Diagnostic Considerations

Conditions to consider in the differential diagnosis of iodine deficiency include the following:

Euthyroid sick syndrome
Hurthle cell carcinoma
Hypothermia
Hypothyroidism
Goiter - Nontoxic, toxic nodular, lithium-induced
Thyroiditis
Infertility
Pericardial effusion
Thyroid nodule
Papillary thyroid carcinoma
Hurthle cell carcinoma
Follicular thyroid carcinoma
Anaplastic thyroid carcinoma
Thyroid lymphoma
Thyroxine-binding globulin deficiency

Endemic goiter can be differentiated from sporadic, nontoxic, multinodular goiter only by a history of iodine deficiency. The nodules of a goiter associated with iodine deficiency disorder (IDD) cannot be distinguished from thyroid cancer based on the results of a physical examination. Any patient with a discrete nodule of at least 1-1.5 cm should be referred to an endocrinologist for evaluation with a fine-needle aspiration biopsy. Hypothyroidism secondary to IDD must be distinguished from Hashimoto disease or subacute thyroiditis.

Differential Diagnoses

Workup

Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet. 2008 Oct 4. 372(9645):1251-62. [QxMD MEDLINE Link].
Pearce EN, Andersson M, Zimmermann MB. Global iodine nutrition: Where do we stand in 2013?. Thyroid. 2013 May. 23(5):523-8. [QxMD MEDLINE Link].
[Guideline] WHO. Guideline: fortification of food-grade salt with iodine for the prevention and control of iodine deficiency disorders. Geneva: World Health Organization; 2014. [Full Text].
Iodine Global Network. Global Scorecard of Iodine Nutrition in 2017 in the general population and in pregnant women (PW). IGN.org. Available at http://www.ign.org/cm_data/IGN_Global_Scorecard_AllPop_and_PW_May2017.pdf. May 30, 2017; Accessed: September 22, 2017.
Zimmermann MB. Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review. Am J Clin Nutr. 2009 Feb. 89(2):668S-72S. [QxMD MEDLINE Link].
WHO Secretariat, Andersson M, de Benoist B, Delange F, Zupan J. Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the Technical Consultation. Public Health Nutr. 2007 Dec. 10(12A):1606-11. [QxMD MEDLINE Link].
Delange F. Optimal iodine nutrition during pregnancy, lactation and neonatal period. Int J Endocrinol Metab. 2004. 89:3851.
Azizi F, Smyth P. Breastfeeding and maternal and infant iodine nutrition. Clin Endocrinol (Oxf). 2009 May. 70(5):803-9. [QxMD MEDLINE Link].
Dasgupta PK, Liu Y, Dyke JV. Iodine nutrition: iodine content of iodized salt in the United States. Environ Sci Technol. 2008 Feb 15. 42(4):1315-23. [QxMD MEDLINE Link].
Pearce EN, Pino S, He X, Bazrafshan HR, Lee SL, Braverman LE. Sources of dietary iodine: bread, cows' milk, and infant formula in the Boston area. J Clin Endocrinol Metab. 2004 Jul. 89(7):3421-4. [QxMD MEDLINE Link].
Hollowell JG, Staehling NW, Hannon WH, et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994). J Clin Endocrinol Metab. 1998 Oct. 83(10):3401-8. [QxMD MEDLINE Link]. [Full Text].
Caldwell KL, Jones R, Hollowell JG. Urinary iodine concentration: United States National Health And Nutrition Examination Survey 2001-2002. Thyroid. 2005 Jul. 15(7):692-9. [QxMD MEDLINE Link].
Caldwell KL, Miller GA, Wang RY, Jain RB, Jones RL. Iodine status of the U.S. population, National Health and Nutrition Examination Survey 2003-2004. Thyroid. 2008 Nov. 18(11):1207-14. [QxMD MEDLINE Link].
Caldwell KL, Pan Y, Mortensen ME, Makhmudov A, Merrill L, Moye J. Iodine status in pregnant women in the National Children's Study and in U.S. women (15-44 years), National Health and Nutrition Examination Survey 2005-2010. Thyroid. 2013 Aug. 23(8):927-37. [QxMD MEDLINE Link].
Zimmermann MB, Aeberli I, Torresani T, et al. Increasing the iodine concentration in the Swiss iodized salt program markedly improved iodine status in pregnant women and children: a 5-y prospective national study. Am J Clin Nutr. 2005 Aug. 82(2):388-92. [QxMD MEDLINE Link]. [Full Text].
Bath SC, Steer CD, Golding J, Emmett P, Rayman MP. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet. 2013 Jul 27. 382(9889):331-7. [QxMD MEDLINE Link].
Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. 2015 Apr. 3(4):286-95. [QxMD MEDLINE Link].
Williams GR. Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol. 2008 Jun. 20(6):784-94. [QxMD MEDLINE Link].
Zimmermann MB, Wegmuller R, Zeder C, et al. Rapid relapse of thyroid dysfunction and goiter in school-age children after discontinuation of salt iodization. Am J Clin Nutr. 2004 Apr. 79(4):642-5. [QxMD MEDLINE Link]. [Full Text].
