Figure 75-6. Ultrasound images of the right thyroid lobe. (A) benign thyroid nodule with isoechoic solid architecture and

hypoechoic halo and (B) papillary thyroid carcinoma with microcalcifications and irregular border. C, carotid artery; J, internal

jugular vein; T, trachea.

Nuclear Medicine Imaging

Radionuclide imaging provides specific information regarding the functional characteristics of the

thyroid usually in the setting of hyperthyroidism; however, it provides little anatomic detail. Nuclear

imaging for thyroid nodules is typically only helpful in determining if the etiology of hyperthyroidism

in a nodular thyroid is due to a hyperfunctional nodule(s) or diffuse hyperplasia.

Technetium Pertechnetate 99mTc Scintigraphy

99mTc pertechnetate is the radionuclide most commonly available for thyroid imaging. The 99mTc

pertechnetate component is actively trapped by functional thyroid cells in a manner similar to iodine

but is not organified or stored in the thyroid. The isotope emits gamma (γ) radiation (the mechanism of

scintigraphic imaging) and very small amounts of other types of radiation. Because the thyroid rapidly

absorbs the injected 99mTc pertechnetate, imaging can occur early after administration and an entire

study may take only an hour. A normal result demonstrates equal distribution bilaterally. Abnormal

results include either concentration of the tracer in the region of a known nodule indicating an area of

hyperfunction or, conversely, an area of photopenia (the “cold nodule”) indicating a region of

hypofunction. Before the era of fine-needle aspiration (FNA) biopsy, photopenic nodules increased the

concern for potential malignancy; however, currently nuclear imaging is typically only used to

determine the etiology of hyperthyroidism in a nodular or enlarged thyroid and should not be used do

determine the oncologic risk of thyroid nodules.

123Iodine Scintigraphy

Because 123I is trapped and organified by the thyroid gland, it can better indicate the functional

characteristics of thyroid tissue. 123I emits x-rays, some β particles, and γ rays. It has a short half-life of

about 13 hours. After administration of an oral dose, the thyroid absorbs sufficient isotope to allow

imaging by 4 hours. Images are also obtained at 24 hours, and the total fraction of dose retained by the

thyroid can then be calculated as the 24-hour radioactive iodine uptake (RAIU).

131Iodine Scintigraphy

131I sodium iodide concentrates in the thyroid by the same mechanism as

123I, but has a much longer

half-life (about 8 days) and emits much more β radiation along with γ radiation at a range that is

suboptimal for clear image creation. However, because of its long half-life and thorough clearance from

background tissues, it remains the isotope of choice for imaging of patients with differentiated thyroid

carcinoma. Treatment or ablation of residual or metastatic carcinoma (largely by the effect of β

irradiation) is accomplished with larger doses of 131I (typically 30 to 150 mCi) than is required for

diagnostic imaging (typically 1 to 5 mCi).

Positron Emission Tomography

18F fluorodeoxyglucose positron emission tomography (PET) scanning with three-dimensional

tomographic reconstruction can be very helpful in imaging thyroid carcinomas, and allows anatomic and

functional evaluation. Because of the expense and the inconsistent insurance coverage, usage is

currently limited to unusual circumstances such as recurrent thyroid malignancy that is otherwise occult

most commonly due to loss of iodine uptake and subsequent negative 131I scans. The sensitivity of PET

in recurrent, radioiodine-resistant thyroid carcinomas is approximately 60% to 70% with some studies

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suggesting improved detection rates with TSH-stimulation or recombinant human TSH (rhTSH).13 PET

scanning is frequently used in the evaluation of other solid malignancies and occult thyroid carcinomas

are discovered in 2% to 3%.14 Incidentally discovered thyroid nodules which are focally PET-avid are

malignant in 30% to 35% and require evaluation with US and FNA biopsy.15,16

Figure 75-7. Example of a multinodular goiter with a large substernal component causing tracheal displacement and compression.

