Overview of the management of benign goiter

INTRODUCTION — Goiter refers to abnormal growth of the thyroid gland. Adults may have goiters that are diffuse or nodular, and the goiters may be associated with normal, decreased, or increased thyroid hormone production. The management of goiter depends upon the cause. This topic provides an overview of the management of benign goiter with specific focus on monitoring nontoxic, nonobstructive goiter. Nontoxic goiter refers to a goiter not associated with increased thyroid hormone production.

The evaluation of goiter as well as the management of iodine deficiency goiter (the most common cause of goiter worldwide), obstructive or substernal goiter, toxic multinodular goiter, Graves' disease, and thyroiditis are reviewed separately.

●(See "Clinical presentation and evaluation of goiter in adults", section on 'Approach to evaluation'.)

●(See "Iodine deficiency disorders", section on 'Diffuse and nodular goiter'.)

●(See "Treatment of benign obstructive or substernal goiter".)

●(See "Treatment of toxic adenoma and toxic multinodular goiter".)

●(See "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment".)

●(See "Subacute thyroiditis".)

●(See "Painless thyroiditis".)

INITIAL APPROACH — Once goiter is detected (on physical examination or incidentally during a radiologic procedure performed for other purposes), an evaluation is performed to assess thyroid function and to identify the underlying cause, presence of obstructive symptoms, and presence of suspicious sonographic features in nodules within the goiter. These factors determine management. Details of the evaluation are reviewed separately (algorithm 1). (See "Clinical presentation and evaluation of goiter in adults", section on 'Approach to evaluation'.)

The goals of management of benign goiter include the following:

●Treat thyroid dysfunction for patients with subclinical or overt hyperthyroidism or hypothyroidism.

●Decrease the size of the goiter for patients with symptoms or cosmetic concerns (algorithm 2).

●Monitor asymptomatic goiter to determine if it is growing.

Treat thyroid dysfunction if present

●Hypothyroidism – If present, overt hypothyroidism is treated with thyroid hormone (levothyroxine) replacement therapy. While not all patients with subclinical hypothyroidism are candidates for treatment with thyroid hormone, a secondary benefit in those who are treated may be goiter reduction. (See "Treatment of primary hypothyroidism in adults" and "Subclinical hypothyroidism in nonpregnant adults", section on 'Candidates for T4 replacement'.).

Over time, treatment with thyroid hormone may reduce the size of the goiter, particularly in patients with goitrous Hashimoto's thyroiditis who have elevated serum thyroid-stimulating hormone (TSH) levels [1]. In many cases, however, the goiter does not resolve completely, and additional therapy is occasionally required. (See 'Subsequent approach based on monitoring' below.)

●Hyperthyroidism – For patients with overt or subclinical hyperthyroidism, the etiology of hyperthyroidism (eg, toxic multinodular goiter, toxic adenoma, Graves' disease) should be confirmed. All patients with overt hyperthyroidism and many patients with subclinical hyperthyroidism require treatment. The treatment of hyperthyroidism differs according to the etiology. (See "Diagnosis of hyperthyroidism", section on 'Our approach' and "Treatment of toxic adenoma and toxic multinodular goiter", section on 'Confirm the etiology of hyperthyroidism' and "Treatment of toxic adenoma and toxic multinodular goiter", section on 'Therapeutic approach' and "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment" and "Subclinical hyperthyroidism in nonpregnant adults", section on 'Management'.)

Treat symptoms, signs, or cosmetic concerns if present — Symptoms and signs may range from mild (eg, feeling of pressure, tracheal deviation on physical examination) to severe (eg, symptoms of obstruction, such as dyspnea, dysphagia, and cough).

●Mild symptoms or signs or cosmetic concerns – For patients with mild symptoms or signs or cosmetic concerns, treatment options include continued surveillance for progression of symptoms or signs, thyroid surgery, radioiodine ablation, or ultrasound-guided thermal ablation (eg, radiofrequency ablation, where expertise is available) (algorithm 2). (See 'Monitoring patients not pursuing definitive therapy' below and "Treatment of benign obstructive or substernal goiter", section on 'Approach to surgery' and "Treatment of benign obstructive or substernal goiter", section on 'Radioiodine administration'.)

