- Clinical science
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.
- Sex: ♀ > ♂ (4:1)
- Incidence: increases with age 50% of the population has thyroid nodules by the age of 50. Most nodules, however, are not palpable.
- Geographic distribution: most common in inland regions without iodine fortification programs, where iodine content in food and water is low
Epidemiological data refers to the US, unless otherwise specified.
Benign thyroid nodules (∼ 95% of cases)
- Thyroid Adenomas Adenomas are benign epithelial tumors derived from glandular epithelium.
- Thyroid cysts
- Dominant nodules of multinodular goiters
Malignant thyroid nodules (∼ 5% of cases)
- Thyroid carcinoma
- Thyroid lymphoma
- Metastatic cancer from breast/renal carcinoma (rare)
- Risk factors for malignancy
- 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
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
- Often presents as a slow-growing solitary nodule
- The nodule grows larger → develops autonomy → over the course of several years becomes a
- Diagnostics: FNA cannot distinguish between follicular adenoma and carcinoma. Thyroid surgery is therefore always indicated both for treatment and definitive diagnosis.
- Lobectomy with histologic analysis of frozen-section specimen
- Thyroidectomy in the case of follicular carcinoma
- Accounts for ∼ 5–10% of hyperthyroidism cases
- ♀ > ♂
- Seen mostly in patients 30–50 years of age
- Gain-of-function mutations of TSH receptor gene in a single precursor cell → autonomous functioning of the follicular cells of a single nodule → focal hyperplasia of thyroid follicular cells → toxic adenoma
- The autonomous nodule overproduces thyroid hormones → hyperthyroidism → decrease in pituitary TSH secretion → suppression of hormone production from the rest of the gland
- Clinical features:
- Chronic iodine deficiency/thyroid dysfunction → decreased hormone production → increased pituitary TSH secretion → persistent TSH stimulation of the thyroid gland → hyperplasia of thyroid nodules, some more active than others → multinodular goiter (non-toxic MNG)
- Multiple somatic mutations occur in long-standing goiters → autonomous functioning of some nodules (toxic MNG) → hyperthyroidism
- Clinical features: hyperthyroidism and multinodular goiter
- Treatment: same as for toxic adenoma; surgery, if required, involves a near-total or total thyroidectomy
- Simple cysts are exclusively fluid-filled nodules lined by benign epithelial cells.
- Complex cysts are partly solid and partly cystic and carry a 5–10% risk of malignancy.
- Hemorrhage into a cyst → pain and rapid enlargement of the nodule
- A large cyst or extensive hemorrhage can cause compression symptoms (e.g., hoarseness, dysphagia)