eMedicine Specialties > Endocrinology > Thyroid

Goiter, Diffuse Toxic

Bernard Corenblum, MD, FRCP(C), Professor of Medicine, Director, Endocrine-Metabolic Testing and Treatment Unit, Ovulation Induction Program, Department of Internal Medicine, Division of Endocrinology, University of Calgary, Canada
Oluyinka S Adediji, MD, Consulting Staff, Department of Adult and General Medicine, Health Services Incorporated, Montgomery, Alabama; Paul Killian, MD, Former Chief of Endocrine Service, Former Associate Professor, Department of Internal Medicine, Harlem Hospital, Harlem Hospital Center

Updated: Jun 4, 2009

Introduction

Background

This condition was first described by the English physician Caleb H. Parry (1755-1822). The disorder is known as Graves disease (after Robert J. Graves) in the English-speaking world and as Basedow disease (after Karl A. von Basedow) in the rest of Europe.

In diffuse toxic goiter, the thyroid gland is diffusely hyperplastic and excessively overproduces thyroid hormone. This results in accelerated metabolism in most body organs. The clinical response and its manifestations are variable in intensity, distribution, and are modified by age, gender, and associated premorbid medical problems. When the diffuse toxic goiter is associated with clinical evidence of oculopathy, or rarely with dermopathy/acropachy, the term Graves’ disease is often applied. Awareness is needed regarding the atypical clinical presentations.

Pathophysiology

The thyroid gland is usually enlarged to a variable degree and is vascular and diffusely affected. This results in a smooth, rubbery-firm consistency, and often a bruit is heard on auscultation. Microscopically, the thyroid follicular cells are hypertrophic and hyperplastic, and they contain little colloid (stored hormone) and show evidence of hypersecretion. Lymphocytes and plasma cells infiltrate into the thyroid gland and may aggregate into lymphoid follicles.

This condition is an autoimmune disorder whereby the thyroid gland is overstimulated by antibodies directed to the thyroid-stimulating hormone (TSH) receptor on the thyroid follicular cells. This antibody stimulates iodine uptake, thyroid hormonogenesis and release, and thyroid gland growth. Although mainly produced within the thyroid gland, these antibodies reach the circulation and can be measured by various assays in most, but not all, cases.

The association with another autoimmune thyroid disease, Hashimoto thyroiditis, and to a lesser degree, with other autoimmune diseases in other endocrine glands and other systems in the same person is high. A strong familial association exists with the same diffuse toxic goiter or the associated disorders, especially Hashimoto thyroiditis. The presence of Hashimoto thyroiditis, which has more of a destructive effect on the thyroid gland, or the presence of another antibody, TSH-receptor blocking antibody, results in a variable natural history of the course of diffuse toxic goiter.

Frequency

United States

Diffuse toxic goiter is the most common cause of spontaneous hyperthyroidism. A Minnesota study found 0.3 new cases per 1000 per year.

In late childhood, the incidence rate is 3 per 100,000 in girls and 0.5 per 100,000 in boys. Prevalence studies show a rate of 2.7% in women and 0.23% in men.

A marked increase in familial incidence is noted.

International

Prewar Copenhagen found 0.2 new cases per 1000 per year.

British studies found 0.08-0.2 new cases per 1000 per year.

Mortality/Morbidity

The natural history is usually of a benign course, which may vary in intensity of the symptoms and even spontaneously remit. The intensity of the symptoms and effect on quality of life are variable from person to person and are affected by age and gender.

Mortality is rare but is due to cardiovascular problems such as heart failure, arrhythmias, or myocardial infarction. Debility and infection may occur. Thyroid storm is rare but may be fatal from dehydration, hyperthermia, and organ failure.

Morbidity may result from increased bone turnover and osteoporosis, especially in postmenopausal women, or from atrial fibrillation and its sequelae, such as thromboembolism, especially in older men. Personality changes and psychopathology, muscular weakness, and systemic symptoms all lead to quality of life changes. Associated oculopathy may be symptomatic, especially with double vision. Rarely it may progress to affect the integrity of the cornea and may even endanger vision.