Cross-Sectional Imaging

Computed tomography (CT) scans and magnetic resonance imaging (MRI) scans are useful in certain

thyroid disease states after initial US and/or nuclear imaging. CT is particularly useful to determine the

extensiveness of invasive thyroid cancer suggested by physical examination findings of fixed nodules,

new vocal cord paralysis, or suspicion of tracheal invasion. CT is also useful in assessing for substernal

extension and tracheal deviation or compression in large goiters (Fig. 75-7). Finally, cross-sectional

imaging is helpful in assessing the degree of nodal involvement in thyroid cancer especially in the low

central neck and superior mediastinum, as these compartments are typically not well visualized by

cervical US.

FUNCTIONAL DISORDERS AND GENERAL TREATMENT

CONSIDERATIONS

Hyperthyroidism

The etiology of hyperthyroidism includes Graves disease, toxic multinodular goiter, solitary toxic

adenoma, thyroiditis, TSH-secretion pituitary adenoma and excess of thyroid hormone supplementation.

Typical symptoms are heat intolerance, sweating, palpitations, tremor, hyperphagia, thirst, weight loss,

and sleep disturbances. Elderly patients can present with muscle wasting, atrial fibrillation, angina

pectoris, or congestive heart failure. Regardless of the specific cause, the need to control

hyperthyroidism before operation is critical to prevent thyroid crisis (i.e., thyroid storm). Maximal

safety is assured with thionamides (methimazole or propothiouracil) combined with beta blockade.17

Adverse reactions of thionamides include agranulocytosis and hepatic toxicity which can be monitored

with white blood cell counts and liver function tests. Titration of thionamides for adequate preoperative

blockade with thyroid function tests should rely on T3 and T4

levels because TSH levels can remain

suppressed for several months even after achievement of normal T3 and T4

levels. Doses of beta

blockers should continue through the morning of surgery and should be weaned in the postoperative

setting.

Graves Disease

Dr. Robert Graves first described Graves disease in the 1830s as a toxic diffuse goiter associated with

exophthalmos and palpitations. It is an autoimmune disorder characterized by the presence of thyroidstimulating autoantibodies with a genetic predisposition and a female predominance (five to seven

times greater than males). These antibodies bind to the TSH receptor on follicular cells, stimulate

thyroid hormone release, and have a trophic effect on the thyroid. The autoimmune disease process may

affect the eyes, causing exophthalmos secondary to inflammatory cell infiltration into the extraocular

muscles and orbital connective tissue. Graves ophthalmopathy can lead to changes in visual acuity,

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ocular dryness, and proptosis which may be so severe as to require aggressive ophthalmologic treatment

in approximately 5% of patients. Graves disease may cause pretibial myxedema which is distinguished

from pedal edema by sparing of the ankles. Patients with Graves disease usually have a diffuse goiter,

which may be smooth or occasionally irregular. The gland is by nature hypervascular and may

occasionally have an audible bruit or palpable thrill in severe cases. T4 and T3

levels are increased and

TSH levels are suppressed. The uptake of radioiodine (RAI) generally shows a symmetrically enlarged

gland with diffuse increased 24-hour uptake.

Three main treatment modalities for Graves disease are medical therapy, radioactive iodine

treatment, and thyroidectomy. Selection of therapy depends on age, disease severity, goiter size, and

patient preference. Practice patterns differ dramatically across the world, especially regarding the use of

radioiodine (it is less common in Europe and especially Japan compared to the United States). The most

common initial treatment involves thionamides and often beta blockade. In a small fraction of patients,

antithyroid drugs may be the only therapy necessary, but in general, this strategy is considered an

impermanent solution as most patients will have persistent hyperthyroidism after cessation of

medication. Although the drugs may theoretically be used long term, they are associated with a small

but real risk of life-threatening agranulocytosis and liver toxicity. Ultimately, most patients pursue a

permanent therapy with RAI or surgery. Treatment with RAI is very effective and has not been

associated with secondary risk of development of a new malignancy, yet there is still hesitancy to use

