Sections

Presentation

History

Thyrotoxic symptoms

Most patients with toxic nodular goiter (TNG) present with symptoms typical of hyperthyroidism, including heat intolerance, palpitations, tremor, weight loss, hunger, and frequent bowel movements.

Elderly patients may have more atypical symptoms, including the following:

Weight loss is the most common complaint in elderly patients with hyperthyroidism.
Anorexia and constipation may occur, in contrast to frequent bowel movements often reported by younger patients.
Dyspnea or palpitations may be a common occurrence.
Tremor also occurs but can be confused with essential senile tremor.
Cardiovascular complications occur commonly in elderly patients, and a history of atrial fibrillation, congestive heart failure, or angina may be present.

F Lahey, MD, first described apathetic hyperthyroidism in 1931; this is characterized by blunted affect, lack of hyperkinetic motor activity, and slowed mentation in a patient who is thyrotoxic.

Obstructive symptoms

A significantly enlarged goiter can cause symptoms related to mechanical obstruction.

A large substernal goiter may cause dysphagia, dyspnea, or frank stridor. Rarely, this goiter results in a surgical emergency.

Involvement of the recurrent or superior laryngeal nerve may result in complaints of hoarseness or voice change.

Asymptomatic or minimal symptoms

Many patients are asymptomatic or have minimal symptoms and are incidentally found to have hyperthyroidism during routine screening. The most common laboratory finding is a suppressed TSH with normal free thyroxine (T4) levels.

Physical Examination

Findings of hyperthyroidism may be more subtle than those of Graves disease. Features may include widened, palpebral fissures; tachycardia; hyperkinesis; moist, smooth skin; tremor; proximal muscle weakness; and brisk deep tendon reflexes.

The size of the thyroid gland is variable. Large substernal glands may not be appreciable upon physical examination.

A dominant nodule or multiple irregular, variably sized nodules are typically present. In a small gland, multinodularity may be apparent only on an ultrasonogram. Chronic Graves disease may present with some nodularity; therefore, establishing the diagnosis is sometimes difficult.

Hoarseness or tracheal deviation may be present upon examination.

Mechanical obstruction may result in superior vena cava syndrome, with engorgement of facial and neck veins (Pemberton sign).^[6]

Stigmata of Graves disease (eg, orbitopathy, pretibial myxedema, acropachy) are not observed.

Differential Diagnoses

Lado-Abeal J, Palos-Paz F, Perez-Guerra O, et al. Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine deficient area in NW Spain. Eur J Endocrinol. 2008 Aug 11. [QxMD MEDLINE Link].
Gabriel EM, Bergert ER, Grant CS, et al. Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter. J Clin Endocrinol Metab. 1999 Sep. 84(9):3328-35. [QxMD MEDLINE Link]. [Full Text].
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Abraham-Nordling M, Törring O, Lantz M, et al. Incidence of hyperthyroidism in Stockholm, Sweden, 2003-2005. Eur J Endocrinol. 2008 Jun. 158(6):823-7. [QxMD MEDLINE Link].
Brandt F, Thvilum M, Almind D, Christensen K, Green A, Hegedüs L, et al. Graves' disease and toxic nodular goiter are both associated with increased mortality but differ with respect to the cause of death: a Danish population-based register study. Thyroid. 2013 Apr. 23(4):408-13. [QxMD MEDLINE Link].
Basaria S, Salvatori R. Images in clinical medicine. Pemberton's sign. N Engl J Med. 2004 Mar 25. 350(13):1338. [QxMD MEDLINE Link].
[Guideline] Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan. 26 (1):1-133. [QxMD MEDLINE Link].
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van Soestbergen MJ, van der Vijver JC, Graafland AD. Recurrence of hyperthyroidism in multinodular goiter after long-term drug therapy: a comparison with Graves' disease. J Endocrinol Invest. 1992 Dec. 15(11):797-800. [QxMD MEDLINE Link].
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Erkan ME, Demirin H, Asik M, Celbek G, Yildirim M, Aydin Y, et al. Efficiency of radioactive I-131 therapy in geriatric patients with toxic nodular goiter. Aging Clin Exp Res. 2012 Dec. 24(6):714-7. [QxMD MEDLINE Link].
Lee YY, Tam KW, Lin YM, Leu WJ, Chang JC, Hsiao CL, et al. Recombinant human thyrotropin before (131)I therapy in patients with nodular goitre: a meta-analysis of randomized controlled trials. Clin Endocrinol (Oxf). 2015 Nov. 83 (5):702-10. [QxMD MEDLINE Link].
Adamali HI, Gibney J, O'Shea D, Casey M, McKenna TJ. The occurrence of hypothyroidism following radioactive iodine treatment of toxic nodular goiter is related to the TSH level. Ir J Med Sci. 2007 Sep. 176 (3):199-203. [QxMD MEDLINE Link].
Adamali HI, Gibney J, O'Shea D, et al. The occurrence of hypothyroidism following radioactive iodine treatment of toxic nodular goiter is related to the TSH level. Ir J Med Sci. 2007 Sep. 176(3):199-203. [QxMD MEDLINE Link].
Bonnema SJ, Bertelsen H, Mortensen J, et al. The feasibility of high dose iodine 131 treatment as an alternative to surgery in patients with a very large goiter: effect on thyroid function and size and pulmonary function. J Clin Endocrinol Metab. 1999 Oct. 84(10):3636-41. [QxMD MEDLINE Link].
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Patchy uptake of iodine (123I) in a toxic multinodular goiter.

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Author

Philip R Orlander, MD, FACP Director and Professor, Division of Endocrinology, Diabetes and Metabolism, Associate Dean for Educational Programs, Vice-Chair of Medicine for Education, Edward Randall III Chair in Internal Medicine, Program Director for Internal Medicine Residency Program, University of Texas Health Science Center at Houston

Philip R Orlander, MD, FACP 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 Physician Leadership, American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society, International Society for Clinical Densitometry, Southern Society for Clinical Investigation

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.

Toxic Nodular Goiter Clinical Presentation

History

Thyrotoxic symptoms

Obstructive symptoms

Asymptomatic or minimal symptoms

Physical Examination

References

Tables

Contributor Information and Disclosures

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