Toxic multinodular goitre

Often the patient has had a chronic goitre for many years:

• appears that areas of autonomous thyroid tissue develop into nodules that secrete thyroid hormones
  • patient may have the signs and symptoms of hyperthyroidism

Multinodular goitre (MNG) is the most common thyroid disease in the world, with more than 300 million people estimated to be affected (1)

Progression to multinodular goitre is typical of both endemic and sporadic simple goitres. The nodules can be considered as the end result of patchy and disorganised thyroid metabolism in which some areas of hyperplasia progress to hyperplastic nodules. Some nodules undergo colloid involution while others develop haemorrhage, form cysts or undergo necrosis. Fibrosis and calcification occur in some of these degenerate nodules.

The goitrous enlargement may be huge; in some cases attaining a weight of over 2 Kg. The gross pattern is unpredictable. One lobe may be predominantly involved causing lateral pressure on midline structures such as the trachea and oesophagous. In others, the enlargement is mainly retrosternal producing an intra-thoracic or plunging goitre. The great veins may be compressed.

Common pitfalls during examination are to mistake a multinodular goitre for a large nodule because the goitre is dominated by one nodule. Failure to recognise retrosternal extension may be avoided by examining the lump with the neck extended.

Occassionally, a multinodular goitre is toxic. However, the ophthalmic and systemic changes typical of Grave's disease are absent

• within a MNG the development of hyperfunctioning nodules, in the absence of an autoimmune stimulus as is the case with diffuse toxic goitre (Graves' disease), determines the clinical picture of toxic MNG (TMNG)
• functionally autonomous areas synthesize and secrete thyroid hormones independently and aimlessly, thus suppressing TSH secretion; as a result, the remaining thyroid tissue becomes functionally quiescent
  • areas of autonomous tissue and areas of inactive tissue thus come to coexist within the same thyroid
    • the functional autonomy acquired by one or more nodules is correlated with goitre "age", nodule size and patient age (>60 yr) mainly in female patients
    • fifteen years are usually thought to be necessary for TMNG to develop
    • Sturnilo et al state that "...the disease to be most prevalent in female patients with an average age of 73 yr. The onset of hyperthyroidism occurred on average 12 yr after diagnosis and ranged from a minimum of 9 to a maximum of 18 yr.."

Malignant change has been stated to occur in 5-10% of untreated multinodular goitres (2)

• however a study in patients undergoing thyroidectomy for MNG revealed:
  • among the 2,306 MNG patients, ITC (incidental thyroid carcinoma) was detected in 49 (2.12%) (44 women and 5 men, with average ages of 52.2 (21-79) and 55.6 (52-62), respectively). Papillary thyroid carcinoma was significantly more frequently observed than other types of ITC (p<0.00001)

Multinodular goitre must be differentiated from anaplastic thyroid carcinoma and thyroid lymphoma.

Reference:

• Sturnilo N et al. Toxic multinodular goitre. Personal case histories and literature review.G Chir. 2013 Sep-Oct; 34(9-10): 257-259
• Tollin SR et al. The use of fine-needle aspiration biopsy under ultrasound guidance to assess the risk of malignancy in patients with a multinodular goiter. Thyroid 2000 Mar; 10(3):235-41.
• Kaliszewski K et al. Should the Prevalence of Incidental Thyroid Cancer Determine the Extent of Surgery in Multinodular Goiter?PLoS One. 2016; 11(12): e0168654.