Goiter pathophysiology

When the thyrotrophin releasing hormone–thyroid stimulating hormone axis (TRH–TSH thyroid hormone axis) is interfered, it results in structural and functional changes in the thyroid gland. Increased TSH production is trigerred by a deficiency in thyroid hormone synthesis or intake. In order to normalize thyroid hormone levels, the increase in TSH leads to increased cellularity and hyperplasia of the thyroid gland and when this process occurs continuously, it leads to goiter.

Pathogenesis:^{[1][2][3][4][5][6][7][8][9][10][11]}

• Goiters may occur as a result of either hypothyroidism, hyperthyroidism, or even with normal levels of thyroid hormone.
• Thyroid enlargement (goiter) and hypothyroidism may occur due to compensatory responses as a result of a severe underlying disorder.
• When the thyroid gland cannot secrete enough thyroid hormone to cater to the metabolic requirements, it may lead to simple goiter (smooth enlargement).
• In order to compensate for inadequate hormone synthesis, the thyroid gland enlarges, this type of compensation overcomes mild to moderate hormonal impairment.
• When the TRH–TSH thyroid hormone axis is interfered, it results in the structural and functional changes of the thyroid gland.
• Increased TSH production is triggered by a deficiency in thyroid hormone synthesis or intake.
• In order to normalize thyroid hormone levels, the increase in TSH leads to increased cellularity and hyperplasia of the thyroid gland and when this process is continuous, it leads to goiter.
• Thyroid hormone deficiency may occur secondary to to iodine deficiency, inborn errors of thyroid hormone synthesis and goitrogens.
• Goiters may form as a result of many TSH receptor agonists. The TSH receptor gets stimulated under the following conditions:
  • Adenoma of the pituitary
  • Adenoma of the hypothalamus
  • Pituitary resistance to thyroid hormone
  • TSH receptor antibodies
  • Tumors producing hCG (human chorionic gonadotropin)

• The pathophysiological consequences of goitres results from one of the following:
  • Thyroid hormone dysfunction
  • Enlarged thyroid gland
  • The effect of primary disease causing goiter

• The effect of thyroid hormone dysfunction:
  • Thyroid hyperfunction (hyperthyroidism) → Features of hyperthyroidism
  • Thyroid hypofunction (hypothyroidism) → Features of hypothyroidism

• The effect of enlarged thyroid gland:
  • Effect on the trachea results in dyspnea
  • Effect on the esophagus results in dysphagia
  • Effect on the superior vena cava results in distended neck veins
  • Effect on the recurrent laryngeal nerve results in hoarseness of voice

• The effect of primary disease causing goitre:
  • The effect depends on the underlying disease

• Goiter may be caused by a mutation in the following genes which vary from one family to the other: ^{[12][13][14][15][16][17]}

• Thyroglobulin (Tg) gene
• Thyroid-stimulating hormone receptor (TSHR) gene
• Sodium–iodine (Na+/I-) symporter (NIS) gene ^[18]

The following conditions are associated with goiter:^[19][20]

• Grave’s disease
• Hashimoto’s thyroiditis

• On gross pathology the following features are observed:^[21][22][23]
  • Enlarged thyroid gland
  • Multiple nodules lacking fibrous capsule
  • Secondary changes such as hemorrhage, calcification and cystic degeneration are observed

Goiter histologic findings:

• Simple non-toxic goiters demonstrate:
  • Hyperplasia
  • Colloid accumulation
  • Nodularity

• Nodular hyperplasia is commonly seen in multinodular goiter. Cytologic findings include:
  • Benign appearing follicular cells
  • Abundant colloid, macrophages
  • Hürthle cells (occasionally)

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