Clinical presentation and evaluation of goiter in adults

INTRODUCTION — The term goiter refers to abnormal growth of the thyroid gland. Goiters can be diffuse or nodular, depending on the cause, and may be associated with normal, decreased, or increased thyroid hormone production. The clinical manifestations vary with thyroid function and with the size and location of the goiter. The evaluation of the adult with goiter will be reviewed here. The treatment of goiter in adults and the evaluation and treatment of goiter in children are reviewed separately. (See "Overview of the management of benign goiter" and "Treatment of benign obstructive or substernal goiter" and "Treatment of toxic adenoma and toxic multinodular goiter" and "Approach to congenital goiter in newborns and infants" and "Approach to acquired goiter in children and adolescents".)

ANATOMICAL RELATIONSHIPS — In healthy adults without iodine deficiency, a normal thyroid gland is approximately 4 to 4.8 x 1 to 1.8 x 0.8 to 1.6 cm in size, with a mean sonographic volume of 7 to 10 mL and weight of 10 to 20 grams [1,2]. Thyroid volume measured by ultrasonography is slightly greater in men than women, increases with age and body weight, and decreases with increasing iodine intake. (See "Technical aspects of thyroid ultrasound", section on 'Estimation of thyroid gland volume'.)

The normal thyroid gland is immediately caudal to the larynx and encircles the anterolateral portion of the trachea (figure 1). The thyroid is bordered by the trachea and esophagus posteriorly and the carotid sheath laterally. Enlarging thyroid lobes usually grow outward because of their location in the anterior neck in front of the trachea, covered only by thin strap muscles, subcutaneous tissue, and skin. As a result of this outward growth, even very large goiters may not compress the trachea or impinge on the great vessels lateral to the lobes. However, in patients with substantial enlargement of one lobe or asymmetric enlargement of both lobes, the trachea, esophagus, or blood vessels may be displaced or, less often, compressed. Bilateral lobar enlargement, especially if the goiter extends posterior to the trachea, may cause either compression or concentric narrowing of the trachea or compression of the esophagus or jugular veins.

The thoracic inlet is an ovoid area that measures approximately 5 x 10 cm bounded by the sternum anteriorly, the first thoracic vertebral body posteriorly, and the first ribs laterally (figure 2). The inlet is traversed by the trachea, esophagus, blood vessels, and nerves. The inferior pole of each thyroid lobe normally lies above the thoracic inlet. However, with some goiters, there is growth of one or both lobes through the inlet into the thoracic cavity, which can result in obstruction of any of the structures in the inlet. Such goiters are called substernal, although retrosternal is probably a more precise term. Most substernal goiters are in the anterolateral mediastinum, but approximately 10 percent are located primarily in the posterior mediastinum [3,4]. The prevalence of substernal goiter as a percentage of thyroidectomies ranges from 2 to 19 percent [4].

ETIOLOGY — Iodine deficiency is the most common cause of goiter worldwide. In mildly and moderately iodine-deficient regions in Denmark, goiter (as determined by ultrasonography) is present in 15 and 22.6 percent of the population, respectively [5] (see "Iodine deficiency disorders", section on 'Diffuse and nodular goiter'). In the United States, where significant iodine deficiency does not exist, multinodular goiter, chronic autoimmune (Hashimoto's) thyroiditis, and Graves' disease are more common causes of goiter. In older adults, multinodular goiter is most common.

Other less common causes of goiter include tumors, thyroiditis, and infiltrative diseases (table 1). (See "Overview of thyroiditis" and "Infiltrative thyroid disease".)

The risk of thyroid cancer within a multinodular goiter is approximately 3 to 5 percent [6], similar to the risk in a solitary thyroid nodule. In a series of 718 patients operated on for goiter in Pakistan, 3 percent of patients were found to have a malignancy [7]. In a surgical series (with potential selection bias) of 3233 patients with multinodular goiter, in which all patients had preoperative ultrasounds and patients who had indeterminate, suspicious, or malignant (Bethesda 3 to 6) preoperative FNA were excluded, 31.7 percent had incidental thyroid cancers, of which 56 percent were papillary microcarcinomas [8].

