There is no specific diagnostic laboratory pattern in patients with MNG. Sensitive TSH should be measured in all patients, and it may be normal, low, or even high. However, in most cases of MNGs, serum TSH is within the normal range [25]. Suppressed TSH (with normal or elevated serum FT4 level) is suggestive of toxic MNG (Plummer’s disease); this needs to be supported by diagnostic imaging. Additional testing, such as anti-thyroperoxidase (TPO) , has limited value in making the diagnosis of MNG but is helpful as elevated levels indicate autoimmune thyroid disease. Hashimoto disease may be associated with the presence of pseudo-nodules rather than true nodules on thyroid US; these are typically benign. Moreover, it might be associated with bilateral, enlarged, but benign-appearing lymphadenopathy . The routine measurement of serum thyroglobulin (Tg) or calcitonin (Ct) has no value in a patient with MNG. Serum Ct should be measured only with suspicion of MTC or if FNA is abnormal [26]. Measurement of serum TSH and Tg levels to assess malignancy risk of thyroid nodules is discussed later in this chapter.

Different imaging modalities are available in evaluating toxic and nontoxic MNG, including neck ultrasonography (US) , computed tomography (CT) , magnetic resonance imaging (MRI) , thyroid scintigraphy , and positron emission tomography (FDG-PET) , though less frequently used.

High-resolution US is a widely used, inexpensive, and sensitive (≈95%) method to detect small, nonpalpable thyroid nodules (Fig. 10.3) and to complement neck palpation. Clinical practice has witnessed detection of more thyroid nodules in the United States and elsewhere [27]. An unintended consequence of US sensitivity has been the detection of incidental, and often insignificant, small solid or cystic thyroid nodules.

All patients with suspected or confirmed thyroid nodules should have a full neck US to evaluate location, size, number, and other features of these. US can help identify thyroid nodules that need fine needle aspiration (FNA) and guide the FNA when needed (Fig. 10.4) [26, 28]. The importance of thyroid sonography is underscored by the fact that up to 50% of patients with single nodules on physical examination will show additional nodules [29]. However, the risk of malignancy is similar if nodules are single or multiple [21, 30, 31].

Computerized tomography (CT) or magnetic resonance imaging (MRI) provides better evaluation of thyroid size and extension in relationship to surrounding structure especially in patients with compressive symptoms and those with large goiter with suspected retrosternal extension (Fig. 10.5). However, these are not used routinely due to high cost. Of note, CT should be preferably used without contrast to avoid possible iodine-induced thyrotoxicosis in the setting of a MNG [23].

This test is not routinely ordered in evaluating MNG except when determining the functional status of thyroid nodule or MNG, associated with low serum TSH [32]. Thyroid scintigraphy can be performed using either technetium 99mTc pertechnetate or I¹²³ scanning with sensitivities to detect functioning nodules about 91% and 83%, respectively [33]. Thyroid scan has low specificity (5–25%), due to interference from normal thyroid tissue with the radioisotope uptake. In the setting of a MNG, thyroid scan should always be done together with a neck US to help determine the need for FNA. Functioning nodules are not suspicious for malignancy and need not be subjected to FNA. Hot nodules account for fewer than 10% of all thyroid nodules and are almost always benign [25]. In toxic MNG, hot nodules trap the radioactive iodine (uptake), while this is inhibited in surrounding thyroid tissue giving the “patchy uptake” image suggestive of toxic MNG (Fig. 10.6).

In recent years, FDG-PET scanning is frequently performed for tumor staging and detection. When FDG-PET scan shows focal uptake in the thyroid bed, the risk of malignancy is high, around 35%; hence nodule warrants FNA [34–36]. On the other hand, diffuse FDG uptake in thyroid bed is suggestive of Hashimoto’s thyroiditis , which can be further evaluated with US but may not require FNA.

Thyroid FNA is established as a safe, valuable, and cost-effective test in the diagnosis and treatment of nodular thyroid disease. In current practice, adequate samples should be obtained in 95% of cases [37, 38]. The use of US-guided FNA and on-site cytological examination can further reduce inadequate sampling [38–40]. Obviously, not all thyroid nodules require FNA. Selecting nodules that require FNA in MNG can be more challenging than in single nodules, because often more than one nodule needs FNA [21, 30, 31, 41]. In general, FNA is recommended for high US-risk thyroid lesions ≥10 mm, intermediate US-risk thyroid lesions >20 mm, and low US-risk thyroid lesions only when >20 mm, associated with high-risk history or increasing in size (Fig. 10.7) [26]. This applies also to glands with multiple nodules; however, it is seldom necessary to perform FNA in more than two nodules in a MNG. Additionally, it is not necessary to biopsy “hot” areas on radioisotope scan in the adult patient [26].

Surgery is preferred to radioiodine therapy in patients with nontoxic, nonobstructive goiters that continue to grow and potentially cause obstructive symptoms or cosmetic concerns.

Near-total or total thyroidectomy should be performed for large or retrosternal goiters with obstructive symptoms (Fig. 10.8). After surgery, recurrence is seen in 10–20% in the first decade depending on the size of residual thyroid tissue [44]. Surgical complications are rare in experienced centers, but can be up to 10% since most surgeries are performed by general, low-volume surgeons [45], and include hypoparathyroidism, injury to trachea, or recurrent laryngeal nerves, especially in large and/or retrosternal goiters [46, 47]. When selecting surgery, one should consider risks and benefits in older patients, paying attention to those with significant comorbidities.