Goiter, Nontoxic

Article Author:
Fadi Alkabban
Article Editor:
Bhupendra Patel
10/30/2018 10:30:27 PM
PubMed Link:
Goiter, Nontoxic


Goiter is the enlargement of the thyroid gland. Nontoxic goiter is thyroid gland enlargement with no disturbance in the thyroid function. It is not due to inflammation or neoplasia. Abnormalities of iodine supplies or metabolism always lead to nontoxic goiter. Thyroid gland normally weighs about 25 grams. It is a butterfly-shaped gland located in the anterior triangle of the neck just in front of the larynx and trachea. It is composed of right and left lobes with a connecting isthmus. The isthmus lies against the second and the third tracheal rings with the lobes extending on either side, from the thyroid cartilage superiorly to the fourth tracheal ring inferiorly. The thyroid gland secretes thyroid hormones (Thyroxin/T4 and triiodothyronine/T3)  in response to thyrotropic hormone (TSH) of the pituitary gland stimulation. They are important for body cells metabolism. It also secretes calcitonin hormone that has an important role in calcium metabolism. With decrease thyroid hormone production due to iodine deficiency as an example, TSH release will increase and this in the long-term will lead to thyroid follicles hyperplasia and as a result increase in thyroid gland size.


Non-functioning goiter can be diffuse or multinodular. It occurs due to many causes:

  • Physiological goiter (puberty, pregnancy)
  • Iodine deficiency (endemic)
  • Dysmorphogenesis (sporadic)
  • Goitrogens (cabbage, goitrogenic drugs such as para-aminosalicylic acid)


Thyroid hormone is synthesized from iodine. Iodine is present in soil and is taken by the human who eats food that absorbs iodine from the soil. In mountainous areas and heavy-rainy places, iodine is washed from the land, and their soils will 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. The 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. Its incidence is about 5% in North America. 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. Those with mild deficiency have 5% to 20% of their individuals have a goiter. In the case of moderate deficiency, the prevalence is 20% to 30%. More than 30% of severely deficient places have a goiter. Goiter is 1.2 to 4.3 times more common in female than in male individuals. The low socioeconomic standard 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.


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 excited.


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 them or the 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 a rare and it may be severe and incremental when there is bleeding in a nodule and the maybe associated with sudden changes in the goiter. On physical examination, there will be a central neck swelling that could be smooth or nodular and moves with swallowing. It may deviate the trachea or extend retrosternally. Any cervical lymphadenopathy should suggest malignancy and more exclusion workup is warranted. Vocal cords must be examined in cases of hoarseness or before and surgical intervention.


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. 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. 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. 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.

Pearls and Other Issues

Nontoxic goiter is not an uncommon disorder especially in iodine-deficient areas that can be prevented with consumption of iodine-containing salt. If present, it must be followed unless it causes symptoms or complications. Exclusion of malignancy is an important issue, and any suspicious nodule mandates tissue biopsy.


Quality of life after thyroidectomy in patients with nontoxic nodular goiter: A prospective cohort study., Sorensen JR,Watt T,Cramon P,Døssing H,Hegedüs L,Bonnema SJ,Godballe C,, Head & neck, 2017 Nov     [PubMed PMID: 28872214]
Increased Cardiovascular Mortality and Morbidity in Patients Treated for Toxic Nodular Goiter Compared to Graves' Disease and Nontoxic Goiter., Giesecke P,Rosenqvist M,Frykman V,Friberg L,Wallin G,Höijer J,Lönn S,Törring O,, Thyroid : official journal of the American Thyroid Association, 2017 Jul     [PubMed PMID: 28471268]
Intrathoracic toxic thyroid nodule causing hyperthyroidism with a multinodular normal functional cervical thyroid gland., Serim BD,Korkmaz U,Can U,Altun GD,, Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India, 2016 Jul-Sep     [PubMed PMID: 27385899]
Total Thyroidectomy versus Bilateral Subtotal Thyroidectomy for Bilateral Multinodular Nontoxic Goiter: A Meta-Analysis., Li Y,Li Y,Zhou X,, ORL; journal for oto-rhino-laryngology and its related specialties, 2016     [PubMed PMID: 27256349]
Surgical Management of Nontoxic Multinodular Goiter: Is the Jury Still Out?, Mohanty D,Dalal AK,, The Indian journal of surgery, 2015 Aug     [PubMed PMID: 26702247]
Etiopathology, clinical features, and treatment of diffuse and multinodular nontoxic goiters., Knobel M,, Journal of endocrinological investigation, 2016 Apr     [PubMed PMID: 26392367]
Large multinodular goiter--outpatient radioiodine treatment., Kaniuka-Jakubowska S,Lewczuk A,Mizan-Gross K,Piskunowicz M,Zapaƛnik A,Lass P,Sworczak K,, Endokrynologia Polska, 2015     [PubMed PMID: 26323466]