PATHOPHYSIOLOGY — In patients with iodine deficiency or chronic autoimmune (Hashimoto's) thyroiditis, an increase in thyroid-stimulating hormone (TSH) secretion is the predominant cause of goiter. In contrast, most patients with sporadic nontoxic multinodular goiters have normal serum TSH concentrations. In these individuals, the thyroid enlargement is probably caused by several growth factors (including TSH) that act over time on thyroid follicular cells that have different synthetic and growth potentials. There is often a family history of goiter, suggesting that genetic factors may also play a role. The result is diffuse and later multinodular thyroid enlargement. Some nodules eventually become autonomous due to activating mutations in the TSH receptor or G proteins within the thyroid follicular cells. The following observations support this sequence of events [9,10]:

●Thyroid volume is larger in older patients

●The longer the patient has a goiter, the larger the size of the goiter

●The larger the size of the goiter, the lower the serum TSH concentration

In patients with Graves' disease, TSH receptor antibodies (TRAb) stimulate the TSH receptor to cause thyroid growth and excessive hormonal secretion. (See "Pathogenesis of Graves' disease".)

CLINICAL PRESENTATION — The clinical manifestations of goiter depend upon the presence of thyroid dysfunction and upon the growth rate of the goiter. Some patients may have symptoms and biochemical evidence of hypothyroidism or hyperthyroidism. However, the majority of patients with goiter are asymptomatic and biochemically euthyroid. Patients with longstanding, large goiters may develop symptoms of obstruction due to progressive compression of the trachea or sudden enlargement (usually accompanied by pain) secondary to hemorrhage into a nodule.

Asymptomatic — Most goiters grow very slowly over many decades. Therefore, the majority of patients with goiter are asymptomatic. The goiter may first be noted on physical examination or found incidentally on cross-sectional imaging studies performed for unrelated reasons.

Thyroid dysfunction — If the goiter is due to Hashimoto's thyroiditis or severe iodine deficiency, patients may have symptoms of hypothyroidism (eg, fatigue, constipation, cold intolerance). If due to multinodular goiter (with autonomy) or Graves' disease, patients may have symptoms of hyperthyroidism (eg, palpitations, dyspnea on exertion, unexplained weight loss). (See "Clinical manifestations of hypothyroidism" and "Overview of the clinical manifestations of hyperthyroidism in adults".)

Obstructive symptoms — Patients with longstanding goiters (cervical or substernal) may develop symptoms of obstruction due to progressive compression of the trachea or sudden enlargement (usually accompanied by pain) secondary to hemorrhage into a nodule. The majority of patients with obstructive cervical goiters have had a visible goiter for many years. Most patients with substernal goiter (77 to 90 percent in two series) also have visible goiters [3,11], although some are found incidentally on imaging studies performed for unrelated reasons. In those without visible goiter, substernal goiters may also be found because of obstructive symptoms. Since goiters tend to grow slowly, substernal goiters are most commonly discovered during the fifth and sixth decades of life and are found more often in women than men [12,13].

The most common symptom in patients with obstructive cervical or substernal goiter is exertional dyspnea, which is present in 30 to 60 percent of patients [3,13-18]. This symptom usually occurs when the tracheal diameter is less than 8 mm [19]. In some patients with substernal goiter, dyspnea is primarily positional or nocturnal and it occurs primarily during maneuvers that force the thyroid into the thoracic inlet, such as reaching and bending. When tracheal compression becomes severe (luminal diameter less than 5 mm), stridor or wheezing occurs at rest [19]. This upper airway wheezing must be distinguished from asthma. An upper respiratory illness may exacerbate upper airway obstruction.

Cough is present in 10 to 30 percent of patients, and it may be positional [17]. Pain is unusual, but a choking sensation is common.

Goiter may contribute to obstructive sleep apnea, and thyroidectomy may improve symptoms [20]. In a study of 45 patients with snoring symptoms who were undergoing thyroidectomy for any reason (42 percent for goiter or compressive symptoms), 29 percent had improved snoring frequency, apnea, and frequency of daytime somnolence after surgery [21].

