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emedicine.medscape.com

Nontoxic Goiter 
Updated: Oct 05, 2021
Author: Stephanie L Lee, MD, PhD; Chief Editor: George T Griffing, MD 

Overview

Practice Essentials
A nontoxic goiter is a diffuse or nodular enlargement of the thyroid gland that does not result from an inflammatory or neoplastic
process and is not associated with abnormal thyroid function. Endemic goiter is defined as thyroid enlargement that occurs in
more than 10% of a population, and sporadic goiter is a result of environmental or genetic factors that do not affect the general
population.

Intrathoracic goiter causing obstruction. This patient has a visible goiter on physical examination. In addition, he has
distension of his left external jugular vein, facial erythema (when compared with his shoulder), and cutaneous varicosities of
venous blood draining from his head into his chest because of jugular obstruction from his goiter.

Signs and symptoms

Pertinent physical findings are limited to the evaluation of the shape, asymmetry, size, and consistency of nontoxic goiters;
ultrasonographic characteristics of individual nodules within the goiter; lymphadenopathy; and assessment of thyroid function.

Examine patients with dyspnea and cough, especially with exertion, for tracheal obstruction. Note any tracheal deviation from
midline.

Assess the patient’s voice for hoarseness.

See Presentation for more detail.

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Diagnosis

Laboratory studies

Assess all patients with goiter for thyroid dysfunction with a serum thyrotropin (TSH) assay. Second-generation or better TSH
assays can detect clinically inapparent (subclinical) hyperthyroidism and hypothyroidism.

Imaging studies

Imaging studies used in the workup include the following:

Ultrasonography
Computed tomography (CT)
Magnetic resonance imaging (MRI)
Barium swallow

Thyroid scintigraphy is not routinely used in the assessment of goiter size unless a concern about thyroid hemiagenesis exists or
the TSH level is suppressed.

See Workup for more detail.

Management

Asymptomatic nontoxic goiters do not require treatment. Therapy is considered if growth of the entire goiter or a specific nodule
is present, especially if intrathoracic extension of the goiter, compressive symptoms, or thyrotoxicosis exists. Thyroidectomy or
surgical decompression provides rapid relief of obstructive symptoms. Other treatments options include radioactive iodine
therapy and levothyroxine (L-thyroxine, or T4) therapy.

See Treatment and Medication for more detail.

Pathophysiology
The histopathology varies with etiology and age of the goiter. Initially, uniform follicular epithelial hyperplasia (diffuse goiter) is
present, with an increase in thyroid mass. As the disorder persists, the thyroid architecture loses uniformity, with the
development of areas of involution and fibrosis interspersed with areas of focal hyperplasia. This process results in multiple
nodules (multinodular or adenomatous goiter). On nuclear scintigraphy, some nodules are hot, with high isotope uptake
(autonomous) or cold, with low isotope uptake, compared with the normal thyroid tissue (as demonstrated in the images below).

The development of nodules correlates with the development of functional autonomy and reduction in thyroid-stimulating
hormone (TSH) levels. Clinically, the natural history of a nontoxic goiter is growth, nodule production, and functional autonomy.
However, abnormally high thyroid function resulting in thyrotoxicosis occurs in a minority of patients. The risk of malignancy is
the same in a patient with a nodular goiter as with a solitary nodule.

See the images below.

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Technetium-99m (99mTc) thyroid scan of a large, nontoxic multinodular goiter. Multiple cold and hot nodules are observed in
the enlarged thyroid gland. The white arrow indicates sternal notch marker.

Areas of autonomy with excess thyroid hormone secretion in a large nodular goiter. This technetium-99m (99mTc) thyroid
scan shows hot and cold nodules in a multinodular goiter. Although the patient's thyroid-stimulating hormone level had
become progressively suppressed, it was within the reference range, at 0.4 mU/mL (reference range 0.35-5.5 mU/mL).

Etiology

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The most common worldwide cause of endemic nontoxic goiter is iodine deficiency. However, in patients with sporadic goiter, the
cause is usually unknown. Nontoxic goiters have many etiologies, including the following:

Iodine deficiency - Goiter formation occurs with moderately deficient iodine intake of less than 50 mcg/d. Severe iodine
deficiency associated with intake of less than 25 mcg/d is associated with hypothyroidism and cretinism.

