Toxic Nodular Goiter

Toxic nodular goiter (TNG) represents a spectrum of disease ranging from a single hyperfunctioning nodule (toxic adenoma) within a multinodular thyroid to a gland with multiple areas of hyperfunction. The natural history of a multinodular goiter involves variable growth of individual nodules; this may progress to hemorrhage and degeneration, followed by healing and fibrosis. Calcification may be found in areas of previous hemorrhage. Some nodules may develop autonomous function. Autonomous hyperactivity is conferred by somatic mutations of the thyrotropin, or thyroid-stimulating hormone (TSH), receptor in 20-80% of toxic adenomas and some nodules of multinodular goiters.[1] Autonomously functioning nodules may become toxic in 10% of patients. Hyperthyroidism predominantly occurs when single nodules are larger than 2.5 cm in diameter. Signs and symptoms of TNG are similar to those of other types of hyperthyroidism.

Functional autonomy of the thyroid gland appears to be related to iodine deficiency. Various mechanisms have been implicated, but the molecular pathogenesis is poorly understood.

The sequence of events leading to toxic multinodular goiter is as follows:

• Iodine deficiency leads to low levels of T4; this induces thyroid cell hyperplasia to compensate for the low levels of T4.

• Increased thyroid cell replication predisposes single cells to somatic mutations of the TSH receptor. Constitutive activation of the TSH receptor may generate autocrine factors that promote further growth, resulting in clonal proliferation. Cell clones then produce multiple nodules.

Somatic mutations of the TSH receptors and G α protein confer constitutive activation to the cyclic adenosine monophosphate (cAMP) cascade of the inositol phosphate pathways. These mutations may be responsible for functional autonomy of the thyroid in 20-80% of cases.[1]

These mutations are found in autonomously functioning thyroid nodules, solitary and within a multinodular gland. Nonfunctioning thyroid nodules within the same gland lack these mutations.

The reported frequency of these mutations varies widely, ranging from 10-80%. Higher incidence is reported in patients with iodine deficiency.

In addition to somatic mutations, polymorphisms of the TSH receptor have been studied in patients with toxic nodular goiter (TNG); notably, polymorphisms involving the carboxyl-terminal tail of the human TSH receptor have been found in nodular and genomic deoxyribonucleic acid (DNA).

Unlike the somatic mutations found in autonomously functioning nodules, these mutations have also been found in other cell lines, indicating a germline mutation. One of these, D727E, was present with greater frequency in patients with TNG than in healthy individuals; this suggests that this polymorphism may be associated with the disease.[2, 3]

The presence of the heterozygous state for the D727E variant of the human TSH receptor alone is not sufficient for the development of the TNG. Approximately 10% of healthy individuals have this polymorphism.

Possible mediators in growth include the following:

• Endothelin-1 (ET-1) production is increased in rat thyroid glands that have undergone hyperplasia; this suggests that ET-1 production may be involved in thyroid gland growth and vascularity. In contrast to normal thyroid tissue and papillary thyroid cancer, thyroid tissue in patients with TNG shows markedly positive staining of the stroma but absent staining of the follicular cells. The significance of this finding is unclear, but ET-1 is, in addition to being a vasoconstrictor, a mitogen for vascular endothelium, smooth muscle cells, and thyroid follicular cells.

• In vitro systems have shown stimulation of thyroid follicular cell proliferation with insulinlike growth factor-1, epidermal growth factor, and fibroblast growth factor. Reduced concentrations of transforming growth factor-β 1 or resistance to transforming growth factor-β have also been associated with follicular cell growth. The role of these multiple factors in the growth and secretory function of TNG needs further investigation.

United States statistics

Toxic nodular goiter accounts for approximately 15-30% of cases of hyperthyroidism in the United States, second only to Graves disease.

International statistics

In areas of endemic iodine deficiency, toxic nodular goiter (TNG) accounts for approximately 58% of cases of hyperthyroidism, 10% of which are from solitary toxic nodules. Graves disease accounts for 40% of cases of hyperthyroidism. In patients with underlying nontoxic multinodular goiter, initial iodine supplementation (or iodinated contrast agents) can lead to hyperthyroidism (Jod-Basedow effect). Iodinated drugs, such as amiodarone, may also induce hyperthyroidism in patients with underlying nontoxic multinodular goiter. Roughly 3% of patients treated with amiodarone in the United States (more in areas of iodine deficiency) develop amiodarone-induced hyperthyroidism.[4]

Sex- and age-related demographics

Toxic nodular goiter occurs more commonly in women than in men. In women and men older than 40 years, the prevalence rate of palpable nodules is 5-7% and 1-2%, respectively.

