INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

In 1656, Thomas Wharton described the distinct nature of what he termed the thyroid gland, distinguishing it from the larynx, as this structure had been considered a laryngeal gland from the time of Andreas Vesalius in the 16th century. It was nearly 200 more years before the function of the thyroid was elucidated. The normal adult thyroid gland weighs 10-25 g and has 2 lobes connected by an isthmus. Nearly 50% of thyroid glands exhibit a pyramidal lobe arising from the center of the isthmus. Longitudinal dimensions of the lobes of the thyroid range up to 5 cm.

A goiter is an enlarged thyroid gland, and it may be diffuse or nodular. A goiter may extend into the retrosternal space, with or without substantial anterior enlargement. Because of the anatomic relationship of the thyroid gland to the trachea, larynx, superior and inferior laryngeal nerves, and esophagus, abnormal growth may cause a variety of compressive syndromes. Thyroid function may be normal (nontoxic goiter), overactive (toxic goiter), or underactive (hypothyroid goiter).

Pathophysiology

The thyroid gland is controlled by thyrotropin (TSH), secreted from the pituitary gland, which, in turn, is influenced by the thyrotropin-releasing hormone (TRH) from the hypothalamus. TSH permits growth, cellular differentiation, and thyroid hormone production and secretion by the thyroid gland. Thyrotropin acts on TSH receptors located on the thyroid gland. Serum thyroid hormones levothyroxine and triiodothyronine feed back to the pituitary, regulating TSH production. Interference with this TRH-TSH thyroid hormone axis causes changes in the function and structure of the thyroid gland. Stimulation of the TSH receptors of the thyroid by TSH, TSH-receptor antibodies, or TSH receptor agonists, such as chorionic gonadotropin, may result in a diffuse goiter. When a small group of thyroid cells, inflammatory cells, or malignant cells metastatic to the thyroid is involved, a thyroid nodule may develop.

A deficiency in thyroid hormone synthesis or intake leads to increased TSH production. Increased TSH causes increased cellularity and hyperplasia of the thyroid gland in an attempt to normalize thyroid hormone levels. If this process is sustained, a goiter is established. Causes of thyroid hormone deficiency include inborn errors of thyroid hormone synthesis, iodine deficiency, and goitrogens.

Goiter may result from a number of TSH receptor agonists. TSH receptor stimulators include TSH receptor antibodies, pituitary resistance to thyroid hormone, adenomas of the hypothalamus or pituitary gland, and tumors producing human chorionic gonadotropin.

Frequency

United States

Autopsy studies suggest a frequency of greater than 50% for thyroid nodules; with high-resolution ultrasound, the value approaches 40% of patients with nonthyroidal illness. In the Wickham study from the United Kingdom, 16% of the population had a goiter. In the Framingham study, ultrasonography revealed that 3% of men older than 60 years had thyroid nodules, while 36% of women aged 49-58 years had thyroid nodules. In the United States, most goiters are due to autoimmune thyroiditis (ie, Hashimoto disease).

International

Worldwide, the most common cause of goiter is iodine deficiency. It is estimated that goiters affect as many as 200 million of the 800 million people who have a diet deficient in iodine.

Mortality/Morbidity

Most goiters are benign, causing only cosmetic disfigurement. Morbidity or mortality may result from compression of surrounding structures, thyroid cancer, hyperthyroidism, or hypothyroidism.

Race

No racial predilection exists.

Sex

The female-to-male ratio is 4:1.

• In the Wickham study, 26% of women had a goiter, compared to 7% of men.
• Thyroid nodules are less frequent in men than in women, but when found, they are more likely to be malignant.

Age

The frequency of goiters decreases with advancing age. The decrease in frequency differs from the incidence of thyroid nodules, which increases with advancing age.

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

A goiter may present in various ways, including the following:

• Incidentally, as a swelling in the neck discovered by the patient or on routine physical examination
• A finding on imaging studies performed for a related or unrelated medical evaluation
• Local compression causing dysphagia, dyspnea, stridor, plethora or hoarseness
• Pain due to hemorrhage, inflammation, necrosis, or malignant transformation
• Signs and symptoms of hyperthyroidism or hypothyroidism
• Thyroid cancer with or without metastases

Physical

The general examination for hyperthyroidism, hypothyroidism, and autoimmune stigmata is followed by systematic examination of the goiter.