Iodine excess - Goiter formation due to iodine excess is rare and usually occurs in the setting of preexisting autoimmune
thyroid disease.

Goitrogens

Drugs - Propylthiouracil, lithium, phenylbutazone, aminoglutethimide, iodine-containing expectorants

Environmental agents - Phenolic and phthalate ester derivatives and resorcinol found downstream of coal and
shale mines

Foods - Vegetables of the genus Brassica (eg, cabbage, turnips, brussels sprouts, rutabagas), seaweed, millet,
cassava, and goitrin in grass and weeds

Dyshormonogenesis - A defect in the thyroid hormone biosynthetic pathway is inherited.

Childhood head and neck radiation - Radiation exposure during childhood results in benign and malignant nodules.

Epidemiology
United States statistics

Iodine comes from ingestion of food. Iodine content of the soil determines the iodine content of plants and animals. Iodine is
washed from the soil by water and is eventually washed out to the oceans. In general, areas with mountain ranges or heavy
rainfall and flooding are iodine deficient. Iodine deficiency occurs in populations that depend on locally grown food and rely on
vegetable protein rather than on animal or fish protein.

Studies have shown that iodine supplementation can eliminate cretinism and is highly effective in the prevention of endemic
goiter. When urinary iodide falls below 25 micrograms per gram of creatinine, a palpable goiter occurs in 40-90% of the
population, hypothyroidism occurs in 30-50% of the population, and cretinism occurs in 1-10% of the population. The seminal
studies by David Marine, MD, in 1917 demonstrated the reduction in goiter among adolescent girls in Ohio from 20% to 5% by
iodine supplementation.

Table salt has been supplemented in the United States since the 1920s for the prevention of cretinism and endemic goiter. The
iodine intake in the United States, according to the National Health and Nutrition Examination Survey III (NHANES III), is
adequate at 145 mcg/mg of creatinine. This adequate iodine intake in the United States eliminates the most common cause of
endemic goiter in most populations.

Sporadic goiter is the most common cause of nontoxic goiter in the United States. The incidence of sporadic nontoxic goiter has
been estimated in North America at approximately 5%. Sporadic goiter does not usually occur in people before puberty, and it
does not have a peak incidence. Generally, the development of palpable thyroid nodules and goiter progressively increases with
age. The prevalence of palpable nodules is approximately 5-6% in people aged 60 years, but on autopsy and ultrasonographic
imaging findings, the incidence of small, nonpalpable nodules approaches 50% in people aged 60 years.

International statistics

More than 2.2 billion people worldwide have some form of iodine deficiency disorder. Twenty-nine percent of the world's
population lives in a region that has iodine deficiency (primarily in Asia, Latin American, central Africa, and regions of Europe).
Of those at risk, 655 million were known to have goiter. In the iodine-deficient regions of the world, goiter is more common than
in the United States. The prevalence of goiter can be estimated based on the iodine intake of the population.

As reported by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), and the International
Council for the Control of Iodine Deficiency Disorders (ICCIDD), the absence of iodine deficiency (ie, median urine iodine >100
mg/dL) is associated with a goiter prevalence of less than 5%; mild iodine deficiency (ie, median urine iodine 50-99 mg/dL), with
a goiter prevalence of 5-20%; moderate iodine deficiency (ie, median urine iodine 20-49 mg/dL), with a goiter prevalence of 20-
30%; and severe iodine deficiency (ie, median urine iodine 20-49 mg/dL), with a goiter prevalence of greater than 30%.

Race-, sex-, and age-related demographics

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No convincing epidemiologic studies suggest that race plays an important role in the development of nontoxic goiter. Generally,
the lower socioeconomic conditions in nonindustrialized countries resulting in iodine deficiency have a more important role than
race does in the development of a goiter.

Diffuse and nodular goiter is more common in women than in men. According to the best estimate, the incidence of goiter in
women is 1.2-4.3 times as great as that in men.

