Thyroid Pathology BMS 200

Thyroid Pathology Overview

• Goiter formation can occur in both hyperthyroidism (excess hormone production) and hypothyroidism (deficient hormone production).
• Clinical features of over-section of thyroid hormones include thyrotoxicosis, weight loss, and increased heart rate; under-section can lead to fatigue, weight gain, and bradycardia.
• Iodine deficiency is a major cause of hypothyroidism, leading to decreased thyroid hormone production and compensatory goiter formation.

Autoimmune Thyroid Diseases

• Hashimoto’s thyroiditis: Common endocrine disorder; incidence is ~4/1000 women and 1/1000 men annually.
• Pathological features include lymphocytic infiltration, germinal center formation, thyroid follicle atrophy, and loss of colloid. Progression can lead to atrophic thyroiditis, with increased fibrosis and limited lymphocyte infiltration.
• Genetic susceptibility linked to HLA haplotypes (HLA-DR3, DR4, DR5) and associated with other autoimmune diseases (Type 1 diabetes, Addison’s disease).
• Damage primarily mediated by cytotoxic T-cells and local inflammatory cytokines (e.g., TNF, IL-1, IFN-gamma); anti-thyroid antibodies (anti-TPO, anti-thyroglobulin) are diagnostically useful.

Clinical Features of Hashimoto’s Thyroiditis

• Symptoms include fatigue, cold intolerance, myxedema (thickened skin), hoarseness, and carpal tunnel syndrome.
• Cardiovascular effects: Bradycardia, mild hypotension, hypercholesterolemia; severe cases can lead to congestive heart failure and pericardial effusion.
• Neurological impacts manifest as paresthesias and delayed reflexes; respiratory issues may involve hypoventilation.
• Reproductive complications can include menstrual irregularities and erectile dysfunction in men.

Subacute Thyroiditis

• Known as de Quervain’s thyroiditis; often follows viral infections (e.g., mumps, influenza).
• Pathological findings show multinucleate giant cells and varying degrees of lymphocytic infiltration.
• Clinical features can include transient thyrotoxicosis, neck pain, and tenderness of the thyroid gland.
• Symptoms may fluctuate between hypothyroidism and thyrotoxicosis based on the disease phase.

Myxedema Coma

• A severe complication of untreated hypothyroidism, often precipitated by stressors (infection, trauma).
• Clinical presentation includes hypotension, bradycardia, lethargy, and hypothermia.
• Neurological symptoms can progress to confusion, severe depression, and potential seizures.
• Respiratory issues may involve hypoventilation and sleep apnea.
• Gastrointestinal findings may include ileus and constipation, while renal effects include hyponatremia.

Thyroid Neoplasms

• Incidence of thyroid cancer is 15 per 100,000 per year, making it the most common endocrine malignancy.
• Most common types:
  • Papillary carcinoma (70-80%): Well-differentiated with a high survival rate; presents with clear nuclei and papillary structures.
  • Follicular carcinoma (5-10%): More common in iodine-deficient regions; difficult to differentiate from adenomas without invasive characteristics.
  • Medullary carcinoma: Derived from calcitonin-secreting C-cells.
  • Anaplastic carcinoma: Highly aggressive with poor prognosis.
• Thyroid adenomas: Non-malignant tumors, often asymptomatic, with a prevalence of up to 5% in the population.

Treatment Mechanisms

• Anti-thyroid medications target hyperthyroidism by inhibiting hormone production; levothyroxine replaces deficient hormone in hypothyroidism.
• TSH suppression therapy may be useful for well-differentiated tumors like follicular and papillary carcinoma.

Thyroid Pathology Overview

• Hypothyroidism involves reduced thyroid function with various causes, including autoimmune conditions, iodine deficiency, and iatrogenic factors.
• Hyperthyroidism can result from Graves' disease, toxic multinodular goiter, or thyroid neoplasms (follicular, papillary, medullary, anaplastic carcinomas).

Goiter Formation

• Goiter develops due to increased TRH and TSH secretion in response to low T3 and T4 levels in hypothyroidism, or due to excessive secretion of thyroid hormones in hyperthyroidism.

Myxedema and Myxedema Coma

• Myxedema coma is a severe complication of prolonged hypothyroidism exacerbated by additional stressors (e.g., infection, trauma).
• Characteristics include lethargy and slowed neurological progression, hypoventilation, and gastrointestinal symptoms like ileus and constipation.
• Cardiovascular features include hypotension, bradycardia, and dangerous dysrhythmias (e.g., heart block).

Thyroid Storm

• Thyroid storm is a life-threatening hyperthyroidism exacerbation, typically triggered by acute illnesses in previously hyperthyroid patients.
• Symptoms include high fever, tachycardia, altered mental status, and increased systemic demands for thyroid hormones.

Thyroid Neoplasms

• Benign adenomas, especially follicular adenomas, are common, while malignant cancers include papillary (70-80%), follicular (5-10%), medullary, and anaplastic carcinomas.
• Papillary carcinoma is the most prevalent, characterized by well-differentiated cells and a good prognosis.
• Anaplastic carcinoma is aggressive with a poor survival rate, typically less than 6 months post-diagnosis.

Genetic Factors

• Activating mutations in the TSH receptor (and RAS, RET signaling pathways) are frequently observed in thyroid cancers.
• p53 mutations are common in poorly differentiated cancers, indicating a more aggressive disease course.

Clinical Features of Thyroid Conditions

• Toxic multinodular goiter presents with mild to subclinical hyperthyroidism and is more common in elderly patients; associated symptoms may include palpitations and weight loss.
• Congenital hypothyroidism can lead to developmental delays (cretinism) and is linked to a higher prevalence of other congenital malformations.

Pharmacological Treatment

• Propylthiouracil (PTU) and methimazole are anti-thyroid medications that inhibit thyroid hormone synthesis. PTU additionally affects T4 to T3 conversion.
• Levothyroxine is used for hypothyroidism treatment, primarily as a synthetic T4.

Autoimmune Thyroid Diseases

• Autoimmune conditions like Graves' and Hashimoto's can be influenced by factors like gut-thyroid axis interactions, infectious triggers, pregnancy, and environmental pollutants.

Relationship Between Infections and Thyroiditis

• Viral infections may contribute to thyroiditis, leading to autoimmune responses that affect hormone production and regulation.

Iodine Deficiency

• Iodine deficiency can directly result in hypothyroidism by impairing thyroid hormone synthesis, leading to compensatory hyperplasia and goiter formation.

Complications of Thyroid Disorders

• Over-secretion of thyroid hormones can lead to thyrotoxicosis, while inadequate secretion contributes to myxedema coma, both presenting distinct clinical challenges and management issues.

This quiz covers key concepts regarding thyroid pathology, including the formation of goiter in hyperthyroidism and hypothyroidism. It also addresses clinical features associated with abnormal thyroid hormone levels and delves into the pathophysiology of autoimmune thyroid diseases such as Graves' and Hashimoto's. Explore the implications of iodine deficiency and various theories of pathogenesis.