[I] How should overt hyperthyroidism due to TMNG or TA be managed?

[I] How should overt hyperthyroidism due to TMNG or TA be managed?

    We suggest that patients with overtly TMNG or TA be treated with either 131I therapy or thyroidectomy. On occasion, long-term, low-dose treatment with methimazole may be appropriate. 2/++0

There are two effective and relatively safe treatment options, 131I therapy and thyroidectomy. The decision regarding treatment should take into consideration a number of clinical and demographic factors, as well as patient preference. The goal of therapy is the rapid and durable elimination of the hyperthyroid state.

For patients with TMNG, the risk of treatment failure or need for repeat treatment is <1% following near-total/total thyroidectomy (147,148), compared with a 20% risk of the need for retreatment following 131I therapy (147,149). Euthyroidism without the need for antithyroid drug therapy is achieved within days after surgery (147,148); after radioactive iodine, the response is 50%–60% by 3 months, and 80% by 6 months (147,149). On the other hand, the risk of hypothyroidism and the requirement for exogenous thyroid hormone therapy is 100% after near-total/total thyroidectomy. In a large study of patients with TMNG treated with 131I, the prevalence of hypothyroidism was 3% at 1 year and 64% at 24 years (150). Hypothyroidism was more common among patients under 50 years of age (61% after 16 years), compared with those over 70 years (36% after 16 years).

For patients with TA, the risk of treatment failure is <1% after surgical resection (ipsilateral thyroid lobectomy or isthmusectomy) (151), whereas following 131I there is a 6%–18% risk of persistent hyperthyroidism and a 5.5% risk of recurrent hyperthyroidism (152). Typically, euthyroidism without the need for antithyroid drug therapy is achieved within days after surgery. There is a 75% response rate by 3 months following 131I therapy for TA (152). The prevalence of hypothyroidism is 2.3% following lobectomy for TA (151,153), and lower after isthmusectomy in the unique circumstance where the TA is confined to the thyroid isthmus. In contrast, the prevalence of hypothyroidism after radioactive iodine is progressive and hastened by the presence of antithyroid antibodies or a nonsuppressed TSH at the time of treatment (152,154,155). A study following 684 patients with TA treated with 131I reported a progressive increase in overt and subclinical hypothyroidism (154). At 1 year, the investigators noted a 7.6% prevalence, with 28% at 5 years, 46% at 10 years, and 60% at 20 years. They observed a faster progression to hypothyroidism among patients who were older and who had incomplete TSH suppression (correlating with only partial extranodular parenchymal suppression) due to prior therapy with ATDs.

In large retrospective series' of patients with TMNG presenting with compressive symptoms, all patients undergoing total thyroidectomy had resolution of these symptoms after treatment, whereas only 46% of patients undergoing radioactive iodine had improvement in such symptoms (156). This may be due in part to the fact that very large goiters treated with high-activity radioactive iodine only decrease in size by 30%–50% (157). The nodule is rarely eradicated in patients with TA undergoing 131I therapy, which can lead to the need for continued surveillance (152,155).

Potential complications following near-total/total thyroidectomy include the risk of permanent hypoparathyroidism (<2.0%) or RLN injury (<2.0%) (158,159). There is a small risk of permanent RLN injury with surgery for TA (151). Following 131I therapy, there have been reports of new-onset GD (up to 4% prevalence) (160), as well as concern for thyroid malignancy (68) and a very minimal increase in late non-thyroid malignancy (161).

Technical remarks: Once the diagnosis has been made, the treating physician and patient should discuss each of the treatment options, including the logistics, benefits, expected speed of recovery, drawbacks, side effects, and costs. This sets the stage for the physician to make a recommendation based upon best clinical judgment and for the final decision to incorporate the personal values and preferences of the patient.

Factors that favor a particular modality as treatment for TMNG or TA:

  1. 131I: Advanced patient age, significant comorbidity, prior surgery or scarring in the anterior neck, small goiter size, RAIU sufficient to allow therapy, and lack of access to a high-volume thyroid surgeon (the latter factor is more important for TMNG than for TA).
  2. Surgery: Presence of symptoms or signs of compression within the neck, concern for coexisting thyroid cancer, coexisting hyperparathyroidism requiring surgery, large goiter size (>80 g), substernal or retrosternal extension, RAIU insufficient for therapy, or need for rapid correction of the thyrotoxic state (156).

Contraindications to a particular modality as treatment for TMNG or TA:

  1. 131I: Definite contraindications to the use of radioactive iodine include pregnancy, lactation, coexisting thyroid cancer, individuals unable to comply with radiation safety guidelines, and females planning a pregnancy within 4–6 months.
  2. Surgery: Factors weighing against the choice of surgery include significant comorbidity such as cardiopulmonary disease, end-stage cancer, or other debilitating disorders. Pregnancy is a relative contraindication and should only be used in this circumstance when rapid control of hyperthyroidism is required and antithyroid medications cannot be used. Thyroidectomy is best avoided in the first and third trimesters of pregnancy because of teratogenic effects associated with anesthetic agents and increased risk of fetal loss in the first trimester, and increased risk of preterm labor in the third. Optimally, thyroidectomy should be performed in the latter portion of the second trimester. Although it is the safest time, it is not without risk (4.5%–5.5% risk of preterm labor) (47,48).

Factors that may impact patient preference:

  1. 131I: Patients with either TMNG or TA choosing 131I therapy would likely place relatively higher value on the avoidance of surgery and attendant hospitalization or complications arising from either surgery or anesthesia; also, patients with TMNG would place greater value on the possibility of remaining euthyroid after 131I.
  2. Surgery: Patients choosing surgery would likely place a relatively higher value on prompt and definitive control of hyperthyroid symptoms and avoidance of exposure to radioactivity and a lower value on potential surgical and anesthetic risks; patients with TA who choose surgery would place greater value on the possibility of achieving euthyroidism without hormone replacement, whereas patients with TMNG choosing surgery would place a lower value on the certain need for lifelong thyroid hormone replacement.