Sporadic goiter from dyshormonogenesis, a genetic error in proteins that are necessary for thyroid hormone synthesis, occurs
during childhood. Endemic goiter due to iodine deficiency occurs during childhood, with the goiter's size increasing with age.
Other causes of sporadic goiter rarely occur before puberty and do not have a peak age of occurrence. Thyroid nodules increase
in incidence with age.

Prognosis
The prognosis is good. Usually, nontoxic goiters grow very slowly over many years. Any rapid growth behavior must be
evaluated for either degeneration or hemorrhage of a nodule or for growth of a neoplasm.

Often, in patients who present with progressive goiter growth, those with significant dysphagia or dyspnea must be evaluated for
subtotal thyroidectomy.

In some patients, radioactive iodine therapy can be considered, especially if the patient is older.

A study by Cramon et al found that both disease-specific and generic health-related quality of life discrepancies continued 6
months after treatment in benign nontoxic goiter patients.[1]

A retrospective German study found that nontoxic goiter, as well as other benign thyroid alterations, is associated with an
increased risk of thyroid cancer. Half of the 2787 study participants with thyroid cancer had nontoxic goiter, compared with only
one-sixth of the 2787 matched controls.[2]

Morbidity/mortality

Endemic goiters arising from iodine deficiency are associated with sometimes immense thyroid hypertrophy, hypothyroidism, and
cretinism. Sporadic goiters are generally asymptomatic and found either by a clinician's physical examination or by the patient's
observation of neck enlargement. Occasionally, the goiter may produce symptoms caused by pressure on anterior neck
structures, including the trachea (wheezing, cough, globus hystericus [anterior neck pressure]), the esophagus (dysphagia), and
the recurrent laryngeal nerve (hoarseness).

Rarely, the obstruction can be dangerous because of narrowing of the trachea and the development of tracheitis with edema and
tracheomalacia, leading to severe narrowing of the airway with serious obstruction resulting in a respiratory emergency.
(Tracheal compression and the results of its surgical treatment are seen in the images below.)

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Nontoxic goiter of the thyroid gland with tracheal compression. An axial, noncontrast computed tomography scan through the
thyroid shows significant tracheal compression.

Relief of tracheal compression after subtotal thyroidectomy of large, obstructive, nontoxic multinodular goiter. (A)
Laryngoscopy demonstrating critical tracheal narrowing before thyroidectomy; (B) laryngoscopy showing widened patent
trachea after thyroidectomy.

Complications

Complications of a nontoxic goiter occur because of growth and compression of neck structures or the development of areas of
autonomy and thyrotoxicosis.[3]

Patient Education
Thyroid self-examination may be taught to patients, allowing them to monitor their own body for early changes in gland size.

For excellent patient education resources, visit eMedicineHealth's Thyroid and Metabolism Center. Also, see eMedicineHealth's
patient education article Thyroid Problems.

Presentation

History
The thyroid gland usually grows outward because of its location anterior to the trachea (see the image below). Occasionally, the
thyroid wraps around and compresses the trachea and/or esophagus or extends inferiorly into the anterior mediastinum.

Multinodular goiter. On visual inspection of the neck (image on left), this patient appears to have a goiter. The computed
tomography scan (image on right) shows the asymmetrical goiter, measuring 9.3 x 7.4 cm, with tracheal deviation, although no
tracheal obstruction is present.

Growth pattern
Determining whether the goiter has been present for many years and whether a change has occurred in the recent past is
important.
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Recent or accelerated growth of a discrete nodule or thyroid lobe should raise the suspicion of malignancy.

Goiters associated with unilateral adenopathy should raise the suspicion of malignancy.[4]

Goiters rarely are painful or grow quickly unless recent hemorrhage into a nodule has occurred.

Obstructive symptoms (see the image below)

Intrathoracic goiter causing obstruction. This patient has a visible goiter on physical examination. In addition, he has
distension of his left external jugular vein, facial erythema (when compared with his shoulder), and cutaneous varicosities of
venous blood draining from his head into his chest because of jugular obstruction from his goiter.

Tracheal compression is generally asymptomatic until critical narrowing has occurred.