this treatment in young children. RAI may take up to 6 months to provide definitive results and thus

antithyroid medications must continue during this period. In a small percentage of patients, a second

treatment may be necessary. After RAI treatment, 95% of patients become hypothyroid within 10 years

and require thyroid hormone replacement. RAI therapy has been occasionally associated with

exacerbation of Graves ophthalmopathy, although the effect is ameliorated by corticosteroids and the

early addition of LT4 posttreatment.18–20 Because of this concern, patients with severe ophthalmopathy

should consider total thyroidectomy instead of RAI to prevent such an exacerbation; however, ultimate

resolution of ophthalmopathy is no more likely with surgery.

Surgery for Graves disease has the advantage of rapid correction of the hyperthyroid state. The

specific operation has typically been either bilateral subtotal thyroidectomy or total thyroidectomy.

Subtotal thyroidectomy attempts to remove enough tissue to resolve the hyperthyroidism but leave

enough to maintain euthyroidism, however, Graves disease is dynamic and remissions after subtotal

thyroidectomy occurs in approximately 10% of patients at 5 years.21 Therefore total thyroidectomy is

the preferred operation for treatment of Graves disease with the intention of eliminating the chance of

recurrence, but accepting postsurgical hypothyroidism requiring thyroid hormone replacement.

Toxic Multinodular Goiter

The term toxic multinodular goiter (MNG) refers to thyrotoxicosis that is caused by a multinodular goiter

due to an endemic or nonendemic etiology. H.S. Plummer first distinguished toxic adenomatous goiter

from Graves disease. Although the eponym “Plummer disease” now more commonly refers to the

patient with a solitary toxic nodule, many clinicians still include toxic MNG under the same historical

blanket. Thyrotoxicosis may occur as a progression from euthyroid multinodular goiter that was initially

TSH-dependent, which then progressed to a state of autonomy which is not suppressible with LT4

.

Although the cause is clearly distinct, it is possible that some patients included in this diagnostic

category actually have Graves disease with nodular degeneration of their diffuse goiter. Patients with

toxic MNG, however, are often easily distinguished from those with Graves disease such that the typical

patient is a female older than 50 years with a previous history of multinodular goiter. Thyrotoxicosis

may be precipitated in an MNG with or without areas of autonomy when an iodide load is provided

(Jod-Basedow phenomenon). Historically, public health efforts to iodinate salt or flour in an iodinedeficient population have caused this phenomenon to follow over a period of years. This can occur after

exposure to iodinated radiographic contrast media, expectorants, or iodide-containing drugs such as

amiodarone.

Hyperthyroidism present in a patient with MNG can involve a wide spectrum of severity such that it

is not uncommon for a patient having structural indications for thyroidectomy, such as continued

nodular growth, substernal extension or compressive symptoms, in addition to hyperthyroidism.

Thyroidectomy or radioiodine treatments are effective treatments for toxic MNG. Radioiodine treatment

may require high doses or repeated treatments because of the large goiter size and low radioiodine

uptake, however, remains a viable option for patients who are not surgical candidates.17 Long-term

remissions from antithyroid drug treatment are even less common or predictable than in Graves disease

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and are not considered a definitive therapy for toxic MNG.22

Solitary Toxic Adenoma

Patients with thyrotoxicosis and a dominant thyroid nodule may have a toxic adenoma. Nodules usually

grow to at least 2 cm in size before hyperthyroidism is clinically evident. As expected, T3 or T4 or both

are elevated and TSH is suppressed. US typically demonstrates a thyroid nodule with benign US

characteristics and FNA is rarely helpful because the incidence of malignancy within these nodules is

negligible. Thyroid scintigraphy will demonstrate a single “hot” area corresponding to the known

nodule with suppression of the remainder of the thyroid. Treatment options include 131I RAI therapy or

thyroidectomy. RAI is effective in controlling the hyperthyroidism, but depending on nodule size, may

leave behind a palpable abnormality. In particular, younger patients with sizable nodules may choose