• A retrosternal goiter may not be evident on physical examination.
• Examination of the goiter is best performed with the patient upright, sitting or standing. Inspection from the side may better outline the thyroid profile (see Image 1). Asking the patient to take a sip of water facilitates inspection. The thyroid should move upon swallowing.
• Palpation of the goiter is performed either facing the patient or from behind the patient, with the neck relaxed and not hyperextended. Palpation of the goiter rules out a pseudogoiter, which is a prominent thyroid seen in individuals who are thin. Each lobe is palpated for size, consistency, nodules, and tenderness. Cervical lymph nodes are then palpated. The oropharynx is visualized for the presence of lingular thyroid tissue.
• The size of each lobe is measured in 2 dimensions using a tape measure. Some examiners make tracings on a sheet of paper, which is placed in the patient's chart. Suitable landmarks are used and documented to ensure consistent measurement of the thyroid gland.
• The pyramidal lobe often is enlarged in Graves disease.
• A firm rubbery thyroid gland suggests Hashimoto thyroiditis, and a hard thyroid gland suggests malignancy or Reidel struma.
• Multiple nodules may suggest a multinodular goiter or Hashimoto thyroiditis. A solitary hard nodule suggests malignancy, whereas a solitary firm nodule may be a thyroid cyst.
• Diffuse thyroid tenderness suggests subacute thyroiditis, and local thyroid tenderness suggests intranodal hemorrhage or necrosis.
• Cervical lymph glands are palpated for signs of metastatic thyroid cancer.
• Auscultation of a soft bruit over the inferior thyroidal artery may be appreciated in a toxic goiter. Palpation of a toxic goiter may reveal a thrill in the profoundly hyperthyroid patient.
• Goiters are described in a variety of ways, including the following:
• • Toxic goiter: A goiter that is associated with hyperthyroidism is described as a toxic goiter. Examples of toxic goiters include diffuse toxic goiter (Graves disease), toxic multinodular goiter, and toxic adenoma (Plummer disease).
  • Nontoxic goiter: A goiter without hyperthyroidism or hypothyroidism is described as a nontoxic goiter. It may be diffuse or multinodular, but a diffuse goiter often evolves into a nodular goiter. Examination of the thyroid may not reveal small or posterior nodules. Examples of nontoxic goiters include chronic lymphocytic thyroiditis (Hashimoto disease), goiter identified in early Graves disease, endemic goiter, sporadic goiter, congenital goiter, and physiologic goiter that occurs during puberty.
• Autonomously functioning nodules may present with inability to palpate the contralateral lobe. Unilobar agenesis may also present like a single thyroid nodule with hyperplasia of the remaining lobe.
• The Pemberton maneuver raises a goiter into the thoracic inlet when the patient elevates the arms. This may cause shortness of breath, stridor, or distention of neck veins.

Causes

The different etiologic mechanisms that can cause a goiter include the following:

• Iodine deficiency
• Autoimmune thyroiditis - Hashimoto or postpartum thyroiditis
• Excess iodine (Wolff-Chaikoff effect) or lithium ingestion, which decrease release of thyroid hormone
• Goitrogens
• Stimulation of TSH receptors by TSH from pituitary tumors, pituitary thyroid hormone resistance, gonadotropins, and/or thyroid-stimulating immunoglobulins
• Inborn errors of metabolism causing defects in biosynthesis of thyroid hormones
• Exposure to radiation
• Deposition diseases
• Thyroid hormone resistance
• Subacute thyroiditis (de Quervain thyroiditis)
• Silent thyroiditis
• Riedel thyroiditis
• Infectious agents
• • Acute suppurative - Bacterial
  • Chronic - Mycobacteria, fungal, and parasitic
• Granulomatous disease
• Thyroid malignancy

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Branchial cleft cyst
Thyroglossal duct cyst
Cystic hygroma
Pseudogoiter
Lymphadenopathy
Carotid artery aneurysm
Parathyroid cyst
Parathyroid adenoma
Sarcoma
Fibroma
Thyroid abscess
Granulomatous disease of the thyroid
Infectious thyroiditis
Thyrotoxicosis

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

• Initial screening should include TSH. Given the sensitive third-generation assays in the absence of symptoms of hyper or hypothyroidism further testing is not required. An assessment of free thyroxine index or direct measurement of free thyroxine would be the next step in the evaluation.
• Further laboratory testing is based on presentation and results of screening studies and may include thyroid antibodies (antithyroid peroxidase formerly the antimicrosomal antibodies and antithyroglobulin), thyroglobulin, sedimentation rate and calcitonin in an individual at high risk for medullary carcinoma of the thyroid.