Patients develop a dry cough, dyspnea, and stridor, especially with exertion. In patients with intrathoracic goiter, the dyspnea
and stridor may be nocturnal or positional (ie, occurring when the patient's arms are raised) when the thoracic outlet is narrowed.

Hemorrhage into a nodule or cyst or development of bronchitis may acutely worsen the respiratory symptoms in a patient with
tracheal narrowing.

The esophagus is more posterior in the neck, and a goiter occasionally extends posteriorly and causes solid food and pill
dysphagia.

Compression of the recurrent laryngeal nerve by a goiter or invasion by a thyroid malignancy results in vocal cord dysfunction
and may cause hoarseness. The superior laryngeal nerve controls the pitch of the voice. An expanding goiter may cause a
change in the character of the voice, especially in individuals who use their voice extensively (eg, in certain occupations).

Compression of the venous outflow through the thoracic inlet by a mediastinal goiter results in facial plethora and dilated neck
and upper thoracic veins.

Iodine intake

Obtain a careful diet history for iodine deficiency, iodine excess from medications (eg, amiodarone), health food store
supplements, or seaweed.

History of radiation

Record any history of head and neck radiation exposure, especially during childhood, which significantly increases the risk of
benign and malignant nodular thyroid disease and thyroid dysfunction (hypothyroidism and hyperthyroidism).[5, 4]

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Family history

Family history is very important in the evaluation of the patient with goiter. Investigate inherited forms of dyshormonogenesis in
the pediatric patient, as well as familial papillary carcinoma of the thyroid and familial forms of medullary thyroid cancer (multiple
endocrine neoplasia and familial medullary carcinoma of the thyroid).[5, 4]

Physical Examination
Pertinent physical findings are limited to the evaluation of the shape, asymmetry, size, and consistency of nontoxic goiters;
ultrasonographic characteristics of individual nodules within the goiter; lymphadenopathy; and assessment of thyroid function.[5,
4, 6]

The thyroid evaluation starts with inspection of the neck for thyroid enlargement. Often, the thyroid enlargement can be detected
only when the patient swallows.

The thyroid isthmus is usually located at or just below the level of the cricoid cartilage of the trachea. The lobes of the thyroid
extend laterally and, if enlarged, may extend posterior to the sternocleidomastoid muscles. Up to 80% of thyroid glands may
have a pyramidal lobe extending superiorly from the isthmus.

Assess the gland for overall size; in the United States, the normal weight is 15-20 grams.

Assess the thyroid for asymmetry and determine whether a dominant nodule is present in an overall nodular goiter or whether a
solitary nodule is present in an otherwise normal gland. Evaluate dominant nodules that are bigger than 1-1.5 cm or a solitary
nodule of the same size by a thin-needle aspiration biopsy.[7]  Diffuse or nodular goiters without a dominant nodule do not
require a biopsy for evaluation.

Obstruction

Examine patients with dyspnea and cough, especially with exertion, for tracheal obstruction. Note any tracheal deviation from
midline.

The patient's voice is assessed for hoarseness.

Venous outflow obstruction of the head and neck can be elicited by the Pemberton maneuver by raising the patient’s arms above
the head until they touch the sides of the head for 1 minute. A positive finding occurs with facial plethora or engorgement of the
neck veins.

Physical assessment of thyroid dysfunction

Examine patients for signs of thyroid dysfunction.

Hypothyroidism is indicated by a sallow complexion, dysarthric speech, mental slowing, weight gain without change in appetite,
cold intolerance, constipation, hypersomnia, and delayed relaxation of deep tendon reflexes.

Hyperthyroidism is indicated by tachycardia, atrial arrhythmia (eg, atrial fibrillation), diaphoresis, weight loss without change in
appetite, heat intolerance, hyperdefecation, palmar erythema, lid lag, tremor, and brisk reflexes.[8]

Lymphadenopathy

Carefully examine the neck to identify any lymphadenopathy.

