagnosis.
In some patients, especially teenagers, the examination discloses peri-thyroidal
lymph nodes or an apparent discrete nodule, in addition to the diffusely enlarged
thyroid of Hashimoto's thyroiditis. Such nodules should be evaluated by FNA,
ultrasound and possibly scintiscan. Thyroid hormone treatment may cause
regression of the nodes or nodule. If after full evaluation uncertainty persists, if
nodes remain present, or if a nodule grows, surgical exploration is indicated.
Treatment of children and adolescents with 1.3ug/kg/day thyroxine for 24
months was shown in a recent study to cause significant reduction in thyroid size
in patients with Autoimmune thyroiditis, but not affect antibody levels, or
significantly alter TSH or freeT4. [60]
Effects of other substances
Certain medications, supplements and some foods may affect your ability to
absorb levothyroxine. However, taking levothyroxine four hours before or after
other medications could remedy the problem. Talk to your doctor if you eat large
amounts of soy foods or a high-fiber diet or if you take any of the following:
1. Iron supplements, including multivitamins that contain iron
2. Cholestyramine (Prevalite), a medication used to lower blood cholesterol
levels
3. Aluminum hydroxide, which is found in some antacids
4. Sucralfate, an ulcer medication
5. Calcium supplements. [37]
Surgical therapy
Surgery has been used as a technique of therapy. This treatment, of course,
removes the goiter but usually results in hypothyroidism. We believe that it is
not indicated unless significant pain, cosmetic, or pressure symptoms remain
after a fair trial of thyroid therapy, and probably steroid therapy, but is
appropriate in some cases. Among patients with postpartum thyroid dysfunction,
the most common type is destructive thyrotoxicosis and simple symptomatic
treatment, using beta-adrenergic--antagonists, is usually sufficient. [61] In the
case of postpartum hypothyroidism, replacement with a submaximal dose of T3

21. 20
is useful to relieve symptoms more quickly and to predict spontaneous recovery
which is detected by an increase of T4.
Indications for surgery include the following:
1. A large goiter with obstructive symptoms, such as dysphagia, voice
hoarseness, and stridor, caused by extrinsic obstruction of airflow -
Evaluate patients with these symptoms with a barium swallow study and
pulmonary function tests, including flow volume loops and a neck
computed tomography (CT) scan.
2. presence of a malignant nodule - As found by cytologic examination via
fine-needle aspiration.
3. Presence of a lymphoma diagnosed on fine-needle aspiration - Thyroid
lymphoma responds very well to radiotherapy and is the treatment
modality of choice in this situation
4. Cosmetic reasons - For large, unsightly goiter.
Long term monitoring
Upon the initiation of the levothyroxine replacement therapy, check thyroid
function tests, specifically TSH, initially every 6-8 weeks as dose adjustments
are made. After the attainment of the clinical euthyroid state and a normal TSH
level, patients and the TSH levels may be checked every 6-12 months.
More frequent follow-up and TSH checks may need to be performed when
patients start taking medications, such as ferrous sulfate, calcium
supplementation, and multivitamins, that have the potential to impair the
absorption of levothyroxine and therefore to affect the TSH level. Patients need
to be advised to separate these medications from levothyroxine by at least 4
hours.
Follow-up care should include clinical evaluation for symptoms of
hypothyroidism or iatrogenic hyperthyroidism.
Physical examination should routinely include weight measurement, pulse and
blood pressure determinations, and thyroid checkup for the presence of nodules.

22. 21
Prevention
Unfortunately, there is no known way to prevent Hashimoto's thyroiditis (or
inflammation of the thyroid gland. But on the bright side, this disorder is very
treatable. The sooner you get diagnosed, the sooner you can start receiving
treatment.
Hashimoto's thyroiditis is an autoimmune disorder. In other words, it's caused
by a malfunction of the immune system. It's still not fully understood why the
immune system attacks the body's healthy tissues instead of protecting them, so
preventing that mechanism isn't currently possible.
Since you can't prevent this disorder, it's that much more important to
recognize the symptoms of Hashimoto's thyroiditis . If you understand the
symptoms and visit your doctor as soon as possible after recognizing them, you'll
have the best chance of preventing the disease's progression.
Like any disease, diagnosing Hashimoto's thyroiditis early is important because
it gives you earlier access to treatment. Some of the most common symptoms of
Hashimoto's thyroiditis—hypothyroidism and goiter—are highly responsive to
treatment. You can read more about this in our article about thyroid hormone
replacement therapy for Hashimoto's thyroiditis.
Though prevention isn't likely when it comes to Hashimoto's thyroiditis, keep in
mind that this thyroid disorder is very treatable. If you are concerned about the
presence of any possible symptoms, don't hesitate to discuss them with your
doctor. [62]