Associated dermopathy is uncommon and is usually minimally symptomatic, but it may be symptomatic to become debilitating.

Associated hypokalemic periodic paralysis, most commonly seen in Asian males, may be sudden, dramatic, and concerning but usually runs a benign course of recovery after a few hours of skeletal muscle paralysis.

A higher risk of associated immunologic diseases, such as adrenal insufficiency, each has their own associated morbidity and mortality, especially if undiagnosed.

Race

No racial predilection exists.

Sex

Diffuse toxic goiter is 7-10 times more common in women than in men. It is often associated with or following a pregnancy.

Age

Diffuse toxic goiter can occur in all ages, but it is rare in children younger than 10 years and unusual in elderly persons. The peak incidence is in third and fourth decades.

Incidence is increased in postpartum women, often the first presentation of disease.

Clinical

History

Symptoms of the hyperthyroidism, the goiter itself, and of comorbid conditions are present. The symptoms may be present for weeks, months, or even years before diagnosis.

The hyperthyroid symptoms may be multisystemic or predominate in a single organ system and mask the correct diagnosis in this manner. Many symptoms are adrenergic in origin and may be misdiagnosed as an anxiety disorder.

Elderly patients may have no adrenergic symptoms and present as weight loss (malignancy), atrial fibrillation (cardiac), or apathy (depression), and this presentation is referred to as apathetic thyrotoxicosis.

The presenting symptoms may be modified by preexisting medical or psychiatric disorders, which may be modified or worsened. Symptoms are described below.

Hypermetabolism with heat generation and protein catabolism - Weight loss with good appetite, heat intolerance, sweating, muscle weakness (proximal more than distal), osteoporosis
Adrenergic - Palpitations, tremor, emotional lability, insomnia, restlessness, hyperdefecation
Other - Gynecomastia, lighter menses, insomnia, decreased concentration, fatigue, shortness of breath on exertion, and decreased exercise tolerance
Goiter - May be mildly tender, may have difficulty swallowing if large
Associated oculopathy (clinically present in about 25% of cases) - Tearing, pain, puffiness, grittiness, double vision, prominent appearance, rarely visual loss

Physical

General physical examination findings may include restless appearance, evidence of weight loss, pruritus, palmar erythema, and onycholysis of the finger nails.

Hypermetabolism with protein catabolism - Warm hands, often with heat radiation, velvety skin, proximal muscle weakness in the arms and legs compared with distal muscle strength
Hyperadrenergic - Bounding and fast pulse, wide pulse pressure with higher systolic and lower diastolic blood pressure, active precordium and abdominal aorta to palpation; lid retraction (upper eyelid more than halfway from pupil to top of iris) and lid lag or globe lag, tremor of fingers, brisk reflexes
Organ decompensation - Atrial fibrillation, congestive heart failure, jaundice
Oculopathy - Periorbital puffiness, chemosis, conjunctival redness, proptosis (sclera visible below iris), double vision with eye movements, loss of color vision (rare), or papilledema (rare)
Thyroid gland - Mildly enlarged (but may be normal in size, many times normal in size, or difficult to palpate); smooth, rubbery firm in texture; nontender or mildly tender; systolic bruit on auscultation
Miscellaneous - Pretibial myxedema (uncommon), rare may be finger clubbing, diffuse lymphadenopathy, and splenomegaly

Causes

Diffuse toxic goiter and its hyperthyroidism are caused by TSH-receptor stimulating antibodies. Although the exact cause is not understood, it has been suggested that there is a genetic lack of suppressor T cells that results in the unregulated production of the antibody, resulting in the autoimmune disease. The antibody may pass the placenta and result in fetal and neonatal hyperthyroidism.

