GRAVE’S

DISEASE
Done by:
Asma Abdelrahman Hassan Khalifa (202249)
Shima Ismail Abdelrahman Hassan (202247)

Lecture: Dr.Tamar Bikashvili (122054)

University of Georgia
Tbilisi
2023/2024

Abstract
 Graves’ disease, in contrast to Hashimoto’s thyroiditis, is characterized by hyperthyroidism.
It is, in fact, the most common cause of hyperthyroidism; due to hyper functional diffuse
thyroid enlargement. Affecting approximately 0.5 present of the population. Women. Exhibit
greater susceptibility by a margin of about 10 to 1, and they most often present with the
disease between the ages of 20 and 50. In this research many details Graves’ disease will be
discussed which manly about its mechanism and how it develops, causes, risk factor, clinical
correlation aspect of this topic. This research paper is based on many pervious studies,
analysis, researches and books that are gathered and organized in different ways to the reader
to achieve the maximum understanding of this topic.
Introduction
Graves’ disease is a state of hyperthyroidism, goiter, and ophthalmopathy. The onset usually
is between the ages of 20 and 40 years, and women are five times more likely to develop the
disease than men. Graves’ disease is an autoimmune disorder characterized by abnormal
stimulation of the thyroid gland by thyroid-stimulating anti-bodies; TSH-receptor antibodies,
that act through the normal TSH receptors.
Thyroid gland and graves’ disease

The thyroid gland is located in the neck, just below the larynx, has a butterfly form, with the
two side lobes lying on and surrounding the windpipe and a small strip of tissue connecting
them at the front. It’s an important hormone gland that affects the human body's metabolism,
growth, and development. By continuously delivering a stable number of thyroid hormones
into the circulation, it aids in the regulation of numerous physiological processes. The thyroid
gland generates extra hormones when the body need more energy in particular conditions,
such as when it is growing, cold, or pregnant.
On average, the thyroid weighs between 20 and 60 grams. It is encased in two fibrous
capsules on all sides. The voice box muscles, as well as several vital arteries and nerves, are
all attached to the outer capsule. The inner and outer capsules are connected by loose
connective tissue, allowing the thyroid to migrate and change position when we swallow. The
thyroid tissue is made up of many tiny individual lobules that are separated by thin
connective tissue layers. Thyroid hormones are stored in the form of microscopic droplets in
these lobules, which include many small vesicles called follicles.
Three hormones are produced by the thyroid gland: T3 Tetraiodothyronine, also known as
thyroxine or T4 Triiodothyronine. Only T3 and T4 are thyroid hormones, created in the
thyroid's follicular epithelial cells. Iodine is a key component in the production of both
hormones. Because our bodies cannot generate this trace element, we must obtain it through
our food. Food in our bowels absorbs iodine into our circulation. It then travels to the thyroid
gland, where it is converted into thyroid hormones. Our bodies require more thyroid
hormones at times and fewer at other times. The thyroid gland requires the assistance of
another organ, the pituitary gland, in order to produce the correct quantity of hormones. The
pituitary gland instructs the thyroid gland on how much hormone to release into the
circulation. Thyroid hormones are also bound to transport proteins in the blood in small
amounts. T3 and T4 can be released from proteins in the blood and complete their work if the
body need extra hormones. Calcitonin is the third hormone produced by the thyroid gland. C-
cells produce calcitonin. Calcium and bone metabolism are both affected by it. The basal
metabolic rate is increased by T3 and T4. They make all the body's cells work harder, thus
the cells themselves require more energy. For instance, this has the following effects: Body
temperature, pulse and heartbeat increases, stored energy breakdown, growth, and brain
development.
Graves’ disease is an autoimmune disease characterized by hyperthyroidism due to
circulating autoantibodies. Thyroid-stimulating immunoglobulins (TSIs) bind to and activate
thyrotropin receptors, causing the thyroid gland to grow and the thyroid follicles to increase
synthesis of thyroid hormone. Graves’ disease, along with Hashimoto thyroiditis, is classified
as an autoimmune thyroid disorder. Ultrasensitive (third-generation) thyrotropin assays
remain the best screening test for thyroid disorders. Treatment involves alleviation of
symptoms and correction of the thyrotoxic state. In some patients, Graves’ disease represents
a part of more extensive autoimmune processes leading to dysfunction of multiple organs.
Graves’ disease is associated with pernicious anemia, vitiligo, diabetes mellitus type
1, autoimmune adrenal insufficiency, systemic sclerosis, myasthenia gravis, Sjögren
syndrome, rheumatoid arthritis, and systemic lupus erythematosus.