operation. The resection is typically a hemithyroidectomy and the contralateral lobe is often normal and

capable of maintaining normal thyroid hormone production in 85% of patients.23

Hypothyroidism

Primary hypothyroidism can arise from intrinsic thyroid disease, iatrogenic thyroid removal or

destruction, and antithyroid drug effects. Secondary hypothyroidism can also occur from failure of

thyrotropic function (via TSH) due to pituitary gland disease, removal, or destruction. Rarely, tertiary

hypothyroidism can occur with destructive disorders of the hypothalamus via decreased production of

thyrotropin-releasing hormone. The most common cause of primary hypothyroidism in adult patients is

Hashimoto thyroiditis. In large part, hypothyroidism is straightforward to address with exogenous LT4

therapy. The role for surgical therapy is limited aside from patients with a structural thyroid disorder

associated with underlying hypothyroidism.

Thyroiditis

Inflammatory conditions of the thyroid are a disparate family of conditions that require surgical therapy

in the minority of situations. Thyroiditis can be quite prevalent in patients undergoing evaluation for

thyroid surgery and a thorough understanding is required to avoid diagnostic and therapeutic

misadventures.

Hashimoto Thyroiditis

Also known as chronic thyroiditis, autoimmune thyroiditis, and lymphocytic thyroiditis, this condition

was described by Hashimoto in 1912 based on its histologic findings. It affects approximately 10% of

the general population, has peak ages from 30 to 60 years and a female-to-male preponderance as high

as 9:1. It is clearly an autoimmune condition and there is a moderate genetic predisposition, associated

with human leukocyte antigen (HLA)-DR3, -DR5, and -B8. The disease prevalence is increased in iodinesufficient regions and this may be because immunogenicity of the thyroglobulin molecule increases with

the degree of iodination. The histologic changes are characterized by lymphocytic infiltration with

fibrosis and germinal centers. Some follicular cells may undergo metaplasia to Hürthle cells. The typical

presentation is that of a painless diffuse goiter in a young woman discovered on physical examination

with or without associated hypothyroidism. Patients often note a sense of fullness in, or awareness of,

the thyroid. When the associated goiter is large, compressive symptoms of dysphagia or dyspnea may

occur. The goiter is typically firm and rubbery and slightly “bumpy” with prominent lateral lobes. The

US appearance of the thyroid is typically heterogeneous in its echotexture with irregular capsular

borders with or without distinct nodules. Nodular disease in a gland affected by Hashimoto disease

should be investigated with FNA to rule out coexisting malignancy. Thyroid autoantibody titers are

elevated, TPOAb primarily and TgAb secondarily. In approximately 5% of patients, a transient phase of

hyperthyroidism, termed “Hashitoxicosis,” occurs at the onset of disease. Following onset,

approximately 5% per year will progress to hypothyroidism.24 For the majority of patients, treatment of

Hashimoto thyroiditis is limited to LT4

therapy in those with hypothyroidism. Surgery is indicated in

patients with large goiters, significant compressive symptoms, local symptoms refractory to LT4

therapy, or the inability to rule out malignancy (typically in the setting of nodules or rapid growth).25

Painless or Postpartum Thyroiditis

Sporadic silent (painless) thyroiditis and postpartum thyroiditis are destruction-induced and are

probably variants of the same process, distinguished only by the relationship to pregnancy.26 Along with

subacute thyroiditis, these conditions are characterized by the onset of thyrotoxicosis and a goiter, and

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low 24-hour RAIU. Even excluding postpartum cases, there is a female predominance by 2:1 and the age

range of affected patients is broad. The cause appears to be autoimmune, but the genetic predisposition

is low. There is no fever or malaise and the goiter is painless but persistent. Thyroid autoantibody titers

are often high, and the erythrocyte sedimentation rate (ESR) is usually normal. Thyroid function is

dynamic and follows a pattern similar to that of subacute thyroiditis with an abrupt onset of

thyrotoxicosis followed by a period of euthyroidism, then hypothyroidism. At the histologic level,

lymphocytic infiltration is present along with destruction of follicular cells. If it is pregnancy associated,

it is likely to relapse with future pregnancies. If symptoms of thyrotoxicosis are significant, βadrenergic–blocking drugs may be used, but antithyroid drugs are not appropriate because the gland is

not hyperfunctioning at the follicular cell level. If LT4

therapy is instituted during the hypothyroid

phase for symptomatic relief, it can be withdrawn after 6 to 9 months to determine if recovery has

occurred.

