Hyperthyroidism: Diagnosis and Treatment

 

Am Fam Physician. 2016 Mar 1;93(5):363-370.

  Patient information: See related handout on overactive thyroid gland (hyperthyroidism), written by the author of this article.

  Related letter: Hyperthyroidism Caused by Thyroid Hormone Therapy

Author disclosure: No relevant financial affiliations.

Hyperthyroidism is an excessive concentration of thyroid hormones in tissues caused by increased synthesis of thyroid hormones, excessive release of preformed thyroid hormones, or an endogenous or exogenous extrathyroidal source. The most common causes of an excessive production of thyroid hormones are Graves disease, toxic multinodular goiter, and toxic adenoma. The most common cause of an excessive passive release of thyroid hormones is painless (silent) thyroiditis, although its clinical presentation is the same as with other causes. Hyperthyroidism caused by overproduction of thyroid hormones can be treated with antithyroid medications (methimazole and propylthiouracil), radioactive iodine ablation of the thyroid gland, or surgical thyroidectomy. Radioactive iodine ablation is the most widely used treatment in the United States. The choice of treatment depends on the underlying diagnosis, the presence of contraindications to a particular treatment modality, the severity of hyperthyroidism, and the patient's preference.

Hyperthyroidism is an excessive concentration of thyroid hormones in tissues causing a characteristic clinical state. In the United States, the overall prevalence of hyperthyroidism is 1.2%, and the prevalences of overt hyperthyroidism and subclinical hyperthyroidism are 0.5% and 0.7%, respectively.1

 Enlarge     Print

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

The choice of treatment modality for hyperthyroidism caused by overproduction of thyroid hormones depends on the patient's age, symptoms, comorbidities, and preference.

C

25, 26

The diagnostic workup for hyperthyroidism includes measuring thyroid-stimulating hormone, free thyroxine (T4), and total triiodothyronine (T3) levels to determine the presence and severity of the condition, as well as radioactive iodine uptake and scan of the thyroid gland to determine the cause.

C

20, 21

Methimazole (Tapazole) is the preferred antithyroid medication except in the first trimester of pregnancy and in patients with an adverse reaction to the medication.

B

26


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

The choice of treatment modality for hyperthyroidism caused by overproduction of thyroid hormones depends on the patient's age, symptoms, comorbidities, and preference.

C

25, 26

The diagnostic workup for hyperthyroidism includes measuring thyroid-stimulating hormone, free thyroxine (T4), and total triiodothyronine (T3) levels to determine the presence and severity of the condition, as well as radioactive iodine uptake and scan of the thyroid gland to determine the cause.

C

20, 21

Methimazole (Tapazole) is the preferred antithyroid medication except in the first trimester of pregnancy and in patients with an adverse reaction to the medication.

B

26


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

 Enlarge     Print

BEST PRACTICES IN ENDOCRINOLOGY: RECOMMENDATIONS FROM THE CHOOSING WISELY CAMPAIGN

RecommendationSponsoring organization

Do not order multiple tests in the initial evaluation of a patient with suspected thyroid disease. Order TSH, and if abnormal, follow up with additional evaluation or treatment depending on the findings.

American Society for Clinical Pathology

Do not routinely order a thyroid ultrasound in patients with abnormal thyroid function tests if there is no palpable abnormality of the thyroid gland.

The Endocrine Society/American Association of Clinical Endocrinologists


TSH = thyroid-stimulating hormone.

Source: For more information on the Choosing Wisely Campaign, see http://www.choosingwisely.org. For supporting citations and to search Choosing Wisely recommendations relevant to primary care, see http://www.aafp.org/afp/recommendations/search.htm.

BEST PRACTICES IN ENDOCRINOLOGY: RECOMMENDATIONS FROM THE CHOOSING WISELY CAMPAIGN

RecommendationSponsoring organization

Do not order multiple tests in the initial evaluation of a patient with suspected thyroid disease. Order TSH, and if abnormal, follow up with additional evaluation or treatment depending on the findings.

American Society for Clinical Pathology

Do not routinely order a thyroid ultrasound in patients with abnormal thyroid function tests if there is no palpable abnormality of the thyroid gland.

The Endocrine Society/American Association of Clinical Endocrinologists


TSH = thyroid-stimulating hormone.

Source: For more information on the Choosing Wisely Campaign, see http://www.choosingwisely.org. For supporting citations and to search Choosing Wisely recommendations relevant to primary care, see http://www.aafp.org/afp/recommendations/search.htm.

Etiology and Pathogenesis

The common endogenous causes of hyperthyroidism are Graves disease, toxic multinodular goiter, toxic adenoma, and painless thyroiditis (Table 1).19 Graves disease, the most common cause of hyperthyroidism in the United States,2 is an autoimmune disorder in which thyroid-stimulating antibodies activate thyroid-stimulating hormone (TSH) receptors, triggering thyroid hormone synthesis. Risk factors for Graves disease include female sex and personal or family history of an autoimmune disorder.2,3

 Enlarge     Print

Table 1.

Etiology and Pathogenesis of Hyperthyroidism

EtiologyMechanism

Most common causes

Graves disease

Autoimmune process in which antibodies stimulate the TSH receptor leading to overproduction of thyroid hormones

Painless or transient (silent) thyroiditis

Autoimmune destruction of thyroid tissue leading to a release of preformed thyroid hormones

Toxic adenoma (Plummer disease)

Somatic mutation in TSH receptor or Gs alpha gene in a thyroid nodule

Toxic multinodular goiter

Expansion of clonogenic cells with an activating TSH receptor mutation

Less common causes

Drug-induced thyroiditis

Overproduction of thyroid hormones (amiodarone-induced thyrotoxicosis type 1) or release of preformed thyroid hormones (amiodarone-induced thyrotoxicosis type 2, interferon alfa, interleukin-2, or lithium)

Hyperemesis gravidarum

High level of β-hCG stimulates TSH receptors

Postpartum thyroiditis

Variant of painless thyroiditis with the same mechanism, occurring after delivery

Subacute granulomatous (de Quervain) thyroiditis

Painful inflammation of the thyroid gland caused by viral infection, often with fever, triggering a release of preformed thyroid hormones

Rare causes

Factitious thyrotoxicosis

Surreptitious ingestion of thyroid hormones

Metastatic follicular thyroid cancer

Metastasis of functional follicular thyroid cancer

Struma ovarii

Ectopic thyroid tissue in ovarian dermoid tumor produces thyroid hormones

Trophoblastic tumor or a germ cell tumor

Tumor produces β-hCG, which stimulates thyroid TSH receptors

TSH-secreting pituitary adenoma

Tumor secreting large quantities of TSH, and not responding to thyroxine and triiodothyronine feedback


β-hCG = beta human chorionic gonadotropin; TSH = thyroid-stimulating hormone.