A variety of other symptoms can be induced by obstructive goiter:

●Dysphagia is a less common complaint because of the posterior position of the esophagus

●Compression of a recurrent laryngeal nerve may cause transient or permanent vocal cord palsy, resulting in hoarseness

●Phrenic nerve paralysis

●Horner's syndrome due to compression of the cervical sympathetic chain

●Rarely, jugular vein compression or thrombosis, cerebrovascular steal syndromes, or even the superior vena cava syndrome [22]

DIAGNOSIS — The diagnosis of a goiter is usually made at the time of a physical examination. One or more discrete nodules may be palpable. Goiter may also be an incidental finding during a radiologic procedure performed for other purposes (eg, carotid ultrasound, chest computed tomography [CT] scan, or magnetic resonance imaging [MRI] cervical spine).

APPROACH TO EVALUATION — Once goiter is detected, the evaluation is aimed at assessment of (algorithm 1):

●Thyroid function

●Goiter size and the presence of nodules

And identifying the:

●Presence of compressive or obstructive symptoms

●Presence of suspicious sonographic features in nodules within the goiter

●Presence of tracheal narrowing

●Underlying cause (table 1)

These factors will determine management. It is important to rule out malignancy through history, clinical examination, ultrasound, and fine-needle aspiration (FNA) biopsy of large or suspicious nodules. In the United States, in the absence of autoimmune thyroid disease (Hashimoto's thyroiditis or Graves' disease) and thyroid malignancy, benign multinodular goiter is the most likely diagnosis.

History and physical examination — In patients with goiter, the following elements of the history should be determined:

●Preexisting chronic autoimmune (Hashimoto's) thyroiditis (the only known risk factor for primary thyroid lymphoma, a relatively rare disease)

●Iodine intake (including country of origin)

●Head and neck irradiation or radioiodine exposure from nuclear power plant accidents (Chernobyl, Fukushima)

●Medication history

●Family history of benign or malignant thyroid disease

●Presence of obstructive symptoms (eg, dyspnea, cough, wheezing) or symptoms of hyper- or hypothyroidism

●Presence of systemic "B" symptoms (eg, fever, weight loss, drenching night sweats)

The thyroid and surrounding neck structures should be carefully examined. We prefer to palpate the thyroid from the front of the patient so that landmarks such as the cricoid cartilage and sternocleidomastoid muscles are visible. The isthmus is located just below the cricoid. Thumbs or fingers are placed obliquely between the sternocleidomastoid and the trachea, compressing thyroid tissue on the tracheal surface. It is helpful to watch the patient swallow a sip of water before palpation, assessing for enlargement and asymmetry. Then, having the patient swallow water during palpation allows the examiner to feel the upward movement of the thyroid gland. The neck should be palpated to assess:

●Size of the thyroid gland

●Presence of firm or dominant nodules

●Presence of cervical adenopathy

The presence of a thyroid bruit (a sign of increased blood flow) may indicate hyperthyroidism, typically due to Graves' disease. One or more discrete nodules may be palpable. However, the physical examination of goiter is highly inaccurate [6,23,24]. Glands that are diffuse on physical exam are often nodular by sonography, and most individuals with thyroid enlargement and a solitary palpable nodule on physical examination actually have multiple nodules when investigated by sonography.

Tracheal deviation may be visible or palpable if the goiter is asymmetric. Rarely, dilated neck veins are present. All patients with obstructive symptoms caused by a cervical goiter alone have obvious thyroid enlargement, as do many patients with substernal goiter. The possibility of substantial substernal extension is suggested by the inability to identify the lower end of the thyroid gland. When the lower end cannot be identified with the patient sitting, it may be possible to do so if the patient lies down with a pillow under the shoulders to hyperextend the neck.

Pemberton's maneuver can be used to exacerbate obstructive symptoms by forcing the thyroid into the thoracic inlet (figure 2). In this maneuver, the examiner holds the patient's arms vertically above the head for approximately 60 seconds. The test is considered positive if the patient's neck veins become more distended or if the patient develops facial plethora, cyanosis, or inability to swallow, or if dyspnea or stridor appear or worsen. Rarely, a cervical goiter becomes impacted in the thoracic inlet by this maneuver or by acute neck flexion or reaching; this is called the "thyroid cork" phenomenon [25].

Apparent bronchospasm may represent upper airway obstruction or bilateral vocal cord paralysis. Careful auscultation of the chest and airway in positions that minimize and maximize potential upper airway obstruction (described above) may suggest the need for further evaluation.