Most patients with toxic nodular goiter (TNG) are older than 50 years.

Thyrotoxicosis often occurs in patients with a history of longstanding goiter. Toxicity occurs in a subset of patients who develop autonomous function. This toxicity usually peaks in the sixth and seventh decades of life, especially in persons with a family history of multinodular goiter or TNG, suggesting a genetic component.

Most treated patients have a good prognosis. A worse prognosis is related to untreated hyperthyroidism. Patients should understand the gravity of hyperthyroidism. If left untreated, hyperthyroidism may lead to osteoporosis, arrhythmia, heart failure, coma, and death. Regular assessment of thyroid function is important in monitoring disease.

Na131 I ablation may result in continued hyperthyroidism, with some patients (up to 73% in some studies, depending on the size of the goiter and the dosing of radioiodine) requiring repeated treatment or surgical removal of the gland. Hypothyroidism after radioiodine ablation has been reported in 0-35% of individuals.

Iodine-131 ablation may result in continued hyperthyroidism, with some patients (up to 73% in some studies depending on size of goiter and dosing of radioiodine) requiring repeated treatment or surgical removal of the gland. Hypothyroidism after radioiodine ablation has been reported in 0-35% of individuals.

Surgical treatment usually consists of a lobectomy of the hyperfunctioning nodule. The rate of hypothyroidism associated with this procedure is very low. Rates of hyperthyroidism recurrence with surgery have been reported to be as low as 0-9%. Larger, multinodular goiters may require total thyroidectomy.

Morbidity/mortality

Morbidity and mortality from toxic nodular goiter (TNG) may be divided into problems related to hyperthyroidism and problems related to growth of the nodules and gland. Local compression problems due to nodule growth, although unusual, include dyspnea, hoarseness, and dysphagia. Both TNG and Graves disease have increased mortality but for different reasons.[5]

TNG is more common in elderly adults; therefore, complications due to comorbidities, such as coronary artery disease, are significant in the management of hyperthyroidism.

Hyperthyroid complications

The most important complications are related to the heart.

Cardiomyopathy resulting in severely depressed function may be observed with hyperthyroidism, possibly in relation to persistent tachycardia. Fortunately, cardiomyopathy resolves remarkably with resolution of the hyperthyroid state.

Using anticoagulants to treat patients exhibiting atrial fibrillation remains controversial, although it is recommended by many authorities. Atrial fibrillation of long duration that is associated with other anatomical defects of the heart should be treated with warfarin or another suitable anticoagulant.

Many patients fear abnormal weight gain with the attainment of the euthyroid state. Provide patients with education regarding the role of thyroid hormone in metabolism, as well as the cardiovascular and thromboembolic risks of hyperthyroidism. Also provide guidelines for lifestyle modification that will allow the patient to avoid weight gain.

Apprise patients treated with PTU or methimazole of the risk of agranulocytosis and instruct them to contact a physician if they develop a fever, rash, or sore throat, so that a complete blood cell (CBC) count with differential can be urgently performed.

Thyrotoxic symptoms

Most patients with toxic nodular goiter (TNG) present with symptoms typical of hyperthyroidism, including heat intolerance, palpitations, tremor, weight loss, hunger, and frequent bowel movements.

Elderly patients may have more atypical symptoms, including the following:

• Weight loss is the most common complaint in elderly patients with hyperthyroidism.

• Anorexia and constipation may occur, in contrast to frequent bowel movements often reported by younger patients.

• Dyspnea or palpitations may be a common occurrence.

• Tremor also occurs but can be confused with essential senile tremor.

• Cardiovascular complications occur commonly in elderly patients, and a history of atrial fibrillation, congestive heart failure, or angina may be present.

F Lahey, MD, first described apathetic hyperthyroidism in 1931; this is characterized by blunted affect, lack of hyperkinetic motor activity, and slowed mentation in a patient who is thyrotoxic.

Obstructive symptoms

A significantly enlarged goiter can cause symptoms related to mechanical obstruction.