As with most such disorders, usually a combination of genetic and environmental factors is present. The familial association indicates a strong genetic factor. Predisposing factors include genetic susceptibility (including HLA factors); female gender; mental stress; viral infection; surgery; postpartum state; iodine administration; drugs such as lithium and iodine-containing agents, such as amiodarone, interferons and interleukins, and antiretroviral agents.

Associated ophthalmopathy is not well understood, but it is a related but separate autoimmune disorder directed toward the extraocular muscles. It may run a course similar to or different from the hyperthyroidism. Smoking is an environmental aggravating factor. The presence and degree of clinical ophthalmopathy does correlate with the degree of elevation of the anti-TSH receptor antibodies.

Dermopathy (pretibial myxedema) may be brought on or aggravated by local trauma.

Differential Diagnoses

Workup

Laboratory Studies

If hyperthyroidism due to diffuse toxic goiter is suspected after history and physical examination, the following should be performed:
- Serum TSH (sensitive or third-generation assay): Levels suppressed below normal indicate the need for more tests. Normal serum TSH level rules out this diagnosis.
- Serum free thyroxin (T4), or equivalent test, that compensates for any changes in thyroid-binding globulin. If levels are elevated, then hyperthyroidism is diagnosed. Levels will be in the normal range in about 5% of cases.
- If free thyroxin is normal, then obtain total or free serum triiodothyronine (T3) level. If levels are elevated, then hyperthyroidism is diagnosed. If levels are normal, then subclinical hyperthyroidism is present.
- The presence of ophthalmopathy indicates the diagnosis, and no more diagnostic testing is needed regarding the cause of the hyperthyroidism.
- Serum anti-TSH receptor antibodies measurements can be obtained. These antibodies are present in more than 90% of cases of diffuse toxic goiter, depending on the assay.
- An alternative test is radioiodine uptake. It will separate diffuse toxic goiter (elevated or normal uptake) from the hyperthyroid phase of thyroiditis (suppressed uptake). If the hyperthyroid symptoms have been present for more than 4 months, then thyroiditis is not the cause. This test is contraindicated in women who are pregnant or breastfeeding.
- An elevated or normal uptake may be found with a single nodular goiter and a multinodular goiter. These may be separated from diffuse toxic goiter by the absence of anti-TSH receptor antibodies, clinical examination, or thyroid scan (technetium-99m or I-123) or ultrasonography.
- Concomitant presence of Hashimoto thyroiditis may be detected by serum antithyroid antibodies (anti-TPO or thyroperoxidase).
- If confirmation of oculopathy is needed, then orbital CT or MRI may be performed.
Diffuse toxic goiter would have a suppressed serum TSH level, elevated serum free thyroxin level (or T3 if needed), elevated titer of anti-TSH receptor antibodies, or elevated radioiodine uptake. No further testing is needed.
Consideration of complications: ECG should be performed if arrhythmia is suspected; liver function tests may be indicated.
Consideration of associated disorders: If clinical suspicion, screen for adrenal insufficiency, type 1 diabetes, gonadal failure, other autoimmune disease (eg, pernicious anemia, rheumatoid arthritis, immune thrombocytopenic purpura). Concomitant Hashimoto thyroiditis may have an effect on spontaneous resolution or progression to a hypothyroid state.
Drugs that may alter T4 laboratory results include anabolic steroids, androgens, estrogens, heparin, iodine, phenytoin, rifampin, salicylates, and thyroxine/triiodothyronine.

Treatment

Medical Care

Even though the natural history of diffuse toxic goiter is to possibly spontaneously remit (and perhaps later relapse), or even progress into hypothyroidism, observation without intervention, even in minimally symptomatic people, is not recommended. The risk of bone loss and atrial fibrillation occur, especially in older women and men, even in subclinical cases.

The goals of therapy are to resolve hyperthyroid symptoms and to restore the euthyroid state.

Each therapeutic choice has advantages and disadvantages, so treatment should be individualized. Patient input into the treatment choice is important and must be discussed and considered.

