eMedicine Specialties > Endocrinology > Thyroid

Goiter, Toxic Nodular: Differential Diagnoses & Workup

Author: Anu Bhalla Davis, MD, Assistant Professor, Department of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Texas Health Science Center at Houston
Coauthor(s): Philip R Orlander, MD, Interim Chair of Medicine, Director of Endocrinology and Metabolism Fellowship, Director and Professor, Department of Medicine, Division of Endocrinology, University of Texas Health Science Center at Houston; Asra Kermani, MBBS, Postdoctoral Fellow, Center for Human Nutrition, University of Texas Southwestern Medical School
Contributor Information and Disclosures

Updated: Jun 4, 2009

Differential Diagnoses

Goiter
Struma Ovarii
Goiter, Diffuse Toxic
Thyroid Nodule
Goiter, Nontoxic
Thyroid, Papillary Carcinoma
Graves Disease
Thyroiditis, Subacute
Hashimoto Thyroiditis
Riedel Thyroiditis

Other Problems to Be Considered

Subclinical hyperthyroidism
Substernal goiter
Amiodarone-associated thyroid disease
Iodine-induced hyperthyroidism

Workup

Laboratory Studies

  • Thyroid function tests6 - Evidence of hyperthyroidism must be present in order to consider a diagnosis of toxic nodular goiter (TNG).
    • Third-generation 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 scintigraphy6
    • Nuclear scans should be performed on patients with biochemical hyperthyroidism. 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, 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]).
    • Thyroid scanning is also useful for helping to determine the presence of substernal extension of the thyroid gland, which may contain toxic nodules.
  • Ultrasonography6
    • 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.
    • 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.7
    • 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.

More on Goiter, Toxic Nodular

Overview: Goiter, Toxic Nodular
Differential Diagnoses & Workup: Goiter, Toxic Nodular
Treatment & Medication: Goiter, Toxic Nodular
Follow-up: Goiter, Toxic Nodular
Multimedia: Goiter, Toxic Nodular
References
Further Reading
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References

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Further Reading

Related eMedicine topics:
 Hyperthyroidism [Endocrinology]
Hyperthyroidism [Pediatrics: General Medicine]
Hyperthyroidism, Thyroid Storm, and Graves Disease
Hypothyroidism [Endocrinology]
Hypothyroidism [Pediatrics: General Medicine]
Iodine Deficiency
Thyroid Dysfunction Induced by Amiodarone Therapy

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Keywords

toxic nodular goiter, goiter, TNG, toxic multinodular goiter, hyperthyroidism, hyperthyroid, Plummer disease, Plummer's disease, toxic uninodular goiter, autonomously functioning thyroid nodule, toxic adenoma, Graves disease, Graves' disease, iodine deficiency, Jod-Basedow phenomenon, Jod-Basedow effect, Jod-Basedow's effect, hyperfunctioning nodule, multinodular thyroid, underlying nontoxic multinodular goiter, amiodarone, amiodarone-induced hyperthyroidism, thyrotoxicosis, apathetic hyperthyroidism, suppressed thyroid-stimulating hormone, TSH, TSH receptors, superior vena cava syndrome, hyperplasia, cyclic adenosine monophosphate, cAMP, thyroxine, T4, iodine-induced hyperthyroidism, triiodothyronine, T3, micronodular growth patterns, follicles, D727E, endothelin-1, ET-1

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Contributor Information and Disclosures

Author

Anu Bhalla Davis, MD, Assistant Professor, Department of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Texas Health Science Center at Houston
Disclosure: Nothing to disclose.

Coauthor(s)

Philip R Orlander, MD, Interim Chair of Medicine, Director of Endocrinology and Metabolism Fellowship, Director and Professor, Department of Medicine, Division of Endocrinology, University of Texas Health Science Center at Houston
Philip R Orlander, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, Endocrine Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Asra Kermani, MBBS, Postdoctoral Fellow, Center for Human Nutrition, University of Texas Southwestern Medical School
Asra Kermani, MBBS is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine
Disclosure: Nothing to disclose.

Medical Editor

Robert A Gabbay, MD, PhD, Associate Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, Laurence M Demers Career Development Professor, Penn State College of Medicine; Director, Diabetes Program, Penn State Milton S Hershey Medical Center; Executive Director, Penn State Institute for Diabetes and Obesity
Robert A Gabbay, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, and Endocrine Society
Disclosure: Novo Nordisk Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kent Wehmeier, MD, Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine
Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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