Information from references 1 through 9.

Table 1.

Etiology and Pathogenesis of Hyperthyroidism

EtiologyMechanism

Most common causes

Graves disease

Autoimmune process in which antibodies stimulate the TSH receptor leading to overproduction of thyroid hormones

Painless or transient (silent) thyroiditis

Autoimmune destruction of thyroid tissue leading to a release of preformed thyroid hormones

Toxic adenoma (Plummer disease)

Somatic mutation in TSH receptor or Gs alpha gene in a thyroid nodule

Toxic multinodular goiter

Expansion of clonogenic cells with an activating TSH receptor mutation

Less common causes

Drug-induced thyroiditis

Overproduction of thyroid hormones (amiodarone-induced thyrotoxicosis type 1) or release of preformed thyroid hormones (amiodarone-induced thyrotoxicosis type 2, interferon alfa, interleukin-2, or lithium)

Hyperemesis gravidarum

High level of β-hCG stimulates TSH receptors

Postpartum thyroiditis

Variant of painless thyroiditis with the same mechanism, occurring after delivery

Subacute granulomatous (de Quervain) thyroiditis

Painful inflammation of the thyroid gland caused by viral infection, often with fever, triggering a release of preformed thyroid hormones

Rare causes

Factitious thyrotoxicosis

Surreptitious ingestion of thyroid hormones

Metastatic follicular thyroid cancer

Metastasis of functional follicular thyroid cancer

Struma ovarii

Ectopic thyroid tissue in ovarian dermoid tumor produces thyroid hormones

Trophoblastic tumor or a germ cell tumor

Tumor produces β-hCG, which stimulates thyroid TSH receptors

TSH-secreting pituitary adenoma

Tumor secreting large quantities of TSH, and not responding to thyroxine and triiodothyronine feedback


β-hCG = beta human chorionic gonadotropin; TSH = thyroid-stimulating hormone.

Information from references 1 through 9.

Toxic multinodular goiter is the second most common cause of hyperthyroidism in the United States and the most common cause in older persons living in iodine-deficient areas.2 Over time, nodules arise from the frequent replication of clonogenic cells that leads to a somatic activating mutation of TSH receptors.4 A single nodule is called a toxic adenoma (Plummer disease).

In contrast with these three disorders, painless or transient (silent) thyroiditis causes a destruction of thyroid follicles via an autoimmune mechanism and a release of preformed thyroid hormones into the circulation.5 Its clinical presentation is the same as with other causes. In a Danish study, its prevalence among patients with thyrotoxicosis was 0.5%, as evaluated by scintigraphy.6 Painless thyroiditis can be triggered by childbirth (postpartum thyroiditis) or by use of medications such as lithium, interferon alfa, interleukin-2, and amiodarone.7

Gestational hyperthyroidism develops in the first trimester of pregnancy as a result of the stimulatory action of placental beta human chorionic gonadotropin (β-hCG), which shares structural features with TSH, on the thyroid gland.8 β-hCG-mediated hyperthyroidism can occasionally be caused by hyperemesis gravidarum and, rarely, by a gestational trophoblastic tumor.8

Other rare causes of hyperthyroidism are TSH-secreting pituitary adenoma, metastatic follicular thyroid cancer, and struma ovarii.9

Clinical Manifestations

The clinical presentation of hyperthyroidism ranges from asymptomatic to thyroid storm (Table 2).1018 Elevated thyroid hormone levels amplify catecholamine signaling through increased numbers of cell surface beta-adrenergic receptors. The resulting adrenergic symptoms (e.g., palpitations, heat intolerance, diaphoresis, tremor, stare [an appearance of a fixed look due to retraction of eyelids], lid lag, hyperdefecation) are the most common manifestations of hyperthyroidism.10 Hypermetabolism induces weight loss despite an increased appetite. Neuromuscular symptoms include weakness of proximal muscles.11 Psychiatric symptoms range from anxiety to frank psychosis.12 Patients with long-standing untreated hyperthyroidism may develop atrial fibrillation (10% to 15% of patients13,14) or heart failure (5.8% of patients15).

 Enlarge     Print

Table 2.

Signs and Symptoms of Hyperthyroidism

Adrenergic

Palpitations, tachycardia, anxiety, tremor, jitteriness, diaphoresis, heat intolerance, stare, lid lag, hyperdefecation (not diarrhea)

Cardiovascular

Tachycardia, irregular pulse (in atrial fibrillation), dyspnea, orthopnea and peripheral edema (in heart failure)

Cutaneous

Onycholysis (Plummer nails), patchy or generalized hyperpigmentation (especially of the face and neck)

Symptoms pathognomonic for Graves disease: pretibial myxedema (thyroid dermopathy) and thyroid acropachy (clubbing of fingers and toes accompanied by soft-tissue swelling of the hands and feet)

Patchy vitiligo can also be observed in Graves disease

Hypermetabolism

Weight loss in spite of increased appetite, fever (in thyroid storm)

Neuromuscular

Brisk peripheral reflexes with accelerated relaxation phase and weakness of proximal muscles

Neuropsychiatric

Anxiety, rapid and pressured speech, insomnia, psychosis (if hyperthyroidism is severe)

Ocular

Increased lacrimation, incomplete closure of the eyes when sleeping reported by the patient's partner, photophobia, increased eye sensitivity to wind or smoke, grittiness or sensation of a foreign body or sand in the eyes

Symptoms pathognomonic for Graves disease: exophthalmos, periorbital edema, diplopia, blurred vision, reduced color perception


Information from references 10 through 18.

Table 2.