Initial testing

Thyroid function tests — Serum TSH should be measured in all patients with goiter (discovered either by palpation or incidentally noted on a radiologic procedure) (algorithm 1). Patients with goiter may have normal thyroid function, hyperthyroidism (subclinical or overt), or hypothyroidism (subclinical or overt). (See "Diagnosis of hyperthyroidism" and "Disorders that cause hyperthyroidism" and "Diagnosis of and screening for hypothyroidism in nonpregnant adults" and "Disorders that cause hypothyroidism".)

●TSH below normal – If the TSH is below normal, serum free thyroxine (T4) and total triiodothyronine (T3) should also be measured. In patients with overt or subclinical hyperthyroidism and goiter, multinodular goiter with autonomy or Graves' disease is the most likely diagnosis.

●TSH above normal – If serum TSH is above normal, free T4 should be measured. In patients with overt or subclinical hypothyroidism, Hashimoto's thyroiditis is the most likely diagnosis, except in areas of endemic goiter due to iodine deficiency.

Thyroid peroxidase antibodies — Many thyroid experts also check serum TPO antibodies in all patients with goiter. We typically measure TPO antibodies in patients with goiter and normal TSH to assess for Hashimoto's thyroiditis.

For patients with elevated TSH (hypothyroidism) and goiter living in the United States, Hashimoto's thyroiditis is most likely, and TPO antibodies are almost always elevated. Therefore, we do not routinely measure TPO antibodies in hypothyroid patients with goiter, although some thyroid experts check serum TPO antibodies in such patients to confirm the diagnosis of Hashimoto's.

Rare causes of hypothyroidism and goiter without TPO antibodies include "seronegative" Hashimoto's thyroiditis, partial biosynthetic defects in thyroid hormone synthesis or iodine utilization, or infiltrative disorders of the thyroid. (See "Approach to congenital goiter in newborns and infants" and "Infiltrative thyroid disease".)

Thyroid ultrasound — We obtain a thyroid ultrasound in most patients, especially those who report rapid growth of a goiter; in patients whose physical examination reveals thyroid asymmetry, focal firm consistency, or tenderness; and in patients who have goiter with normal TSH and negative TPO antibodies. We do not routinely obtain a thyroid ultrasound for patients with small, non-nodular goiter on physical examination due to Hashimoto's thyroiditis or for patients with low TSH (subclinical or overt hyperthyroidism) and a non-nodular goiter on physical exam whose hyperthyroidism is due to Graves' disease. (See 'Goiter with low TSH' below.)

Additional tests — Patients with abnormal TSH, worrisome features on physical examination (asymmetry, focal firm consistency, tenderness) or thyroid ultrasound, and/or obstructive symptoms require additional testing.

Goiter with worrisome features — Thyroid ultrasound should be obtained in all patients, regardless of TSH results, who report rapid growth of a goiter or in patients whose physical examination reveals thyroid asymmetry, focal firm consistency, or tenderness. These findings are suggestive of possible coexisting cancer or lymphoma. The rare anaplastic thyroid cancers (see "Anaplastic thyroid cancer") or primary lymphomas of the thyroid often present with a rapidly enlarging neck mass that may cause obstructive symptoms such as dyspnea, wheezing, and cough. Less commonly, patients with thyroid lymphoma may present with longstanding history of goiter, often in association with hypothyroidism, or with a solitary nodule. Its prognosis and treatment differ substantially from these other thyroid disorders. (See "Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma", section on 'Clinical presentation' and "Clinical manifestations, pathologic features, and diagnosis of extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT)", section on 'Clinical features'.)

Rapid thyroid growth also occurs in patients with infectious (suppurative) or subacute thyroiditis. However, the growth is typically accompanied by pain and fever. In patients with infection, the thyroid abnormalities are predominantly unilateral, whereas most patients with subacute thyroiditis have bilateral thyroid enlargement and pain. (See "Overview of thyroiditis", section on 'Infectious thyroiditis' and "Subacute thyroiditis".)

