Laboratory Studies
Thyroid function tests
Evidence of hyperthyroidism must be present in order to consider a diagnosis of toxic nodular goiter (TNG). [7]
Third-generation thyroid-stimulating hormone (TSH) assays are generally the best initial screening tool for hyperthyroidism. Patients with TNG will have suppressed TSH levels.
Free T4 levels or surrogates of free T4 levels (ie, free T4 index) may be elevated or within the reference range. An isolated increase in T4 is observed in iodine-induced hyperthyroidism or in the presence of agents that reduce peripheral conversion of T4 to triiodothyronine (T3) (eg, propranolol, corticosteroids, radiocontrast agents, amiodarone).
Some patients may have normal free T4 levels (or free T4 index) with an elevated T3 level (T3 toxicosis); this may occur in 5-46% of patients with toxic nodules. Note that the total T3 and T4 levels may often be within the reference range but may be higher than the normal range for a particular individual; this is especially true in patients with nonthyroidal illness in which T3 levels are decreased.
Subclinical hyperthyroidism
Some patients may have suppressed TSH levels with normal free T4 and total T3 levels.
Imaging Studies
Nuclear scintigraphy
Nuclear scans should be performed on patients with biochemical hyperthyroidism. [7] Nuclear medicine scans can be performed with radioactive iodine-123 (123 I) or with technetium-99m (99m Tc). These isotopes are chosen for their shorter half-life and because they provide lower radiation exposure to the patient when compared with sodium iodide-131 (Na131 I).
99m Tc is trapped in the thyroid but is not organified. Although convenient,99m Tc scanning may provide misleading results. Some nodules that appear hot or warm on99m TC scan results may be cold on123 I scan results. Nodules with discordant99m Tc and123 I scan results may be malignant; therefore,123 I scanning is preferred.
Nuclear scans allow determination of the cause of hyperthyroidism. Patients with Graves disease usually have homogeneous diffuse uptake. Glands with thyroiditis have low uptake.
In patients with toxic nodular goiter (TNG), the scan results usually reveal patchy uptake (see the image below), with areas of increased and decreased uptake. The uptake rate of radioiodine in 24 hours averages approximately 20-30%. Radioactive Na131 I ablation of the thyroid gland may be considered if the thyroid uptake value is elevated. Several therapeutic modalities have been suggested to increase uptake (eg, low iodine diet, lithium, recombinant TSH, propylthiouracil [PTU]).
Patchy uptake of iodine (123I) in a toxic multinodular goiter.
Thyroid scanning is also useful for helping to determine the presence of substernal extension of the thyroid gland, which may contain toxic nodules.
Ultrasonography
Ultrasonography is a highly sensitive procedure for delineating discrete nodules that are not palpable during thyroid examination. Ultrasonography is helpful when correlated with nuclear scans to determine the functionality of nodules. [7]
Dominant cold nodules should be considered for fine-needle aspiration biopsy prior to definitive treatment of a TNG.
This technique may be used to serially examine the size of thyroid nodules.
Other imaging modalities
In the workup of patients with compressive or obstructive symptoms, computed tomography (CT) scanning of the neck may help to establish whether the trachea is patent and if tracheal deviation or the impingement of other structures is caused by a nodular goiter.
Multinodular goiters, especially those with a substernal component, are often incidental findings on chest radiographs, CT scans, or magnetic resonance imaging (MRI) scans. CT scans with iodinated contrast may induce thyrotoxicosis in individuals with an underlying nontoxic, multinodular goiter by supplying an iodine load (Jod-Basedow effect). This type of thyrotoxicosis is self-limited but may last longer if areas of autonomy already exist within the goiter.
Procedures
Fine-needle aspiration
Fine-needle aspiration is not usually indicated in an autonomously functioning (ie, hot) thyroid nodule. The risk of malignancy is quite low. Interpretation of the cytology specimen is difficult, because it is likely to demonstrate a follicular neoplasm (ie, sheets of follicular cells with little or no colloid), and distinguishing between a benign lesion and a malignant lesion is not possible without histologic sectioning to examine for the presence of vascular or capsular invasion. [8]
Perform a fine-needle aspiration biopsy if a dominant cold nodule is present in a multinodular goiter. A clinically significant nodule is larger than 1 cm in maximum diameter, based on either palpation or ultrasonographic images, unless there is an increased risk of malignancy. Nonpalpable nodules may be biopsied with the assistance of ultrasonography.
A history of head or neck irradiation during childhood increases the risk of malignancy. Head or neck irradiation in an adult increases the frequency of toxic nodular goiter and of carcinoma of the thyroid. Patients from iodine-replete areas have the same risk of malignancy as persons from iodine-deficient areas.
Histologic Findings
Autonomous nodules may be monoclonal or polyclonal. Many nodules studied in multinodular goiters may actually be monoclonal, even in the setting of histologically marked phenotypic variation.
The histologic appearance of a multinodular goiter can be highly variable and may involve the presence of normal-sized follicles, microfollicles, or macrofollicles, all coexisting within the same gland. Early goiters display micronodular growth patterns. Actively proliferating follicular cells can be observed within some thyroid follicles, resulting in budding intraluminal projections, while other cells within the same follicle appear to be in the resting phase. Conversely, some follicles show a more uniform appearance of cells. Periods of alternating active and quiescent growth appear to occur within the goiter. Areas of fresh and old hemorrhage with calcification are also occasionally present.
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Patchy uptake of iodine (123I) in a toxic multinodular goiter.