Signs and Symptoms of Hyperthyroidism

Adrenergic

Palpitations, tachycardia, anxiety, tremor, jitteriness, diaphoresis, heat intolerance, stare, lid lag, hyperdefecation (not diarrhea)

Cardiovascular

Tachycardia, irregular pulse (in atrial fibrillation), dyspnea, orthopnea and peripheral edema (in heart failure)

Cutaneous

Onycholysis (Plummer nails), patchy or generalized hyperpigmentation (especially of the face and neck)

Symptoms pathognomonic for Graves disease: pretibial myxedema (thyroid dermopathy) and thyroid acropachy (clubbing of fingers and toes accompanied by soft-tissue swelling of the hands and feet)

Patchy vitiligo can also be observed in Graves disease

Hypermetabolism

Weight loss in spite of increased appetite, fever (in thyroid storm)

Neuromuscular

Brisk peripheral reflexes with accelerated relaxation phase and weakness of proximal muscles

Neuropsychiatric

Anxiety, rapid and pressured speech, insomnia, psychosis (if hyperthyroidism is severe)

Ocular

Increased lacrimation, incomplete closure of the eyes when sleeping reported by the patient's partner, photophobia, increased eye sensitivity to wind or smoke, grittiness or sensation of a foreign body or sand in the eyes

Symptoms pathognomonic for Graves disease: exophthalmos, periorbital edema, diplopia, blurred vision, reduced color perception


Information from references 10 through 18.

Signs that are pathognomonic for Graves disease include orbitopathy, pretibial myxedema (thyroid dermopathy), and thyroid acropachy, which occur in 25%, 1.5%, and 0.3% of patients, respectively.16 Goiters that develop in Graves disease are usually smooth and may have a thrill on palpation or a bruit on auscultation. Single or multiple nodules on palpation raise suspicion for a toxic adenoma or a toxic multinodular goiter, although nonfunctioning thyroid nodules may coexist with a goiter in Graves disease.16

Graves orbitopathy manifests as exophthalmos or periorbital edema, and it can trigger photophobia, excessive lacrimation, increased eye sensitivity to wind or smoke, or a sensation of a foreign body in the eyes. In severe cases, blurred vision, diplopia, or reduced color perception may develop.16 Smoking increases the risk of developing Graves orbitopathy (odds ratio = 3.7).17

Pretibial myxedema, a less common finding, develops from fibroblast activation and manifests as swelling over the tibiae with the skin assuming a peau d'orange (orange peel) appearance.18 Thyroid acropachy, an uncommon sign, is the clubbing of fingers and toes with soft-tissue swelling of the hands and feet.19 Other skin manifestations of Graves disease include patchy hyperpigmentation and vitiligo.19

Laboratory and Radiographic Assessment

Clinical suspicion of hyperthyroidism should prompt laboratory testing (Figure 12023). Some physicians first order a TSH test, which has the highest sensitivity and specificity for hyperthyroidism, and then subsequently obtain free thyroxine (T4) and total triiodothyronine (T3) levels (free T3 assays are poorly validated1) if the TSH level is low. Others prefer to order all three tests if hyperthyroidism is suspected to make the diagnosis more efficiently. Many laboratories perform reflex free T4 testing if TSH is suppressed. Table 3 lists patterns of thyroid function tests in hyperthyroidism.20,21 The serum level of thyroid-stimulating immunoglobulins or TSH-receptor antibodies helps distinguish Graves disease from other causes of hyperthyroidism in patients who lack signs pathognomonic of Graves disease and have a contraindication to radioactive iodine uptake and scan.

 Enlarge     Print

Diagnostic Workup of Hyperthyroidism

Figure 1.

Algorithm for the diagnostic workup of hyperthyroidism. (T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.)

Information from references 20 through 23.

Diagnostic Workup of Hyperthyroidism


Figure 1.

Algorithm for the diagnostic workup of hyperthyroidism. (T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.)

Information from references 20 through 23.

THYROID FUNCTION TEST RESULTS SIMULATING HYPERTHYROIDISM

Excess estrogen from pregnancy or estrogen therapy leads to elevated levels of thyroxine-binding globulin, which manifests as elevated total T4 and T3 levels while TSH and free T4 levels remain normal (Table 3).20,21 These findings do not indicate hyperthyroidism and require no treatment.21

 Enlarge     Print

Table 3.

Thyroid Function Test Results in Hyperthyroidism and in Conditions Simulating Hyperthyroidism

ConditionTSHTotal T4Free T4Total T3

Overt hyperthyroidism

Suppressed

Elevated

Elevated

Elevated

Subclinical hyperthyroidism*

Suppressed or low

Normal

Normal

Normal

TSH-secreting pituitary adenoma

Normal or elevated

Elevated

Elevated

Elevated

Estrogen excess

Normal

Elevated

Normal

Elevated

Nonthyroidal illness syndrome

Low

Normal or mildly decreased

Normal

Low (and reverse T3 is elevated)

Glucocorticoid and/or dopamine therapy

Low

Normal

Normal

Normal


note: Suppressed TSH is < 0.1 mIU per mL; low TSH is 0.1 to 0.4 mIU per mL.

T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

*—Subclinical hyperthyroidism does not refer to the absence of signs and symptoms.

Information from references 20 and 21.

Table 3.

Thyroid Function Test Results in Hyperthyroidism and in Conditions Simulating Hyperthyroidism

ConditionTSHTotal T4Free T4Total T3

Overt hyperthyroidism

Suppressed

Elevated

Elevated

Elevated

Subclinical hyperthyroidism*

Suppressed or low

Normal

Normal

Normal

TSH-secreting pituitary adenoma

Normal or elevated

Elevated

Elevated

Elevated

Estrogen excess

Normal

Elevated

Normal

Elevated

Nonthyroidal illness syndrome

Low

Normal or mildly decreased

Normal

Low (and reverse T3 is elevated)

Glucocorticoid and/or dopamine therapy

Low

Normal

Normal

Normal


note: Suppressed TSH is < 0.1 mIU per mL; low TSH is 0.1 to 0.4 mIU per mL.

T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

*—Subclinical hyperthyroidism does not refer to the absence of signs and symptoms.

Information from references 20 and 21.

