Nontoxic Goiter

Etiology

Nontoxic goiter can be diffuse or multinodular. It occurs due to many causes: [1][2][3][4]

• Physiological goiter (puberty, pregnancy)
• Iodine deficiency (endemic)
• Dysmorphogenesis (sporadic)
• Goitrogens (cabbage, goitrogenic drugs such as para-aminosalicylic acid)
• Radiation exposure
• TSH release from the pituitary glands
• Autoimmunity
• Infections
• Granulomatous disease

Epidemiology

The thyroid hormone is synthesized from iodine. Iodine is present in soil and is ingested in food that absorbs iodine from the soil. In mountainous areas and rainy environments, iodine is washed from the land, and the soil may become deficient in iodine. This explains why inhabitants of these areas are at greater risk for developing goiter due to low dietary iodine they consume. There is evidence that giving iodine as a supplement decreases the incidence of goiter in these people. Seminal studies confirmed that supplementation of iodine in table salts decreases the risk of endemic goiter from 20% to 5% in the adolescent girls of Ohio. In the United States, sporadic goiter is the most common cause of nontoxic goiter where it's incidence is about 5%.

The prevalence of palpable nodules is about 5% to 6% in those who are 60 years old. However, the incidence of nonpalpable nodules found at autopsy is about 50% of those who are 60 years old. Internationally, 2.2 billion people have some form of iodine deficiency, most of them being people of iodine-deficient areas. The prevalence of goiter is corollated with the severity of iodine deficiency. The absence of iodine deficiency is associated according to studies with 5% prevalence of goiter. When there is a mild deficiency of iodine, the incidence of goiters is 5% to 20%. In the case of moderate deficiency, the prevalence is 20% to 30%. In areas with severe deficiency, the incidence rises to more than 30%. Goiter is 1.2 to 4.3 times more common in female than in male individuals. A low socioeconomic status is a risk factor for goiter. This may be related to decreasing iodine intake. Sporadic goiter due to dysmorphogenesis and endemic goiter mostly occur during childhood, and the thyroid gland increases more in size with age. There is no racial relation to the prevalence of goiter. [5][2]

Pathophysiology

The deficiency of iodine or increasing demands for thyroid hormones leads to pituitary gland stimulation that increases TSH secretion. TSH stimulates thyroid follicular cells and with continuous long-term stimulation leads to follicular hyperplasia and thyroid enlargement. When iodine is supplied again or when thyroid hormone deficiency is corrected thyroid gland may decrease in size due to decreased TSH levels and the thyroid gland is not more stimulated. 

Histopathology

In cases of diffuse goiter, there will be follicular cells hyperplasia. In the chronic settings with the continued TSH stimulus, some follicles become autonomous and secrete hormones that will depress other areas which will involute. This will lead to multinodular goiter with areas of focal hyperplasia and areas of involution and fibrosis.

History and Physical

Most of the nontoxic goiter patients are asymptomatic. The swelling may be discovered accidentally by the patient or others. Some individuals may have compressive symptoms like dysphagia, dyspnea, and hoarseness of voice due to mechanical compression of laryngeal nerves by the nearby huge goiter. Large thyroids may compress neck veins leading to facial congestion and discomfort. Pain is rare and it may be severe and incremental when there is bleeding in a nodule and it may be associated with sudden changes in the goiter.

On physical examination, there will be a central neck swelling that could be smooth or nodular and the mass moves with swallowing. It may deviate the trachea or extend retrosternally. Any cervical lymphadenopathy should suggest malignancy: a workup is warranted. Vocal cords must be examined in cases of hoarseness or before and surgical intervention.

