In recent years, the incidence of thyroid diseases has been on the rise, with nodular goiter being the most frequently observed. Nodular goiter, also referred to as adenomatous goiter, is essentially a condition characterized by the late-stage development of multiple nodules in endemic or sporadic goiter. At different stages of progression, it may be referred to by various terms and is considered a relatively common clinical condition. The prevalence in adults is approximately 4%. Nodular goiters are categorized as either benign or malignant, with the majority being benign and a malignancy rate of less than 1%.
Pathophysiology
Epidemiological studies indicate that in iodine-sufficient regions, the male-to-female ratio of nodular goiter cases is approximately 1:5. This is primarily due to insufficient thyroid hormone production, which stimulates the pituitary gland to secrete thyroid-stimulating hormone (TSH), subsequently inducing thyroid hyperplasia and resulting in nodule formation. Pathological features of nodular goiter include nodular enlargement, weighing between 60 and 1,000 g, with nodules, fibrosis, hemorrhage, and calcification visible on cross-section. In the early stages of the disease, the entire thyroid gland exhibits follicular hyperplasia and increased vascularity. As the condition progresses, some follicles undergo degeneration while others enlarge and become colloid-rich, with fibrous tissue forming septa between the follicles.
Nodular goiter is generally subdivided into solitary nodular goiter and multinodular goiter. Depending on the presence or absence of hyperthyroidism, multinodular goiter may be further classified into nontoxic multinodular goiter (MNG) or toxic multinodular goiter (TMNG). MNG, also known as simple goiter, primarily results from iodine deficiency in the environment or other causes leading to insufficient thyroid hormone production, causing compensatory thyroid enlargement without functional impairment or autoimmune thyroid disease. TMNG, on the other hand, refers to multinodular goiter that causes hyperthyroidism and represents a form of secondary hyperthyroidism. It is a common condition in China, often characterized by long-standing nodular thyroid enlargement that eventually develops into functional thyroid overactivity, presenting symptoms such as exophthalmos and an increased risk of myocardial damage, which may lead to changes in heart rate.
Clinical Manifestations
Nodular goiter is more commonly observed in adult women, predominantly developing on the basis of endemic goiter. The disease course is long with insidious symptoms, and it is often detected incidentally during physical examinations or noted due to neck swelling or localized sense of pressure. On palpation, the thyroid gland typically presents as mildly to moderately enlarged, with smooth-surfaced nodules of soft consistency. Severe thyroid enlargement may lead to compressive symptoms such as coughing, dyspnea, dysphagia, or hoarseness. Retrosternal goiter can obstruct venous return from the head, neck, and upper extremities. Rapid enlargement of a thyroid nodule over a short period may indicate cystic degeneration with hemorrhage.
Diagnosis
Diagnosis is based on a long-standing history of thyroid swelling, palpation findings of smooth, soft, and mobile thyroid nodules that move vertically during swallowing, and normal thyroid function on serological tests. Serum total T4 levels in nodular goiter patients are typically normal or slightly low, while total T3 levels may be slightly elevated to maintain normal thyroid function. Thyroglobulin levels correlate with nodule size, and serum TSH levels are generally normal. However, serological tests have no value in distinguishing between benign and malignant nodular goiter. They are typically used in differentiated thyroid cancer patients with a history of surgery or radionuclide therapy to detect early recurrence.
Ultrasound findings in nodular goiter often reveal solid or cystic nodules, with cystic nodules more likely to be benign. Solid nodules appear smooth-surfaced with an intact capsule, displaying hypoechoic or isoechoic characteristics. Additionally, radionuclide scans, CT, and MRI can assist in diagnosis, though they lack specific features for differentiating malignancy. Careful evaluation is required to rule out the possibility of malignant tumors (see section on thyroid cancer for details). Definitive diagnosis ultimately relies on pathological examination.
Treatment
Nodular goiter usually does not require treatment. For patients with significant thyroid enlargement, levothyroxine may be used. Serum TSH levels must be monitored during treatment, as levothyroxine should not be used when TSH levels are reduced or at the lower limit of the normal range. Patients with evidence of autonomous functional thyroid areas confirmed by radionuclide scanning are also not suitable candidates for levothyroxine therapy. Levothyroxine administration should start at a low dose to avoid triggering or worsening coronary heart disease.
Additionally, diagnostic treatment with levothyroxine can serve as a criterion for considering surgery. If fine-needle aspiration cytology (FNAC) reveals suspicious or malignant features, early surgical intervention is required to obtain a pathological diagnosis. If FNAC results suggest benign characteristics but malignancy cannot be completely ruled out, further diagnostic workup involving thyroid scans and thyroid function tests may be necessary. For cold nodules with normal or reduced thyroid function, levothyroxine tablets may be prescribed to suppress TSH production, with follow-up scheduled after 3 months. If the nodules enlarge, surgical intervention is indicated regardless of TSH suppression adequacy. However, if the nodules decrease in size or remain unchanged, TSH suppression therapy may be continued, with follow-up conducted after another 3 months. If no reduction in nodule size is observed over a total of 6 months, surgical intervention is indicated.
In addition to diagnostic treatment, surgery is considered under the following circumstances: cytological findings from FNAC suggest suspicious or confirmed malignant changes; the thyroid mass is large and affects appearance; the nodular goiter exerts pressure on the trachea, esophagus, recurrent laryngeal nerve, or causes other localized compressive symptoms; the patient has secondary hyperthyroidism; or there is retrosternal goiter.
Surgical options include thyroid nodule excision, partial thyroidectomy, subtotal thyroidectomy, or near-total thyroidectomy. The choice of procedure depends on the location, size, number of nodules, and the degree of thyroid hyperplasia. Intraoperative frozen pathology should be performed. If thyroid cancer is detected, further management should follow established protocols for malignant tumors.