Patients with critical or acute illness often develop the nonthyroidal illness syndrome manifesting as mildly decreased TSH levels (0.1 to 0.4 mIU per mL) and normal or mildly decreased T4 levels. In contrast to subclinical hyperthyroidism, the T3 level is usually low and the reverse T3 level is elevated. This condition resolves spontaneously when the patient recovers from the acute illness.21

Exogenous glucocorticoids or dopamine may cause a mild decrease of TSH levels, a situation often occurring in the intensive care unit. Total T4, total T3, and free T4 levels remain normal. TSH levels return to normal after these medications are discontinued.21

RADIOACTIVE IODINE UPTAKE AND THYROID SCAN

A radioactive iodine uptake test and thyroid scan help determine the cause of hyperthyroidism (Table 4). Uptake is the percentage of an iodine 123 (I-123) tracer dose taken up by the thyroid gland, ranging from 15% to 25% at 24 hours. The uptake is very low (0% to 2%) in patients with thyroiditis and high in patients with Graves disease, a toxic adenoma, or a toxic multinodular goiter.23,24

 Enlarge     Print

Table 4.

Patterns Observed in Radioactive Iodine Uptake and Scan

ConditionRadioactive iodine uptake (normal = 15% to 25%)Radiotracer distribution in the thyroid gland

Graves disease

High

Homogeneous

Toxic adenoma

High

Iodine 123 is concentrated in one spot

Toxic multinodular goiter

High

Iodine 123 is concentrated in multiple spots

Thyroiditis

Low

Not applicable

Table 4.

Patterns Observed in Radioactive Iodine Uptake and Scan

ConditionRadioactive iodine uptake (normal = 15% to 25%)Radiotracer distribution in the thyroid gland

Graves disease

High

Homogeneous

Toxic adenoma

High

Iodine 123 is concentrated in one spot

Toxic multinodular goiter

High

Iodine 123 is concentrated in multiple spots

Thyroiditis

Low

Not applicable

The thyroid scan shows the distribution of radiotracer in the gland. A homogeneous distribution indicates Graves disease, but accumulation of I-123 in one area points to a toxic adenoma (Figure 2) or in multiple areas to a toxic multinodular goiter.23,24

 Enlarge     Print

Figure 2.

Toxic adenoma on radioactive iodine scan.


Figure 2.

Toxic adenoma on radioactive iodine scan.

Ultrasonography is sometimes used as a cost-effective and safe alternative to radioactive iodine uptake and scan. It is the primary imaging modality used during pregnancy, lactation, and in amiodarone-induced thyrotoxicosis.24

Treatment

Regardless of the cause of hyperthyroidism, the adrenergic symptoms are controlled by beta blockers (Table 5).2528 Propranolol has the theoretical advantage of also inhibiting 5′-monodeiodinase, thus blocking peripheral conversion of T4 to T3.25 The choice of treatment modality for hyperthyroidism caused by overproduction of thyroid hormones depends on the patient's age, symptoms, comorbidities, and preference.25,26

 Enlarge     Print

Table 5.

Pharmacologic Treatment of Hyperthyroidism

First-line agentsDosageAdverse effectsCommentsCost*

Beta blockers

Atenolol

25 to 100 mg orally once per day

Exacerbation of congestive heart failure

Selective beta1 blocker; safer than propranolol in asthma or chronic obstructive pulmonary disease; once-daily dosing improves compliance

$5

Propranolol

Immediate release: 10 to 40 mg orally every eight hours

Extended release: 80 to 160 mg orally once per day

Exacerbation of congestive heart failure or asthma

Decreases T4 to T3 conversion; nonselective beta blocker

$20 to $84 for immediate release

$76 to $152 for extended release

Antithyroid medications

Methimazole (Tapazole)

5 to 120 mg orally per day (can be given in divided doses)

Dose-related agranulocytosis

Contraindicated in the first trimester of pregnancy

$20 to $100 ($45 to $900)

Propylthiouracil

50 to 300 mg orally every eight hours

Agranulocytosis not related to dose; liver dysfunction; rash, including ANCA-associated vasculitis

Drug of choice in the first trimester of pregnancy; carries a higher risk of liver failure than methimazole

$60 to $400

Radioactive iodine

Usually 10 to 30 millicurie, depending on uptake and the size of the thyroid gland

May aggravate hyperthyroidism in the early posttreatment period

Causes hypothyroidism three to six months after treatment

Contraindicated in severe Graves orbitopathy and in patients who are pregnant or nursing

Ancillary agents

Cholestyramine

1 to 2 g orally twice per day

Constipation or diarrhea; bloating

Binds thyroid hormones in the intestine and thus increases fecal excretion

$50

Glucocorticoids

Prednisone: 20 to 40 mg orally per day for up to four weeks

Hydrocortisone: 100 mg intravenously every eight hours with subsequent taper

Hyperglycemia in patients with diabetes mellitus, otherwise few short-term adverse effects

Used in severe hyperthyroidism or thyroid storm to reduce T4 to T3 conversion; also used in severe subacute thyroiditis

Prednisone: $20

Hydrocortisone: NA

Nonsteroidal anti-inflammatory drugs

Depends on the specific agent

Nephrotoxicity; gastrointestinal bleeding

Treats pain in subacute thyroiditis

Supersaturated potassium iodide

5 drops orally every eight hours

May aggravate hyperthyroidism if given before an antithyroid agent

Give at least one hour after methimazole or propylthiouracil

Do not give before radioactive iodine treatment


ANCA = antineutrophil cytoplasmic autoantibodies; NA = not applicable; T3 = triiodothyronine; T4 = thyroxine.

*—Estimated retail price of one month's treatment based on information obtained at http://www.goodrx.com (accessed November 11, 2015). Generic price listed first; brand price listed in parentheses.

Information from references 25 through 28.

Table 5.