Imaging Studies

• Ultrasound
• • Establish and follow goiter size, consistency, and nodularity.
  • Localize nodules for ultrasound-guided biopsy.
• Roentgenography
• • Roentgenography is used to assess extent of a goiter and presence of calcification. Ultrasound has replaced this modality.
  • Roentgenography is used to visualize calcifications within a goiter and regional lymph glands.
• Computed tomography scan
• • CT scan is more precise than x-rays.
  • CT scan can be used to delineate size and goiter extent. Due to the superficial placement of the thyroid gland, ultrasound is more useful in following size. CT scan does a much better job of determining the effect of the thyroid gland on nearby structures. It also may be useful in the follow-up of patients with thyroid cancer that shows evidence of recurrence.
  • CT scan can be used to guide biopsy of the thyroid.
• Magnetic resonance imaging has the same indications as CT scan (see above).
• Radionuclide uptake and radionuclide scan are used to assess thyroid function and anatomy in hyperthyroidism (see Image 2). Additionally, thyroid scanning may be useful in the patient with neck or superior mediastinal masses. Radionuclide scanning allows determination of the function of a nodule. Function of a thyroid nodule has value both diagnostically and therapeutically.
• Barium swallow is used to assess esophageal obstruction.
• Spirometry: The flow-volume loop is useful in determining the functional significance of compressive goiters.
• Perchlorate discharge test is used in individuals with inborn errors of thyroid hormone synthesis. It is used rarely today to determine the ability to trap and organify iodine.

Procedures

• Fine-needle aspiration biopsy is used for cytologic diagnosis. Fine-needle aspiration of the thyroid is used to determine the cause of an enlarged gland. In general, the procedure is not used in the workup of autonomously functioning nodules. The procedure has little morbidity and can be tailored to the situation.
• Core biopsy, or large-needle biopsy, of the thyroid uses a larger gauge needle providing a fragment of tissue. This procedure also carries with it a higher morbidity. Core biopsy has the advantage of more complete sampling.
• Partial thyroidectomy may be used as a first-line procedure for patients with a high probability of cancer. It is reserved mostly if the result of a fine-needle aspiration is suspicious or if the patient/physician prefers it.
• Total thyroidectomy is performed for malignant goiters.

Histologic Findings

Simple nontoxic goiters show hyperplasia, colloid accumulation, and nodularity. Nodular hyperplasia is commonly seen in multinodular goiter. Cytologic findings include benign appearing follicular cells, abundant colloid, macrophages, and, sometimes, Hürthle cells. Inflammatory disorders of the thyroid, such as chronic lymphocytic (Hashimoto) thyroiditis, contain a mixed population of lymphocytes mixed with benign appearing follicular cells. Malignant nodules may be follicular cell in origin, ie, papillary (most common), follicular, Hürthle cell, or anaplastic. They also may be from parafollicular cells, medullary carcinoma or lymphoma, or other categories.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

Small benign euthyroid goiters do not require treatment. The effectiveness of medical treatment using thyroid hormone for benign goiters is controversial. Large and complicated goiters may require medical and surgical treatment. Malignant goiters require medical and surgical treatment.

• The size of a benign euthyroid goiter may be reduced with levothyroxine suppressive therapy. The patient is monitored to keep serum TSH in a low but detectable range to avoid hyperthyroidism, cardiac arrhythmias, and osteoporosis. The patient has to be compliant with monitoring. Some authorities suggest suppressive treatment for a definite time period instead of indefinite therapy. Patients with Hashimoto thyroiditis respond better.
• Treatment of hypothyroidism or hyperthyroidism often reduces the size of a goiter.
• Thyroid hormone replacement is often required following surgical and radiation treatment of a goiter. Use of radioactive iodine for the therapy of nontoxic goiter has been disappointing and is controversial.
• Medical therapy of autonomous nodules with thyroid hormone is not indicated.
• Ethanol infusion into benign thyroid nodules has not been approved in the United States, but it is used elsewhere.