The ultrasonic texture of a goiter and Doppler dynamics may yield information about diagnosis, function, and possibly even prognosis and medical management. When worrisome features are present on physical examination or ultrasound, FNA biopsy is indicated. (See "Overview of the clinical utility of ultrasonography in thyroid disease", section on 'Goiter' and "Thyroid biopsy" and "Diagnostic approach to and treatment of thyroid nodules", section on 'Sonographic criteria for FNA'.)

Goiter with normal TSH

●TPO antibodies negative – For patients with goiter and normal TSH and absent TPO antibodies (nontoxic goiter), the most likely diagnosis is multinodular goiter (if nodules present), diffuse goiter due to a biosynthetic (organification) defect (nodules absent), "seronegative" Hashimoto's thyroiditis, or iodine deficiency goiter (if patient is from an iodine-deficient region) (algorithm 1). (See "Iodine deficiency disorders", section on 'Diffuse and nodular goiter'.)

A thyroid ultrasound should be obtained (regardless of findings on physical exam) to assess sonographic features and the presence of nodularity [26].

Differentiated thyroid cancers grow slowly and may be indistinguishable clinically from a uninodular or multinodular benign goiter. Ultrasound may identify distinctive, nonpalpable thyroid nodules within a nodular or diffuse goiter. Nodules with indeterminate or suspicious ultrasound features should be considered for biopsy based on an ultrasound scoring system such as American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). The prevalence of cancer in an individual nodule in a goiter is independent of the number of sonographically identified nodules. The evaluation and management of thyroid nodules are reviewed separately. (See "Diagnostic approach to and treatment of thyroid nodules".)

●TPO antibodies positive – Patients with goiter and positive antibodies have Hashimoto's thyroiditis. Early in the disease, the TSH will be within the normal range. Many thyroid experts check serum TPO antibodies in such patients to confirm the diagnosis of Hashimoto's, especially if the diagnosis is not evident based on a strong family history of autoimmune thyroid disease or a typical examination (a slightly firm, rubbery, symmetrical gland, possibly with a palpable pyramidal lobe).

A diagnosis of Hashimoto's does not exclude a coexistent multinodular goiter or a malignancy. For patients with Hashimoto's thyroiditis, ultrasound should be reserved for patients with larger goiters, thyroid asymmetry, or a concern for thyroid nodularity. Thyroid ultrasound in patients with Hashimoto's thyroiditis should be interpreted with caution due to the diffuse heterogeneity and the presence of pseudonodules related to ongoing inflammation.

Goiter with high TSH — Most patients with goiter and hypothyroidism (subclinical or overt) who are living in North America have Hashimoto's thyroiditis (algorithm 1). Many thyroid experts check serum TPO antibodies in such patients to confirm the diagnosis of Hashimoto's, especially if the diagnosis is not evident based on a strong family history of autoimmune thyroid disease or a typical examination (a slightly firm, rubbery, symmetrical gland, possibly with a palpable pyramidal lobe).

For patients with Hashimoto's thyroiditis, ultrasound should be reserved for patients with larger goiters, thyroid asymmetry, or a concern for thyroid nodularity. Thyroid ultrasound in patients with Hashimoto's thyroiditis should be interpreted with caution, due to the diffuse heterogeneity and the presence of pseudonodules related to ongoing inflammation.

If TPO antibodies are negative, diagnostic possibilities include seronegative Hashimoto's thyroiditis, infiltrative disease of the thyroid, or biosynthetic defects in thyroid hormone synthesis or iodine utilization. The clinical presentation for these diseases may be similar, ie, painless progressive enlargement of the thyroid gland, which can be diffuse or nodular. In this setting, we obtain a thyroid ultrasound to assess the morphology of the thyroid.

Hypothyroidism (subclinical or overt) only occurs if the infiltration is sufficiently extensive to destroy the thyroid, which is uncommon (see "Infiltrative thyroid disease"). Mild or congenital overt hypothyroidism occurs in patients with severe biosynthetic defects. Those with milder defects may be euthyroid. (See 'Goiter with normal TSH' above.)

Hypothyroidism, if present, should be treated with thyroid hormone (levothyroxine) replacement therapy (see "Treatment of primary hypothyroidism in adults"). Over time, treatment with thyroid hormone may reduce the size of the goiter, particularly in patients with Hashimoto's thyroiditis with elevated serum TSH levels (see "Overview of the management of benign goiter", section on 'Treat thyroid dysfunction if present'). In many cases, however, the goiter does not resolve completely.