Pharmacologic Treatment of Hyperthyroidism

First-line agentsDosageAdverse effectsCommentsCost*

Beta blockers

Atenolol

25 to 100 mg orally once per day

Exacerbation of congestive heart failure

Selective beta1 blocker; safer than propranolol in asthma or chronic obstructive pulmonary disease; once-daily dosing improves compliance

$5

Propranolol

Immediate release: 10 to 40 mg orally every eight hours

Extended release: 80 to 160 mg orally once per day

Exacerbation of congestive heart failure or asthma

Decreases T4 to T3 conversion; nonselective beta blocker

$20 to $84 for immediate release

$76 to $152 for extended release

Antithyroid medications

Methimazole (Tapazole)

5 to 120 mg orally per day (can be given in divided doses)

Dose-related agranulocytosis

Contraindicated in the first trimester of pregnancy

$20 to $100 ($45 to $900)

Propylthiouracil

50 to 300 mg orally every eight hours

Agranulocytosis not related to dose; liver dysfunction; rash, including ANCA-associated vasculitis

Drug of choice in the first trimester of pregnancy; carries a higher risk of liver failure than methimazole

$60 to $400

Radioactive iodine

Usually 10 to 30 millicurie, depending on uptake and the size of the thyroid gland

May aggravate hyperthyroidism in the early posttreatment period

Causes hypothyroidism three to six months after treatment

Contraindicated in severe Graves orbitopathy and in patients who are pregnant or nursing

Ancillary agents

Cholestyramine

1 to 2 g orally twice per day

Constipation or diarrhea; bloating

Binds thyroid hormones in the intestine and thus increases fecal excretion

$50

Glucocorticoids

Prednisone: 20 to 40 mg orally per day for up to four weeks

Hydrocortisone: 100 mg intravenously every eight hours with subsequent taper

Hyperglycemia in patients with diabetes mellitus, otherwise few short-term adverse effects

Used in severe hyperthyroidism or thyroid storm to reduce T4 to T3 conversion; also used in severe subacute thyroiditis

Prednisone: $20

Hydrocortisone: NA

Nonsteroidal anti-inflammatory drugs

Depends on the specific agent

Nephrotoxicity; gastrointestinal bleeding

Treats pain in subacute thyroiditis

Supersaturated potassium iodide

5 drops orally every eight hours

May aggravate hyperthyroidism if given before an antithyroid agent

Give at least one hour after methimazole or propylthiouracil

Do not give before radioactive iodine treatment


ANCA = antineutrophil cytoplasmic autoantibodies; NA = not applicable; T3 = triiodothyronine; T4 = thyroxine.

*—Estimated retail price of one month's treatment based on information obtained at http://www.goodrx.com (accessed November 11, 2015). Generic price listed first; brand price listed in parentheses.

Information from references 25 through 28.

GRAVES DISEASE

Graves disease requires one of the three treatment options: an antithyroid medication (methimazole [Tapazole] or propylthiouracil), radioactive iodine (I-131) ablation of the thyroid gland, or surgical thyroidectomy. The choice of treatment depends on the benefits vs. risks in a specific clinical situation and on the patient's preference25  (eTable A).

 Enlarge     Print

eTable A.

Benefits and Risks of Graves Disease Treatment Options

Treatment optionsBenefitsRisks

Antithyroid medication (methimazole [Tapazole] or propylthiouracil)

No exposure to radiation or to surgical risks

No permanent hypothyroidism

Propylthiouracil is safe for the fetus in the first trimester of pregnancy

Agranulocytosis, hepatotoxicity (especially with propylthiouracil), rash

Methimazole can cause aplasia cutis and other birth defects in the first trimester of pregnancy

Radioactive iodine ablation

No exposure to potential adverse effects of an antithyroid medication or to surgical risks

Treatment of choice in the United States

Aggravation of Graves orbitopathy, especially in smokers

Permanent hypothyroidism (occurs in most patients)

Radiation exposure

Failure to cure hyperthyroidism if the radioactive iodine dose is insufficient

Risk of Graves disease recurrence even after successful treatment

Contraindicated in pregnancy

Thyroidectomy

No exposure to adverse effects of an antithyroid medication or to radiation

Little chance of Graves disease recurrence

Risk of general anesthesia

Risk of damaging recurrent laryngeal nerve leading to hoarse voice (if damage is unilateral) or of respiratory distress (if damage is bilateral)

Risk of inadvertent damage or removal of parathyroid glands leading to permanent hypoparathyroidism


Information from: Abraham P, Avenell A, Park CM, Watson WA, Bevan JS. A systematic review of drug therapy for Graves' hyperthyroidism. Eur J Endocrinol. 2005;153(4):489–498

Bartalena L. Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol. 2013;9(12):724–734.

Cappelli C, Pirola I, De Martino E, et al. The role of imaging in Graves' disease: a cost-effectiveness analysis. Eur J Radiol. 2008;65(1):99–103.

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. 2007;92(6):2157–2162.

eTable A.

Benefits and Risks of Graves Disease Treatment Options

Treatment optionsBenefitsRisks

Antithyroid medication (methimazole [Tapazole] or propylthiouracil)

No exposure to radiation or to surgical risks

No permanent hypothyroidism

Propylthiouracil is safe for the fetus in the first trimester of pregnancy

Agranulocytosis, hepatotoxicity (especially with propylthiouracil), rash

Methimazole can cause aplasia cutis and other birth defects in the first trimester of pregnancy

Radioactive iodine ablation

No exposure to potential adverse effects of an antithyroid medication or to surgical risks

Treatment of choice in the United States

Aggravation of Graves orbitopathy, especially in smokers

Permanent hypothyroidism (occurs in most patients)

Radiation exposure

Failure to cure hyperthyroidism if the radioactive iodine dose is insufficient

Risk of Graves disease recurrence even after successful treatment

Contraindicated in pregnancy

Thyroidectomy

No exposure to adverse effects of an antithyroid medication or to radiation

Little chance of Graves disease recurrence

Risk of general anesthesia

Risk of damaging recurrent laryngeal nerve leading to hoarse voice (if damage is unilateral) or of respiratory distress (if damage is bilateral)

Risk of inadvertent damage or removal of parathyroid glands leading to permanent hypoparathyroidism


Information from: Abraham P, Avenell A, Park CM, Watson WA, Bevan JS. A systematic review of drug therapy for Graves' hyperthyroidism. Eur J Endocrinol. 2005;153(4):489–498

Bartalena L. Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol. 2013;9(12):724–734.

Cappelli C, Pirola I, De Martino E, et al. The role of imaging in Graves' disease: a cost-effectiveness analysis. Eur J Radiol. 2008;65(1):99–103.