If surveillance is chosen, ideally treatment should be pursued before symptoms increase or patient develops comorbidities that may preclude surgery. (See 'Monitoring patients not pursuing definitive therapy' below and 'Subsequent approach based on monitoring' below.)

The thyroid enlargement that can occur in patients with goitrous autoimmune thyroiditis is usually asymptomatic. Rare patients have significant thyroid enlargement, sometimes with thyroid pain and tenderness. Such patients may require surgery for symptomatic relief. (See "Pathogenesis of Hashimoto's thyroiditis (chronic autoimmune thyroiditis)", section on 'Clinical phenotypes'.)

●Obstructive symptoms – Evaluation of obstructive symptoms may reveal tracheal narrowing on computed tomography (CT) scan, abnormal flow volume loop on pulmonary function tests, and/or extrinsic compression on barium swallow. Obstructive goiters may or may not have a substernal component. Most patients with obstructive symptoms or signs are treated with thyroid surgery (algorithm 2). If patient comorbidities preclude surgery or if the patient refuses surgery, radioiodine or thermal ablation (if the goiter is above the sternal notch with neck extended) may be reasonable options. (See "Treatment of benign obstructive or substernal goiter", section on 'Goiter with obstructive symptoms'.)

Asymptomatic substernal goiter — Substernal goiters are often suspected when the lower poles of an enlarged thyroid gland are not palpable on physical examination. On chest radiograph, substernal goiter may be suspected because of a mass that causes tracheal deviation or superior mediastinal widening. Because goiters are generally slow growing, patients with a substernal goiter may remain asymptomatic. In asymptomatic patients, treatment is based on the degree of substernal extension identified on CT scan.

●Extension below the brachiocephalic vein – Most patients are treated with surgery. Some goiters may continue to enlarge and become more difficult to remove if obstructive symptoms develop. In addition, it is difficult to monitor the substernal component for thyroid cancer. (See "Treatment of benign obstructive or substernal goiter", section on 'Extension below the brachiocephalic vein'.)

●Extension to the level of the brachiocephalic vein or higher – Most asymptomatic patients with goiters above the brachiocephalic vein can be monitored. (See 'Monitoring patients not pursuing definitive therapy' below and "Treatment of benign obstructive or substernal goiter", section on 'Extension to the level of the brachiocephalic vein or higher'.)

Asymptomatic cervical goiter — Most patients with asymptomatic benign multinodular goiter are monitored for the development of thyroid test abnormalities and/or for evidence of growth (see 'Monitoring patients not pursuing definitive therapy' below). Some patients with very large goiters (>80 mL) at the time of initial diagnosis may choose to have definitive treatment with thyroid surgery.

Benign multinodular goiter is the most common nontoxic goiter in older adults. Globally, longstanding iodine deficiency is the most common etiology. Adults with longstanding iodine deficiency goiter are unlikely to experience any reduction in goiter size with initiation of an iodine-sufficient diet. Iodine administration may result in hyperthyroidism in patients with iodine deficiency goiter who have autonomously functioning tissue. (See "Iodine deficiency disorders", section on 'Diffuse and nodular goiter'.)

MONITORING PATIENTS NOT PURSUING DEFINITIVE THERAPY — Patients who do not pursue definitive treatment of goiter should be monitored annually to detect thyroid function test abnormalities or evidence of growth. Multinodular goiters gradually may develop areas of autonomy and cause subclinical or overt hyperthyroidism. In addition, they may slowly grow and cause obstructive symptoms.

We perform the following assessment annually, or sooner if the patient develops new symptoms:

●Measurement of TSH and free thyroxine (T4)

●Assessment for growth of goiter

•Symptom assessment (eg, new-onset dysphagia, dyspnea, cough)

•Physical examination (eg, assessment for new nodules, substernal growth)

•Imaging, typically thyroid ultrasound

If the inferior extent of the goiter is not well seen on neck ultrasound, periodic neck noncontrast CT or magnetic resonance imaging (MRI) may be necessary to monitor for tracheal compression or if there is retrosternal extent of the goiter, as these findings warrant additional testing (eg, flow-volume loop) and, potentially, surgical management. Some experts routinely obtain noncontrast CT scans every few years in asymptomatic patients to monitor for tracheal compression or retrosternal extension of the goiter. (See "Clinical presentation and evaluation of goiter in adults", section on 'Radiologic testing'.)