DDx

Differential Diagnoses
Follicular Thyroid Carcinoma

Hashimoto Thyroiditis

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Medullary Thyroid Carcinoma

Papillary Thyroid Carcinoma

Riedel Thyroiditis

Subacute Thyroiditis

Thyroid Lymphoma

Thyroid Nodule

Workup
 

Workup

Laboratory Studies
Assess all patients with goiter for thyroid dysfunction with a serum thyrotropin (TSH) assay. Second-generation or better TSH
assays can detect clinically inapparent (subclinical) hyperthyroidism and hypothyroidism.

If the TSH is high, consider chronic autoimmune thyroiditis (Hashimoto thyroiditis) or ingestion of a goitrogen, such as lithium or
amiodarone, as well as dyshormonogenesis in a child. Correction of the hypothyroid status by withdrawal of the goitrogen or
institution of thyroid hormone replacement therapy may greatly reduce the size of the goiter.

If the TSH is low, measurement of serum free thyroxine (free T4) or free T4 index and total triiodothyronine (T3) is used to
confirm the diagnosis of thyrotoxicosis. After many years, a nontoxic goiter may develop areas of functional autonomy (as seen
in the image below) and thyrotoxicosis. Treatment of thyrotoxicosis includes stabilization of the hyperthyroid state with antithyroid
medications and then surgical removal of the goiter or the administration of radioactive iodine ablative therapy.

Areas of autonomy with excess thyroid hormone secretion in a large nodular goiter. This technetium-99m (99mTc) thyroid
scan shows hot and cold nodules in a multinodular goiter. Although the patient's thyroid-stimulating hormone level had
become progressively suppressed, it was within the reference range, at 0.4 mU/mL (reference range 0.35-5.5 mU/mL).

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Imaging Studies
Assessment of size and extent of the goiter is necessary to determine if progressive growth of the thyroid is occurring. Clinical
assessment by an experienced clinician is often accurate until the thyroid increases to 4-5 times the normal size.

Measurement of neck circumference is a crude measure of thyroid size. Ultrasonography is good for estimating the number,
size, and sonographic characteristics of nodules but is inaccurate in the clinical setting for measuring the volume of large goiters.
Suspicious ultrasound characteristics, including hypoechogenicity, microcalcifications, macrocalcifications, intranodular
vascularity, taller-than-wide dimensions, and blurred margins, guide the clinician as to which nodule requires biopsy for
malignancy.[5, 4] Computed tomography (CT) scanning and magnetic resonance imaging (MRI), although expensive, are
excellent for assessing tracheal compression and intrathoracic extension of the goiter.

A barium swallow may be used to document esophageal obstruction in patients with significant symptoms of dysphagia.

Thyroid scintigraphy is not routinely indicated in the assessment of goiter size unless a concern of thyroid hemiagenesis exists
or the TSH is suppressed consistent with hyperthyroidism. A nodule with equivocal findings on thin-needle aspiration may be
further evaluated using thyroid scintigraphy. A hot area supports the presence of a benign lesion. Examples of technetium-99m
(99m Tc) thyroid scans are shown below.[5, 4]

Technetium-99m (99mTc) thyroid scan of a large, nontoxic multinodular goiter. Multiple cold and hot nodules are observed in
the enlarged thyroid gland. The white arrow indicates sternal notch marker.

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Areas of autonomy with excess thyroid hormone secretion in a large nodular goiter. This technetium-99m (99mTc) thyroid
scan shows hot and cold nodules in a multinodular goiter. Although the patient's thyroid-stimulating hormone level had
become progressively suppressed, it was within the reference range, at 0.4 mU/mL (reference range 0.35-5.5 mU/mL).

Other Tests
Pulmonary function tests may be used as a functional assessment of tracheal compression. Characteristic changes of external
tracheal compression can be detected in flow-volume loop tracings in asymptomatic patients with goiter. Direct laryngoscopy
can, as indicated in the image below, also demonstrate tracheal compression.

Relief of tracheal compression after subtotal thyroidectomy of large, obstructive, nontoxic multinodular goiter. (A)
Laryngoscopy demonstrating critical tracheal narrowing before thyroidectomy; (B) laryngoscopy showing widened patent
trachea after thyroidectomy.