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. 2007;92(6):2157–2162.

Antithyroid Medications. Antithyroid medications are thionamides; they inhibit thyroid peroxidase, blocking the synthesis of T3 and T4. Thionamides can serve as a long-term therapy or as a bridge to I-131 ablation or thyroidectomy, with the goal of normalizing thyroid function and preventing exacerbation of hyperthyroidism after I-131 ablation or avoiding surgical risks associated with uncontrolled hyperthyroidism. Because Graves disease remits in up to 30% of patients treated with thionamides, these medications can be used as the initial treatment, with ablation or thyroidectomy performed if remission does not occur.25,26 Once medical therapy is discontinued, relapse occurs in 30% to 70% of patients, mostly within the first year.27 After discontinuation, thyroid function should be monitored every one to three months for six to 12 months, and the patient should be instructed to contact the physician if symptoms recur.

Because use of propylthiouracil has a higher risk of causing severe liver injury, as highlighted in the U.S. Food and Drug Administration's boxed warning, methimazole is preferred except during the first trimester of pregnancy (can cause birth defects) and in patients with an adverse reaction to methimazole.28,29 For patients using methimazole, the prevalence of agranulocytosis is 0.17%, the incidence of hepatitis is 3.17 per 1,000 person-years, and the incidence of acute hepatic failure is 0.32 per 1,000 person-years.30,31 Patients should be instructed to discontinue medication use and contact their physician if they develop jaundice, acholic stools, dark urine, arthralgias, abdominal pain, nausea, vomiting, fever, or sore throat. A baseline complete blood count (CBC) with differential and a hepatic panel should be obtained before initiating an antithyroid medication. Subsequent routine monitoring of CBC is unnecessary, but CBC with differential should be obtained if fever and/or pharyngitis develop.

Free T4 and total T3 should be obtained four weeks after starting a thionamide and every four to eight weeks thereafter with the dosage adjusted based on results. Once free T4 and total T3 levels normalize, they should be monitored every three months. Serum TSH is of limited value early in the treatment course because levels may remain suppressed for several months after treatment is started. An antithyroid medication should be continued for 12 to 18 months, then tapered or discontinued if the TSH level is normal at the time. Elevated or above-normal TSH levels (greater than 4.0 mIU per mL) at antithyroid drug discontinuation is associated with an increased likelihood of permanent remission.27

Radioactive Iodine Ablation. Radioactive iodine ablation of the thyroid gland is the most common treatment of Graves disease in the United States. It is contraindicated in pregnancy. Moderate to severe Graves orbitopathy is a relative contraindication, especially in patients who smoke, because radioactive iodine may exacerbate the eye disease.32,33 In mild cases of Graves orbitopathy, radioactive iodine ablation can be performed with concomitant glucocorticoid therapy. Nonradioactive iodine impedes radioactive iodine uptake by iodide transporter; therefore, exposure to large amounts of nonradioactive iodine (e.g., iodinated contrast, amiodarone) should be avoided within three months before radioactive iodine ablation. Pregnancy should be ruled out within 48 hours before radioactive iodine ablation and avoided for six months thereafter.1 A thionamide should be discontinued at least five days before the treatment but can be restarted three to five days after to maintain control of thyroid function, because it may take up to 12 weeks to achieve the full effect of radioactive iodine.

Most patients develop permanent hypothyroidism between two and six months after radioactive iodine ablation and require thyroid hormone supplementation.1,33 Free T4 and total T3 should be measured four to eight weeks after ablation; if hyperthyroidism persists, these indices should be monitored every four to six weeks and thyroid hormone replacement started in the early stages of hypothyroidism.1

Thyroidectomy. This treatment option is preferred in patients with goiter-induced compressive symptoms and in patients with contraindications to radioactive iodine ablation or thionamides. Besides general anesthesia risk, thyroidectomy carries a risk of inadvertently injuring parathyroid glands and recurrent laryngeal nerves.34

TOXIC ADENOMA OR TOXIC MULTINODULAR GOITER

Antithyroid medications can control hyperthyroidism, but do not induce remission of hyperthyroidism associated with toxic adenoma or toxic multinodular goiter. Therefore, radioactive iodine ablation and thyroidectomy are the main treatment options for these conditions. Thyroidectomy is favored if a nodule or goiter causes compressive symptoms. Antithyroid medications may be used for long-term treatment in select patients who refuse ablation or who have a contraindication to thyroidectomy.35,36

THYROIDITIS

Painless thyroiditis and subacute thyroiditis are self-limiting conditions that usually resolve spontaneously within six months. There is no role for antithyroid medications or radioactive iodine ablation in the treatment of thyroiditis. Beta blockers may be used if needed to control adrenergic symptoms. Pain associated with subacute thyroiditis may be relieved with a nonsteroidal anti-inflammatory drug.5

THYROID STORM

Graves disease, toxic adenoma, and toxic multinodular goiter can sometimes cause severe hyperthyroidism, which is termed a thyroid storm. The Burch-Wartofsky score is a helpful tool for diagnosing thyroid storm37  (eTable B). Treatment of thyroid storm is summarized in eTable C.

 Enlarge     Print

eTable B.

Burch-Wartofsky Score: Diagnostic Criteria for Thyroid Storm

CriteriaScore

Thermoregulatory dysfunction

Temperature (°F)

99 to 99.9

5

100 to 100.9

10

101 to 101.9

15

102 to 102.9

20

103 to 103.9

25

≥ 104

30

Central nervous system effects

Absent

0

Mild

10

Agitation

Moderate

20

Delirium

Psychosis

Extreme lethargy

Severe

30

Seizure

Coma

Gastrointestinal-hepatic dysfunction

Absent

0

Moderate

10

Diarrhea

Nausea/vomiting

Abdominal pain

Severe

20

Unexplained jaundice

Cardiovascular dysfunction

Tachycardia (bpm)

90 to 109

5

110 to 119

10

120 to 129

15

130 to 139

20

≥ 140

25

Congestive heart failure

Absent

0

Mild

5

Pedal edema

Moderate

10

Bibasilar rales

Severe

15

Pulmonary edema

Atrial fibrillation

Absent

0

Present

10

Precipitant history

Negative

0

Positive

10


bpm = beats per minute.

note: A score of 45 or greater is highly suggestive of thyroid storm, a score of 25 to 44 is suggestive of impending storm, and a score below 25 is unlikely to represent thyroid storm.