Therapy may be by subtotal thyroidectomy, administration of radioiodine, antithyroid drugs, or a combination of these. In North America, radioiodine is the most common treatment and is available for all ages. Adjunctive symptomatic therapy, such as beta-blockers, may help adrenergic symptoms. Nonsurgical therapy occurs in the outpatient setting. Surgical therapy requires first normalization of the hyperthyroid state by medication.

Cardiac decompensation or arrhythmias may require hospitalization.

Thyroid storm is a rare emergency requiring intensive care support and therapy.

Surgical Care

Subtotal thyroidectomy may be considered if it is the choice of the patient, second trimester of pregnancy, failure (resistance or intolerance) of drug therapy, or poor compliance to drug therapy. Risks are low with experienced surgeons but include anesthetic risks, hemorrhage, hypoparathyroidism, and vocal cord paralysis. Patients should be made euthyroid prior to surgery to minimize anesthetic risks, cardiovascular/hemodynamic complications, and risk of thyroid storm. If normalizing with antithyroid drugs is not possible, then beta-blockers and potassium iodide 4 drops/day for 10 days will decrease vascularity of the thyroid gland.

Consultations

Oculopathy usually requires ophthalmologic consultation, and dermopathy may require dermatologic consultation.

Diet

Diet must include caloric intake to meet the energy expenditure of the hypermetabolism. High iodine-containing substances, such as kelp, should be avoided.

Activity

Physical activity is limited by the presence of symptoms, until recovery occurs. Usually, shortness of breath on exertion, fatigue, and palpitations are the limiting symptoms.

Medication

No standard treatment protocols exist; individualization of treatment based on clinical experience is protocol. Patient preference after informed consent affects all therapeutic decisions.

Beta-blockers

Beta-blockers are used if symptomatic tremor or palpitations require their use. They may be used even as investigation is ongoing because they have no effect on thyroid gland function, but they block the beta-adrenergic peripheral manifestations of the hyperthyroid state. Propranolol has an effect in decreasing the peripheral conversion of T4 to T3, but this is of unknown clinical significance with the usual doses. The dose may be decreased and then stopped when the euthyroid state occurs. They should not be used in the presence of bronchospasm, even the beta1-selective agents. Calcium channel blockers may be substituted.

Thionamides

Thionamide drugs, propylthiouracil (PTU) and methimazole (MTZ), inhibit hormonogenesis within the thyroid gland. PTU has an effect in decreasing the peripheral conversion of T4 to T3, but this is of unknown added clinical significance. Other than in pregnancy and breastfeeding, MTZ has advantages over PTU by a longer half-life with once-a-day dosing, and possibly more rapid return to the euthyroid state. Although rare, agranulocytosis, lupuslike vasculitis, and hepatitis are more commonly associated with PTU than with MTZ. Agranulocytosis occurs in less that 0.1% of cases but is unpredictable; it may occur at any time. Routine monitoring of WBC count is not useful. Should any infection occur, such as a sore throat, the WBC count should then be measured. Discontinuation of the drug results in a rise of WBC within a few days.

Granulocyte colony-stimulating factor may need to be administered. Skin rash may perhaps be more common with MTZ; incidence is about 3%, and itusually occurs within the first few weeks of therapy. Methimazole is the drug of choice.¹

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)²:

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.

Monitor the serum thyroid indices monthly until euthyroid, and then the dose of the drug may be decreased for maintenance. The lowest dose needed to maintain the euthyroid state is then used for long-term therapy.

Normalization of thyroid function with these drugs must occur for some time, at least 6 months and perhaps for 1-2 years, to maximize the remission rate after drug discontinuation. Despite this, the relapse rate is 50-70%, usually within the first few weeks or months, but occasionally after a few years. Remission is weakly predicted by a short duration of symptoms, age younger than 40 years, minimal enlargement of the thyroid gland, and concomitant presence of Hashimoto thyroiditis.

Relapse after discontinuation of the drug requires a decision regarding radioiodine therapy or surgery for more definitive therapy, or return to the antithyroid drug. Although general practice is not to use these drugs long-term, there is no reason why this cannot occur, if that is what the patient chooses.

