GRAVE’S DISEASE

Graves' disease, also known as Basedow's disease or hyperthyroidism, is an autoimmune

disorder that affects the thyroid gland, the largest endocrine gland, which has a butterfly
shape located around the trachea. It is bilobed and interconnected by a flap of connective
tissue called isthmus.

HISTORY
Robert Grave, an Irish physician, first provided one of the earliest comprehensive clinical
descriptions of the disease. Although Graves did not discover the underlying cause of the
disease, he made significant contributions by describing the clinical features and symptoms
associated with it. His work, published in the early 19th century, laid the foundation for
understanding and diagnosing this thyroid disorder.

Caleb Hillier Parry, a British physician who lived in the late 18th and early 19th centuries,
also made notable contributions to the understanding of this disease. It wasn't until the
20th century that the autoimmune nature of Graves' disease began to be understood

PREVALENCE
Graves’ disease is the most common cause of hyperthyroidism accounting for 60% to 80% of
hyperthyroid cases

Graves' disease affects about 1 in 200 people. The disease occurs more often in women than in men, which
may be related to hormonal factors.

It is more common in monozygotic twins than in dizygotic twins.

CAUSES
Hyperthyroidism

Grave Disease Thyroid nodules Thyroiditis

 Chart Title

Genetical Predisposition Enviromental Factors

 Genetic Predisposition:

There is evidence to suggest that a genetic predisposition plays a role in the

development of Graves' disease. Individuals with a family history of autoimmune
thyroid disorders, such as Graves' disease or Hashimoto's thyroiditis, may be at a
higher risk.

 Environmental Triggers:

While genetics may make a person more susceptible, environmental factors can
trigger the autoimmune response. These triggers may include viral or bacterial
infections, exposure to certain medications, physical or emotional stress, or other
environmental factors that are not fully understood.
 Immune System Dysfunction:

In Graves' disease, the immune system produces antibodies called thyroid-

stimulating immunoglobulins (TSIs) or thyroid-stimulating antibodies (TSAs). These
antibodies mimic the action of thyroid-stimulating hormone (TSH) and bind to
receptors on the thyroid gland, stimulating it to produce excessive amounts of
thyroid hormones (T3 and T4). This results in hyperthyroidism.
 Overactive Thyroid Gland:

The constant stimulation of the thyroid gland by these antibodies leads to the
overproduction of thyroid hormones, causing hyperthyroidism. This excess of thyroid
hormones affects various body systems and leads to the characteristic symptoms of
Graves' disease, such as rapid heart rate, weight loss, and heat intolerance.
 Iodine Intake:
Excessive iodine intake, whether through diet or medication, can exacerbate thyroid
dysfunction in people with Graves' disease. Iodine is a key component of thyroid
hormones, and high levels of iodine can stimulate the thyroid gland.
  Infection:
Some infections, particularly viral infections like Epstein-Barr virus or adenovirus,
have been suggested as potential triggers for autoimmune thyroid diseases,
including Graves' disease. These infections may contribute to the immune system's
misrecognition of the thyroid as a target.

SYMPTOMS
It can manifest with a wide range of symptoms, which can vary in severity from person to
person. Here are some common symptoms associated with Graves' disease:

 Hyperactivity and Nervousness:

People with Graves' disease often feel anxious, irritable, and restless. They may have
difficulty concentrating and may experience mood swings.

 Rapid Heartbeat (Tachycardia):

Increased heart rate (tachycardia) is a hallmark symptom. Palpitations, heart racing, or an
irregular heartbeat (arrhythmia) can occur.

 Weight Loss:
Despite an increased appetite, individuals with Graves' disease often lose weight
unintentionally.

 Heat Intolerance:
People with Graves' disease tend to be overly sensitive to heat and may sweat excessively.
They may feel warm or hot even in normal temperature environments.

 Tremors:
Fine trembling of the hands and fingers (tremors) can be a noticeable symptom.
Fatigue: Paradoxically, patients may feel tired and weak despite the excess energy
expenditure due to hyperactivity.

 Muscle Weakness:
Weakness and muscle fatigue are common, and individuals may have difficulty with tasks
that require muscle strength.

 Changes in Bowel Habits:

Some people experience frequent bowel movements or diarrhea.

 Goitre:
The thyroid gland can become visibly enlarged, causing a swelling in the neck known as a
goitre. This can sometimes cause discomfort or difficulty swallowing or breathing.

 Eye Problems (Graves' Ophthalmopathy):

Some patients develop eye-related symptoms, including bulging eyes (exophthalmos),
double vision, eye irritation, dry eyes, and light sensitivity. These eye issues can range from
mild to severe.

 Skin Changes:
In some cases, the skin on the shins may become thickened and reddish in appearance, a
condition known as pretibial myxoedema.

 Menstrual Irregularities:
Women with Graves' disease may experience changes in their menstrual cycle, including
irregular periods.

 Hair Changes:
Hair may become fine and brittle, and some individuals may experience hair loss.

 Emotional Disturbances:
Anxiety and depression can be associated with Graves' disease, partly due to the effects of
excessive thyroid hormones on mood.

TESTING
The following are some of the common tests and procedures used to confirm the
diagnosis of Graves' disease:

Thyroid Function Tests:

TSH (Thyroid-Stimulating Hormone) Test:
In Graves' disease, TSH levels are usually abnormally low because the overactive
thyroid gland doesn't need stimulation from TSH. Therefore, a low TSH level can be
an initial indicator of hyperthyroidism.

T4 (Thyroxine) and Free T3 (Triiodothyronine) Tests:

Elevated levels of free T4 and free T3, the active thyroid hormones, are typically seen
in Graves' disease. These tests help confirm hyperthyroidism.

Antibody Tests:
Thyroid Stimulating Immunoglobulins (TSI) Test:
This blood test detects the presence of TSI, antibodies that stimulate the thyroid
gland to produce excessive amounts of thyroid hormones. TSI is often elevated in
Graves' disease and is a specific marker for the condition.

Thyroid Peroxidase Antibodies (TPOAb) and Thyroglobulin Antibodies (TgAb):

While TSI is specific to Graves' disease, TPOAb and TgAb are markers for
autoimmune thyroid disorders and can be tested to help confirm the autoimmune
nature of the condition.

Radioactive Iodine Uptake (RAIU) Test:

 In this test, a small, safe amount of radioactive iodine is administered orally, and the
thyroid's ability to absorb iodine is measured. In Graves' disease, the thyroid typically
takes up excess iodine due to overactivity. This test can help differentiate Graves'
disease from other causes of hyperthyroidism.

PATHALOGY
- The thyroid gland is symmetrically enlarged due to diffuse hypertrophy and
hyperplasia of thyroid follicular epithelial cells

- Follicular epithelial cells are crowded i.e.

hyperplasia

- Small Papillae which projects into the

follicular lumen and encroach on the colloid