Some large goiters appear to achieve a stable size, while many multinodular goiters gradually increase in size over time with the development of additional nodules, compressive symptoms, and cosmetic concerns [2]. The goal is to offer definitive treatment before development of symptoms or patient comorbidities that may preclude surgery. (See "Treatment of benign obstructive or substernal goiter", section on 'Goiter with obstructive symptoms' and "Treatment of benign obstructive or substernal goiter", section on 'Substernal goiter'.)

SUBSEQUENT APPROACH BASED ON MONITORING

Asymptomatic, stable goiter — Asymptomatic, euthyroid patients with stable, benign, multinodular or diffuse goiters should continue to be monitored annually for the development of thyroid dysfunction and for evidence of growth and/or the development of obstructive symptoms. We obtain thyroid tests (TSH, free T4) annually and a thyroid ultrasound, initially annually and then at increasing intervals (eg, two to five years) if stable.

Incident hypothyroidism — Overt hypothyroidism and most cases of subclinical hypothyroidism are treated with thyroid hormone (levothyroxine) replacement therapy. In patients with goitrous Hashimoto's thyroiditis, treatment with thyroid hormone may reduce the size of the goiter. (See "Treatment of primary hypothyroidism in adults".)

Incident hyperthyroidism — If subclinical or overt hyperthyroidism develop, the etiology of hyperthyroidism (eg, toxic multinodular goiter, toxic adenoma, Graves' disease) should be confirmed and treated appropriately. (See "Diagnosis of hyperthyroidism", section on 'Determining the etiology' and "Treatment of toxic adenoma and toxic multinodular goiter", section on 'Confirm the etiology of hyperthyroidism' and "Treatment of toxic adenoma and toxic multinodular goiter", section on 'Therapeutic approach' and "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment" and "Subclinical hyperthyroidism in nonpregnant adults", section on 'Endogenous subclinical hyperthyroidism'.)

New suspicious nodule(s) — New nodules with indeterminate or suspicious ultrasound features warrant fine-needle aspiration (FNA) because the prevalence of cancer in an individual nodule in a goiter is independent of the number of sonographically identified nodules. Patients with nodules within a goiter that are malignant or suspicious for malignancy on FNA biopsy require surgery. The evaluation and management of thyroid nodules are reviewed separately. (See "Diagnostic approach to and treatment of thyroid nodules" and "Diagnostic approach to and treatment of thyroid nodules", section on 'Management' and "Differentiated thyroid cancer: Surgical treatment".)

Growing benign goiter — For many patients with benign goiters that continue to grow on serial imaging, we prefer active treatment rather than monitoring. The decision to pursue active treatment is based on the trajectory of growth, the age of the patient, and the anticipated risk of developing obstructive symptoms over time. The goal is to offer definite treatment before the development of obstructive symptoms or patient comorbidities that may preclude surgery. For patients with minimally substernal goiters, the goal is to treat before the goiter extends into the chest.

In the absence of adequate randomized trial data, management decisions should be individualized based upon patient factors, regional medical practices, and advantages and disadvantages of each modality (table 1) [2-5]. (See "Treatment of benign obstructive or substernal goiter", section on 'Radioiodine administration'.)

●Preferred treatment – For most euthyroid patients with benign goiters that continue to grow and potentially cause obstructive signs, symptoms, or cosmetic concerns, we suggest surgery. The decision to perform thyroidectomy may also be based upon the development of other concomitant conditions such as hyperparathyroidism requiring surgery. Total or near-total thyroidectomy is preferred over subtotal thyroidectomy. In a Cochrane review of four randomized trials including 1305 patients, recurrent goitrous growth occurred in 0.2 percent of patients after total thyroidectomy and 8.4 percent of patients after a subtotal thyroidectomy [6]. (See "Treatment of benign obstructive or substernal goiter", section on 'Approach to surgery' and "Thyroidectomy".)

●Other reasonable options – Radioiodine or ultrasound-guided thermal ablation techniques (if expertise is available) may be reasonable options for patients with nontoxic benign nodular goiter who have comorbidities that preclude thyroid surgery or who prefer to avoid surgery (table 1). (See "Treatment of benign obstructive or substernal goiter", section on 'Complications'.)