Subacute Thyroiditis

Subacute thyroiditis is a common form of thyroiditis that affects women more often than men by a 5:1

ratio and often in the age group of 20 to 60 years. There are a number of synonymous terms, such as de

Quervain thyroiditis, giant cell thyroiditis, pseudogranulomatous thyroiditis, subacute painful

thyroiditis, and subacute granulomatous thyroiditis. The cause is not entirely certain, but it appears to

be virally related and a prodrome consistent with an upper respiratory viral infection is very common.

The patient often has fever, malaise, and an exquisitely painful and firm goiter that is transient. The

goiter is usually unilaterally dominant, and the patient may have pain that radiates to the ipsilateral ear.

Giant cells (which may also be observed on FNA) support the diagnosis and granulomas often infiltrate

the thyroid. Consistent with follicular cell destruction, serum Tg levels may be elevated. Antithyroid

antibodies may be present in low titers and the ESR is often high. A 24-hour RAIU is usually quite low

(<5%). Management is similar to painless thyroiditis in that beta blockers may be used, but antithyroid

medications are not useful. Salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs) are adequate

to control pain in most cases, with the occasional need for oral glucocorticoids. Although the course of

disease can be protracted for weeks or months, resolution is common and management is usually

limited to management of symptoms.

Amiodarone-Induced Thyrotoxicosis or Thyroiditis

The antiarrhymic drug amiodarone causes thyroid dysfunction in 15% to 20% of patients. Thyroid

dysfunction can include hypothyroidism and amiodarone-induced thyrotoxicosis (AIT) which has two

forms: Type I which is often associated with pre-existing multinodular goiter and is the result of the

iodine load provided by amiodarone; Type II is more frequent and is the result of destructive

thyroiditis. Type I AIT is characterized by a diffuse or nodular goiter with increased vascularity noted

on thyroid US and is primarily treated with withdrawal of amiodarone (if feasible) and initiation of

methimazole with or without potassium iodide.27 Type II AIT is characterized by a normal thyroid gland

without hypervascularity on thyroid US and is treated with withdrawal of amiodarone (if feasible) and

corticosteroids, while methimazole is ineffective.27 Medical treatment of AIT is difficult because of both

the long half-life of the drug and the effects of thyrotoxicosis on cardiac function in patients already

with underlying heart disease. If hyperthyroidism is severe in either type I or II, thyroidectomy may be

required to resolve the thyrotoxicosis rapidly and definitively and in some cases to allow for

continuation of amiodarone.

Acute Thyroiditis

Acute thyroiditis refers to a rare suppurative condition most commonly caused by the bacterial

pathogens Staphylococcus aureus and Streptococcus pyogenes. A clinical prodrome, usually a viral or

bacterial upper respiratory infection, may occur and the patient is often affected by a significant fever

and malaise and may have radiating pain to the region of the ipsilateral ear. A painful but ultimately

transient goiter may be evident, which is often the result of a thyroidal or perithyroidal abscess. The

patient usually remains euthyroid and antithyroid antibody titers are normal. ESR may be elevated.

Bacterial infection of the thyroid may occur via hematologic spread from a distant site or local

infiltration from other head and neck infections. Recurrent cases of acute thyroiditis may be related to a

fistulous communication with the pyriform sinus and is an indication for surgical intervention.

Riedel Thyroiditis

Also known as Riedel struma or invasive fibrous thyroiditis, this rare disorder affects mainly women (by

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