Goiter – an enlarged thyroid gland (at least 40g or twice normal size)

• Clinical Presentation – usually asymptomatic (most never know they have it)
• can cause obstruction of adjacent tissue, pain due to hemorrhage, or hyperthyroidism – very few progress to cancer
• Epidemiology – worldwide prevalence of 20 million – incidence of 5% in U.S. and other non-endemic areas
• Classification of Goiters – mainly classified as diffuse or nodular (uninodular or multinodular)
• can be endemic (>10% of population)/non-endemic; sporadic/compensatory; functional/nonfunctional; toxic/non-toxic
• Complications – hemorrhage due to sudden enlargement, hyperthyroidism (if goiter is functional), carcinoma (rarely)
• Pathogenesis of Goiters
• Goiters are caused by proliferation of follicular epithelial cells that enlarges the follicle and eventually forms new follicles
• net thyroid growth is mainly from development of new follicles – Ý follicular size and fibrosis do not Ý total size
• Why do goiters have such different characteristics from normal thyroid tissue?
• since follicles are polyclonal, hyperplastic follicles can differ significantly from their progenitors
• hyperplastic cells often have different hormone production patterns from normal cells
• autonomy of growth and function (i.e., activity without stimulation) varies significantly among goiters–important for treatment
• Etiology of Goiter Hyperplasia
• TSH-dependent – TSH controls cell replication and hormone synthesis
• if serum thyroid hormone levels fall for any reason, feeback mechanisms will Ý TSH Þ thyroid hyperplasia
• iodine deficiency is a major cause of TSH-dependent goiters outside the U.S.
• TSH-independent – TSH does not produce sporadic goiters – other possible etiologies:
• stimulatory immunoglobulin (as in Grave’s disease) that stimulates proliferation only (no hyperthyroidism)
• locally-produced growth factors (EGF, NGF, PDGF, VEGF, etc.) may also contribute
• Treatment of Goiters
• Exogenous T₄ can trigger negative feedback mechanisms that ß TSH secretion
• this may not work on goiters with strongly autonomous characteristics, and may even lead to hyperthyroidism

• Epidemiology – largely asymptomatic (in 50% of patients at autopsy); occur more often in women
• cancer risk increased in uninodular but not multinodular goiters; 50% are uninodular
• Risk of Cancer in Nodules:
• male gender – nodules are 3x more likely to be malignant in men
• history of radiation treatment – leads to 2-100x increased risk of malignant and benign neoplasms
• family history of multiple endocrine adenomas – possibly a genetic component
• recent history of thyroid growth, dysphagia, dyspnea, local adenopathy
• Causes of Solitary Nodules:
• infection – granulomatous, pyogenic, or viral
• congenital – unilateral lobe agenesis, cystic hygroma, dermoid cyst, teratoma
• focal growth – thyroid cyst, adenoma, carcinoma
• generalized thyroiditis
• Characteristics of Malignant Nodules: firm, irregular, fixed in surrounding tissue, local lymph nodes palpable
• patients with malignant nodules usually have normal thyroid function
• How can a malignant nodule be distinguished from a benign nodule?
• (1) thyroid scan – radioactive iodine will accumulate only in areas actively secreting thyroid hormone ("hot")
• cancerous cells are dedifferentiated, so malignant nodules do not produce thyroid hormone ("cold")
• but most "cold" nodules are benign, so thyroid scan can only be used to rule out cancer in "hot" nodules
• (2) ultrasound – cystic lesions are less likely malignant, but ultrasound usually shows mixed cystic/solid lesions
• (3) find needle aspiration – best way to exclude thyroid cancer; 0.99 specificity, 0.75 sensitivity
• classified as positive, suspicious, or negative for carcinoma; 10% are inconclusive and must be repeated
• Treatment – controversial – attempt suppression with TSH and use surgery only if nodule does not respond
• can use cytological analysis of fine needle aspiration to determine whether surgery is appropriate

• Characteristics – rare, slow growth, delayed symptoms
• low morbidity and mortality – 13% prevalence at autopsy, but account for only 0.4% of cancer deaths
• Classifications
• 50-80% are mixed papillary and follicular forms (size is important in prognosis); spread via lymphatics
• 15% are follicular – more dangerous, more in women, often lymph node involvement and metastasis to lungs and bone
• size and metastasis do not affect prognosis as much as for papillary form
• 1% are anaplastic – may be familial; usually multifocal, but always originates in C-cells so calcitonin will be elevated
• Treatment of Thyroid Cancer – standard approach is near-total thyroidectomy (hopefully preserves parathyroid function)
• followed by TSH suppression, iodine scan (for metastasis and residual tissue), monitor thyroglobulin (Ý = recurrence)
• since thyroid cancer has low morbidity and mortality, risks of treatment may be greater – no treatment may be best option