Graves' Disease Overview Quiz

Thyroid Function & Disease

• RCSI Royal College of Surgeons in Ireland, Department of Medicine, focused on thyroid function and disease.
• RCSI aims to develop healthcare leaders globally.

Learning Outcomes

• Students will define hypothyroidism and hyperthyroidism.
• Students will explain the pathophysiology of both conditions.
• Students will list cardinal symptoms and signs of both conditions.
• Students will explain the cause of each symptom in both conditions.
• Students will develop differential diagnoses for both conditions.
• Students will understand investigative and management principles for thyroid disorders.

Thyroid Hormone

• Thyroid hormone significantly impacts all body organs, especially in response to stress.
• It increases basal metabolic rate and thermogenesis.
• Cardiovascular system: Increases beta-receptor expression leading to enhanced cardiac output and contractility.
• Respiratory system: Increases oxygenation by stimulating respiratory centers and enhancing lung perfusion.
• Skeletal muscle: Increases fast-twitch muscle fiber expression.
• Metabolism: Enhances basal metabolic rate, carbohydrate metabolism, and protein anabolism.
• Growth: Works synergistically with growth hormone to promote bone growth during childhood.
• Central nervous system: Influences brain maturation prenatally, affecting mood, memory, and sleep in adults.
• Reproductive system: Influences fertility, ovulation, and menstruation.

Hypothyroidism

• Definition: A pathological condition characterized by insufficient thyroid hormone synthesis and secretion.
• Primary hypothyroidism (high TSH, low free T4): Thyroid gland failure. Despite pituitary stimulation (TSH), the thyroid gland cannot respond to produce T4.
• Central/secondary hypothyroidism: Deficient TSH production commonly due to pituitary lesions (e.g., tumors). Low T4; normal or low TSH. No compensatory increase in TSH despite low T4 levels.
• Differentials (primary hypothyroidism):
  • Congenital: Agenesis of the thyroid gland. Screened at birth.
  • Autoimmune: Hashimoto's thyroiditis (most common cause in iodine-sufficient areas; characterized by thyroid peroxidase antibodies (TPO))., Reidel's thyroiditis (T cell/IgG4-mediated inflammation leading to fibrosis extending beyond the thyroid capsule), Radiation (e.g., radioactive iodine treatment for hyperthyroidism), Post-thyroidectomy, and Infiltrative diseases (e.g., haemochromatosis).
  • Anti-thyroid drugs (e.g., lithium, iodine-containing drugs, radiographic contrast material, amiodarone, checkpoint inhibitors).

Hyperthyroidism

• Definition: A pathological disorder characterized by excessive thyroid hormone synthesis and secretion.
• Hyperthyroidism is often associated with thyrotoxicosis.
• Primary hyperthyroidism: Elevated free T4; suppressed/undetectable TSH (<0.1).
• Secondary hyperthyroidism: Elevated T4; elevated TSH.

Pathophysiology

• Hypothalamic-Pituitary-Thyroid Axis: TRH released from the hypothalamus stimulates the anterior pituitary gland to release TSH. TSH then stimulates the thyroid gland to produce T3 and T4.
• TSH binds to TSH receptors on thyroid cells, leading to T3 and T4 production and thyroid gland hyperplasia.
• T3 and T4 impact various organs, enhancing metabolism, growth, development, and catecholamine effects.

Hypothyroidism Causes

• Primary gland insufficiency is most common.
• Pituitary and hypothalamus (secondary & tertiary) less common.
• Iodine deficiency is a widespread global cause.
• Autoimmune (Hashimoto's thyroiditis) is common in developed and iodine-sufficient countries.

Hypothyroidism Symptoms

• Symptoms related to decreased metabolic rate include: Bradycardia, weight gain, cold intolerance, poor appetite, hair loss, cold dry skin, constipation, myopathy.
• Children may exhibit cretinism (short stature, intellectual disability).

Hypothyroidism Signs and Symptoms

• Psychological: poor memory, poor concentration, poor hearing, hoarseness.
• Heart: Slow pulse rate, pericardial effusion
• Muscular: Delayed reflex relaxation
• Extremities: Coldness, carpal tunnel syndrome
• Other: fatigue, anorexia, dry skin (coarse), brittle nails.

Hashimoto's Thyroiditis

• Inflammation of thyroid tissue.
• Most frequent cause of hypothyroidism in iodine sufficient regions.
• Associated with autoimmune factors: Primarily T cell mediated response and circulating antibodies (TPO antibodies), leading to thyroid gland damage and progressive failure.

Subclinical Hypothyroidism

• High TSH, normal T4.
• Usually treated if TSH exceeds 10, or during pregnancy/infertility, or in symptomatic patients especially in older age groups.
• Progression to overt hypothyroidism is possible (2-5% per year).

