In multinodular goiter, or MNG, the thyroid enlarges by forming several nodules instead of growing evenly. MNG occurs mostly in regions with iodine deficiency, though it can also be seen in iodine-sufficient areas because of genetic, autoimmune and environmental effects. Thyroid nodules are very common in adults: a nodular finding is felt on examination of the neck in about 3-7% of adults, while up to 50% of adults carry nodules smaller than 1 cm that only ultrasound finds. Nodules may be solitary or multiple, and functioning or non-functioning, and they do not always enlarge the gland — discrete nodules can be present in a thyroid of completely normal size. Less than 7% of the nodules found by both palpation and neck ultrasound are malignant; more than 93% of them are benign lesions. The nodules themselves are of two broad forms: hyperplasia-related nodules and neoplastic-related nodules.
The histological features of the nodules are quite variable: hypercellular areas and cystic areas filled with colloid, extensive fibrosis, haemorrhage, and lymphocyte infiltration. Molecular studies of the nodules reveal that their cells are clonally different, which suggests hyperplasia in response to local growth factors and cytokines rather than the spread of a single clone.
Benign lesions of the thyroid gland
Two forms of benign nodule can be found in the thyroid gland. Hyperplastic nodules reflect both micro- and macrofollicular architecture and mostly appear as a combination of cysts and cells, or, on ultrasound, as the spongiform pattern — defined as a nodule that is more than 50% cysts. Adenomatous nodules are mostly monotonous microfollicular encapsulated nodules. The majority of solid nodules of the thyroid are benign.
Clinical manifestation of non-toxic MNG
Most patients with non-toxic MNG are asymptomatic and euthyroid, meaning their thyroid hormone levels are normal. The change develops over several years, so it is mostly an incidental finding, noticed either by the patient or by the clinician during physical examination or imaging. Compressive effects appear only as very uncommon manifestations, when a large enough goiter presses on the peripheral structures. Plethora, that is venous congestion, comes from obstruction of venous outflow; respiratory distress (dyspnoea) comes from tracheal compression; and dysphagia comes from oesophageal compression. Hoarseness of the voice reflects laryngeal nerve involvement and is specific for malignant forms of the MNG. Sudden pain in an MNG is due to haemorrhage inside a nodule.
Diagnosis
Physical examination of an MNG reveals a distorted thyroid gland, produced by the different nodules inside it. Some nodules are not appreciable because of their location, such as posterior or substernal nodules. In an MNG with a substantial goiter, Pemberton’s sign can be elicited: the patient raises both hands, and cyanosis of the face appears because of an increase of pressure in the upper thoracic inlet.
In patients with these signs and symptoms, a few functional and biochemical values should be checked: the TSH level (thyroid-stimulating hormone, the pituitary hormone that drives the gland), mainly to exclude thyroid dysfunction (in MNG the TSH level is mostly normal); pulmonary function tests, to see how much tracheal compression is present; and CT or MRI, to see the amount of enlargement, the extent of substernal extension, and the degree of tracheal narrowing or oesophageal compression.
Whether a nodule in an MNG is risk-stratified and biopsied depends on its size and its sonographic (ultrasound) pattern. The American College of Radiology Thyroid Imaging Reporting and Data System, or ACR TI-RADS, is used for that stratification. Because the TSH level is mostly normal in MNG, a low TSH in a nodular gland points instead to nodules that make hormone on their own.