Toxic multinodular goiter - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Toxic multinodular goiter is most common in older patients.
Onset of symptoms is more insidious and symptoms less dramatic than for Graves disease. Patients may have apathetic hyperthyroidism (minimal signs/symptoms) or subclinical hyperthyroidism (isolated thyroid-stimulating hormone suppression).
Spontaneous remission is rare. Definitive treatment, most commonly radioactive iodine, is usually required.
If untreated, complications may include sequelae of hyperthyroidism, such as cardiac dysfunction or bone loss, or tracheal compression by large goiters.

Thyroid scan showing variegated uptake in toxic multinodular goiter

Courtesy of Dr Elizabeth Pearce; used with permission

Quick Reference

History & Exam
- Key Factors
- Other Factors
More information...
Diagnostics Tests
More information...
Treatment Options
More information...

Definition

Epidemiology

Etiology

Pathophysiology

Images

Goiter due to a dietary iodine deficiency
Thyroid scan showing variegated uptake in toxic multinodular goiter
Chest CT showing marked enlargement of the thyroid gland with an extensive intrathoracic component causing trachea compression
Hyperfunctioning thyroid nodule suppressing contralateral gland on thyroid scan (SSN = suprasternal notch)

Citations

Key Articles

Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules - 2016 update. Endocr Pract. 2016 May;22(5):622-39.[Abstract][Full Text]
Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. 2015 Apr;3(4):286-95.[Abstract]
Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26:1343-1421.[Abstract][Full Text]
Haugen BR, Alexander EK, Bible KC, 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;26:1-133.[Abstract][Full Text]

Other Online Resources

Iodine Global Network: Global scorecard of iodine nutrition in 2021 in the general population based on school-age children (SAC)