Immunogenetics
The pathogenesis involves IgG autoantibodies to the TSH receptor on the surface of human
thyroid cells. Almost all patients with Graves’ disease have TSH receptor antibodies that
stimulate the thyroid cell (thyroid-stimulating antibodies), resulting in thyrotoxicosis or
overactive thyroid; however, it is not necessary to measure these autoantibodies routinely for
diagnosis. The autoimmune thyroid is characteristically infiltrated by T lymphocytes: both
CD8+ and CD4+ cells are present. These T cells express a more limited number of T-cell
receptor genes than do peripheral blood T cells from the same patient; the implication is that
intrathyroid T cells are less diverse because they are enriched for T cells specific for
thyroidderived peptides.
Risk Factors

 Family history:  Because a family history of Graves' disease is a known risk factor,
there is likely a gene or genes that can make a person more susceptible to the disorder.
 Sex: Women are much more likely to develop Graves' disease than are men.
 Age:  Graves' disease usually develops in people before age 40.
 Other autoimmune disorders:  People with other disorders of the immune system, such
as type 1 diabetes or rheumatoid arthritis, have an increased risk.
 Emotional or physical stress:  Stressful life events or illness may act as a trigger for the
onset of Graves' disease among people who have genes that increase their risk.
 Pregnancy: Pregnancy or recent childbirth may increase the risk of the disorder,
particularly among women who have genes that increase their risk.
 Smoking: Cigarette smoking, which can affect the immune system, increases the risk of
Graves' disease. Smokers who have Graves' disease are also at increased risk of
developing Graves' ophthalmopathy.
Symptoms
Clinical symptoms include nervousness, insomnia, depression, weight loss, heat intolerance,
sweating, rapid heartbeat, palpitations, breathlessness, fatigue, cardiac dysrhythmias, and
restlessness. Another sign present in approximately 35 present of patients is exophthalmos,
in which hypertrophy of the eye muscles and increased connective tissue in the orbit cause
the eyeball to bulge out so that the patient has a large-eyed staring expression. There is
evidence that orbital fibroblasts express TSH receptor-like proteins that are affected by
thyroid-stimulating immunoglobulin just as the thyroid is. Thus, Graves’ disease is now seen
as a multiorgan auto-immune disorder, causing hyperthyroidism, ophthalmopathy, and
localized edema in the lower legs. The thyroid shows uniform hyperplasia with a patchy
lymphocytic infiltration. The follicles have little colloid but are filled with hyperplastic
epithelium. A large number of these cells express HLA-DR antigens on their surface in
response to interferon (IFN)-λ produced by infiltrating T cells. This allows presentation of
self-antigens such as the thyrotropin receptor to activated T cells. B cells, in turn, are
stimulated to produce antibody.
Diagnosis
Ultrasensitive thyrotropin assays remain the best screening test for thyroid disorders. With
the exception of thyrotropin-induced hyperthyroidism, subnormal or suppressed thyrotropin
levels are seen in most patients with thyrotoxicosis. Liver function test results should be
obtained to monitor for liver toxicity caused by thioamides. A complete blood count with
differential should be obtained at baseline and with the development of fever or symptoms of
infection. Graves’ disease may be associated with normocytic anemia, low-normal to slightly
depressed total white blood cell count with relative lymphocytosis and monocytosis, and low-
normal to slightly depressed platelet count. Thioamides may rarely cause severe hematologic
side effects, but routine screening for these rare events is not cost-effective.
Radioactive iodine scanning and measurements of iodine uptake are useful in differentiating
the causes of hyperthyroidism. In Graves’ disease, the radioactive iodine uptake is increased,
and the uptake is diffusely distributed over the entire gland.

Treatment
Treatment involves alleviation of symptoms and correction of the thyrotoxic state.
Adrenergic hyperfunction is treated with beta-adrenergic blockade. Correcting the high
thyroid hormone levels can be achieved with antithyroid medications that block the synthesis
of thyroid hormones or by treatment with radioactive iodine. Radioactive iodine is, in fact,
the most commonly used therapy for Graves’ disease. Indications for radioactive iodine over
antithyroid agents include a large thyroid gland, multiple symptoms of thyrotoxicosis, high
levels of thyroxine, and high titers of TSI. Thyroidectomy is not the recommended first-line
therapy for hyperthyroid Graves’ disease in the United States, although it may be appropriate
in the presence of a thyroid nodule that is suggestive of carcinoma.

Conclusion
Graves' disease is an immune system disorder that results in the overproduction of thyroid
hormones (hyperthyroidism). Although a number of disorders may result in hyperthyroidism,
Graves' disease is a common cause. Thyroid hormones affect many body systems, so signs
and symptoms of Graves' disease can be wide ranging. Although Graves' disease may affect
anyone, it's more common among women and in people younger than age 40.The primary
treatment goals are to reduce the amount of thyroid hormones that the body produces and
lessen the severity of symptoms

Citatiton
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