A large substernal goiter may cause dysphagia, dyspnea, or frank stridor. Rarely, this goiter results in a surgical emergency.

Involvement of the recurrent or superior laryngeal nerve may result in complaints of hoarseness or voice change.

Asymptomatic or minimal symptoms

Many patients are asymptomatic or have minimal symptoms and are incidentally found to have hyperthyroidism during routine screening. The most common laboratory finding is a suppressed TSH with normal free thyroxine (T4) levels.

Findings of hyperthyroidism may be more subtle than those of Graves disease. Features may include widened, palpebral fissures; tachycardia; hyperkinesis; moist, smooth skin; tremor; proximal muscle weakness; and brisk deep tendon reflexes.

The size of the thyroid gland is variable. Large substernal glands may not be appreciable upon physical examination.

A dominant nodule or multiple irregular, variably sized nodules are typically present. In a small gland, multinodularity may be apparent only on an ultrasonogram. Chronic Graves disease may present with some nodularity; therefore, establishing the diagnosis is sometimes difficult.

Hoarseness or tracheal deviation may be present upon examination.

Mechanical obstruction may result in superior vena cava syndrome, with engorgement of facial and neck veins (Pemberton sign).[6]

Stigmata of Graves disease (eg, orbitopathy, pretibial myxedema, acropachy) are not observed.

Thyroid function tests

Evidence of hyperthyroidism must be present in order to consider a diagnosis of toxic nodular goiter (TNG).[7]

Third-generation thyroid-stimulating hormone (TSH) assays are generally the best initial screening tool for hyperthyroidism. Patients with TNG will have suppressed TSH levels.

Free T4 levels or surrogates of free T4 levels (ie, free T4 index) may be elevated or within the reference range. An isolated increase in T4 is observed in iodine-induced hyperthyroidism or in the presence of agents that reduce peripheral conversion of T4 to triiodothyronine (T3) (eg, propranolol, corticosteroids, radiocontrast agents, amiodarone).

Some patients may have normal free T4 levels (or free T4 index) with an elevated T3 level (T3 toxicosis); this may occur in 5-46% of patients with toxic nodules. Note that the total T3 and T4 levels may often be within the reference range but may be higher than the normal range for a particular individual; this is especially true in patients with nonthyroidal illness in which T3 levels are decreased.

Subclinical hyperthyroidism

Some patients may have suppressed TSH levels with normal free T4 and total T3 levels.

Nuclear scintigraphy

Nuclear scans should be performed on patients with biochemical hyperthyroidism.[7] Nuclear medicine scans can be performed with radioactive iodine-123 (123 I) or with technetium-99m (99m Tc). These isotopes are chosen for their shorter half-life and because they provide lower radiation exposure to the patient when compared with sodium iodide-131 (Na131 I).

99m Tc is trapped in the thyroid but is not organified. Although convenient,99m Tc scanning may provide misleading results. Some nodules that appear hot or warm on99m TC scan results may be cold on123 I scan results. Nodules with discordant99m Tc and123 I scan results may be malignant; therefore,123 I scanning is preferred.

Nuclear scans allow determination of the cause of hyperthyroidism. Patients with Graves disease usually have homogeneous diffuse uptake. Glands with thyroiditis have low uptake.

In patients with toxic nodular goiter (TNG), the scan results usually reveal patchy uptake (see the image below), with areas of increased and decreased uptake. The uptake rate of radioiodine in 24 hours averages approximately 20-30%. Radioactive Na131 I ablation of the thyroid gland may be considered if the thyroid uptake value is elevated. Several therapeutic modalities have been suggested to increase uptake (eg, low iodine diet, lithium, recombinant TSH, propylthiouracil [PTU]).

Thyroid scanning is also useful for helping to determine the presence of substernal extension of the thyroid gland, which may contain toxic nodules.

Ultrasonography

Ultrasonography is a highly sensitive procedure for delineating discrete nodules that are not palpable during thyroid examination. Ultrasonography is helpful when correlated with nuclear scans to determine the functionality of nodules.[7]

Dominant cold nodules should be considered for fine-needle aspiration biopsy prior to definitive treatment of a TNG.

This technique may be used to serially examine the size of thyroid nodules.

Other imaging modalities

In the workup of patients with compressive or obstructive symptoms, computed tomography (CT) scanning of the neck may help to establish whether the trachea is patent and if tracheal deviation or the impingement of other structures is caused by a nodular goiter.

