Epidemiology

Thyroid nodules are typically benign growths of thyroid cells that form within the thyroid gland. Goiter is an enlargement of the thyroid gland; simple goiter describes diffuse swelling of the gland, nodular goiter describes the presence of a solid or filled lump in the thyroid gland, and multinodular goiter occurs when several abnormal growths of thyroid cells are present.¹ Goiter may occur as a result of hyperthyroidism or hypothyroidism, and factors contributing to the development of multinodular goiter include iodine deficiency and genetic or environmental causes.²

The prevalence of goiter varies geographically and may be influenced by the iodine intake of the population. Studies have reported the prevalence of goiter in the adult population to range from 30% to 50% based on sonography data, and the prevalence of goiter may be higher in older adults and those residing in areas with iodine deficiency.²

Because goiter has been diagnosed in people who reside in areas without iodine deficiency, other factors may contribute to its development.Some of these include other environmental causes, gene abnormalities, and demographic causes.Environmental contributors that may interfere with the endocrine system and contribute to the development of goiter include exposure to the following²:

Perchlorate
Thiocyanate
Phthalates
Nitrates
Isoflavones
Organochlorines

Illicit drugs, smoking, and alcohol consumption may contribute to the development of goiter, as may oral contraceptives, pregnancy, insulin resistance, and selenium deficiency.²

Diagnosis of Multinodular Goiter

Patients may feel a lump in their neck, which prompts them to seek medical attention.² Nodules may also be found after routine thyroid laboratory tests show abnormalities.¹ Thyroid nodules may also be incidental findings on imaging studies — such as ultrasound, computerized tomography (CT), or magnetic resonance imaging (MRI) of the head, neck, or chest — performed for unrelated health concerns.²

Although thyroid nodules are typically noncancerous (benign), large ones can cause problems, such as²:

Dysphagia (choking and difficulty swallowing)
Tightness of the neck
Hoarseness due to compression of the laryngeal nerve

Although most thyroid nodules do not produce thyroid hormone, increased thyroid hormone secretion may occur with multinodular goiter.² Some patients may notice pain in their ear, neck, or jaw, but this is not a common complaint.¹

Diagnostic Workup for Multinodular Goiter

Approximately 5% to 15% of nodules may be cancerous (malignant).²

Nodules that are 1 to 1.5 cm in diameter or larger should prompt further evaluation. Laboratory testing, imaging studies, and fine-needle aspiration biopsy should be considered for nodules of this size. Malignancy may be more likely if the patient has the following characteristics²:

30 years of age or younger;
Male sex;
History of radiation to the neck as a child or young adult;
History of radiation therapy due to a bone marrow transplant;
Rapid growth of a nodule;
Significant changes in swallowing, breathing, or speaking; and/or
A family history of multiple endocrine neoplasia type 2 (MEN2), although this is a rare occurrence.

Nodules that are large, firm, and fixed are suspicious for cancer, particularly with concurrent local lymphadenopathy.² When multiple nodules are present, each must be evaluated. Higher thyroid-stimulating hormone (TSH) levels, including those that may be considered within the normal range, may indicate that a nodule is cancerous.²

Serum anti-thyroid peroxidase antibody concentration may be helpful in diagnosing Hashimoto thyroiditis (chronic lymphocytic thyroiditis) when TSH is elevated. Ultrasound is the preferred method of determining risk of malignancy, with nodules classified as high (70% to 90% risk of malignancy), intermediate (25% risk of malignancy), low (10% risk of malignancy), or very low risk.²

Management of Multinodular Goiter

The first step in the management of multinodular goiter is to correct any underlying causes of thyroid dysfunction. After physical examination, laboratory assessment, and imaging studies, the goiter should be evaluated for active growth and if there is any obstruction of the trachea or esophagus. Patients with suspicious nodules should undergo fine needle aspiration biopsy to rule out malignancy. The risks and benefits of different treatment options, including surgery, should be discussed with the patient.³

Treatment options for multinodular goiter include surgery, radioiodine, or levothyroxine. Surgery to remove either a portion of or the entire thyroid gland (thyroidectomy) is the preferred treatment when the goiter is large or when the trachea, esophagus, or other vital structures are compressed. Risks associated with thyroidectomy include possible hemorrhage after surgery or damage to the laryngeal nerve.