Adapted with permission from Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993;22(2):266.

eTable B.

Burch-Wartofsky Score: Diagnostic Criteria for Thyroid Storm

CriteriaScore

Thermoregulatory dysfunction

Temperature (°F)

99 to 99.9

5

100 to 100.9

10

101 to 101.9

15

102 to 102.9

20

103 to 103.9

25

≥ 104

30

Central nervous system effects

Absent

0

Mild

10

Agitation

Moderate

20

Delirium

Psychosis

Extreme lethargy

Severe

30

Seizure

Coma

Gastrointestinal-hepatic dysfunction

Absent

0

Moderate

10

Diarrhea

Nausea/vomiting

Abdominal pain

Severe

20

Unexplained jaundice

Cardiovascular dysfunction

Tachycardia (bpm)

90 to 109

5

110 to 119

10

120 to 129

15

130 to 139

20

≥ 140

25

Congestive heart failure

Absent

0

Mild

5

Pedal edema

Moderate

10

Bibasilar rales

Severe

15

Pulmonary edema

Atrial fibrillation

Absent

0

Present

10

Precipitant history

Negative

0

Positive

10


bpm = beats per minute.

note: A score of 45 or greater is highly suggestive of thyroid storm, a score of 25 to 44 is suggestive of impending storm, and a score below 25 is unlikely to represent thyroid storm.

Adapted with permission from Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993;22(2):266.

 Enlarge     Print

eTable C.

Treatment of Thyroid Storm

Supportive treatment

Airway maintenance

Oxygen

IV fluids

Cooling blanket (do not use salicylate to treat fever because salicylates increase free T4 and free T3 levels)

Inhibit T4 and T3 synthesis

Methimazole (Tapazole) orally, rectally, via nasogastric tube, or IV, 20 to 40 mg every eight hours

Propylthiouracil orally, rectally, or via nasogastric tube, 200 to 400 mg every eight hours

Inhibit T4 and T3 release

Saturated solution of potassium iodide, five drops orally every six hours to be started at least one hour after administration of an antithyroid agent

Heart rate control

Esmolol (Brevibloc) IV, 50 to 100 mcg per kg per minute

Propranolol, 60 to 80 mg orally every four hours

Metoprolol IV, 5 to 10 mg every two to four hours

If beta-blockade is contraindicated, use diltiazem IV, 0.25 mg per kg over two minutes, then 10 mg per hour IV infusion or 60 to 90 mg orally every six to eight hours

Inhibit T4 to T3 conversion

Hydrocortisone 100 mg IV every eight hours (also suppresses autoimmune process in Graves disease)

Treat precipitating cause


IV = intravenous; T3 = triiodothyronine; T4 = thyroxine.

Information from Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006;35(4):663–686, vii.

eTable C.

Treatment of Thyroid Storm

Supportive treatment

Airway maintenance

Oxygen

IV fluids

Cooling blanket (do not use salicylate to treat fever because salicylates increase free T4 and free T3 levels)

Inhibit T4 and T3 synthesis

Methimazole (Tapazole) orally, rectally, via nasogastric tube, or IV, 20 to 40 mg every eight hours

Propylthiouracil orally, rectally, or via nasogastric tube, 200 to 400 mg every eight hours

Inhibit T4 and T3 release

Saturated solution of potassium iodide, five drops orally every six hours to be started at least one hour after administration of an antithyroid agent

Heart rate control

Esmolol (Brevibloc) IV, 50 to 100 mcg per kg per minute

Propranolol, 60 to 80 mg orally every four hours

Metoprolol IV, 5 to 10 mg every two to four hours

If beta-blockade is contraindicated, use diltiazem IV, 0.25 mg per kg over two minutes, then 10 mg per hour IV infusion or 60 to 90 mg orally every six to eight hours

Inhibit T4 to T3 conversion

Hydrocortisone 100 mg IV every eight hours (also suppresses autoimmune process in Graves disease)

Treat precipitating cause


IV = intravenous; T3 = triiodothyronine; T4 = thyroxine.

Information from Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006;35(4):663–686, vii.

DRUG-ASSOCIATED HYPERTHYROIDISM

Amiodarone-induced thyrotoxicosis can be classified as type 1 (thyroid hormone overproduction, treated with antithyroid medications) or type 2 (thyroid tissue destruction, treated with steroids). Amiodarone should not be discontinued unless it can be stopped safely, without triggering cardiac complications.38,39

Hyperthyroidism associated with use of other medications (e.g., lithium, interferon alfa, tyrosine kinase inhibitors, highly active antiretroviral therapy) is usually self-limited. The physician should determine whether the medication may be discontinued safely or replaced with a different medication.

Data Sources: A PubMed search was performed in Clinical Queries using the key terms hyperthyroidism, thyrotoxicosis, Graves disease, toxic multinodular goiter, toxic adenoma, and thyroiditis. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Also searched were Essential Evidence Plus, the Cochrane database, the National Guideline Clearinghouse database, and UpToDate. Search dates: December 26, 2014, and August 24, 2015.

The author thanks Dr. Harold E. Carlson and Dr. Marie C. Gelato for reviewing this manuscript.

The Author

IGOR KRAVETS, MD, is an assistant professor of medicine in the endocrinology division of Stony Brook (NY) University School of Medicine.

Address correspondence to Igor Kravets, MD, Stony Brook University School of Medicine, 101 Nicolls Rd., HSC T-15, Rm. 060, Stony Brook, NY 11733 (e-mail: igor.kravets@stonybrookmedicine.edu). Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.

REFERENCES

show all references

1. Bahn Chair RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists [published corrections appear in Thyroid. 2011;21(10):1169, and Thyroid. 2012;22(11):1195]. Thyroid. 2011;21(6):593–646....

2. Vanderpump MP. The epidemiology of thyroid disease. Br Med Bull. 2011;99:39–51.

3. Villanueva R, Greenberg DA, Davies TF, Tomer Y. Sibling recurrence risk in autoimmune thyroid disease. Thyroid. 2003;13(8):761–764.

