Management of Goiter and Multinodular Goiter

• Suppressive Therapy
  • Reports about the effectiveness of thyroid hormone suppression in nontoxic goiter suppression have varied greatly in the literature
  • In 1997, Lima et al. studied prospectively thyroxine (T₄) treatment at 200 μg, to suppress thyroid-stimulating hormone (TSH) to less than 0.1 μU/L in patients with nontoxic multinodular goiter:
    • Response defined as a greater than 50% decrease in combined nodular volume occurred in:
      • Only 29.1% of patients
        • 47% of patients were non-responders
  • Berghout et al. found that in patients responding to thyroid treatment:
    • Goiter size reduction averaged only 25%
    • In addition, when thyroid hormone treatment was discontinued:
      • Thyroid volume was found to return to pretreatment values within a few months
  • Hurley and Gharib found that thyroid hormone:
    • Was able to reduce goiter size by 50%:
      • In only 27% of patients
  • Ross noted that when thyroid hormone is affected:
    • A size reduction occurs with a lag of approximately three months relative to initiation of therapy
  • Zorrilla found that thyroid hormone-induced size reduction:
    • Was unpredictable
  • Generally, diffuse goiters are thought to be more thyroid hormone responsive as compared with multinodular goiters
  • Burgi et al. found that nodules larger than 2 or 3 cm are less likely to respond to thyroid hormone therapy
  • Other studies looking at combined nodular volume reduction show response rates ranging:
    • From 20% to 58% of patients suppressed
  • T₄ suppression is generally not offered to patients who present with subclinical hyperthyroidism with a TSH level less than or equal to 1 μU/L or in elderly patients
  • Thyroid hormone suppressive therapy for goiter, which must be carried out indefinitely because of the tendency for goiter to recur after cessation of therapy:
    • Risks atrial fibrillation in patients older than age 60 and those with bone loss, especially in postmenopausal women
  • Overall, a review of the literature suggests that T₄ suppressive therapy has variable efficacy in reducing goiter size:
    • Is characterized by a high regrowth rate of goiter when T₄ is discontinued, and is limited in the elderly population and in patients with subclinical hyperthyroidism
• Radioiodine
  • Radioiodine can be used for the treatment of nontoxic multinodular goiter
  • Although not widely used currently in the United States, radioiodine as a treatment for large goiter with compressive symptoms has become more common place in Europe
  • Higher doses of ¹³¹I:
    • Similar to ablative doses used in thyroid cancer patients are required for nontoxic multinodular goiter, as compared with doses used for Graves’ disease:
      • Because of the large volume and lower uptake of nontoxic multinodular goiters
  • Generally, uptake is lower in nontoxic multinodular goiters than in diffuse (anodular) goiters (i.e., Graves’ disease)
  • Studies looking at radioiodine as a treatment for nontoxic multinodular goiter:
    • Show volume reduction of one third to two thirds occurring in more than 80% of patients:
      • With 70% to 80% of patients having a decrease in obstructive symptomatology
  • Complications include radiation thyroiditis:
    • With acute worsening of airway symptoms in less than 5% of patients
    • The need for greater than one dose of radioiodine in up to 20% of patients
    • Hypothyroidism in 60% of patients:
      • Increased risk if:
        • Positive anti-thyroid peroxidase autoantibodies
        • Family history of hypothyroidism
        • In patients with small goiters
    • Radiation-induced Graves’ disease:
      • In up to 10% of patients
    • The high doses of radioiodine used:
      • Increase the estimated lifetime risk of cancers outside the thyroid gland by:
        • 1.6% overall
        • 0.5% for patients older than age 65
  • Radioiodine in the treatment of large goiter that is affecting the airway deserves special attention:
    • Le Moli found the larger the goiter:
      • The less responsive to radioiodine
    • Nygaard found transient increase in goiter size in approximately 7% of patients treated:
      • In these patients, increased size averaged 25%, with a range from 11% to 60%
    • Bonnema also found that within 1 week of radioiodine treatment:
      • The tracheal cross-sectional area decreased by 9.2% from an initial value:
        • With 33% being the greatest reduction in tracheal caliber seen
  • Radioiodine treatment should be considered only:
    • In patients with smaller goiters without airway impact
    • In patients who could not otherwise tolerate surgery
  • The use of radioiodine is ill advised in patients with substernal goiter who have a substantial increased rate of airway compression
• Surgery:
  • Rationale:
    • Surgery represents a rational treatment option for many patients with cervical goiter and most patients with substernal goiter
    • Regional compressive symptoms resolve postoperatively:
      • Faster than with suppressive or radioiodine therapy
    • Complication rates are low
    • Subclinical hyperthyroidism remits
    • Airway complications are avoided
    • A pathology report is provided
    • Goiter surgery is most safely offered when it is not offered with undue delay:
      • Waiting until a goiter is massive will likely increase operative complication rates
    • Surgery brings no risk of radioiodine-induced immediate airway complications, malignancies, or Graves’ disease
    • Surgery also brings no risk of thyroid hormone–induced atrial fibrillation or osteoporosis
    • A patient cannot be a “non-responder” to surgery
  • Indications:
    • Surgery is recommended in patients with multinodular goiter who present with hyperthyroidism:
      • As they do not generally respond well to anti-thyroid drugs, including perchlorate and iopanoic acid
    • Furthermore, surgery may be preferred over radioactive iodine treatment in elderly patients with goiter and subclinical or frank hyperthyroidism:
      • To forestall the risk of radioiodine-induce Graves’ disease in this cardiac-frail population
• Cervical and Substernal Surgery Rationale:
  • Natural history of goiter is of progressive growth
  • Treats existent regional / compressive symptoms
  • Avoids rapid and unpredictable increase in size and airway compression
  • Provides pathology report
  • Rules out malignancy
  • Treats hyperthyroidism and subclinical hyperthyroidism
  • Has low operative morbidity
  • Thyroid hormone (suppressive) treatment is associated with a high non-response rate, requires lifetime treatment, cannot be offered if TSH is <1, risks atrial fibrillation and osteoporosis, and is less likely to be effective with large nodular goiters
  • Radioactive iodine treatment of goiter risks acute radiation thyroiditis and airway compression and, in approximately 10% of patients, induces Graves’ disease
• Patients can be reasonably considered for cervical goiter surgery in the following situations:
  • If a patient has clear-cut regional upper aerodigestive tract symptoms without other cause:
    • As such symptoms may first manifest with positional provocation or nocturnally
  • If radiographic evaluation through axial CT scanning is showing evidence of tracheal compression
  • For thyroids greater than 5 cm or masses with significant cosmetic issues:
    • As regional symptoms typically emerge when the mass is 5 cm or greater, and fine-needle aspiration is less accurate to exclude malignancy in a mass of this size or greater
  • Goiter patients with subclinical hyperthyroidism
  • Patients in whom carcinoma is suspected or proved
  • All patients with substernal extension:
    • The presence of substernal goiter in general is a surgical indication because of the strong association of tracheal compression and substernal growth and because the mediastinal component is difficult to follow on physical exam or with fine-needle biopsy
  • Patients with goiter in whom carcinoma is suspected or proved should undergo surgical excision
• The typical pathology report for substernal or surgical goiter:
  • Reveals adenomatous nodules with old hemorrhage, calcification, cyst formation, fibrosis, and, sometimes, focal thyroiditis
  • The pathology report may also be primarily thyroiditis in some circumstances
• The rate of malignancy varies in cervical and substernal goiter surgical specimens:
  • Singh, Lucente, and Shaha, in reviewing the surgical literature, noted an average rate of 8.3%:
    • With a range of 0% to 40%
  • Katlic, Grillo, and Wang in 80 substernal goiters:
    • Noted only a 2% rate
  • Sanders et al. noted a rate as high as 21%
• The alternative to surgical extirpation of multiple thyroid nodules is multiple fine-needle aspiration (FNA) of all sizable nodules:
  • It is a matter of judgment as to whether this implies simply aspiration of the dominant nodule or all nodules within the goiter greater than 1 cm
  • Given that negative FNAs of all sizable nodules do not rule out malignancy, I believe it is reasonable to abstain from aspirating all nodules in a patient who is scheduled for goiter surgery and who is not suspected to harbor malignancy based on physical exam and CT scanning especially when total thyroidectomy is planned
• Surgery for Substernal Goiter:
  • I believe that all patients, whether symptomatic or not, with substernal goiter should be considered for surgery
  • Substernal extension in series of more than 200 large cervical and substernal goiters:
    • Highly correlates with airway compression:
      • This is not surprising, considering the bony confines of the thoracic inlet
  • The thoracic component of a substernal goiter is also unavailable for ongoing clinical examination or FNA
  • If the substernal component acutely enlarges, the airway is affected on a mediastinal level
  • Most substernal goiter series note a small but significant rate of acute airway emergency
  • Neither tracheotomy nor intubation may relieve an obstruction associated with mediastinal airway compression
  • Aside from typical regional symptoms, benign substernal goiter has also been associated with superior vena cava (SVC) syndrome, downhill esophageal varices, recurrent laryngeal nerve paralysis, phrenic paralysis, Horner’s syndrome, chylothorax, abscess formation, and cerebral vascular accident
  • Given the propensity for regional symptomatology, the lack of other reasonable treatment options, and the low complication rate of surgery, all patients with substernal goiter should be considered for surgery, assuming their medical condition permits

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