eMedicine Specialties > Endocrinology > Thyroid
Goiter, Toxic Nodular: Treatment & Medication
Updated: Jun 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
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.8 Therefore, patients who have autonomously functioning nodules should be treated definitely with radioactive iodine or surgery. 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.
- 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).9
- 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%.10
- 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, PTU, or recombinant TSH can increase the effectiveness of iodine uptake and treatment.11,12 This treatment may be valuable in elderly patients in whom surgery is considered high risk.
- 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.13
- Tracheal compression due to thyroid swelling after radiation therapy is no longer thought to be a risk.14
- 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 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.
- The US Food and Drug Administration (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)15 :- 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.
- 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.
Surgical Care
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.
- Subtotal thyroidectomy results in rapid cure of hyperthyroidism in 90% of patients and allows for rapid relief of compressive symptoms.
- 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%).
- 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.
- The mortality rate is almost zero.
Consultations
- 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.
Activity
- Activity should be restricted to maintain a heart rate of less than 90 beats per minute.
Medication
The goals of pharmacotherapy are to reduce morbidity, prevent complications, and provide a bridge to definitive therapy.
Antithyroid agents
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 therapy16 ; 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.
Adult
Note: Only available in 50-mg size
Initial: 100-150 mg PO q8h; not to exceed 900-1200 mg/d (except in treatment of thyroid storm)
Maintenance: 100-300 mg/d PO
Thyroid storm: 200mg q6h for first 24 hours; may be given via NG tube or PR if unable to tolerate PO
Pediatric
Disease not observed in children
Monitor aPTT; hyperthyroidism increases metabolism of vitamin K – dependent clotting factors, resulting in increased sensitivity to oral anticoagulants; antithyroid drugs reduce hyperthyroidism and decrease metabolism of clotting factors, thus reducing effects of oral anticoagulants
Documented hypersensitivity; breastfeeding; pediatric patients (unless allergic or intolerant to methimazole and no other treatment is an option)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Commonly used in pregnancy, but close monitoring required for prevention of fetal goiter and hypothyroidism; aplasia cutis not identified with use, thus, preferred antithyroid medication during pregnancy; smallest dose to control disorder should be used because drug does cross the placenta and may result in hypothyroidism of fetus with possible goiter; fever, rash, agranulocytosis, leukopenia, aplastic anemia, hemolytic anemia, DIC, and acute myelocytic anemia; vasculitis; galactorrhea; CNS toxicity; nausea, vomiting, and dysgeusia; rarely, acute hepatitis or liver failure
Risk of serious liver injury, including liver failure and death, has been reported in adults and children by the FDA (carefully consider drug therapy, and if PTU initiated, monitor for symptoms and signs of liver injury, especially during first 6 mo of therapy)
Methimazole (Tapazole)
Active moiety of parent compound carbimazole. A thiourea agent that blocks production of thyroid hormones.
Adult
Mild hyperthyroidism: 30 mg/d PO divided q8-12h initially
Moderate or severe hyperthyroidism: 60 mg/d PO divided q8h initially
Maintenance or treatment of subclinical hyperthyroidism: 5-15 mg/d PO
Pediatric
Disease not observed in children
Monitor aPTT if patient is on anticoagulants; hyperthyroidism increases metabolism of vitamin K – dependent clotting factors, resulting in increased sensitivity to oral anticoagulants; antithyroid drugs reduce hyperthyroidism and decrease metabolism of clotting factors, thus reducing effects of oral anticoagulants; coadministration with amiodarone leads to a greater decline in T4 and T3 levels than with methimazole therapy alone, possibly related to increased iodide release and inhibition of T4-to-T3 conversion
Documented hypersensitivity; breastfeeding; pregnancy or planned pregnancy
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Aplasia cutis reported in infants born to women taking methimazole in pregnancy; liver disease; leukopenia, agranulocytosis, rash, signs or symptoms of infection, fever, sore throat; CNS toxicity; nausea, vomiting, dysgeusia
Radioactive iodines
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.