•Radioiodine – Compared with surgery, the reduction in thyroid volume with radioiodine is only moderate (eg, approximately 50 percent after two years for nodular goiter) [4]. The magnitude of the reduction is directly related to iodine dose and indirectly to goiter size [4,7]. The treated nodular goiter requires continued monitoring for growth, and monitoring must be interpreted carefully. Goitrous tissues treated with radioiodine acquire falsely suspicious ultrasonographic characteristics and also falsely suspicious FNA cytology findings, which may require surgery for reassurance. (See "Treatment of benign obstructive or substernal goiter", section on 'Radioiodine administration'.)

There are few observational studies of radioiodine therapy for the treatment of nontoxic diffuse goiter [8,9]. In one study, median thyroid volume reduction was 50 percent within two years of therapy [9]. There is one report of the use of radioiodine in goitrous Hashimoto's thyroiditis unresponsive to levothyroxine-suppressive therapy [10]. Thirteen patients received two to six doses of 13 millicuries radioiodine at one- to six-month intervals, which resulted in a 59 percent reduction in goiter size.

•Ultrasound-guided thermal ablation – Ultrasound-guided thermal ablation (where expertise is available) is also an option to reduce nodular growth (table 1) [5,11-14]. In observational studies, the mean reduction in thyroid volume at 6 to 12 months ranges from 65 to 80 percent [5]. (See "Diagnostic approach to and treatment of thyroid nodules", section on 'Symptomatic benign nodules'.)

●Limited role in selected patients – We do not typically treat patients with nontoxic benign goiters with thyroid hormone suppressive therapy. The efficacy of thyroid hormone suppressive therapy in euthyroid patients with sporadic nontoxic goiter is controversial, and its use has declined due to concerns about potential long-term side effects from the induction of iatrogenic subclinical or overt hyperthyroidism. Thyroid hormone suppressive therapy is not an option for patients with serum TSH concentrations at the lower limit of or just below the normal range, because these patients already have endogenous suppression of TSH. When used, levothyroxine must be continued long term as any reduction in goiter size during therapy is lost upon discontinuation of levothyroxine [15]. This topic is reviewed in detail separately. (See "Thyroid hormone suppressive therapy for thyroid nodules and benign goiter", section on 'Irradiated patients'.)

There are few trials comparing interventions. In one trial, 64 patients with sporadic nontoxic multinodular goiter (average size 60 mL) were randomly assigned to radioiodine (120 microcuries [4.44 megabecquerels]/g thyroid) or suppressive levothyroxine treatment (goal TSH between 0.01 and 0.1 mU/L). After two years, 97 percent of the patients treated with radioiodine and 43 percent of those treated with levothyroxine had a decrease in goiter size. The median decrease in goiter size (by ultrasound) was 41 percent in the group treated with radioiodine compared with a clinically insignificant 5 percent in the suppressive levothyroxine treatment group as a whole, but the responders in the suppressive levothyroxine group had a 22 percent reduction in goiter size [16]. Although none of the patients had overt hyperthyroidism at baseline, 17 had subclinical hyperthyroidism (low TSH, normal free T4), which may bias the results in favor of radioiodine. Hypothyroidism developed in 45 percent of patients receiving radioiodine. Patients who were treated with suppressive doses of thyroid hormone were more likely to have thyrotoxic symptoms and a decrease in bone mineral density (BMD; mean decrease of 3.6 percent at the lumbar spine, compared with no change in the radioiodine group).

In an observational study examining quality-of-life indicators in patients with nontoxic benign goiter, the treatment modality (predominantly surgery or radioiodine) did not affect change in scale scores, which improved posttreatment but remained worse than those in the general population [17].

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

●Initial approach – For patients with benign goiter, the goals of management include (see 'Initial approach' above):

•Treating thyroid dysfunction for patients with subclinical or overt hyperthyroidism or hypothyroidism

•Decreasing the size of the goiter for patients with symptoms or cosmetic concerns (algorithm 2)

•Monitoring asymptomatic goiter to determine if it is growing

●Symptomatic goiter

•Obstructive signs or symptoms – Most patients with obstructive substernal or cervical goiter are treated with thyroid surgery. If patient comorbidities preclude surgery or if the patient refuses surgery, radioiodine or thermal ablation (if the goiter is above the sternal notch with neck extended) may be reasonable options (algorithm 2). (See "Treatment of benign obstructive or substernal goiter", section on 'Approach to surgery'.)