Procedures
A subset of patients presenting with goiter who do not have hyperthyroidism or has a cold nodule on nuclear thyroid scan with
hyperthyroidism should have a fine-needle aspiration biopsy as the first diagnostic procedure. Clinical indication for biopsy
includes suspicious sonographic characteristics listed above, asymmetrical and/or rapid growth of a nodule or lobe of a thyroid

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gland or unilateral adenopathy. Generally, in patients with the usual nonnodular nontoxic goiter that is long-standing with slow
growth, fine-needle biopsy is not necessary unless sonographically suspicious nodules are present.[5, 4]

Histologic Findings
A variety of features may be observed with fine-needle aspiration cytology of a multinodular goiter.[7] This variation is mostly
explained by different stages of nodule formation. A proliferative phase exists in which the sample may contain many follicular
cells. This can sometimes be difficult to distinguish from a follicular adenoma versus a follicular carcinoma. Colloid is another
prominent feature. It represents the stored thyroid hormone within the follicle. Its absence suggests a more worrisome diagnosis.

After proliferation of follicular cells, a hemorrhage may occur inside the nodule. Erythrocytes and foamy macrophages that have
ingested colloid material may be observed. Another potential area of concern is an aspiration that only returns cyst contents, ie,
erythrocytes and macrophages without follicular cells. This cannot be used to definitively rule out the presence of thyroid cancer,
and a reaspiration should be performed.

Treatment

Medical Care
Nontoxic goiters usually grow very slowly over decades without causing symptoms. Without evidence of rapid growth,
obstructive symptoms (eg, dysphagia, stridor, cough, shortness of breath), or thyrotoxicosis, no treatment is necessary. Therapy
is considered if growth of the entire goiter or a specific nodule is present, especially if intrathoracic extension of the goiter,
compressive symptoms, or thyrotoxicosis exists. The intrathoracic extension of the goiter cannot be assessed by palpation or
biopsy. The goiter, if significant in size, should be removed surgically.[9] The currently available therapies include thyroidectomy,
radioactive iodine therapy, and levothyroxine (L-thyroxine, or T4) therapy.

Radioactive iodine therapy - Radioiodine therapy of nontoxic goiters is often performed in Europe. It is a reasonable therapeutic
option, particularly in patients who are older or have a contraindication to surgery.[10, 11, 12]

Radioactive iodine therapy for nontoxic goiters was reintroduced in the 1990s. Careful studies have shown a reduction in thyroid
volume in nearly all patients after a single dose of therapy.[4] Of patients with nontoxic diffuse goiter treated with radioactive
iodine, 90% have an average of 50-60% reduction in goiter volume after 12-18 months, with a reduction in compressive
symptoms. The decrease in goiter size has positively correlated with the dose of iodine-131 (131 I). Reduction in goiter size is
greater in younger patients and in individuals who have only a short history of goiter or who have a small goiter. Baseline TSH is
not a predictor of response to radioactive iodine.

Obstructive symptoms improved in most patients who received radioactive iodine.

Adverse effects, including thyroiditis, occurred, but no patient reported worsening of compressive symptoms requiring treatment.
No long-term follow-up reports on patients treated with radioactive iodine exist. Patients should always be monitored clinically
after131 I therapy, for evidence of goiter regrowth.

Transient hyperthyroidism is rare and typically occurs in the first 2 weeks after treatment.

Unlike patients with Graves hyperthyroidism who almost all become hypothyroid after treatment with radioactive iodine, only a
small percentage (~20%) of patients with nontoxic goiter develop hypothyroidism after radioactive iodine treatment

Recombinant human TSH (rhTSH) may have a role in radioactive iodine treatment for nontoxic goiter. Pretreatment with rhTSH
24 hours prior to therapy can reduce the amount of radioiodine needed to shrink the goiter (up to a 50% reduction).[13, 14, 15,
16]

Thyroid hormone suppressive therapy - The use of T4 in a euthyroid individual to shrink a nontoxic goiter is controversial.

One study showed that T4 therapy for nontoxic goiter reduced thyroid volume in 58% of patients, compared with 4% of patients
treated with a placebo. However, these results have not yet proven to be reproducible, and the benefit of using T4 needs to be
weighed against the risk of the resultant subclinical hyperthyroidism associated with an increased risk of decreased bone
mineral density and increased atrial fibrillation. Goiter growth typically resumes after cessation of T4 therapy.