Goiter with low TSH — Most patients with goiter and hyperthyroidism have either multinodular goiter with autonomy (frequently subclinical hyperthyroidism) or Graves' disease (overt or subclinical hyperthyroidism) (algorithm 1). When thyroid tests are indicative of hyperthyroidism (low TSH, elevated free T4 and/or T3) or subclinical hyperthyroidism (low TSH, normal free T4 and T3), and the etiology is not apparent from physical examination (eg, diffuse goiter with ophthalmopathy is consistent with Graves' disease), the cause of the hyperthyroidism should be distinguished by the findings on 24-hour radioiodine uptake and scan, by measurement of TSH receptor antibodies (TRAb), or by measurement of thyroidal blood flow on ultrasonography. Focal areas of increased uptake should be correlated with possible nodules on ultrasound. Determining the etiology of hyperthyroidism is reviewed in detail separately. (See "Diagnosis of hyperthyroidism", section on 'Our approach' and "Disorders that cause hyperthyroidism".)

Goiter with obstructive symptoms or suspected substernal goiter — Additional evaluation of obstructive or substernal goiter includes imaging studies (noncontrast CT or MRI) to evaluate the extent of the goiter and its effect upon surrounding structures and a flow-volume loop study in patients with obstructive symptoms or in those with tracheal narrowing (<1 cm) on cross-sectional imaging. Unless there is need for immediate surgery, ultrasound should be obtained to assess the features of the goiter and characteristics of any nodules.

FNA biopsy is indicated if malignancy is suspected (prominent discrete nodules; a history of rapid growth, pain, or tenderness; unusual firmness in one region of the goiter; or suspicious sonographic features). (See 'Fine-needle aspiration biopsy' below and "Thyroid biopsy" and "Diagnostic approach to and treatment of thyroid nodules", section on 'Sonographic criteria for FNA'.)

Most obstructive cervical or substernal goiters are benign. However, in a systematic review of a retrospective cohort study and several case series of patients with substernal goiter undergoing thyroidectomy, the incidence of thyroid cancer ranged from 3 to 23 percent [4]. The incidence of thyroid cancer was no higher than the incidence in patients with cervical goiters. Risk factors for malignancy may include family history of thyroid disease, history of head and neck radiation, recurrent goiter, and the presence of cervical adenopathy.

Radiologic testing — Substernal goiters are often seen on chest radiograph as a mass that causes tracheal narrowing or deviation or as superior mediastinal widening (image 1). Past radiographs, if available, permit an estimate of the rate of growth of the goiter, and neck radiographs may show narrowing of the airway. However, the extent of the goiter and its effect upon surrounding structures should be assessed by CT or MRI (image 2A-B) [27,28].

CT is very useful for evaluating the extent of both large cervical goiters and substernal goiters. There are, however, three important caveats regarding CT scans:

●The entire vertical length of the goiter should be imaged. Although it may be necessary to order both neck and chest CT, it should be possible to specify that images be obtained to the lowest extent of the goiter. It is unusual for a substernal goiter to extend more than 1 to 2 cm below the level of the aortic arch.

●CT scanning is often performed with the patient's neck in the neutral position or slightly flexed, which may exaggerate the extent of substernal extension of the goiter. A small goiter that extends 1 to 1.5 cm below the sternal notch on CT may be entirely cervical when the neck is extended and, therefore, is less likely to be the cause of any obstructive symptoms the patient may have.

●Iodinated radiocontrast agents should not be given routinely, because the iodine may induce overt hyperthyroidism in those patients who have subclinical hyperthyroidism [29] and exacerbate hyperthyroidism in those who have overt hyperthyroidism. In fact, because of the iodine content within the gland, contrast is never needed to image the thyroid. If imaging after administration of a radiocontrast agent is required to identify vascular structures, a patient with subclinical or overt hyperthyroidism should be pretreated with an antithyroid drug to prevent thyroidal organification of iodine. One such regimen is to administer methimazole 10 mg twice daily for two weeks beginning at least two hours before the contrast agent is given. Alternatively, MRI can be performed. (See "Iodine-induced thyroid dysfunction", section on 'Management'.)

