Multinodular Goiter

The thyroid gland, shaped like a butterfly and situated at the front of the neck, can sometimes become enlarged, a condition known as a goiter. A large goiter can cause discomfort, leading to symptoms like coughing and difficulty in breathing or swallowing. The primary cause of goiters is often insufficient dietary intake of iodine, resulting in iodine deficiency. However, goiters can also stem from over- or underproduction of thyroid hormones or the development of nodules on the gland itself.

1.0Multinodular Goiter Definition

• Multinodular goiter (MNG) is a commonly encountered condition characterized by an enlarged thyroid gland with multiple areas of nodularity . 
• Histologically, MNG manifests as thyroid enlargement with follicles that undergo significant morphological and functional alterations over time, typically developing gradually over years . 
• This condition is endemic in regions with iodine-deficient diets, particularly affecting women in their 4th and 5th decades of life .
• Various factors contribute to the development of MNG, with iodine deficiency being the most common. 

2.0Sign and Symptoms of Multinodular Goiter

• Often, a family history of benign thyroid disease
• Slowly developing mass in front of the neck
• Presence of one or multiple nodules upon examination
• Enlargement during pregnancy
• Concerns related to appearance
• Asymmetry, deviation of the trachea, and/or compression
• Rarely, obstruction of the upper airway, difficulty in breathing, coughing, and swallowing difficulties
• Sudden, temporary pain or enlargement due to bleeding
• Gradual onset of hyperthyroidism
• Occasional superior vena cava syndrome (rare)
• Infrequent recurrent nerve paralysis

3.0Causes of Multinodular Goiter

Iodine deficiency - It is the primary cause of goiter, often resulting from insufficient iodine levels in water and food sources, or impaired intestinal absorption. Goiter can develop when iodine intake falls below 50 µg/day.

Dyshormonogenesis - A less common cause of non-toxic goiter involves six distinct intrathyroidal disturbances. The formation of goiter in these cases is influenced by the severity of the defect and environmental factors. In regions with adequate iodine intake, environmental factors may compensate, whereas iodine-deficient areas may exacerbate these conditions.

• Impairments in iodine trapping.
• Deficiencies in organification, which are the most frequently observed abnormalities.
• Defects in hormone coupling.
• Deficiencies in protease enzymes.
• Abnormal synthesis of iodo proteins.

Goitrogens

These substances interfere with thyroid hormone synthesis or inhibit iodine uptake, leading to a hyperplastic gland with compensated thyroid function.

Drugs:  Thiocarbamides (Antithyroid drugs), Chlorpropamide, PAS, Amiodarone, Glutethimide, Reserpine, Phenylbutazone, Lithium, large doses of Iodine, Sulfonylureas, and Calcium.

Food:  Vegetables from the brassica family (such as cabbage, kale, and rape), turnips, soybean flour, and cassava . Cabbage, for instance, contains thiocyanates that inhibit iodine uptake.

Radiation

Previous thyroid irradiation increases the likelihood of benign and malignant nodules in the gland . The risk of malignancy in palpable nodules under these conditions ranges from 20% to 50%. 

• Radiation exposure typically ranges from 400 to 1500 rads, with nodular thyroid disease often developing 6 to 35 years post-exposure, predominantly around 30 years after exposure. Radiation stimulates thyroid epithelium through increased TSH, especially when combined with goitrogens, and is more impactful in children due to their active gland proliferation. Higher radiation doses can destroy the thyroid gland, leading to hypothyroidism rather than nodular disease or malignancy. 

Genetic influences

A gene located on chromosome 14q, known as MNG-1, has been linked to familial non-toxic multinodular goiter. 

• Polymorphisms at codon 727 have been associated with toxic multinodular goiter.

4.0Pathology of Multinodular Goiter

• Macroscopically, the thyroid gland appears enlarged and distorted. There is significant variability in the size of the lobes. 
• The gland's surface exhibits a knobby texture, enclosed by a stretched but intact capsule. On cross-section, multiple nodules of various sizes are observed. 
• Some nodules may be partially or completely encapsulated, while others lack capsules and are somewhat distinct from the surrounding tissue. Whitish fibrous bands, occasionally calcified, may separate or traverse these nodules.
• Nodules rich in colloid are gelatinous and exhibit a yellowish, tan-red-brown, translucent appearance. More cellular nodules appear fleshy or rubbery. 
• Degenerative changes such as fresh or old hemorrhage, necrosis accompanied by fibrosis, cholesterol deposition, calcifications, and cyst formation are commonly observed within the gland.

5.0Toxic Multinodular Goiter Definition

• The thyroid tissue surrounding nodules often displays hyperplastic alterations, with frequent lymphoid infiltration in the stroma. Nodules themselves may exhibit oxyphilic or clear cell changes. In some instances, both nodules and the tissue between them demonstrate marked epithelial hyperplasia.

6.0Toxic Multinodular Goiter Hyperthyroidism

• The diagnosis of hyperthyroidism relies on identifying symptoms and findings from a physical examination, which are further confirmed by laboratory tests demonstrating elevated levels of thyroid hormones (refer to the Hyperthyroidism brochure). In hyperthyroidism, there is an excess of thyroid hormone in the bloodstream accompanied by low levels of TSH. 
• Following the diagnosis of hyperthyroidism, a thyroid scan can be conducted using radioactive iodine to visualize thyroid function. This scan identifies a toxic nodule as a single area of excessive activity, while a toxic multinodular goiter presents with multiple active areas. 
• Additionally, a thyroid ultrasound can provide detailed assessment of thyroid nodules.