Iodine

In severe cases, such as thyroid storm, iodine in the form of potassium iodide (SSKI) 10 drops twice a day or iopanoic acid 1-3 g/d may be given. They inhibit the release of thyroxin from the gland and inhibit peripheral conversion of T4 to T3. They help render a euthyroid state more rapidly in response to antithyroid drugs, or prepare for surgery, but will eliminate the use of radioiodine for many months due to expansion of the iodine pool and thus decrease the delivery of radioiodine to the thyroid gland.

Radioiodine

Oral administration of I 131 is incorporated into the thyroid follicular cells, and the beta emission results in cell destruction and glandular fibrosis. The effect is seen in 1 and a half to 4 months. Off medications, the thyroid hormone levels become normal (requiring continued monitoring), fall below normal (requiring thyroid hormone replacement therapy, likely for life), or remain elevated (requiring another administration of radioiodine). In those becoming euthyroid, the chance every year of becoming hypothyroid due to ongoing disease in the gland is 5%; occasionally, hyperthyroidism may reoccur. The usual dose is 6-8 mCi. The dose is adjusted based on size of the thyroid gland, age of the patient, and severity of the clinical picture. Resistance is increased by age older than 40 years, large goiters, prior therapy with PTU, and nodularity (not seen with diffuse toxic goiter). Recent reviews confirm the safety of the use of radioiodine.³

Radioiodine therapy is not used in clinically severe hyperthyroidism or thyroid storm until the hyperthyroid state is medically controlled.

Because of transplacental transfer and lactation transfer, it is contraindicated in women who are pregnant or breastfeeding. For the theoretical ovarian exposure, conception in treated women is empirically discouraged for 3-6 months.

It may be administered to children, if clinically indicated. Long-term safety data in children are not available.

Worsening of the hyperthyroid state may occur after radioiodine therapy due to release of prestored hormone. Gland tenderness and swelling is uncommon and may be treated with nonsteroidal anti-inflammatory drugs (NSAIDs) (not aspirin), and they rarely require steroid administration.

Radioiodine administration has been associated with worsening or progression of symptomatic ophthalmopathy. Either radioiodine is avoided in very symptomatic individuals or corticosteroids (prednisone 0.5 mg/kg) are used beginning the day after the radioiodine administration for 1-3 months, or they are administered if any worsening of the ophthalmopathy occurs after radioiodine administration. Cessation of smoking and avoidance of hypothyroidism also help the course of ophthalmopathy.

The return to the euthyroid state, regardless of therapy, is best monitored by serum free thyroxin, or its equivalent, because the pituitary is suppressed and TSH secretion may remain low for some time after a normal or hypothyroid state occurs. Relapse from a euthyroid state to hyperthyroidism is first monitored by new suppression of the serum TSH, and often the serum T3 then increases above normal before the serum T4 increases above normal.

Pregnancy and breastfeeding

Pregnancy often has an effect on improving the immunologic disease state during the pregnancy and then often relapses following delivery. The treatment of choice is PTU, which has less placental transfer than MTZ. Rare congenital anomalies reported with MTX (eg, aplasia cutis) are even less associated with PTU. Overall, the congenital abnormality rate with these drugs is similar to background normal rate. MTZ may be used if a problem exists with PTU.

The goal is to keep the free thyroxin in the upper part of normal to minimize fetal drug exposure. Monthly monitoring of serum free thyroxin usually allows the dose of PTU to be decreased and often discontinued in the third trimester. Both PTU and MTZ may be used in breastfeeding mothers. A small amount of drug does enter the milk, but neonatal thyroid levels generally remain normal. PTU and MTZ are not contraindicated in pregnancy or lactation.

Antithyroid agents

These agents may either inhibit hormonogenesis within the thyroid gland or inhibit release of thyroid hormone from the gland.