Multinodular goiters, especially those with a substernal component, are often incidental findings on chest radiographs, CT scans, or magnetic resonance imaging (MRI) scans. CT scans with iodinated contrast may induce thyrotoxicosis in individuals with an underlying nontoxic, multinodular goiter by supplying an iodine load (Jod-Basedow effect). This type of thyrotoxicosis is self-limited but may last longer if areas of autonomy already exist within the goiter.

Fine-needle aspiration

Fine-needle aspiration is not usually indicated in an autonomously functioning (ie, hot) thyroid nodule. The risk of malignancy is quite low. Interpretation of the cytology specimen is difficult, because it is likely to demonstrate a follicular neoplasm (ie, sheets of follicular cells with little or no colloid), and distinguishing between a benign lesion and a malignant lesion is not possible without histologic sectioning to examine for the presence of vascular or capsular invasion.[8]

Perform a fine-needle aspiration biopsy if a dominant cold nodule is present in a multinodular goiter. A clinically significant nodule is larger than 1 cm in maximum diameter, based on either palpation or ultrasonographic images, unless there is an increased risk of malignancy. Nonpalpable nodules may be biopsied with the assistance of ultrasonography.

A history of head or neck irradiation during childhood increases the risk of malignancy. Head or neck irradiation in an adult increases the frequency of toxic nodular goiter and of carcinoma of the thyroid. Patients from iodine-replete areas have the same risk of malignancy as persons from iodine-deficient areas.

Autonomous nodules may be monoclonal or polyclonal. Many nodules studied in multinodular goiters may actually be monoclonal, even in the setting of histologically marked phenotypic variation.

The histologic appearance of a multinodular goiter can be highly variable and may involve the presence of normal-sized follicles, microfollicles, or macrofollicles, all coexisting within the same gland. Early goiters display micronodular growth patterns. Actively proliferating follicular cells can be observed within some thyroid follicles, resulting in budding intraluminal projections, while other cells within the same follicle appear to be in the resting phase. Conversely, some follicles show a more uniform appearance of cells. Periods of alternating active and quiescent growth appear to occur within the goiter. Areas of fresh and old hemorrhage with calcification are also occasionally present.

The optimal therapy for toxic nodular goiter (TNG) remains controversial and differs slightly between a single dominant nodule and multiple toxic nodules. 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 has 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.[11]

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).[12]  A recent study proposes the use of a personalized dose calculation algorithm rather than fixed doses of radioiodine.[13]

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%.[14, 15]

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.

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, propylthiouracil (PTU), or recombinant TSH can increase the effectiveness of iodine uptake and treatment.[16, 17] This treatment may be valuable in elderly patients in whom surgery is considered high risk and volume reduction is needed.

Complications of treatment

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.[18]

Tracheal compression due to thyroid swelling after radiation therapy is no longer thought to be a risk.[19]

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.

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 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. Methimazole is more likely to cause a cholestatic picture while PTU is more likely to cause a transaminitis. Beta blockers should be used with caution in those patients that have contraindications such as pulmonary or cardiac disorders. 

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)[20] :

• 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.

Surgical therapy is usually reserved for young individuals, patients with 1 or more large nodules or with obstructive symptoms, patients with dominant nonfunctioning or suspicious nodules, patients who are pregnant, patients in whom radioiodine therapy has failed, or patients who require a rapid resolution of the thyrotoxic state.

Total or near-total thyroidectomy results in rapid cure of hyperthyroidism in 90% of patients and allows for rapid relief of compressive symptoms.[21]  Goiter recurrence is lower patients who undergo total or near-total thyroidectomy compared to subtotal thyroidectomy. [22]

Restoring euthyroidism prior to surgery is preferable.

Complications of surgery include the following:

• In patients who are treated surgically, the frequency of hypothyroidism is similar to that found in patients treated with radioiodine (15-25%), and is strongly dependent on the extent of the surgery.

• Complications include permanent vocal cord paralysis (2.3%), permanent hypoparathyroidism (0.5%), temporary hypoparathyroidism (2.5%), and significant postoperative bleeding (1.4%).

• Other postoperative complications include tracheostomy, wound infection, wound hematoma, myocardial infarction, atrial fibrillation, and stroke.

• In experienced hands the mortality rate is almost zero.

