The optimal therapy for treatment of toxic nodular goiter (TNG) remains controversial.

Unlike Graves disease, TNG is not an autoimmune disease and rarely, if ever, remits.[9]
Therefore, patients who have autonomously functioning nodules should be treated definitely
with radioactive iodine or surgery. The American Thyroid Association and American
Association of Clinical Endocrinologists have released guidelines for the management of
hyperthyroid and other causes of thyrotoxicosis, including the use of radioactive iodine or
surgery to treat toxic multinodular goiter.[10]
Patients with subclinical hyperthyroidism should be monitored closely for overt disease.
Some suggest that elderly patients, women with osteopenia, and patients with risk factors for
atrial fibrillation should be treated, even those who have subclinical disease.

Na131 I treatment - In the United States and Europe, radioactive iodine is considered
the treatment of choice for TNG. Except for pregnancy, there are no absolute
contraindications to radioiodine therapy.
o Much debate exists regarding optimal dosing of radioactive iodine. Patients
with TNG tend to have less uptake than do patients with Graves disease;
therefore, they are generally considered to need higher doses of Na131 I.
However, studies by Allahabadia and colleagues suggest that fixed doses of
radioiodine do not demonstrate any difference in response in these 2 groups of
patients (using a fixed dose of 370 megabecquerels).[11]
o A single dose of radioiodine therapy has a success rate of 85-100% in patients
with TNG. Radioiodine therapy may reduce the size of the goiter by up to
40%.[12, 13]
o Failure of initial treatment with radioactive iodine has been associated with
increased goiter size and higher T3 and free T4 levels, which suggests that
these factors may present a need for higher doses of Na131 I.
o A positive correlation exists between radiation dose to the thyroid and
decrease in thyroid volume. In patients with uptake of less than 20%,
pretreatment with lithium, PTU, or recombinant TSH can increase the
effectiveness of iodine uptake and treatment.[14, 15] This treatment may be
valuable in elderly patients in whom surgery is considered high risk.
o Complications
Hypothyroidism occurs in 10-20% of patients; this is similar to the
incidence rate after surgery and is substantially less than in the
treatment of Graves disease.[16]
Tracheal compression due to thyroid swelling after radiation therapy is
no longer thought to be a risk.[17]
Mild thyrotoxic symptoms after radioiodine occur in about one-third of
patients, and about 4% of patients develop a clinically significant
radiation-induced thyroiditis. These patients should be treated
symptomatically with beta blockers.
Elderly patients may have exacerbation of congestive heart failure and
atrial fibrillation. Pretreat elderly patients with antithyroid drugs.
Thyroid storm is a rare complication, particularly in patients with
rapidly enlarging goiters or high total T3 levels. Patients with these
conditions should receive pretreatment with antithyroid drugs.
Pharmacotherapy - Antithyroid drugs and beta blockers are used for short courses in
the treatment of TNG; they are important in rendering patients euthyroid in
preparation for radioiodine or surgery and in treating hyperthyroidism while awaiting

full clinical response to radioiodine. Patients with subclinical disease at high risk of
complications (eg, atrial fibrillation, osteopenia) may be given a trial of low dose
methimazole (5-15 mg/d) or beta blockers and should be monitored for a change in
symptoms or for disease progression that requires definitive treatment.
o Thioamides - The role of therapy with thioamides (eg, PTU, methimazole) is
to achieve euthyroidism prior to definitive treatment with either surgery or
radioiodine therapy. Data suggest that pretreated patients have decreased
response to radioiodine. The general recommendation is to stop antithyroid
agents at least 4 days prior to radioiodine therapy in order to maximize the
radioiodine effect.
Antithyroid drugs are often administered for 2-8 weeks before
radioiodine therapy in order to avoid the risk of precipitating thyroid
storm. Although many physicians no longer consider this treatment
necessary, the general consensus is that elderly patients or patients
with high risk of cardiac complications should receive this treatment.
Antithyroid drugs and beta blockers have side effects, the most
common being pruritic rash, fever, gastrointestinal upset, and
arthralgias. More serious potential side effects include agranulocytosis,
drug-induced lupus and other forms of vasculitis, and liver damage.
o The US Food and Drug Administration (FDA) added a boxed warning, the
strongest warning issued by the FDA, to the prescribing information for PTU.
The boxed warning emphasizes the risk for severe liver injury and acute liver
failure, some of which have been fatal. The boxed warning also states that
PTU should be reserved for use in patients who cannot tolerate other
treatments, such as methimazole, radioactive iodine, or surgery.
The decision to include a boxed warning was based on the FDA's
review of postmarketing safety reports and on meetings held with the
American Thyroid Association, the National Institute of Child Health
and Human Development, and the pediatric endocrine clinical
community.
The FDA has identified 32 cases (22 adult and 10 pediatric) of serious
liver injury associated with PTU. Of the adults, 12 deaths and 5 liver
transplants occurred, and among the pediatric patients, 1 death and 6
liver transplants occurred. PTU is indicated for hyperthyroidism due to
Graves disease. These reports suggest an increased risk for liver
toxicity with PTU compared with methimazole. Serious liver injury
has been identified with methimazole in 5 cases (3 resulting in death).
PTU is considered to be a second-line drug therapy, except in patients
who are allergic to or intolerant of methimazole, or in women who are
in the first trimester of pregnancy. Rare cases of embryopathy,
including aplasia cutis, have been reported with methimazole during
pregnancy. The FDA recommends the following criteria be considered
for prescribing PTU (for more information, see the FDA Safety
Alert)[18] :
Reserve PTU use during first trimester of pregnancy, or in
patients who are allergic to or intolerant of methimazole.
Closely monitor PTU therapy for signs and symptoms of liver
injury, especially during the first 6 months after initiation of
therapy.

For suspected liver injury, promptly discontinue PTU therapy,

evaluate the patient for evidence of liver injury, and provide
supportive care.
PTU should not be used in pediatric patients unless the patient
is allergic to or intolerant of methimazole and no other
treatment options are available.
Counsel patients to promptly contact their health care provider
for the following signs or symptoms: fatigue, weakness, vague
abdominal pain, loss of appetite, itching, easy bruising, or
yellowing of the eyes or skin.
Beta-adrenergic receptor antagonists - These drugs remain useful in the
treatment of symptoms of thyrotoxicosis; they may be used alone in patients
with mild thyrotoxicosis or in conjunction with thioamides for treatment of
more severe disease.
Propranolol, a nonselective beta blocker, may help to lower the heart
rate, control tremor, reduce excessive sweating, and alleviate anxiety.
Propranolol is also known to reduce the conversion of T4 to T3.
In patients with underlying asthma, beta-1 selective antagonists, such
as atenolol or metoprolol, would be safer options.
In patients with contraindications to beta blockers (eg, moderate to
severe asthma), calcium channel antagonists (eg, diltiazem) may be
used to help control the heart rate.