Propylthiouracil (PTU)

Actively transported into the thyroid gland and inhibits incorporation of iodine to thyroid hormones, and inhibits peripheral conversion of T4 to T3. Drug recommended in pregnancy and lactation with dose adjustment to minimum needed. Laboratory monitoring of free T4 to adjust dose therapy. The serum TSH may lag behind the changes in free T4. Long-term experience with this drug.

Dosing

Adult

Not first-line agent
200-400 mg/d PO divided q8-12h initially, then 50-300 mg/d PO divided bid; minimize dose needed to maintain euthyroid state

Pediatric

Not first-line agent
5-7 mg/kg/d PO divided tid, daily maintenance dose (one half to two thirds of initial dose) PO divided bid

Interactions

Has activity against vitamin K; may potentiate action of oral anticoagulants

Contraindications

Documented hypersensitivity; liver impairment; pediatric patients (unless allergic or intolerant to methimazole and no other treatment is an option)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Warn patient of common adverse effects (eg, skin rash) and rare but severe adverse effect, agranulocytosis (fever and sore throat); monitor TFTs at intervals and use lower maintenance dose once TSH level rises; warn of relapse of hyperthyroidism after drug discontinuation, and monitor patient accordingly
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)

Actively transported in thyroid gland and inhibits thyroid synthesis by preventing oxidation of trapped iodine. Ten times more potent than PTU, and once-a-day dose is effective. Euthyroid state is achieved in 4-6 wk, and maintenance treatment continued for 12-24 mo. Relapse may be observed 1-6 mo after stopping therapy, occasionally later.
Less desirable than propylthiouracil in pregnancy and lactation but may be used if propylthiouracil cannot be used.

Dosing

Adult

10-40 mg PO qd; decrease dose once euthyroid; minimize dose needed to maintain euthyroid state

Pediatric

0.4 mg/kg/d PO divided tid initially, 0.2 mg/kg/d PO divided tid maintenance; not to exceed 30 mg qd

Interactions

Has activity against vitamin K; may potentiate action of oral anticoagulants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Rashes occur in about 3%; agranulocytosis is a rare but severe complication; measure WBC if sore throat or fever occurs; monitor TFTs during therapy, and adjust dose once patient is euthyroid

Lugol solution (Pima, Thyro-Block)

Inhibits thyroid hormone secretion. Contains 8 mg of iodide per gtt. May be mixed with juice or water for intake.
May decrease thyroid gland secretion and vascularity for a short time, such as 2 wk; may be used in severe cases of hyperthyroidism, such as thyroid storm, or to prepare patient for thyroidectomy

Dosing

Adult

4-10 gtt (1 mL) PO q8h

Pediatric

Administer as in adults

Interactions

Increases lithium toxicity by inducing additive hypothyroid effects

Contraindications

Documented hypersensitivity; tuberculosis; bronchitis; pulmonary edema; hyperkalemia; renal failure

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Prolonged use may result in hypothyroidism; caution in renal failure or GI obstruction

Supersaturated potassium iodide (SSKI)

Contains 50 mg of iodide per drop. May be mixed with juice or water for ingestion. Inhibits thyroid hormone release.

Dosing

Adult

1-5 gtt PO q8h

Pediatric

Administer as in adults

Interactions

Increases lithium toxicity by producing additive hypothyroid effects

Contraindications

Documented hypersensitivity; tuberculosis; pulmonary edema; bronchitis; hyperkalemia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Prolonged use may result in hypothyroidism; caution in renal failure or GI obstruction

Corticosteroids

These agents have profound and varied metabolic effects.

Dexamethasone (Decadron)

Steroids block peripheral conversion of T4 to T3. Used as adjunct in management of thyroid storm and symptomatic progressive Graves ophthalmopathy.

Dosing

Adult

0.5-2 mg PO/IV q6h

Pediatric

Administer as in adults

Interactions

Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; decreases effects of salicylates and vaccines used for immunization

Contraindications

Documented hypersensitivity; active bacterial or fungal infection

Precautions

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

Increased risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use

Radiopharmaceuticals

These agents are used to destroy thyroid cells.