Hyperthyroidism Differentials

• Graves' disease
• Toxic multinodular goitre (MNG)
• Toxic adenoma
• Drug-induced (e.g., amiodarone)
• factitious hyperthyroidism
• Subacute viral thyroiditis
• Thyrotoxicosis (or thyroid storm)

Hyperthyroidism Causes

• Graves' disease: Autoimmune.
• Toxic multinodular goitre: Multiple nodules with autonomous hormone production. Often benign, but there is potential for malignancy.
• Toxic adenoma: Solitary nodule with autonomous hormone production.
• Viral thyroiditis (de Quervain's): Subacute granulomatous variant, often tender diffuse goitre.
• Less common: pituitary adenoma, drug-induced (e.g., amiodarone), factitious hyperthyroidism (excessive exogenous use).

Hyperthyroidism Symptoms

• Hypermetabolism- Heat intolerance, weight loss, increased appetite, sweating.
• Palpitations, tachycardia; sinus, atrial fibrillation, hypertension, heart failure.
• Tremor, myopathy, restlessness, anxiety, depression.

Hyperthyroidism Additional Symptoms

• Nervousness/tremor
• Mental disturbance; irritability; difficulty sleeping
• Bulging eyes/unblinking stare; vision changes
• Enlarged thyroid (goiter); menstrual irregularities; light periods
• Frequent bowel movements; warm, moist palms
• First-trimester miscarriage/ excessive vomiting

Graves' Disease

• Antibody-mediated autoimmune thyroid disease characterized by TSH receptor antibody (TRAb)-mediated stimulation of thyroid hormone synthesis, leading to hyperthyroidism.
• Inappropriate activation of thyroid cells (TSH agonist).
• Increased T4 and T3 production.
• Hyperplasia and growth of the gland.
• Increased TSH receptor activation.
• Associated risk factors: Genetic susceptibility, immune tolerance failure, molecular mimicry, greater prevalence in females, smoking, and certain drugs. (e.g., iodine/iodide containing drugs, amiodarone, CT contrast media)
• High incidence (4.6/1000 during observation)
• Antibody: TRAb: (sensitivity and specificity over 90%)

Thyroid Eye Disease

• Autoimmune condition affecting orbital tissues.
• Often seen in combination with Graves' disease; but may occur with less severe Hashimoto's thyroiditis.
• Orbital inflammation, fibrous tissue, muscular dysfunction, and impaired venous drainage. Leading to periorbital swelling.
• Symptoms: Proptosis (bulging eyes), conjunctival inflammation, periorbital edema, lid retraction, lagophthalmos, strabismus (eye misalignment), optic neuropathy from compression.
• Risk factors: Smoking, Radioactive iodine therapy.
• Treatment: Depends on severity, mild cases can be treated with selenium, or selenium therapy; moderate-severe cases benefit from steroids, immunosuppressants, or more novel treatments like teprotumumab.

Myxoedema

• Severe hypothyroidism that is life-threatening (rare).
• Characterized by accumulation of mucopolysaccharides in subcutaneous tissues (thickening of the skin).
• Associated with multiple low systems: Hyponatremia, hypoglycemia, hypotension, hypothermia, heart failure, confusion, and coma.
• High mortality (severe cases)

Thyroid Storm/Thyrotoxic Crisis

• Life-threatening emergency (acute severe hyperthyroidism)
• Often triggered by stress, infection, or surgery.
• Rapid onset with multiple serious symptoms: Fever, agitation, seizures, coma, tachycardia or atrial fibrillation (AFib), heart failure.
• Treatment: Use of beta-blockers (selective), high dose thionamides, iodine solutions, corticosteroids.

Goitre

• Enlargement of the thyroid gland (swelling in the anterior neck).
• Multiple causes: Iodine deficiency, excess TSH stimulation, inflammation, scarring, masses.

Thyroid Function Tests

• Useful to investigate both hypo & hyperthyroidsim.
• Elevated TSH (low T4): Hypothyroidism
• Low TSH (high T4): Hyperthyroidism

Investigations

• Blood tests for thyroid function (TSH, T4, T3).
• Antibodies, e.g., anti-TPO, TSH receptor antibodies (TRAbs)
• Radioiodine or technetium uptake
• Thyroid ultrasound (selected cases).

Hypothyroidism Treatment

• Levothyroxine (T4).
• Dose is approximately 1.6 mcg/kg body weight daily.
• Administered on an empty stomach with water, avoiding medications interfering with absorption (e.g., calcium, iron, soy).
• "Start low and go slow" in elderly patients.
• Exclude/treat concurrent adrenal insufficiency prior to Levothyroxine treatment.

Subclinical Hypothyroidism Treatment

• Treatment depends on multiple patient factors, including age, symptoms, concomitant conditions (e.g., coronary heart disease, heart failure), and thyroid peroxidase antibody status.
• Options: Observation ("wait-and-see"), treatment might be considered at certain levels dependent on clinical assessment.

Hyperthyroidism Treatment

• Pharmacological: Thyroid hormone synthesis inhibitors (e.g., carbimazole, propylthiouracil), antithyroid drugs; beta-blockers; and iodine solution.
• Procedures: Radioactive iodine ablation, Total thyroidectomy.
• Treatment of associated symptoms is important; and management is based on the cause and severity of the condition.

Test your knowledge on Graves' disease with this quiz that covers its manifestations, associated factors, and symptoms. Explore various questions about the underlying mechanisms and related conditions for a comprehensive understanding of this thyroid disorder.