Adult
Hyperthyroidism: Total amount to achieve clinical remission without destroying entire thyroid varies widely; usual dose range is 4-20 MCi PO; TNG and other special situations require even larger doses, depending on the size and activity of the gland; decay by beta and gamma emissions with half-life of 8.04 d; following PO administration, approximately 40% of activity has half-life of 0.34 d and 60% has half-life of 7.61 d
Pediatric
Disease not observed in children
Increases lithium toxicity by producing additive hypothyroid effects; uptake is affected by stable iodine, iodinated contrast, thyroid hormone, and antithyroid agents; amiodarone may block radioactive iodine uptake into goiter; many herbal products contain iodine and should be discontinued prior to radioactive iodine uptake and therapy
Critical obstruction from goiter (edema after treatment and radiation thyroiditis theoretically may worsen condition); pregnancy and breast-feeding (drug may pass through placenta and is secreted in milk)
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May cause bone marrow depression, acute leukemia, anemia, blood dyscrasias, leukopenia, thrombocytopenia, radiation sickness, angina, sinus tachycardia, pruritus, skin rash, or hives; high doses may cause radiation thyroiditis with painful thyroid or release of stored thyroid hormone, causing temporary thyrotoxicosis
Beta-adrenergic receptor antagonists
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.
Adult
Initial: 40 mg PO bid, titrate dose for heart rate less than 90 beats/min
Maintenance dose: 120-240 mg PO qd; rarely, 640 mg/d may be required
Life-threatening arrhythmias: 1-3 mg IV; rate of administration should not exceed 1 mg/min; wait 4 h before administering additional dose
Pediatric
Disease not observed in children
Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase
Low-output congestive heart failure, bronchospasm, diabetes mellitus with risk of hypoglycemia unawareness, and Wolff-Parkinson-White syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May mask some clinical signs of thyrotoxicosis (withdraw slowly to avoid exacerbation of clinical symptoms or thyroid storm); caution in patients with impaired renal or hepatic function; may lower intraocular pressure and, therefore, interfere with measurements for glaucoma
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.
Adult
25 mg PO qd; increase to 100 mg/d as symptoms of palpitations, tremor, or pulse rate dictate
Pediatric
Disease not observed in children
Coadministration with aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity
Documented hypersensitivity; low-output congestive heart failure, bronchospasm, diabetes mellitus with risk of hypoglycemia unawareness, Wolff-Parkinson-White syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May mask some clinical signs of thyrotoxicosis (withdraw slowly to avoid exacerbation of clinical symptoms or thyroid storm); caution in patients with impaired renal or hepatic function; may lower intraocular pressure and, therefore, interfere with measurements for glaucoma
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.
Adult
PO: 25-50 mg bid, may need to increase to 100 mg bid or higher as symptoms of palpitations, tremor, or pulse rate dictate
IV (metoprolol tartrate): 5 mg, may repeat at 3-min intervals, not to exceed 15 mg in a patient with thyroid storm; during IV administration, carefully monitor blood pressure, heart rate, and ECG
Pediatric
Disease not observed in children
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Documented hypersensitivity; low-output congestive heart failure, bronchospasm, diabetes mellitus with risk of hypoglycemia unawareness, and Wolff-Parkinson-White syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG
More on Goiter, Toxic Nodular |
| Overview: Goiter, Toxic Nodular |
| Differential Diagnoses & Workup: Goiter, Toxic Nodular |
 Treatment & Medication: Goiter, Toxic Nodular |
| Follow-up: Goiter, Toxic Nodular |
| Multimedia: Goiter, Toxic Nodular |
| References |
| Further Reading |
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Further Reading
Related eMedicine topics:
Hyperthyroidism [Endocrinology]
Hyperthyroidism [Pediatrics: General Medicine]
Hyperthyroidism, Thyroid Storm, and Graves Disease
Hypothyroidism [Endocrinology]
Hypothyroidism [Pediatrics: General Medicine]
Iodine Deficiency
Thyroid Dysfunction Induced by Amiodarone Therapy
Keywords
toxic nodular goiter, goiter, TNG, toxic multinodular goiter, hyperthyroidism, hyperthyroid, Plummer disease, Plummer's disease, toxic uninodular goiter, autonomously functioning thyroid nodule, toxic adenoma, Graves disease, Graves' disease, iodine deficiency, Jod-Basedow phenomenon, Jod-Basedow effect, Jod-Basedow's effect, hyperfunctioning nodule, multinodular thyroid, underlying nontoxic multinodular goiter, amiodarone, amiodarone-induced hyperthyroidism, thyrotoxicosis, apathetic hyperthyroidism, suppressed thyroid-stimulating hormone, TSH, TSH receptors, superior vena cava syndrome, hyperplasia, cyclic adenosine monophosphate, cAMP, thyroxine, T4, iodine-induced hyperthyroidism, triiodothyronine, T3, micronodular growth patterns, follicles, D727E, endothelin-1, ET-1