Radioiodine (I-131)

Agent of choice because it is selectively taken up by the thyroid gland. Causes dysfunction or death of thyroid cells over time. Long-term experience suggests good safety profile.

Dosing

Adult

Dosage is calculated based on size of goiter and percentage of uptake; usual dose is 5-8 mCi PO; may increase dose if clinically indicated
Repeat administration occasionally needed

Pediatric

Not established

Interactions

None reported; if iodine has been administered to patient, such as contrast agents, radioiodine will lose effectiveness until iodine pool has returned to normal over a few months

Contraindications

Documented hypersensitivity; pregnant or lactating patients; uncontrolled thyroid storm/crisis

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Women of childbearing age; latent period can last 3 wk to 3 mo; beta-blockers are used adjunctively to suppress symptoms; hypothyroidism occurs in more than 50% of patients during first year and occurs in 2-3% each year thereafter; risk of worsening ophthalmopathy can be reduced by treatment with glucocorticoid 1 day after administration of radioiodine; administer pregnancy test before treatment begins, and advise patient to use contraception for the first 6 mo after treatment

Beta-adrenergic receptor blockers

Relief of adrenergic symptoms, especially cardiac and neurologic. Propranolol blocks peripheral conversion of T4 to T3, but this is of unknown clinical significance.

Propanolol (Inderal)

Nonselective beta-adrenergic receptor blocker. Also blocks peripheral conversion of T4 to T3. Used along with antithyroid drugs, before and after radioiodine treatment. Useful in thyroid crisis/storm, or in cardiac complications such as atrial fibrillation. Oral or intravenous use controls cardiac and psychomotor manifestations within minutes. Continue until euthyroid state is achieved.

Dosing

Adult

40-80 mg PO q6h, long-acting formulations 80 mg q12h

Pediatric

2-4 mg/kg/d PO divided bid

Interactions

Has synergistic effect with calcium channel blockers; barbiturate, aluminium salts, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease plasma levels and possibly pharmacologic effect; MAOIs, hydralazine, loop diuretics, and haloperidol may increase metoprolol level; severe hypotension has been reported with haloperidol

Contraindications

Documented hypersensitivity; cardiogenic shock; sinus bradycardia; second- and third-degree heart block; congestive heart failure; bronchial asthma

Precautions

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

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Pregnancy category D in second and third trimesters of pregnancy; liver and renal disease; may mask signs of hypoglycemia; abrupt withdrawal may worsen symptoms of hyperthyroidism; withdraw drug slowly when euthyroid and monitor closely

Follow-up

Further Inpatient Care

Hospitalization is rarely necessary. Severe disease with cardiac or other organ compensation, or thyroid storm may require more intense and controlled therapy.
Complications, such as agranulocytosis, may need specialized hospital care.
Thyroidectomy, if uncomplicated, requires a short hospital stay from 1-3 days.

Further Outpatient Care

Regardless of the therapy used, long-term follow-up is needed to monitor thyroid status, especially with a high risk of becoming hypothyroid in the near and distant future or relapse again into hyperthyroidism.
Ophthalmopathy runs its own course, independent of the thyroid course. Although generally benign, it may become symptomatic years after the thyroid status has been rendered normal.

Deterrence/Prevention

Cessation of smoking has a beneficial effect on the course of ophthalmopathy.
The strong familial nature dictates that first-degree relatives, especially siblings and children, be aware of the increased risk of developing this or associated disorders. Routine testing is not recommended, but consideration for this risk is needed with new symptom development.
Associated autoimmune disease in other glands is uncommon but is of increased incidence and may clinically occur at presentation or in the near or distant future. New symptoms dictate consideration for these.