When the patient is asked to elevate the arms, it lifts the goiter into the thoracic inlet and may cause stridor, dyspnea or enlargement of the neck veins (Pemberton maneuver). [6][7][8]

Evaluation

Initially, TSH, free T4, and T3 should be measured to assess whether the patient is thyrotoxic, subclinically toxic, hypothyroid, or euthyroid. Then ultrasonography (US) must be done to assess nodules. Features that make nodules suspicious are hypoechogenicity, microcalcification, hypervascularity, and if there are solid components of complex nodules. In these situations, fine needle aspiration cytology under US guidance is recommended. A chest x-ray is useful in assessing retrosternal goiter and if there any tracheal deviation. Sometimes computerized tomography (CT) scan or magnetic resonance imaging (MRI) are useful in describing anatomical relations regarding tracheal deviation, airway compression, retrotracheal, or retrosternal extension. [9][10]

Radionuclide scanning can be used to assess thyroid anatomy and function.

In some cases, radioisotope scanning, pulmonary function tests, flow volume loops, and barium swallow studies have some role in evaluating goiter patients. Preoperative vocal cord movement assessment is important using laryngoscopy.

Treatment / Management

Nontoxic goiter usually evolves slowly and asymptomatic, so it needs no treatment and left for follow up. Medical therapy for nontoxic goiter is controversial as it has little or no results in longstanding goiters. [11][12][13](B3)

Some goiters may respond to levothyroxine therapy but close monitoring of the patient is required to avoid arrhythmias, hyperthyroidism, and bone thinning. However, thyroid hormone therapy is not recommended if the goiter is autonomous.

Non-emergent surgical treatment is indicated in patients with compressive symptoms or complications. Thyroidectomy is indicated in retrosternal goiter even if asymptomatic because delaying treatment to symptoms appearance may need more complicated surgical procedures. However, the patient's preoperative workup should be thorough. If the surgery is an emergency for an active goiter, the patient will require beta-blockers, antithyroid medications and a stress dose of corticosteroids. Close monitoring is required intra-and postoperatively. A common complication postoperatively is hypocalcemia.

Radioiodine ablation is another modality of therapy that can lead to goiter involution but has more complications.

Differential Diagnosis

Nontoxic goiter must be differentiated from other causes of goiter. The most important issue here is to exclude malignancy. Thyroid cancers that must be excluded include papillary thyroid cancer, follicular thyroid cancer, and medullary thyroid cancer, and thyroid lymphoma. Anaplastic thyroid cancer is usually presented as huge, large, and fixed swelling. Other cause of goiter that must be differentiated from nontoxic goiter include inflammatory goiter. Hashimoto thyroiditis, De Quervain thyroiditis, and Riedle thyroiditis are important inflammatory goiters that should be differentiated from nontoxic goiter.

Surgical Oncology

Thyroidectomy is the mainstay of nontoxic goiter that is causing symptoms or complications. It is always tolerated by most patients including those with limited functional reserve. It must include total or near-total gland excision. It has the advantage that the recurrence rate is quietly low. However, many complications may occur during or after thyroidectomy including recurrent laryngeal nerve injury and hypoparathyroidism. Also, the patients who undergo total thyroidectomy need long-life thyroid supplements.

Radiation Oncology

Radioactive iodine ablation is indicated when there is a contraindication to surgery or in the nonfit patient. It can cause a reduction in goiter size by 40% to 60% within 2 years. Radiation thyroiditis, hypothyroidism, and transient increase in thyroid gland size are the most common complications for which the use of radioactive iodine ablation is limited.

Medical Oncology

Medical therapy for nontoxic goiter depends on TSH suppression using thyroxine. However, it has been shown that medical therapy has been ineffective in reducing goiter size especially those who have been for a long time.

Prognosis

A non-toxic goiter is a benign entity and only causes aesthetic problems. However, if the size is large, it may compress the trachea, laryngeal nerves, and the esophagus. Most benign goiters have an excellent prognosis. A small percentage may cause hyperthyroidism and some may become malignant, hence life long surveillance is necessary. In people with compression, after surgical removal, the tracheal narrowing reverses and results in improved lung function.

Complications

Large goiters may cause:

• Hyperthyroidism (Job basedow phenomenon)
• Tracheal compression
• May transform into a malignancy
• Bleed in the neck
• May become infected