•Mild symptoms or signs or cosmetic concerns – For patients with mild symptoms or cosmetic concerns, treatment options include continued surveillance for progression of symptoms or signs, thyroid surgery, radioiodine, or ultrasound-guided thermal ablation (eg, radiofrequency ablation, where expertise is available) (table 1). If surveillance is chosen, ideally treatment should be pursued before symptoms increase or patient develops comorbidities that may preclude surgery. (See 'Treat symptoms, signs, or cosmetic concerns if present' above.)

●Asymptomatic substernal goiter – For patients with asymptomatic substernal goiter, treatment is based on the degree of substernal extension identified on CT scan. (See 'Asymptomatic substernal goiter' above and "Treatment of benign obstructive or substernal goiter", section on 'Substernal goiter'.)

●Asymptomatic cervical goiter – Most patients with benign nonobstructive cervical goiter (including benign multinodular goiter, goitrous Hashimoto's thyroiditis, and iodine deficiency goiter) are monitored for the development of thyroid test abnormalities and/or for evidence of growth (algorithm 2). Some patients with very large goiters (>80 mL) at the time of initial diagnosis may choose to have definitive treatment with thyroid surgery. (See 'Asymptomatic cervical goiter' above.)

●Monitoring in patients not pursuing definitive therapy – We perform the following assessment annually, or sooner if the patient develops new symptoms (see 'Monitoring patients not pursuing definitive therapy' above):

•Measurement of thyroid-stimulating hormone (TSH) and free thyroxine (T4)

•Assessment for growth of goiter

-Symptom assessment (eg, new-onset dysphagia, dyspnea, cough)

-Physical examination (eg, assessment for new nodules, substernal growth)

-Imaging, typically thyroid ultrasound

A noncontrast CT scan may also be obtained at less frequent intervals to better assess tracheal compression and retrosternal extension of the goiter.

●Subsequent approach based on monitoring – Some large goiters appear to achieve a stable size, while many multinodular goiters gradually grow over time with the development of additional nodules, compressive symptoms, and cosmetic concerns. The goal is to offer definitive treatment before development of symptoms or patient comorbidities that my preclude surgery.

•Asymptomatic, stable goiter – Asymptomatic, euthyroid patients with stable, benign, multinodular or diffuse goiters should continue to be monitored annually for the development of thyroid dysfunction and for evidence of growth and/or the development of obstructive symptoms. We obtain thyroid tests (TSH, free T4) annually and a thyroid ultrasound, initially annually and then at increasing intervals (eg, two to five years) if stable. (See 'Asymptomatic, stable goiter' above.)

•Incident hypothyroidism, hyperthyroidism, or suspicious nodule(s) – Incident hypothyroidism or hyperthyroidism should be treated. New suspicious nodules warrant fine-needle aspiration (FNA) biopsy. (See 'Incident hypothyroidism' above and 'Incident hyperthyroidism' above and 'New suspicious nodule(s)' above and "Treatment of primary hypothyroidism in adults" and "Treatment of toxic adenoma and toxic multinodular goiter" and "Diagnostic approach to and treatment of thyroid nodules".)

•Growing benign goiter – For many euthyroid patients with benign goiters that continue to grow on serial imaging, we suggest active treatment rather than ongoing surveillance (Grade 2C). The decision to pursue active treatment is based on the trajectory of growth, the age of the patient, and the anticipated risk of developing obstructive symptoms over time. (See 'Growing benign goiter' above.)

The choice of active treatment should be individualized based upon patient factors, regional medical practices, and advantages and disadvantages of each modality (table 1). For most patients we suggest surgery (Grade 2C). Radioiodine or ultrasound-guided thermal ablation techniques (if expertise is available) may be reasonable options for patients with nodular goiters who have comorbidities that preclude thyroid surgery or who prefer to avoid surgery. In addition, radioiodine may be particularly useful for those patients with low-normal TSH concentrations whose nodular goiters have autonomous areas with relatively higher radioiodine uptake. (See 'Growing benign goiter' above.)

The role of thyroid hormone suppression therapy is controversial, and its use has declined primarily due to concerns about potential long-term side effects from the induction of subclinical or overt hyperthyroidism. (See "Thyroid hormone suppressive therapy for thyroid nodules and benign goiter".)