Nontoxic Multinodular Goiter

Background

• Nontoxic multinodular goiter is defined as an enlarged thyroid with multiple nodules confirmed by ultrasound and with thyroid function tests demonstrating normal levels of serum thyroid-stimulating hormone (TSH) and normal free thyroxine (free T4).
• Over time, a nontoxic multinodular goiter can increase in size and progress to a toxic multinodular goiter with signs and symptoms of hyperthyroidism, including decreased TSH and potentially increased free T4.
• The incidence of malignancy among nodules present in a nontoxic multinodular goiter is similar to that of an isolated nodule.

Evaluation

• A small multinodular goiter may be asymptomatic and diagnosed as an incidental finding on clinical exam.
• Clinical signs and symptoms associated with multinodular goiter may include:
  • slow, progressive growth of the thyroid
  • multinodularity on thyroid exam
  • cosmetic complaints due to cervical enlargement
  • tracheal compression/deviation, upper airway obstruction, or dyspnea
  • occasional cough or dysphagia
  • acute pain or cervical enlargement secondary to bleeding
  • superior vena cava obstruction syndrome
  • Pemberton sign (an upper thoracic inlet obstruction when arms are extended above the head)
• Blood tests:
  • Perform thyroid function tests at initial evaluation in patients with known or suspected thyroid nodules.
    • Check TSH levels at initial evaluation in all patients with known or suspected thyroid nodules (Strong recommendation).
    • If TSH is low (< 0.5 microunits/mL), check free T4 and triiodothyronine (T3) and perform scintigraphy (radionuclide scanning) (Strong recommendation).
    • If TSH is high (> 5 microunits/mL), check free T4 and thyroid peroxidase antibody; do not perform scintigraphy (Strong recommendation).
    • In patients with nontoxic multinodular goiter, thyroid function tests will show:
      • normal TSH
      • normal free T4
  • Check serum calcitonin if cytology results or family history suggests medullary thyroid carcinoma or a multiple endocrine neoplasia syndrome (Strong recommendation).
• Imaging studies:
  • An ultrasound with a survey of the cervical lymph nodes is recommended for all patients with clinically detected multinodular goiter (Strong recommendation).
    • Ultrasound findings associated with malignancy include:
      • absence of a halo
      • undefined borders
      • presence of microcalcifications
      • marked hypoechogenicity
      • nodules that are taller than wide
      • central vascular flow at Doppler evaluation
  • Perform thyroid scintigraphy (using iodine 123 [¹²³I] or ^99mTcO₄^-) if (Strong recommendation):
    • TSH level is low
    • ectopic thyroid tissue or retrosternal goiter is suspected
  • Use of other imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) is generally not recommended for initial evaluation of multinodular goiter, but may be indicated for select cases.
• For patients who are at increased risk for malignancy based on clinical and ultrasound findings, perform fine-needle aspiration (FNA) biopsy of suspicious nodules for cytologic classification and determination of malignancy risk (Strong recommendation).

Management

• Goals of management in patients with nontoxic multinodular goiter include:
  • Correct underlying thyroid dysfunction, if any.
  • Decrease goiter size or prevent further growth.
• Conservative management (clinical observation with annual follow-ups) is the preferred option for asymptomatic patients with benign goiter who have normal thyroid function and no cosmetic concerns.
• Surgery is the treatment of choice for most patients with nontoxic multinodular goiters when conservative management is not possible.
  • Consider surgery for benign nodules if the nodule is causing local pressure symptoms, or if suspicious ultrasound features are present despite benign results on fine-needle aspiration (Weak recommendation).
  • Other indications for surgery include:
    • large (> 100 cm³) and obstructive goiters
    • suspected malignancy
    • compressive symptoms (dysphagia, choking sensation, airway obstruction)
    • substernal extension
    • inadequate response to radioiodine therapy
  • Total or near-total thyroidectomy is the recommended surgical procedure for multinodular goiter (Strong recommendation).
• Radioactive iodine (RAI) therapy alone or preceded by recombinant human TSH (rhTSH) is an alternative to surgery in select patients. However, this mode of therapy should be used with caution as RAI therapy can cause acute swelling of an already large multinodular goiter. Adverse effects may be minimized with concomitant use of corticosteroids and beta-blockers.
  • Consider RAI therapy in patients with asymptomatic nontoxic nodular goiters without evidence of malignancy.
  • RAI therapy is recommended for patients with hyperfunctioning or symptomatic goiter, especially those with previous thyroid surgery, at high risk with surgery, or who decline surgery (Strong recommendation).
  • Radioactive agents are contraindicated in pregnancy.
    • Do not use RAI therapy in pregnant or breastfeeding patients (Strong recommendation).
    • Perform a pregnancy test before starting radioiodine therapy in patients of childbearing age (Strong recommendation).
• In general, levothyroxine (LT4) suppressive therapy is not recommended for management of patients with nontoxic multinodular goiter, particularly older patients who are at increased risk for adverse effects with LT4 treatment.
  • Consider a trial of LT4 suppressive therapy in young patients with small nodular goiter and high-normal TSH levels who live in iodine-deficient regions, alone or in addition to iodine supplementation (Weak recommendation).
  • If LT4 suppressive therapy is used, long-term therapy is necessary as goiter regrowth can occur if therapy is stopped.