When radioactive iodine, surgery, or long-term antithyroidal drugs are inappropriate or contraindicated, radiofrequency ablation can be considered in select patients.[23]  A literature review showed that radiofrequency ablation normalizes thyroid function in 45-50% of medium-size autonomously functioning thyroid nodules and in more than 80% of small autonomously functioning nodules. In addition, ablation reduces nodule volume by 68-84%.[24]

Consult an endocrinologist for hyperthyroidism that has not responded to medical therapy or if other comorbid conditions are complicating the patient's condition. Refer patients with amiodarone-associated hyperthyroidism to an endocrinologist. In a multinodular goiter with cold and hot areas on thyroid scan findings, fine-needle aspiration may be required to determine the histologic nature of the cold lesions.

Consult an endocrine surgeon if medical therapy fails to maintain the euthyroid state, if compromise of the trachea is noted on imaging studies, or if the patient requests surgical removal.

Consult a thoracic surgeon in the case of a toxic substernal goiter, because the surgeon may be helpful in further diagnostic and therapeutic measures.

Diet

Avoidance of iodine rich foods is recommended (eg, seaweed, kelp).

Activity

Activity should be restricted to maintain a heart rate of less than 90 beats per minute.

The American Thyroid Association published updated guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis in 2016.[10]

The goals of pharmacotherapy are to reduce morbidity, prevent complications, and provide a bridge to definitive therapy.

Class Summary

Inhibition thyroid hormone production. PTU and methimazole are thionamide derivatives. PTU is a thiourea antithyroid drug that blocks the production of thyroid hormones. A high doses, this drug also inhibits the peripheral deiodination of T4 to T3 and is used (1) in the management of hyperthyroidism, including treatment of Graves disease; (2) in the preparation of patients who are hyperthyroid for thyroidectomy; (3) as an adjunct to radioiodine therapy[25] ; and (4) as treatment for thyroid storm. Unlike PTU, methimazole lacks the ability to block peripheral conversion of T4 to T3.

Propylthiouracil

Thiourea agent that blocks the synthesis of thyroid hormones and inhibits peripheral deiodination of T4 to T3.

Methimazole (Tapazole)

Active moiety of parent compound carbimazole. A thiourea agent that blocks production of thyroid hormones.

Class Summary

Radioisotopes that decay by beta and gamma emissions are used to destroy autonomously functioning follicular cells of the thyroid gland.

Sodium iodide-131 (Na131 I; Iodotope)

Used to treat hyperthyroidism by destroying follicular cells of the thyroid gland. The dose is determined by radioactivity calibration system just prior to administration.

Class Summary

These inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic activity observed in hyperthyroidism.

Propranolol (Inderal)

Nonselective, competitive beta-receptor antagonist with no intrinsic sympathetic activity.

Propranolol treats cardiac arrhythmias resulting from hyperthyroidism, controls cardiac and psychomotor manifestations immediately, and blocks conversion of T4 to T3.

Atenolol (Tenormin)

Selectively blocks beta-1 receptors with little or no effect on beta-2 types. Atenolol treats cardiac arrhythmias resulting from hyperthyroidism and controls cardiac and psychomotor manifestations within min.

Metoprolol, metoprolol succinate, metoprolol tartrate (Lopressor, Toprol XL)

Selective beta-1 – adrenergic receptor blocker that decreases automaticity of contractions. Helps to treat cardiac arrhythmias resulting from hyperthyroidism. Controls cardiac and psychomotor manifestations within min.

After starting PTU or methimazole in patients with toxic nodular goiter (TNG), repeat free T4 or free T4 index measurements at 4-6 weeks. TSH levels rise slower because of suppression by elevated thyroid hormone levels and may take several months to normalize.

Radioiodine ablation may take 10 weeks to achieve clinical response. Patients may require treatment with antithyroid drugs and beta blockers in the interim period. Check biochemical evaluation of thyroid function approximately 4 weeks after initial treatment.

Patients who undergo total thyroidectomy should be started on levothyroxine at the time of discharge, unless they are clinically hyperthyroid. Evaluate thyroid function 4-6 weeks after surgery. In the case of subtotal thyroidectomy, thyroid hormone replacement is not required; evaluate thyroid function approximately 1 month after surgery.

Monitor patients with subclinical hyperthyroidism on initial biochemical evaluation every 6 months for the development of overt hyperthyroidism.