Surgical Care

Surgery is reserved for the following situations:

• Large goiters with compression
• Malignancy
• When other forms of therapy are not practical or ineffective

Consultations

An endocrinologist should assess a patient at least once, and assessment should be even more frequent if the goiter is complicated by thyroid dysfunction or malignancy or if the patient is being considered for surgical management.

Diet

Nutrition plays a role in the development of endemic goiters. Dietary factors include iodine deficiency, goitrogens, protein malnutrition, and energy malnutrition. Often these factors occur concurrently.

• Iodine: If it is practical, treat endemic goiters in iodine-deficient regions with iodine supplementation in the diet and avoidance of goitrogens. Treatment with iodine supplementation or levothyroxine may reduce goiter size.
• Goitrogens
• • Cyanoglucosides are naturally occurring goitrogens that are digested to release cyanide, which is converted to thiocyanate. Thiocyanate inhibits iodide transport in the thyroid and, at higher levels, inhibits organification. Foods that contain cyanoglucosides include cassava, lima beans, maize, bamboo shoots, and sweet potatoes.
  • Thioglucosides are natural goitrogens found in the Cruciferae family of vegetables and weeds eaten by animals. When digested, they release thiocyanate and isothiocyanate, which have thionamidelike properties and are passed to humans via milk ingestion.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Thyroid hormone replacements

Benign goiters can be treated with thyroid hormone. The most widely used thyroid hormone is levothyroxine sodium, administered once a day. Liothyronine sodium requires more frequent administration. Desiccated thyroid powder, thyroglobulin, and liotrix are less predictable following ingestion.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Further Inpatient Care

• Preoperative management
• • Establish euthyroid state prior to surgical treatment.
  • Evaluation must include the stability of the airway. This must be secured immediately if ventilatory status appears tenuous.
  • Emergency surgical treatment of a goiter in a patient with hypothyroidism requires intravenous levothyroxine and glucocorticoids at stress doses.
  • Emergency surgical treatment of a goiter in a thyrotoxic patient requires antithyroid medications, beta-blockers, and glucocorticoids at stress doses. Suppressive doses of iodine are helpful.
• Intraoperative and postoperative management: Hemodynamic monitoring is important in patients with preoperative hyperthyroidism or hypothyroidism.
• Postoperative management also includes monitoring of serum calcium.

Further Outpatient Care

Patients are monitored for hypothyroidism by history, examination, and TSH measurements. Initially, monitoring occurs every 6-8 weeks.

In/Out Patient Meds

Benign euthyroid goiters do not require any medication. Goiters with primary thyroid malignancy require levothyroxine replacement after surgery and radioactive iodine ablation. Metastatic lesions to the thyroid gland require treatment of the primary malignancy. Granulomatous and infectious etiologies for goiter require specific treatment depending on the underlying cause.

Deterrence/Prevention

• Goiter prevention is based on etiology.
• • Correct iodine deficiency and avoid dietary or iatrogenic goitrogens if practical. In the United States, it is difficult to find iodine deficiency, given the supplementation of table salt with iodine, iodine in cattle feed, and the use of iodine as a dough conditioner. Judicious use of levothyroxine is helpful in patients with a previous diagnosis of nodular hyperplasia who have had a lobectomy to prevent occurrences in the contralateral lobe.
  • Goiters due to autoimmune thyroiditis may be controlled with careful use of levothyroxine and, when indicated, anti-inflammatory medication.
  • Congenital goiters due to inborn errors of metabolism may be reduced or prevented by careful use of levothyroxine during the postpartum period. Newborns are screened for congenital hypothyroidism.

Complications

• Large goiters may cause compression of the trachea, with tracheomalacia and asphyxiation.
• Hyperthyroidism occurs in some patients exposed to iodine (ie, Jodbasedow phenomenon).
• A patient with autoimmune goiters may develop lymphoma. Multinodular goiters may undergo malignant transformation.
• Nodular goiters may cause pain, intranodular necrosis, or hemorrhage.
• Thyroid abscess may be associated with pain, fever, bacteremia, or sepsis.

Prognosis

• Benign goiters have a good prognosis. However, all goiters should be monitored by examination and biopsy for possible malignant transformation, which may be signaled by a sudden change in size, pain, or consistency. Fortunately, the risk of this is low. In patients exposed to low levels of radiation the risk rises.
• Based on the Wickham study, a few of the goiters increased in size.
• A small percentage of multinodular goiters do cause hyperthyroidism. Lifelong surveillance is necessary.
• Patients with chronic lymphocytic thyroiditis generally have glands that become atrophic.

