Thyroid nodules

Thyroid nodules are abnormal growths within the thyroid gland. They are present in approx. 50% of the general population but only palpable in 5–10% of the population. They are more common in women, especially in iodine-deficient regions, and their incidence increases with age. Thyroid nodules are the clinical manifestation of various underlying thyroid diseases. The majority of them are benign (∼ 95%), with colloid cysts, follicular adenomas, and Hashimoto's thyroiditis being the most common causes. Approx. 5% of thyroid nodules are malignant, with papillary carcinoma being the most common. Thyroid hormone assay is the best initial test in the evaluation of thyroid nodules. Thyroid ultrasonography can detect features suspicious of malignancy in a nodule and the diagnosis can be confirmed on ultrasound-guided fine needle aspiration cytology. Radioiodine uptake scan (thyroid scintigraphy) is used to evaluate nodules in patients with hyperthyroidism, to localize the autonomously functioning tissue. Based on their iodine uptake on radioiodine scans, thyroid nodules may be autonomous/hot (increased uptake) or non-functional/cold (decreased uptake). The most common hot nodules are toxic adenomas and dominant nodules of toxic multinodular goiters. With a 5–15% risk of malignancy, cold nodules are clinically significant. Treatment depends on the underlying etiology and includes, e.g., surgery (thyroidectomy) for malignant and autonomous nodules, fine needle aspiration for thyroid cysts, and observation for small, benign nodules.

Benign thyroid nodules (∼ 95% of cases)

• Thyroid adenomas
  • Follicular adenoma (most common)
  • Hürthle cell adenoma
  • Toxic adenoma
  • Papillary adenoma (least common)
• Thyroid cysts
• Dominant nodules of multinodular goiters
• Hashimoto thyroiditis

Malignant thyroid nodules (∼ 5% of cases)

• Thyroid carcinoma
• Thyroid lymphoma
• Metastatic cancer from breast/renal carcinoma (rare)
• Risk factors for malignancy
  • Male gender
  • Extremes in age (< 20 years and > 65 years)
  • History of radiation to the head or neck
  • Family history of thyroid cancer or polyposis
  • Solid nodule
  • Cold nodule

References:^[1][3]

• Nodule revealed during physical examination or incidentally on imaging
• Initial tests: thyroid ultrasound and TSH levels
  • ↑ Or normal TSH → consider FNA based on sonographic criteria or follow-up if criteria are not met
  • ↓ TSH → thyroid scintigraphy
    • Hot nodule → check T3 and FT4 to assess cause of hyperthyroidism
    • Cold nodule → consider either FNA (based on sonographic criteria) or monitoring (with repeat ultrasounds) if criteria are not met
• Sonographic criteria for fine-needle aspiration (FNA)
  • Solid nodule with suspicious appearance (e.g., oval shape, irregular border, calcifications) that are ≥ 1 cm in diameter
  • Nodules ≤ 1 cm in patients with risk factors for malignancy (see “Etiology” above)
  • Large thyroid nodules (≥ 1.5–2 cm), even if they appear benign

Malignancy is rare in hyperfunctioning (hot) nodules!

References:^[1][3]

• Epidemiology
  • Follicular adenoma is the most common type of thyroid adenoma
  • 10–15% of follicular neoplasms are malignant
• Clinical features
  • Often presents as a slow-growing solitary nodule
  • The nodule can develop into a toxic adenoma, which produces thyroid hormones autonomously
• Diagnostics
  • FNA cannot distinguish between follicular adenoma and carcinoma
  • Thyroid surgery is therefore always indicated both for treatment and definitive diagnosis
  • Follicular adenoma histology shows normal follicular structure with no tumor invasion into the surrounding tissues (e.g., capsule, blood vessels)
• Treatment
  • Lobectomy with histologic analysis of frozen-section specimen
  • Thyroidectomy in the case of follicular carcinoma

References:^[4]

• Epidemiology
  • Accounts for ∼ 5–10% of hyperthyroidism cases
  • ♀ > ♂
  • Seen mostly in patients 30–50 years of age
• Pathophysiology
  • Gain-of-function mutations of TSH receptor gene; in a single precursor cell → autonomous functioning of the thyroid follicular cells of a single nodule → focal hyperplasia of thyroid follicular cells → toxic adenoma
  • The autonomous thyroid nodule overproduces thyroid hormones → hyperthyroidism → decrease in pituitary TSH secretion → suppression of hormone production from the rest of the gland
• Clinical features: hyperthyroidism
• Diagnostics
  • ↑ T3 and ↓ TSH
  • Thyroid scintigraphy: solitary, hot nodule
    • Shows radioiodine uptake by the hyperfunctioning nodules with suppression of rest of the gland
• Treatment
  • Control symptoms with beta-blockers and thioamides until euthyroidism is achieved, followed by tapering of beta-blockers
  • Definitive treatment
    • Radioactive iodine ablation or
    • Lobectomy or hemithyroidectomy for pure toxic adenomas

References:^[5][6]

• Epidemiology
  • Sex: ♀ > ♂
  • Age: often > 60 years
  • Second most common cause of hyperthyroidism
  • Develops in 10% of patients with a long-standing nodular goiter
  • More prevalent in iodine-deficient regions
• Pathophysiology
  • Chronic iodine deficiency/thyroid dysfunction → decreased hormone production → increased hypothalamic TRH secretion → persistent TSH stimulation of the thyroid gland → hyperplasia of thyroid nodules, some more active than others → multinodular goiter (nontoxic MNG)
  • Multiple somatic mutations of TSH receptor occur in long-standing goiters (> 60% of cases) → autonomous functioning of some nodules (toxic MNG) → hyperthyroidism (due to ↑ release of both T3 and T4)
• Clinical features
  • Hyperthyroidism and multinodular goiter
• Diagnostics
  • ↑ T3 with ↓ TSH
  • Thyroid scintigraphy: shows radioiodine uptake by the hyperfunctioning nodules with suppression of the rest of the gland
  • Histopathology: patches of enlarged follicular cells distended with colloid and with flattened epithelium
• Treatment: same as for toxic adenoma; surgery, if required, involves a near-total or total thyroidectomy

References:^{[7][8][9][10][11]}