Following total removal of the thyroid gland, patients will need to take thyroxine hormone replacement (levothyroxine, 1.4 to 2.2 μg/kg/d), with the dose adjusted based on the patient’s age. Treatment with levothyroxine is not required for patients undergoing partial thyroidectomy who do not experience hypothyroidism, as the benefit of prophylactic levothyroxine treatment to prevent recurrence of goiter has not been confirmed in clinical trials.³

Radioiodine has grown in favor for patients with multinodular goiter who are not willing or not able to undergo surgery. Giving recombinant human TSH prior to radioiodine increases radioiodine uptake in the thyroid gland. There are few side effects associated with radioiodine and treatment can be repeated, if needed. Risks associated with treatment include the development of thyroiditis, Graves disease, or hypothyroidism. Very large goiters will take time to shrink compared with surgery, which results in rapid relief of goiter symptoms.³

Adverse effects and lack of efficacy have caused levothyroxine to become less favorable as a treatment for multinodular goiter. Long-term suppression of TSH can result in subclinical hyperthyroidism, arrhythmias, and bone demineralization. Advantages of using levothyroxine include its low cost, ease of use in the outpatient setting, and possible prevention of the development of nodules.³

Patients with smaller goiters should undergo fine needle aspiration biopsy to rule out malignancy. If thyroid function is normal in these patients, further treatment may not be necessary unless the goiter changes in size or other symptoms develop.³

Side Effects and Drug-Drug Interactions Associated With Levothyroxine

Patients who are prescribed levothyroxine as treatment for multinodular goiter should be counseled about possible side effects and drug interactions. The following side effects have been reported with levothyroxine treatment⁴:

Headache
Cardiac arrhythmias
Shortness of breath
Weight loss
Feeling nervous and irritable
Increased appetite
Insomnia
Heat intolerance

Drug interactions may occur with coadministration of levothyroxine and the following agents⁴:

Androgens
Bile acid sequestrants
Beta-blockers
Phosphate binders, such as calcium carbonate
Orlistat
Proton pump inhibitors
Glucocorticoids
Clofibrate
Salicylates
Estrogens
Methadone
5-Fluorouracil
Tamoxifen
Carbamazepine and phenobarbital
Heparin
Nonsteroidal anti-inflammatory drugs
Rifampin
Amiodarone
Digitalis glycosides (eg, digoxin)
Tricyclic (eg, amitriptyline) or tetracyclic (eg, maprotiline) antidepressants
Ketamine

Multinodular Goiter ICD 10 Codes

The following are ICD 10 codes relevant to multinodular goiter, specified or otherwise:

E01.1	Iodine-deficiency related multinodular (endemic) goiter
E04.2	Nontoxic multinodular goiter
E05.2	Thyrotoxicosis with toxic multinodular goiter
E05.20	Thyrotoxicosis with toxic multinodular goiter without thyrotoxic crisis or storm
E05.21	Thyrotoxicosis with toxic multinodular goiter with thyrotoxic crisis or storm

Multinodular Goiter ICD-10 Codes

References

1. American Thyroid Association. Thyroid nodules. Accessed February 9, 2023. https://www.thyroid.org/thyroid-nodules/

2. Filetti S, Tuttle RM, Leboulleux S, Alexander EK. Nontoxic diffuse goiter, nodular thyroid disorders, and thyroid malignancies. In: Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, eds. Williams Textbook of Endocrinology. 14th ed. Elsevier, Inc; 2020:433-478.

3. Knobel M. Which is the ideal treatment for benign diffuse and multinodular non-toxic goiters? Front Endocrinol (Lausanne). 2016;7:48. doi:10.3389/fendo.2016.00048

4. Synthroid^® [package insert]. North Chicago, IL: AbbVie Inc.; 2002.

Author Bio

Jen Seabright, PharmD, is a freelance medical writer in Pittsburgh, Pennsylvania.