Patient Education

• Educate a patient about potential etiologies, eg, adequate dietary iodine intake, avoidance of goitrogens, regular personal neck examination, and physician examination.
• For patients on medical therapy, reinforce the need to take medications on a regular basis. Review symptoms of hyperthyroidism.
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Autoimmune thyroiditis goiter may develop into thyroid lymphoma.
• Evaluate a goiter with diastolic hypertension for pheochromocytoma.
• A thyroid nodule could be a parathyroid tumor.
• Pain and enlargement of a nodule may be due to hemorrhage or anaplastic carcinoma.
• Rapid growth of the thyroid in a patient with extrathyroidal cancer may signal metastasis to the thyroid.
• A goiter with prior radiation exposure may develop lymphoma.
• Levothyroxine use for goiter control warrants close monitoring to avoid hyperthyroidism, arrhythmias, and osteoporosis.
• Hyperthyroidism may masquerade as a papillary carcinoma.
• Thyroid fine-needle aspiration becomes less reliable in large goiters because of sampling bias. Thyroid cysts should not be left without first detecting the underlying cause. Nondiagnostic biopsy findings should precipitate further investigation, which may include performing an additional biopsy or more invasive procedures, depending on the clinical situation.

Special Concerns

• Withhold treatment of a benign euthyroid goiter in patients who are pregnant until after delivery.
• Thyroidectomy, if necessary, can be more safely performed in the second trimester.

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

I acknowledge my mentors for the foundations, my patients for their contributions to my knowledge, and my family for their patience.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Patient with a goiter. Prominent side-view outline.
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Media file 2:  Thyroid nuclear scan of a patient with a euthyroid goiter showing different projections.
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Media type:  Graph

Media file 3:  Patient with goiter.
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Media type:  Photo

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

• Arda IS, Yildirim S, Demirhan B, Firat S. Fine needle aspiration biopsy of thyroid nodules. Arch Dis Chil. 2001;85(4):313-7. [Medline].
• Bardin CW. Endemic goiter. In: Current Therapy in Endocrinology and Metabolism. 6^th ed. Mosby-Year Book; 1997:101-112.
• Becker KL, Bilezikian JP, Bremner WJ. Nontoxic goiter. In: Principles and Practice of Endocrinology and Metabolism. 2^nd ed. Lippincott Williams & Wilkins; 1995:338-345.
• Bostanci I, Sarioglu A, Ergin H, Aksit A, Cinbis M, Akalin N. Neonatal goiter caused by expectorant usage. J Pediatr Endocrinol Metab. Sep-Oct 2001;14(8):1161-2. [Medline].
• Braverman LE, Utiger RD. Thyroid diseases: nontoxic diffuse and multinodular goiter. In: Werner and Ingbar, eds. The Thyroid: A Fundamental and Clinical Text. 7^th ed. Lippincott-Raven; 1996:889-900.
• Gross JL. Ultrasonography in management of nodular thyroid disease. Annals of internal medicine. 2001;135(5):383-4. [Medline].
• Romanchishen AF, Iakovlev PN. [Special surgical treatment of patients with nodular tumors of the thyroid gland against the background of diffuse toxic goiter]. Vestn Khir Im I I Grek. 2005;164(1):21-4. [Medline].
• Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med. Nov 10 1994;331(19):1249-52. [Medline].
• Schumm-Draeger PM. [Every third German has a sick thyroid gland. Nodules and goiter are a challenge that needs to be met]. MMW Fortschr Med. Feb 5 2004;146(6):20. [Medline].
• Thompson L. Dyshormonogenetic goiter of the thyroid gland. Ear Nose Throat J. Apr 2005;84(4):200. [Medline].
• Vetshev PS, Chilingaridi KE, Bannyi DA, Dmitriev EE. [Repeated surgeries on the thyroid gland in nodular euthyroid goiter]. Khirurgiia (Mosk). 2004;37-40. [Medline].
• Wilson JD, Foster DW. The thyroid gland. In: Williams Textbook of Endocrinology. 8^th ed. Harcourt Brace & Co; 1992:463-465.

Article Last Updated: Sep 25, 2007