Thyroid ultrasonography, although more accurate than CT for defining thyroid anatomy in the anterior neck, is not satisfactory for imaging of posterior neck structures or the substernal region. Ultrasound is useful to assess the features of the goiter and characteristics of any nodules. (See "Overview of the clinical utility of ultrasonography in thyroid disease", section on 'Goiter' and "Overview of the clinical utility of ultrasonography in thyroid disease", section on 'Thyroid nodules'.)

Thyroid radionuclide imaging with radioiodine will define areas of autonomous function in patients with large cervical goiters and may be useful but is occasionally misleading in patients with substernal goiter. It can identify possible substernal extension of a goiter (image 3A-B) and can identify a substernal mass as being thyroid tissue, particularly if it is hyperfunctioning. However, some substernal goiters are not identified, because they take up radioiodine poorly and the radioactivity is attenuated by the sternum and clavicles [27,30].

While radionuclide imaging is unnecessary if thyroidectomy is planned, it should be obtained to identify areas of function if either limited surgery in a hyperthyroid patient or treatment with radioiodine is being considered. When radionuclide imaging is performed, anatomic markers should be placed on palpable cervical thyroid tissue and the suprasternal notch so that substernal tissue can be identified; a size marker should also be added.

Flow-volume loop — A flow-volume loop study to assess for airway obstruction should be performed in patients with obstructive symptoms and in those with substernal goiter with tracheal narrowing to less than 10 mm, even in the absence of obstructive symptoms, particularly if the patient or physician is reluctant to proceed with surgery and the results of the study would influence the decision to proceed with surgery [16,19]. The study may be abnormal even when the patient is asymptomatic [16,31]. Mechanical fixed upper airway obstruction from a goiter results in a blunted flow-volume loop, a pattern that is distinct from that of chronic obstructive pulmonary disease (figure 3). (See "Flow-volume loops" and "Treatment of benign obstructive or substernal goiter", section on 'Preoperative assessment'.)

Rarely, stridor may be due to bilateral recurrent laryngeal nerve palsy.

Fine-needle aspiration biopsy — FNA biopsy of goiter is indicated if there is a history of rapid growth, pain, or tenderness; unusual firmness in one region of the goiter; or sonographically detected nodules with indeterminate or suspicious sonographic features. A history of rapid growth raises the suspicion of cancer, particularly anaplastic cancer or thyroid lymphoma [32]. Although the diagnosis of lymphoma may be suggested by the fine-needle aspiration initially performed for suspicion of thyroid malignancy, subsequent large-bore needle biopsy or excisional biopsy is required in order to obtain sufficient material for definitive diagnosis by immunohistochemical studies [33].

The selection of nodules for FNA biopsy is reviewed separately. (See "Thyroid biopsy" and "Diagnostic approach to and treatment of thyroid nodules", section on 'Sonographic criteria for FNA'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis in a patient presenting with a neck mass is extensive and varies with the age of the patient at presentation. Neck masses that are not goiter may be congenital (ie, vascular anomaly), inflammatory (lymph node enlargement), or neoplastic (primary or metastatic disease) disorders. The differential diagnosis of a neck mass is reviewed separately. (See "Differential diagnosis of a neck mass".)

Patients with substernal goiter present with a mediastinal mass. Several studies have examined the causes of a mediastinal mass. The following results have been obtained with an estimate of frequency [34-36] (see "Approach to the adult patient with a mediastinal mass"):

●Substernal goiter – 5 to 24 percent

●Neurogenic tumors (eg, ganglioneuromas in the posterior mediastinum) – 20 percent

●Thymoma – 18 percent

●Bronchogenic and pericardial cysts – 15 percent

●Lymphoma – 5 to 10 percent

●Teratoma (anterior mediastinum) – 8 percent

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Thyroid nodules and cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Hyperthyroidism (overactive thyroid) (The Basics)" and "Patient education: Thyroid nodules (The Basics)" and "Patient education: Nodular goiter (The Basics)")

●Beyond the Basics topics (see "Patient education: Hyperthyroidism (overactive thyroid) (Beyond the Basics)" and "Patient education: Antithyroid drugs (Beyond the Basics)" and "Patient education: Thyroid nodules (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical manifestations – The clinical manifestations of goiter depend upon the presence of thyroid dysfunction and upon the growth rate of the goiter. Some patients may have symptoms of hypothyroidism or hyperthyroidism. However, the majority of patients with goiter are asymptomatic. Patients with longstanding goiters may develop symptoms of obstruction, due to progressive compression of the trachea or sudden enlargement (usually accompanied by pain) secondary to hemorrhage into a nodule. (See 'Clinical presentation' above and "Clinical manifestations of hypothyroidism" and "Overview of the clinical manifestations of hyperthyroidism in adults".)

