Toxic Nodular Goiter: Background, Pathophysiology, Epidemiology

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Sections Toxic Nodular Goiter
Overview
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Overview

Background

A toxic nodular goiter (TNG) is a thyroid gland that contains autonomously functioning thyroid nodules, with resulting hyperthyroidism. There are distinct considerations if the patient has a single solitary toxic nodule (see Solitary Thyroid Nodule). TNG, or Plummer's disease, was first described by Henry Plummer in 1913. TNG is the second most common cause of hyperthyroidism in the Western world, after Graves disease. In elderly individuals and in areas of endemic iodine deficiency, TNG is the most common cause of hyperthyroidism.

Pathophysiology

Toxic nodular goiter (TNG) represents a spectrum of disease ranging from a single hyperfunctioning nodule (toxic adenoma) within a multinodular thyroid to a gland with multiple areas of hyperfunction. The natural history of a multinodular goiter involves variable growth of individual nodules; this may progress to hemorrhage and degeneration, followed by healing and fibrosis. Calcification may be found in areas of previous hemorrhage. Some nodules may develop autonomous function. Autonomous hyperactivity is conferred by somatic mutations of the thyrotropin, or thyroid-stimulating hormone (TSH), receptor in 20-80% of toxic adenomas and some nodules of multinodular goiters.^[1]Autonomously functioning nodules may become toxic in 10% of patients. Hyperthyroidism predominantly occurs when single nodules are larger than 2.5 cm in diameter. Signs and symptoms of TNG are similar to those of other types of hyperthyroidism.

Frequency

United States

Toxic nodular goiter accounts for approximately 15-30% of cases of hyperthyroidism in the United States, second only to Graves disease.

International

In areas of endemic iodine deficiency, toxic nodular goiter (TNG) accounts for approximately 58% of cases of hyperthyroidism, 10% of which are from solitary toxic nodules. Graves disease accounts for 40% of cases of hyperthyroidism. In patients with underlying nontoxic multinodular goiter, initial iodine supplementation (or iodinated contrast agents) can lead to hyperthyroidism (Jod-Basedow effect). Iodinated drugs, such as amiodarone, may also induce hyperthyroidism in patients with underlying nontoxic multinodular goiter. Roughly 3% of patients treated with amiodarone in the United States (more in areas of iodine deficiency) develop amiodarone-induced hyperthyroidism.^[2]

Mortality/Morbidity

Morbidity and mortality from toxic nodular goiter (TNG) may be divided into problems related to hyperthyroidism and problems related to growth of the nodules and gland. Local compression problems due to nodule growth, although unusual, include dyspnea, hoarseness, and dysphagia. Both TNG and Graves disease have increased mortality but for different reasons.^[3]

TNG is more common in elderly adults; therefore, complications due to comorbidities, such as coronary artery disease, are significant in the management of hyperthyroidism.

Sex

Toxic nodular goiter occurs more commonly in women than in men. In women and men older than 40 years, the prevalence rate of palpable nodules is 5-7% and 1-2%, respectively.

Age

Most patients with toxic nodular goiter (TNG) are older than 50 years.

Thyrotoxicosis often occurs in patients with a history of longstanding goiter. Toxicity occurs in a subset of patients who develop autonomous function. This toxicity usually peaks in the sixth and seventh decades of life, especially in persons with a family history of multinodular goiter or TNG, suggesting a genetic component.

Clinical Presentation

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Media Gallery

Patchy uptake of iodine (123I) in a toxic multinodular goiter.

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Author

Philip R Orlander, MD Director and Professor, Division of Endocrinology, Associate Dean for Educational Programs, Vice-Chair of Medicine for Education, Program Director, Internal Medicine Residency Program, 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, Texas Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Caroline B Chiu, MD Fellow, Department of Endocrinology, University of Texas Health Science Center at Houston

Caroline B Chiu, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Anu Bhalla Davis, MD Assistant Professor, Department of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Texas Medical School at Houston

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

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, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

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

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.

Sections Toxic Nodular Goiter
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
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Toxic Nodular Goiter

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