- Chronic iodine deficiency
- The most common cause worldwide. Sustained dietary iodine below 100 µg/day reduces thyroid hormone production; the pituitary responds by increasing TSH, which drives thyroid hyperplasia. Endemic iodine deficiency persists in mountain and inland regions of Africa, South Asia, and Eastern Europe.
- Hashimoto's thyroiditis (chronic autoimmune thyroiditis)
- The leading cause of goiter in iodine-sufficient countries. Anti-thyroid peroxidase and anti-thyroglobulin antibodies drive lymphocytic infiltration, fibrosis, and slowly progressive thyroid failure. The gland is initially enlarged and firm, becoming smaller and atrophic in late disease.
- Graves' disease
- Autoimmune diffuse toxic goiter driven by TSH-receptor stimulating antibodies (TRAb), which mimic TSH and cause both diffuse enlargement and overproduction of thyroid hormone. Often accompanied by orbitopathy and pretibial myxedema.
- Multinodular goiter (sporadic, non-toxic)
- Develops over years from focal hyperplasia and clonal expansion within the thyroid. Each nodule reflects a small genetic or acquired change in a single thyrocyte lineage. Prevalence rises with age, reaching 30-50% by age 60 on ultrasound.
- Inherited dyshormonogenesis
- Rare autosomal recessive defects in thyroid hormone synthesis (TPO, TG, DUOX2, SLC5A5, SLC26A4 mutations) cause congenital goiter, usually with hypothyroidism. Pendred syndrome combines goiter with sensorineural deafness.
- Goitrogenic foods and medications
- Cassava, soy, millet, and cabbage-family vegetables can contribute to goiter in iodine-deficient settings. Lithium, amiodarone, perchlorate, and excess iodine itself (Wolff-Chaikoff effect or Jod-Basedow) all alter thyroid function and can drive goiter.
- Thyroid neoplasms
- Both benign (follicular adenoma) and malignant (papillary, follicular, medullary, anaplastic) thyroid neoplasms present as nodules within a goiter. Rapid growth, hard fixed nodules, vocal cord paralysis, and lymphadenopathy raise concern for malignancy.