Taylor PN, Okosieme OE, Dayan CM, Lazarus JH. Therapy of endocrine disease: Impact of iodine supplementation in mild-to-moderate iodine deficiency: systematic review and meta-analysis. Eur J Endocrinol. 2014 Jan. 170(1):R1-R15. [QxMD MEDLINE Link]. [Full Text].
Santiago-Fernandez P, Torres-Barahona R, Muela-Martinez JA, et al. Intelligence quotient and iodine intake: a cross-sectional study in children. J Clin Endocrinol Metab. 2004 Aug. 89(8):3851-7. [QxMD MEDLINE Link]. [Full Text].
Leung AM, Lamar A, He X, Braverman LE, Pearce EN. Iodine status and thyroid function of Boston-area vegetarians and vegans. J Clin Endocrinol Metab. 2011 Aug. 96(8):E1303-7. [QxMD MEDLINE Link]. [Full Text].
Lee SY, Stagnaro-Green A, MacKay D, Wong AW, Pearce EN. Iodine contents in prenatal vitamins in the United States. Thyroid. 2017 Aug. 27(8):1101-2. [QxMD MEDLINE Link]. [Full Text].
Pearce EN, Caldwell KL. Urinary iodine, thyroid function, and thyroglobulin as biomarkers of iodine status. Am J Clin Nutr. 2016 Sep. 104(Suppl 3):898S-901S. [QxMD MEDLINE Link]. [Full Text].
Faix JD, Miller WG. Progress in standardizing and harmonizing thyroid function tests. Am J Clin Nutr. 2016 Sep. 104(Suppl 3):913S-7S. [QxMD MEDLINE Link]. [Full Text].
Zimmermann MB, Moretti D, Chaouki N, et al. Development of a dried whole-blood spot thyroglobulin assay and its evaluation as an indicator of thyroid status in goitrous children receiving iodized salt. Am J Clin Nutr. 2003 Jun. 77(6):1453-8. [QxMD MEDLINE Link]. [Full Text].
Zimmermann MB, Aeberli I, Andersson M, et al. Thyroglobulin is a sensitive measure of both deficient and excess iodine intakes in children and indicates no adverse effects on thyroid function in the UIC range of 100-299 µg/L: a UNICEF/ICCIDD study group report. J Clin Endocrinol Metab. 2013 Mar. 98(3):1271-80. [QxMD MEDLINE Link]. [Full Text].
Long SE, Catron BL, Boggs AS, Tai SS, Wise SA. Development of Standard Reference Materials to support assessment of iodine status for nutritional and public health purposes. Am J Clin Nutr. 2016 Sep. 104(Suppl 3):902S-6S. [QxMD MEDLINE Link]. [Full Text].
Krejbjerg A, Pedersen IB, Laurberg P. Can elastography predict growth of incidental thyroid nodules? A pilot two-year follow-up study. Ultrason Imaging. 2016 Sep. 38(5):303-13. [QxMD MEDLINE Link].
Zimmermann MB. Iodine requirements and the risks and benefits of correcting iodine deficiency in populations. J Trace Elem Med Biol. 2008. 22(2):81-92. [QxMD MEDLINE Link].
Cerqueira C, Knudsen N, Ovesen L, et al. Association of iodine fortification with incident use of antithyroid medication--a Danish Nationwide Study. J Clin Endocrinol Metab. 2009 Jul. 94(7):2400-5. [QxMD MEDLINE Link]. [Full Text].
[Guideline] De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012 Aug. 97(8):2543-65. [QxMD MEDLINE Link]. [Full Text].
[Guideline] 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 Mar. 27(3):315-89. [QxMD MEDLINE Link]. [Full Text].
Fisher W, Wang J, George NI, Gearhart JM, McLanahan ED. Dietary iodine sufficiency and moderate insufficiency in the lactating mother and nursing infant: a computational perspective. PLoS One. 2016. 11(3):e0149300. [QxMD MEDLINE Link]. [Full Text].
Trumbo PR. FDA regulations regarding iodine addition to foods and labeling of foods containing added iodine. Am J Clin Nutr. 2016 Sep. 104 Suppl 3:864S-7S. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. 2014 European Thyroid Association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014 Jun. 3(2):76-94. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Iodine Deficiency. Distribution of iodine deficiency in developing countries.
Iodine Deficiency. Typical endemic goiters in 3 women from the Himalayas, an area of severe iodine deficiency. Image courtesy of F. DeLange.
Iodine Deficiency. A man and 3 females (age range, 17-20 y) with myxedematous cretinism from the Republic of the Congo in Africa, a region with severe iodine deficiency. Image courtesy of F. DeLange.
Iodine Deficiency. Histologic sections from a normal thyroid and from an endemic goiter that was removed because of compressive symptoms. The normal thyroid (A) contains thyroid cells arranged in a monolayered sheet around a storage form of thyroid hormone, colloid, while the endemic goiter (B) shows intense hyperplasia with no colloid. Image courtesy of F. DeLange.