4. Gozu HI, Lublinghoff J, Bircan R, Paschke R. Genetics and phenomics of inherited and sporadic non-autoimmune hyperthyroidism. Mol Cell Endocrinol. 2010;322(1–2):125–134.

5. Pearce EN, Farwell AP, Braverman LE. Thyroiditis [published correction appears in N Engl J Med. 2003;349(6):620]. N Engl J Med. 2003;348(26):2646–2655.

6. Schwartz F, Bergmann N, Zerahn B, Faber J. Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies. Scand J Clin Lab Invest. 2013;73(3):240–244.

7. Sweeney LB, Stewart C, Gaitonde DY. Thyroiditis: an integrated approach. Am Fam Physician. 2014;90(6):389–396.

8. Carney LA, Quinlan JD, West JM. Thyroid disease in pregnancy [published correction appears in Am Fam Physician. 2014;90(1):8]. Am Fam Physician. 2014;89(4):273–278.

9. Usui T, Izawa S, Sano T, et al. Clinical and molecular features of a TSH-secreting pituitary microadenoma. Pituitary. 2005;8(2):127–134.

10. Silva JE, Bianco SD. Thyroid-adrenergic interactions: physiological and clinical implications. Thyroid. 2008;18(2):157–165.

11. Duyff RF, Van den Bosch J, Laman DM, van Loon BJ, Linssen WH. Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study. J Neurol Neurosurg Psychiatry. 2000;68(6):750–755.

12. Gulseren S, Gulseren L, Hekimsoy Z, Cetinay P, Ozen C, Tokatlioglu B. Depression, anxiety, health-related quality of life, and disability in patients with overt and subclinical thyroid dysfunction. Arch Med Res. 2006;37(1):133–139.

13. Selmer C, Olesen JB, Hansen ML, et al. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ. 2012;345:e7895.

14. J N, Francis J. Atrial fibrillation and hyperthyroidism. Indian Pacing Electrophysiol J. 2005;5(4):305–311.

15. Siu CW, Yeung CY, Lau CP, Kung AW, Tse HF. Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism. Heart. 2007;93(4):483–487.

16. Bartalena L, Fatourechi V. Extrathyroidal manifestations of Graves' disease: a 2014 update. J Endocrinol Invest. 2014;37(8):691–700.

17. Hegediüs L, Brix TH, Vestergaard P. Relationship between cigarette smoking and Graves' ophthalmopathy. J Endocrinol Invest. 2004;27(3):265–271.

18. Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol. 2005;6(5):295–309.

19. Fatourechi V. Thyroid dermopathy and acropachy. Best Pract Res Clin Endocrinol Metab. 2012;26(4):553–565.

20. van Deventer HE, Mendu DR, Remaley AT, Soldin SJ. Inverse log-linear relationship between thyroid-stimulating hormone and free thyroxine measured by direct analog immunoassay and tandem mass spectrometry. Clin Chem. 2011;57(1):122–127.

21. Dufour DR. Laboratory tests of thyroid function: uses and limitations. Endocrinol Metab Clin North Am. 2007;36(3):579–594, v.

22. Beck-Peccoz P, Persani L. TSH-induced hyperthyroidism caused by a pituitary tumor. Nat Clin Pract Endocrinol Metab. 2006;2(9):524–528.

23. Werner SC, Ingbar SH, Braverman LE, Utiger RD. Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text. 9th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 2005.

24. Cappelli C, Pirola I, De Martino E, et al. The role of imaging in Graves' disease: a cost-effectiveness analysis. Eur J Radiol. 2008;65(1):99–103.

25. Abraham P, Avenell A, Park CM, Watson WA, Bevan JS. A systematic review of drug therapy for Graves' hyperthyroidism. Eur J Endocrinol. 2005;153(4):489–498.

26. Abraham P, Avenell A, McGeoch SC, Clark LF, Bevan JS. Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev. 2010(1):CD003420.

27. Liu X, Qiang W, Liu X, et al. A second course of antithyroid drug therapy for recurrent Graves' disease: an experience in endocrine practice. Eur J Endocrinol. 2015;172(3):321–326.

28. Bartalena L. Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol. 2013;9(12):724–734.

29. 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. 2007;92(6):2157–2162.

30. Huang CH, Li KL, Wu JH, Wang PN, Juang JH. Antithyroid drug-induced agranulocytosis: report of 13 cases. Chang Gung Med J. 2007;30(3):242–248.

31. Wang MT, Lee WJ, Huang TY, Chu CL, Hsieh CH. Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: a population-based cohort study. Br J Clin Pharmacol. 2014;78(3):619–629.

32. Weetman AP. Radioiodine treatment for benign thyroid diseases. Clin Endocrinol (Oxf). 2007;66(6):757–764.

33. Acharya SH, Avenell A, Philip S, Burr J, Bevan JS, Abraham P. Radioiodine therapy (RAI) for Graves' disease (GD) and the effect on ophthalmopathy: a systematic review. Clin Endocrinol (Oxf). 2008;69(6):943–950.

34. Randolph GW, Shin JJ, Grillo HC, et al. The surgical management of goiter: Part II. Surgical treatment and results. Laryngoscope. 2011;121(1):68–76.

35. Vidal-Trecan GM, Stahl JE, Eckman MH. Radioiodine or surgery for toxic thyroid adenoma: dissecting an important decision. A cost-effectiveness analysis. Thyroid. 2004;14(11):933–945.

36. Ceccarelli C, Bencivelli W, Vitti P, Grasso L, Pinchera A. Outcome of radioiodine-131 therapy in hyperfunctioning thyroid nodules: a 20 years' retrospective study. Clin Endocrinol (Oxf). 2005;62(3):331–335.

37. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993;22(2):263–277.

38. Eskes SA, Endert E, Fliers E, et al. Treatment of amiodarone-induced thyrotoxicosis type 2: a randomized clinical trial. J Clin Endocrinol Metab. 2012;97(2):499–506.

39. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med. 2005;118(7):706–714.

 

 

Copyright © 2016 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions


More in AFP

More in Pubmed

MOST RECENT ISSUE


Oct 15, 2017

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article