●Diagnosis – The diagnosis of a goiter is usually made at the time of a physical examination. One or more discrete nodules may be palpable. Goiter may also be an incidental finding during a radiologic procedure performed for other purposes (eg, carotid ultrasound or chest CT or cervical MRI). (See 'Diagnosis' above.)

●Evaluation – Once goiter is detected, the goals of the evaluation include assessment of goiter size and for the presence of nodules, identification of compressive or obstructive symptoms, assessment of thyroid function, and identification of the underlying cause (table 1).

•History and physical examination – In patients with goiter, a history of iodine intake (including country of origin), medication history, family history of benign or malignant thyroid disease, and history of head and neck irradiation or radioiodine exposure from nuclear power plant accidents (Chernobyl, Fukushima) should be obtained. In addition, patients should be questioned about the presence of obstructive symptoms (dyspnea, cough, wheezing) or symptoms of hyper- or hypothyroidism. The thyroid and surrounding neck structures should be carefully examined. (See 'History and physical examination' above.)

•Initial tests – The initial evaluation in patients with goiter (discovered either by palpation or incidentally noted on a radiologic procedure) is measurement of serum thyroid-stimulating hormone (TSH) (algorithm 1). Many thyroid experts also check serum TPO antibodies in all patients with goiter. We typically measure TPO antibodies in patients with goiter and normal TSH to assess for Hashimoto's thyroiditis. (See 'Initial testing' above.)

We obtain a thyroid ultrasound in most patients, especially those who report rapid growth of a goiter; in patients whose physical examination reveals thyroid asymmetry, focal firm consistency, or tenderness; and in patients who have goiter with normal TSH and negative TPO antibodies. In patients with goiter due to Hashimoto's thyroiditis or Graves' disease, ultrasound should be reserved for patients with larger goiters, thyroid asymmetry, or a concern for thyroid nodules. (See 'Thyroid ultrasound' above and 'Goiter with worrisome features' above and 'Goiter with normal TSH' above and 'Goiter with high TSH' above.)

•Additional tests – Patients with abnormal TSH, worrisome features on physical examination (asymmetry, focal firm consistency, tenderness) or thyroid ultrasound, and/or obstructive symptoms require additional testing.

-Goiter with low TSH – If thyroid tests show overt hyperthyroidism (low TSH, elevated free thyroxine [T4] and/or triiodothyronine [T3]) or subclinical hyperthyroidism (low TSH, normal free T4 and T3), the cause of the hyperthyroidism should be distinguished by the findings on 24-hour radioiodine uptake and scan, by measurement of TSH receptor antibodies (TRAb), or by measurement of thyroidal blood flow on ultrasonography. (See 'Goiter with low TSH' above and "Diagnosis of hyperthyroidism", section on 'Determining the etiology'.)

-Goiter with obstructive symptoms – Additional evaluation of obstructive or substernal goiter includes imaging studies (noncontrast CT or MRI) to evaluate the extent of the goiter and its effect upon surrounding structures (image 2A-B) and a flow-volume loop study in patients with obstructive symptoms or in those with tracheal narrowing (<1 cm) on cross-sectional imaging. Unless there is need for immediate surgery, ultrasound should be obtained to assess the features of the goiter and characteristics of any nodules. (See 'Goiter with obstructive symptoms or suspected substernal goiter' above.)

-Goiter with worrisome features – Fine-needle aspiration (FNA) biopsy of goiter is indicated if there is a history of rapid growth, pain, or tenderness; unusual firmness in one region of the goiter; or sonographically detected nodules with indeterminate or suspicious sonographic features. (See 'Goiter with worrisome features' above and 'Fine-needle aspiration biopsy' above.)