of 4

Author

Stephanie L Lee, MD, PhD Associate Professor, Department of Medicine, Boston University School of Medicine; Director of Thyroid Health Center, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Fellow, Association of Clinical Endocrinology

Stephanie L Lee, MD, PhD is a member of the following medical societies: American College of Endocrinology, American Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Sonia Ananthakrishnan, MD Assistant Professor of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center, Boston University School of Medicine

Disclosure: Nothing to disclose.

Elizabeth N Pearce, MD, MSc Associate Professor of Medicine, Boston Medical Center, Boston University School of Medicine

Elizabeth N Pearce, MD, MSc is a member of the following medical societies: American Association of Clinical Endocrinologists, American Thyroid Association, Endocrine Society, Massachusetts Medical Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: President-Elect of the American Thyroid Assocaiiton, Member of the Management Council of the Iodine Global Network<br/>Serve(d) as a speaker or a member of a speakers bureau for: received honorarium for one talk from Merck Serono<br/>Received research grant from: SQM.

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

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

Iodine Deficiency	None	Mild	Moderate	Severe
Median urine iodine, mcg/L	>100	50-99	20-49	< 20
Goiter prevalence	< 5%	5-20%	20-30%	>30%
Neonatal thyroid-stimulating hormone (TSH), >5 IU/mL whole blood	< 3%	3-20%	20-40%	>40%
Cretinism	0	0	+	+
Adapted from the World Health Organization (WHO)/United Nations Children's Fund (UNICEF)/International Council for Control of Iodine Deficiency Disorders (ICCIDD).

Iodine Deficiency Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

References

Tables

Contributor Information and Disclosures

What would you like to print?