23. 22
Prognosis
With early diagnosis, timely institution of levothyroxine replacement therapy,
informed patient follow-up care, and attention to other attendant complications,
the prognosis in Hashimoto thyroiditis is excellent, with patients leading a
normal life. Untreated myxedema coma has a poor prognosis and a high
mortality rate.
Morbidity related to Hashimoto thyroiditis typically results from failure to
make the diagnosis of hypothyroidism or to institute L-thyroxine replacement
therapy in adequate doses, or from failure on the part of the patient to take the
replacement medication.
The increased occurrence of lipid disorders in association with untreated
hypothyroidism has the potential to increase morbidity from coronary artery
disease.
The risk for papillary thyroid carcinoma is increased in patients with
Hashimoto thyroiditis. [63] These cancers are not clearly more aggressive than
other papillary thyroid carcinomas.
A study by Kahaly et al indicated that a strong link exists between the presence
of TSH receptor-stimulating antibodies (TSAbs) in patients with Hashimoto
thyroiditis and the development of thyroid-associated orbitopathy (TAO). The
study, which included 700 patients with Hashimoto thyroiditis, found higher
serum levels of TSAbs in those with TAO than in those without this condition,
whereas patients with active and severe TAO had higher TSAb levels than did
patients with mild and inactive TAO. Healthy controls were negative for TSAbs.
[64]

24. 23
Summary
1. Hashimoto's thyroiditis (HT) is one of the most common human
autoimmune diseases responsible for numerous morbidity in women.
2. The disorder affects up to 2% of the general population and is more
common in older women and ten times more frequent in women than in
men.
3. The etiology of Hashimoto’s thyroiditis is considered to be multifactorial,
involving the interplay of different environmental and genetic factors.
4. The clinical features depending on type and stages of the disease:
Subclinical hypothyroidism and goiter, Primary thyroid failure,
Hypothyroidism, Adolescent goiter.
5. In Hashimoto’s thyroiditis there is an extensive infiltration of thyroid by
lymphocytes, plasma cells and macrophages. There is formation of
germinal center and giant (Langerhans) cell can occur.
6. Left untreated, an underactive thyroid gland (hypothyroidism) caused by
Hashimoto's thyroiditis can lead to a number of health problems: goiter,
heart problems, mental health issues, myxedema coma, birth defects.
7. Assessing the metabolic status of the patient and identifying the type of
lesion present are of vital importance in making an accurate diagnosis of
Hashimoto’s thyroiditis.
8. The treatment of choice for Hashimoto thyroiditis (or hypothyroidism from
any cause) is thyroid hormone replacement.
9. If Hashimoto's disease causes thyroid hormone deficiency, you may need
replacement therapy with thyroid hormone.
10. Surgery has been used as a technique of therapy. This treatment, of
course, removes the goiter but usually results in hypothyroidism.
11. Unfortunately, there is no known way to prevent Hashimoto's
thyroiditis (or inflammation of the thyroid gland. But on the bright side,
this disorder is very treatable. The sooner you get diagnosed, the sooner
you can start receiving treatment.
12. With early diagnosis, timely institution of levothyroxine
replacement therapy, informed patient follow-up care, and attention to
other attendant complications, the prognosis in Hashimoto thyroiditis is
excellent.

25. 24
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Figures' references
1- https://www.newmedicineonline.com/hypothyroidism-hashimotos-disease/
2- https://en.m.wikipedia.org/wiki/Goitre
3- http://www.jorl.net/otolaryngology/hasimotos-thyroiditis-a-review.pdf
4- Casselman WG. (1996). Thyroid, In: Index of Medical Word origins, (1996), Available from:
<Hashimoto’s
Thyroiditistp://www.billcasselman.com/dictionary_of_medical_derivations/dmd_nine.Hashimoto'
sThyroiditism>.
5- http://cdn.intechopen.com/pdfs/28726/InTech-Hashimoto_s_thyroiditis.pdf