The American Thyroid Association and American Association of Clinical Endocrinologists have released guidelines for the
management of hyperthyroid and other causes of thyrotoxicosis, including the use of radioactive iodine or surgery to treat toxic
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multinodular goiter.[17]

Surgical Care
Thyroidectomy or surgical decompression causes rapid relief for obstructive symptoms.[4, 9, 18]

Most intrathoracic goiters may be removed from a cervical incision without sternotomy. Performing bilateral subtotal
thyroidectomy has been recommended to reduce the risk of continued goiter growth. The rate of goiter recurrence depends on
the extent of surgery but should not be higher than 10% in 10 years.

After bilateral subtotal thyroidectomy, all patients require thyroid hormone replacement therapy. The full replacement therapy
should start immediately after surgery, with TSH levels checked 3-4 weeks postoperatively. Adjust thyroid hormone therapy, such
as T4, to maintain a TSH level in the reference range. Some evidence exists that thyroid hormone replacement therapy prevents
recurrence of nontoxic goiter after surgical removal.[19]

The use of total thyroidectomy to treat benign multinodular goiter has met with some concern, owing to the risk of parathyroid
function damage and laryngeal nerve injury posed by the procedure. Nonetheless, total thyroidectomy is also seen as a means
of avoiding the pitfalls of subtotal thyroidectomy, specifically, the recurrence of goiter and the inadequate treatment of thyroid
cancers, which can occur in apparently benign goiters. Results from a 2008 literature review indicated that the rate of permanent
complications is the same for subtotal and total thyroidectomy; consequently, the report's authors concluded that total
thyroidectomy should be the procedure of choice for the surgical treatment of benign multinodular goiters.[9]

The same conclusion was reached in a study of 600 patients with nontoxic multinodular goiter. Barczynski et al compared
outcomes from total thyroidectomy (200 patients), the Dunhill procedure (unilateral total lobectomy plus contralateral subtotal
lobectomy; 200 patients), and bilateral subtotal thyroidectomy (200 patients). The authors found that over a 5-year follow-up
period the incidence of recurrent goiter after total thyroidectomy was 0.52%, while that following the Dunhill operation was
4.71%, and recurrence after bilateral subtotal thyroidectomy was 11.58%. The frequency of completion thyroidectomies was also
lower in total thyroidectomy than in the other operations.

The incidence of transient hypoparathyroidism in the above study, as well as that of transient and permanent laryngeal nerve
injuries, was greater in total thyroidectomy than in the other types of surgery. Nonetheless, the authors concluded that, owing to
the fact that following total thyroidectomy there was a reduced incidence of goiter recurrence requiring repeat thyroidectomy,
total thyroidectomy should be considered the procedure of choice for patients with nontoxic multinodular goiter.[20]

Results from a Swiss study of 72 patients indicated that a single dose of steroid prior to thyroidectomy for benign disease can,
within 48 hours postsurgery, significantly reduce pain, nausea, vomiting, and voice alteration related to the procedure.[21]

Consultations
Consult an endocrinologist in the complicated nontoxic goiter with obstructive symptoms, rapid growth, and/or evaluation for
thyroid malignancy within the nontoxic goiter.

If a high index of suspicion for malignancy exists in a patient with hoarseness, lymphadenopathy, and previous radiation
exposure as a child, consult an endocrinologist or a surgeon specializing in thyroid disease.

Diet
Diets low in iodine need supplementation, especially in developing countries where government-supported iodine
supplementation is not available. Adult patients require 150 mcg/day, which has been the average intake in the United States,
but patients should be encouraged to use iodized salt at home and take multivitamins with iodine to ensure adequate intake.
Patients should not take iodine supplements such as seaweed, as the amount of iodine is excessive and may result in iodine-
induced thyroid hormone dysfunction in predisposed individuals.

Prevention of endemic goiter may be accomplished by iodine supplementation, using iodine supplements in drinking water
sources or iodized oil on bread (strategies that can be applied to a whole country).