Patient Education

For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

Miscellaneous

Medicolegal Pitfalls

Missed or delayed diagnosis in patients with symptoms dominant in one system
Failure to recognize the different presentation in elderly patients
Lack of informed consent regarding therapeutic choices, advantages, and risks of each
Inadequate monitoring of the disease process and of its treatment
Premorbid conditions may modify the symptoms and may continue to be symptomatic even after treatment of the hyperthyroid state. Patient education is important here.
Failure to do a pregnancy test before administration of radioiodine or to counsel the patient not to get pregnant soon after

References

Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease. J Clin Endocrinol Metab. Jun 2007;92(6):2157-62. Epub 2007 Mar 27. [Medline].
FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU). US Food and Drug Administration. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm. Accessed June 3, 2009.
Vanderpump M. Cardiovascular and cancer mortality after radioiodine treatment of hyperthyroidism. J Clin Endocrinol Metab. Jun 2007;92(6):2033-5. [Medline].
Cawood T, Moriarty P, O'Shea D. Recent developments in thyroid eye disease. BMJ. Aug 14 2004;329(7462):385-90. [Medline].
Cooper DS. Antithyroid drugs. N Engl J Med. Mar 3 2005;352(9):905-17. [Medline].
deGroot LJ, Larsen RP, Hennemann G. The Thyroid and Its Diseases. 1996;371-489.
Franklyn JA, Maisonneuve P, Sheppard M, et al. Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study. Lancet. Jun 19 1999;353(9170):2111-5. [Medline].
Mestman JH. Hyperthyroidism in pregnancy. Best Pract Res Clin Endocrinol Metab. Jun 2004;18(2):267-88. [Medline].
Sarlis NJ, Gourgiotis L. Thyroid emergencies. Rev Endocr Metab Disord. May 2003;4(2):129-36. [Medline].
Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. Dermopathy of Graves' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab. Feb 2002;87(2):438-46. [Medline].
Weetman AP. Graves' disease. N Engl J Med. Oct 26 2000;343(17):1236-48. [Medline].

Keywords

Graves’ disease, Graves disease, Basedow disease, diffuse toxic goiter, thyroid hormone, overproduction of thyroid hormone, Hashimoto’s thyroiditis, Hashimoto thyroiditis, autoimmune thyroid disease, thyroid gland, hyperthyroidism, apathetic thyrotoxicosis

Contributor Information and Disclosures

Author

Coauthor(s)

Oluyinka S Adediji, MD, Consulting Staff, Department of Adult and General Medicine, Health Services Incorporated, Montgomery, Alabama
Oluyinka S Adediji, MD is a member of the following medical societies: American College of Physicians and American Medical Association
Disclosure: Nothing to disclose.

Paul Killian, MD, Former Chief of Endocrine Service, Former Associate Professor, Department of Internal Medicine, Harlem Hospital, Harlem Hospital Center
Paul Killian, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Diabetes Association, and Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Steven R Gambert, MD, MACP, Chairman, Department of Medicine, Physician-in-Chief, Sinai Hospital of Baltimore; Professor of Medicine, Program Director, Internal Medicine Program, Johns Hopkins University School of Medicine
Steven R Gambert, MD, MACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American Geriatrics Society, Association of Professors of Medicine, Endocrine Society, and Gerontological Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Yoram Shenker, MD, Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison
Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

Further Reading

eMedicine Specialties > Endocrinology > Thyroid

Goiter, Diffuse Toxic

Introduction

Background

Pathophysiology

Frequency

United States

International

Mortality/Morbidity

Race

Sex

Age

Clinical

History

Physical

Causes

Differential Diagnoses

Other Problems to Be Considered

Workup

Laboratory Studies

Treatment

Medical Care

Surgical Care

Consultations

Diet

Activity

Medication

Antithyroid agents

Propylthiouracil (PTU)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Methimazole (Tapazole)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Lugol solution (Pima, Thyro-Block)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Supersaturated potassium iodide (SSKI)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Corticosteroids

Dexamethasone (Decadron)

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Radiopharmaceuticals

Radioiodine (I-131)

Dosing

Adult

Pediatric

Interactions