Referenced Articles

1. Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules - 2016 update. Endocr Pract. 2016 May;22(5):622-39.[Abstract][Full Text]
2. 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;84:3328-35.[Abstract][Full Text]
3. De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016 Aug 27;388(10047):906-18.[Abstract]
4. Taylor PN, Albrecht D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018 May;14(5):301-16.[Abstract]
5. Thiruvengadam S, Luthra P. Thyroid disorders in elderly: A comprehensive review. Dis Mon. 2021 Nov;67(11):101223.[Abstract][Full Text]
6. Guille JT, Opoku-Boateng A, Thibeault SL, et al. Evaluation and management of the pediatric thyroid nodule. Oncologist. 2015 Jan;20(1):19-27.[Abstract][Full Text]
7. Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. 2015 Apr;3(4):286-95.[Abstract]
8. Li M, Eastman CJ. The changing epidemiology of iodine deficiency. Nat Rev Endocrinol. 2012 Apr 3;8(7):434-40.[Abstract][Full Text]
9. Tonacchera M, Chiovato L, Pinchera A, et al. Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma. J Clin Endocrinol Metab. 1998;83:492-8.[Abstract][Full Text]
10. Tonacchera M, Agretti P, Chiovato L, et al. Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter. J Clin Endocrinol Metab. 2000;85:2270-4.[Abstract][Full Text]
11. Krohn K, Führer D, Bayer Y, et al. Molecular pathogenesis of euthyroid and toxic multinodular goiter. Endocr Rev. 2005;26:504-24.[Abstract][Full Text]
12. Fiore E, Tonacchera M, Vitti P. Influence of iodization programmes on the epidemiology of nodular goitre. Best Pract Res Clin Endocrinol Metab. 2014 Aug;28(4):577-88.[Abstract]
13. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26:1343-1421.[Abstract][Full Text]
14. Derwahl M. TSH receptor and Gs-alpha gene mutations in the pathogenesis of toxic thyroid adenomas - a note of caution. J Clin Endocrinol Metab. 1996;81:2783-2785.[Abstract]
15. Morris AJ, Malbon CC. Physiological regulation of G protein-linked signaling. Physiol Rev. 1999;79:1373-1430. [Abstract]
16. Poertl S, Kirner J, Saller B, et al. T3-release from autonomously functioning thyroid nodules in vitro. Exp Clin Endocrinol Diabetes. 1998;106:489-493.[Abstract]
17. Polak M. Hyperfunctioning thyroid adenoma and activating mutations in the TSH receptor gene. Arch Med Res. 1999;30:510-513. [Abstract]
18. Krohn K, Führer D, Holzapfel HP, et al. Clonal origin of toxic thyroid nodules with constitutively activating thyrotropin receptor mutations. J Clin Endocrinol Metab. 1998;83:130-134.[Abstract]
19. Derwahl M, Hamacher C, Russo D, et al. Constitutive activation of the Gs alpha protein-adenylate cyclase pathway may not be sufficient to generate toxic thyroid adenomas. J Clin Endocrinol Metab. 1996;81:1898-1904.[Abstract]
20. Pearce EN, Pino S, He X, et al. Sources of dietary iodine: bread, cows' milk, and infant formula in the Boston area. J Clin Endocrinol Metab. 2004;89:3421-3424.[Abstract]
21. Maniakas A, Davies L, Zafereo ME. Thyroid disease around the world. Otolaryngol Clin North Am. 2018 Jun;51(3):631-42.[Abstract]
22. Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med. 2003;26:348:2646-2655. [Erratum in: N Engl J Med. 2003;349:620.][Abstract]
23. De Filippis EA, Sabet A, Sun MR, et al. Pemberton's sign: explained nearly 70 years later. J Clin Endocrinol Metab. 2014;99:1949-1954.[Abstract]
24. National Institute for Health and Care Excellence. Thyroid disease: assessment and management. Oct 2023 [internet publication].[Full Text]
25. American Society for Clinical Pathology. Thirty five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. Jul 2021 [internet publication].[Full Text]
26. American College of Radiology. ACR Appropriateness Criteria®. Thyroid disease. 2018 [internet publication].[Full Text]
27. Singh Ospina N, Iñiguez-Ariza NM, Castro MR. Thyroid nodules: diagnostic evaluation based on thyroid cancer risk assessment. BMJ. 2020 Jan 7;368:l6670.[Abstract][Full Text]
28. Haugen BR, Alexander EK, Bible KC, 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;26:1-133.[Abstract][Full Text]
29. Cibas ES, Ali SZ. The 2017 Bethesda system for reporting thyroid cytopathology. Thyroid. 2017 Nov;27(11):1341-6.[Abstract][Full Text]
30. Scappaticcio L, Maiorino MI, Maio A, et al. Neutropenia in patients with hyperthyroidism: systematic review and meta-analysis. Clin Endocrinol (Oxf). 2021 Mar;94(3):473-83.[Abstract][Full Text]
31. Scappaticcio L, Longo M, Maiorino MI, et al. Abnormal liver blood tests in patients with hyperthyroidism: systematic review and meta-analysis. Thyroid. 2021 Jun;31(6):884-94.[Abstract][Full Text]
32. Endocrine Society. Five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. Jun 2022 [internet publication].[Full Text]
33. Belfiore A, La Rosa GL, La Porta GA, et al. Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity. Am J Med. 1992;93:363-369.[Abstract]
34. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27:315-389.[Abstract][Full Text]
35. LeFevre ML; US Preventive Services Task Force. Screening for thyroid dysfunction: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;162:641-650.[Abstract][Full Text]
36. Garber JR, Papini E, Frasoldati A, et al. American Association of Clinical Endocrinology And Associazione Medici Endocrinologi thyroid nodule algorithmic tool. Endocr Pract. 2021 Jul;27(7):649-60.[Abstract][Full Text]
37. Nygaard B, Hegedus L, Ulriksen P, et al. Radioiodine therapy for multinodular toxic goiter. Arch Intern Med. 1999;159:1364-1368. [Abstract]
38. Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352:905-917.[Abstract]
39. Patel KN, Yip L, Lubitz CC, et al. The American Association of Endocrine Surgeons guidelines for the definitive surgical management of thyroid disease in adults. Ann Surg. 2020 Mar;271(3):e21-e93.[Abstract][Full Text]
40. Biondi B, Cooper DS. Subclinical hyperthyroidism. N Engl J Med. 2018 Jun 21;378(25):2411-9.[Abstract]
41. Delitala AP, Scuteri A, Doria C. Thyroid hormone diseases and osteoporosis. J Clin Med. 2020 Apr 6;9(4):1034.[Abstract][Full Text]
42. Pearce EN. Diagnosis and management of thyrotoxicosis. BMJ. 2006 Jun 10;332(7554):1369-73.[Abstract]
43. Adam MA, Thomas S, Youngwirth L, et al. Is there a minimum number of thyroidectomies a surgeon should perform to optimize patient outcomes? Ann Surg. 2017;265:402-407.[Abstract]
44. Franklyn JA, Boelaert K. Thyrotoxicosis. Lancet. 2012;379:1155-1166.[Abstract]
45. American College of Radiology (ACR), the American College of Nuclear Medicine (ACNM), the American Society for Radiation Oncology (ASTRO), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), and the Society for Pediatric Radiology (SPR). ACR-ACNM-ASTRO-SNMMI-SPR pracrice parameter for treatment of benign and malignant thyroid disease with I-131 sodium iodide. 2019 [internet publication].[Full Text]
46. Sisson JC, Freitas J, McDougall IR, et al; American Thyroid Association Taskforce On Radioiodine Safety. Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I: practice recommendations of the American Thyroid Association. Thyroid. 2011;21:335-346.[Abstract][Full Text]
47. Stachura A, Gryn T, Kałuża B, et al. Predictors of euthyreosis in hyperthyroid patients treated with radioiodine <sup>131</sup>I<sup>-</sup>: a retrospective study. BMC Endocr Disord. 2020 Jun 1;20(1):77.[Abstract][Full Text]
48. Kahraman D, Keller C, Schneider C, et al. Development of hypothyroidism during long-term follow-up of patients with toxic nodular goitre after radioiodine therapy. Clin Endocrinol (Oxf). 2012 Feb;76(2):297-303.[Abstract][Full Text]
49. Toft AD. Clinical practice. Subclinical hyperthyroidism. N Engl J Med. 2001;345:512-516.[Abstract]
50. Bednarczuk T, Brix TH, Schima W, et al. 2021 European Thyroid Association guidelines for the management of iodine-based contrast media-induced thyroid dysfunction. Eur Thyroid J. 2021 Jul;10(4):269-84.[Abstract][Full Text]