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Medication

Medication Summary
No specific treatment for nontoxic goiter exists. Childhood or adult goiter that is established because of iodine deficiency does
not shrink after supplementation with iodine. Goiters due to a defect in thyroid hormone synthesis, dyshormonogenesis, are
often reduced in size by thyroid hormone therapy in children. T4 is less effective in shrinking dyshormonogenesis goiter in adults
once hyperplastic nodules have developed. Attempting to shrink sporadic or nontoxic goiters with T4 used to be standard
practice, but this therapy has fallen out of favor because of the risks of hyperthyroidism, with its detrimental effects on bone and
cardiac function, and lack of efficacy to shrink thyroid nodules and goiters.

Thyroid hormones (L-thyroxine)

Class Summary
T4 has been used to reduce the size or suppress the further growth of goiters.

Levothyroxine (Synthroid, Levoxyl, Unithroid, Levothroid)

Minimal excess doses of T4 suppress thyrotropin (TSH) secretion from the pituitary. TSH is the primary stimulator of thyroid
gland growth and thyroid hormone synthesis. For many years, the standard therapy of nontoxic goiter has been suppression of
thyroid function by exogenous T4 therapy. This practice has been largely abandoned because of data showing cortical bone loss
with chronic excess of thyroid hormone therapy and lack of benefit in suppressing growth of large nodular goiters. Studies have
shown that T4 therapy is most effective in decreasing the size of small diffuse goiters in patients with a basal TSH within the
reference range.

Antithyroid agents

Class Summary
Reduce goiter size.

Sodium iodide, or131 I (Iodotope)

Ultrasonographic studies have shown a decrease in thyroid volume after131 I therapy in the majority of patients with nontoxic
goiter. When administered at a dose of 100 µCi per g of goiter (corrected for percent uptake of131 I at 24 h), thyroid volume
decreases an average of 50-60% in 12-18 mo. In most patients, radioactive iodine therapy reduces compressive symptoms.
Commonly used in Europe and Latin America but is not standard therapy in the United States unless the patient has
contraindication for surgery. Theoretical concerns of radiation-induced swelling and worsening of compressive symptoms have
not been supported in European studies. Often, low-iodine diets are recommended for 5 d up to several wk before therapy.

Follow-up

Further Outpatient Care

The patient with a large goiter and no obstructive symptoms can be monitored in an outpatient setting. Conduct a physical
examination every 6 months to determine if obstructive symptoms have developed or worsened and to perform thyroid function
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tests (ie, TSH, free T4).

Depending on iodine intake in the diet, some of these patients develop thyroid autonomy and thyrotoxicosis.

Often, thyroid imaging is not necessary when the patient is examined by an endocrinologist experienced in thyroid examinations.
The method of choice is ultrasonography unless the goiter extends into the thoracic inlet.

Routine nuclear scintigraphy is not necessary.

Transfer
Transfer may be required in patients with significant tracheomalacia who require surgery. Long-term compression of the trachea
by a nontoxic goiter causes tracheal cartilage to lose its strength. This can be life threatening, and tracheal intubation or
tracheotomy may be required.

Additionally, if a goiter extends significantly into the thorax, a thoracic surgeon may be needed to open the chest wall to fully
excise the goiter.

Contributor Information and Disclosures

Author

Stephanie L Lee, MD, PhD Associate Professor, Department of Medicine, Boston University School of Medicine; Director of
Thyroid Health Center, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Fellow, Association of Clinical
Endocrinology

Stephanie L Lee, MD, PhD is a member of the following medical societies: American College of Endocrinology, American
Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Sonia Ananthakrishnan, MD Assistant Professor of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston Medical
Center, Boston University School of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy;
Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kent Wehmeier, MD Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis
University School of Medicine

Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society,
International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus 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,
International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice
Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association,
American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational
Research, Endocrine Society
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Disclosure: Nothing to disclose.

Additional Contributors

Steven R Gambert, MD Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine,
University of Maryland Medical Center and R Adams Cowley Shock Trauma Center

Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician
Leadership, American College of Physicians, American Geriatrics Society, Endocrine Society, Gerontological Society of America,
Association of Professors of Medicine

Disclosure: Nothing to disclose.

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